Nitrate controversy and cancer causation: An environmental viewpoint

The environmental problem of excess nitrate in food and drink is discussed. In 1982, Dr Geoffrey Taylor died of cancer primarily of gastric origin. Before his death through TV, radio and lectures he stressed the need for research to ascertain upper safe levels for nitrate-nitrite content, especially in vegetables. Additionally he indicated possible links between cancer causation and the ingestion of nitrate-nitrite-derived nitrosamines. This paper is a tribute to his work.Lecture delivered on April 14th, 1983, to the Environmental Science Dept., Farnborough College of Technology, UK.

Population screening and intensity of screening are associated with reduced breast cancer mortality: evidence of efficacy of mammography screening in Australia

BackgroundEfficacy of breast screening may differ in practice from the results of randomized trials. We report one of the largest case–control evaluations of a screening service.

The Accuracy of Sentinel Lymph Node Biopsy in the Treatment of Multicentric Invasive Breast Cancer Using a Subareolar Injection of Tracer

BackgroundThe aim of this study was to evaluate the feasibility and the accuracy of sentinel lymph node biopsy in multicentric breast cancer (MBC) performed by means of a subareolar (SA) injection of both 99Tc-labeled human albumin colloid and lymphazurin.

Expression of CDC25 Phosphatases in Human Gastric Cancer

Background Gastric cancer may be considered the final step of a progressive imbalance between mucosal cell proliferation and apoptosis. CDC25 phosphatases comprise a multigene family, including CDC25A and CDC25B, that plays a crucial role in the control of cell cycle progression and has been linked to the development of human cancers. The role of CDC25 phosphatases in the pathogenesis of gastric cancers is, however, still largely unknown. Material and methods Immunohistochemical expression of CDC25A and CDC25B was investigated in matched normal and cancerous tissues from 70patients with gastric cancer (52 intestinal and 18 diffuse type). Results In non-cancerous gastric tissues the expression of CDC25A and CDC25B was absent or weak. In gastric cancer tissues, the enhanced immunoreactivity of CDC25 phosphatases was independent of intestinal or diffuse type of gastric cancer. However, the intensity of immunostaining was related to the grade of differentiation of the tumors. Interestingly, c-myc expression was directly correlated with CDC25A and B expression. Conclusions The overexpression of CDC25A and B seems to be a common and very early event in the development of both intestinal and diffuse types of gastric cancer and may play an important role in gastric carcinogenesis. KeywordsCDC25A-CDC25B-c-myc-Cell cycle-Gastric cancer

Complete Response of Esophageal Cancer Achieved by Combination Therapy with 5-Fluorouracil, Low-Dose Cisplatin, and Radiation: Report of a Case

per day, from days 1–5 combined with the daily administration of low-dose cisplatin, 10 mg/m2 per day before each fraction of radiation, given as 2 Gy each time, throughout the entire treatment period of 3 weeks beginning on day 1. The benefits of our preoperative chemoradiation therapy included no severe side effects, down-staging and resectability of the tumor, as well as a pathological complete response, which could prolong the survival time. Our experience of this case prompts us to recommend the concurrent daily preoperative chemoradiation therapy for patients with locally advanced esophageal cancer. Key Words: esophageal cancer-chemoradiation-cisplatin-5-fluorouracil-radiosensitization(Received for publication on June 20, 1997; accepted on Jan. 6, 1998)

A Systematic Review and Meta-analysis of the Randomized Controlled Trials on Adjuvant Intraperitoneal Chemotherapy for Resectable Gastric Cancer

BackgroundThe purpose of this systematic review and meta-analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with locally advanced resectable gastric cancer.

Preventing chemoresistance of human breast cancer cell line, MCF-7 with celecoxib

PurposeTo investigate the preventive effect of celecoxib, a specific cyclooxygenase-2 (Cox-2) inhibitor, on the development of chemoresistance in breast cancer cell line, MCF-7, and explore the mechanism of the action.

Intensity-modulated radiation therapy for head and neck cancer

Intensity-modulated radiation therapy (IMRT) involves the delivery of optimized nonuniform beam intensities to the patient. In the head and neck region, there are many critical structures in close proximity to the target, with little influence from internal organ motion. Because IMRT produces tightly conformal doses and steep-dose gradients next to normal tissues, it provides the potential for organ sparing and improved tumor control. The dosimetric superiority of head and neck IMRT over conventional techniques has been demonstrated. The initial results of clinical IMRT studies showed reduction in xerostomia with no compromise in locoregional control if caution and appropriate knowledge are exercised in target determination and delineation.

Stomach-preserving gastric bypass for unresectable pancreatic cancer

From 1992 to 1995, we treated 25 patients who had unresectable pancreatic cancer witha stomach-preserving gastric bypass (SPGB). After as much of the stomach as possible was preserved, it was bypassed to the jejunum by end-to-side anastomosis. During the same period, five patients underwent other types ofbypasses while 47similar patients did not undergo gastric bypass. Althoughthe mean operative time for SPGB was significantly longer than for other types of bypass,the mean intraoperative blood loss was similar. Operative morbidity with SPGB was 28%, and there were no operative deaths. In patients undergoing SPGB, the incidence of delayed gastric emptying was high (24%), but the comfort index (ratio of duration of good palliation to duration of survival) exceeded 50% when metastases wereeither regional or systemic but limited. The comfort index of patients undergoing other types of bypass or not undergoing bypass was less than 40%. However,the patients with extensive systemic metastases survived less than 100 days and the comfort index was less than 30%for all treatment groups. Our resultsthus suggest that SPGB is safe and effective for patients witheither regional metastases or limited systemic metastases. Key Wordspancreatic cancer-gastric bypass-stomach-preserving-quality of life

Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer

IntroductionNonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531.

Cost-Effectiveness of Colorectal Cancer Screening in the Average Risk Population

Colorectal cancer (CRC) is a leading cause of cancer death in North America and in Israel. Risk of CRC increases exponentially with age starting at the age of 50 years. Therefore, people older than 50 years are being considered as an average risk population for CRC. The objective of this study was to obtain an improved assessment of the cost-effectiveness analysis of screening for CRC in the average risk population by using a more accurate technique, namely the Partially Observed Markov Decision Process (POMDP). We conducted a cost-effectiveness analysis within the specific probability rates and costs in Israel.This study revealed that it is highly cost-effective to screen average-risk asymptomatic individuals.

High PRL-3 expression in human gastric cancer is a marker of metastasis and grades of malignancies: an in situ hybridization study

Phosphatase of regenerating liver (PRL)-3, encoding a 22-kD low molecular weight tyrosine phosphatase, has been reported to be associated with metastasis of colorectal carcinoma. We assessed the levels of PRL-3 mRNA expression to know whether its up-regulation was involved in progression and metastasis of gastric carcinoma. Levels of PRL-3 expression in 94 human gastric adenocarcinomas and 54 matched lymph node metastases were detected by in situ hybridization and compared with clinicopathological characteristics including prognosis. High PRL-3 expression was detected in 36.2% of primary gastric carcinoma (with nodal metastasis, 55.6%; without nodal metastasis, 10%; P < 0.001) and in 74.1% of lymph node metastases. The incidence of high PRL-3 expression in lymph node metastasis was significantly higher than in primary tumors (P < 0.044). Moreover, high expression of PRL-3 was closely associated with tumor size, lymphatic invasion, venous invasion, extent of lymph node metastasis, and tumor stage. These results suggest that high PRL-3 expression may participate in the progression and metastasis of gastric carcinoma. PRL-3 might be a novel molecular marker for aggressive gastric cancer. Keywords PRL-3 -Gastric carcinoma- in situ hybridization-Lymph node metastasis

Hookah smoking and cancer: carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers

BackgroundWe have recently published some work on CEA levels in hookah (also called narghile, shisha elsewhere) and cigarette smokers. Hookah smokers had higher levels of CEA than non-smokers although mean levels were low compared to cigarette smokers. However some of them were also users of other tobacco products (cigarettes, bidis, etc.).

Salvage therapy for locally recurrent prostate cancer after external beam radiotherapy

The greatest obstacle in the cure of patients with locally recurrent prostate cancer after radiation therapy is the lack of early detection markers. The majority of patients who are candidates for local salvage therapy have locally advanced disease, precluding successful salvage therapy. A low pretreatment prostate specific antigen (PSA) has shown to be a favorable prognostic variable for disease progression, regardless of the specific local salvage therapy used. Of all the local salvage treatment options for these patients, we believe that salvage radical prostatectomy (RP) offers patients the great-est likelihood of a cure. The salvage RP results approach those achieved with standard RP for patients of similar pathologic stage. When patients are treated early in the course of recurrent disease (preoperative PSA < 10 ng/mL), an estimated two-thirds of patients will be disease-free 5 years after salvage RP alone. With better patient selec-tion and continued technical modifications, the morbidity associated with salvage RP has substantially improved. Perioperative complications approach those observed with standard RP and approximately two-thirds of patients will recover urinary continence. Select patients may also recover functional erections when nerve-sparing techniques are used. Salvage cryotherapy and brachytherapy are minimally invasive alternatives to salvage RP. The cancer control results of these procedures appear to be inferior to results achieved with salvage RP. Each of these procedures is associated with signifi-cant morbidity and do not appear to provide a clear advantage over salvage RP in terms of posttreatment complications, urinary continence, and erectile function. A long-term cure is possible for patients with locally recurrent prostate cancer after radiation therapy. Local salvage therapy must be instituted early to be successful in the course of progressive disease.

Perception of risk, anxiety, and health behaviors in women at high risk for breast cancer

Perception of risk, anxiety, psychological distress, and early detection behavior were investigated in 23 women with a family history of breast cancer who attended genetic counseling and 21 women without a family history of breast cancer. In addition to a breast cancer-specific questionnaire, the Symptom Checklist 90-Revised and the State-Trait Anxiety Inventory were used. Thirty-nine percent of the women with a family history of breast cancer correctly identified and 48% overestimated their own lifetime risk. Risk perception was independent of genetic counseling. Levels of general psychological morbidity were similar between women with a family history of breast cancer and controls. For controls, early detection behavior was related to lifetime risk estimate and was, in general, independent of level of anxiety. Despite genetic counseling, many women continued to perceive their own lifetime risk of breast cancer inaccurately. They might benefit from additional counseling on risk assessment. Key wordsbreast cancer-genetic risk-risk perception-early detection behavior-psychological distress

Notes on the operative treatment of uterine cancer

[Read in the Section of Obstetrics, November 28, 1890.]

High polymorphism in the trisomic portion of a gastric cancer cell line

BackgroundGenetic instability is a hallmark of malignancy, and microsatellite instability is a widely appreciated mechanism of generating genetic changes. We have recently observed four markers clustered on chromosome 20 that showed the effects of microsatellite instability in the gastric adenocarcinoma cell line SNU-1. Each affected marker had alleles of three different sizes. The aim of this study was to investigate the origin for this high-density polymorphism on a single chromosome.

Neural Cell Adhesion Molecule in Cancer: Expression and Mechanisms

This article has been withdrawn due to changed publication policy. Its content will be published in a book instead.

Prognostische relevanz von mutiertem P53-Protein und DNA-Flu?zytometrie beim Mammakarzinom

GrundlagenBei Patientinnen mit Brustkrebs k?nnen sich im Frühstadium lokale Rezidive und/oder Fernmetastasen bilden. Das Hauptziel klinischer Studien ist verl??liche Prognosekriterien zu finden, um Patientengruppen, die von einer adjuvanten Therapie zur Verhinderung eines Fortschreitens der malignen Grundkrankheit profitieren, selektieren zu k?nnen.

Multiple primary cancers: With reference to atomic bomb survivors in Hiroshima

We treated 44 patients with multiple primary cancers, at the Second Department of Surgery, Hiroshima University, during the 14 year period from 1968–1981. The total number of malignant tumors was 1,934 during this period, thus the incidence of multiple primary cancers was 2.3 per cent. Nine of the 44 were atomic bomb survivors in Hiroshima and were characterized by the frequent incidence of the second tumor about 30 years after exposure to the atomic bomb. In addition, the second tumor tended to develop later in patients prescribed radiotherapy for the first tumor. As for the site of tumor, there was no tendency of more frequent development of tumors in organs highly sensitive to radiation other than the thyroid. Key Wordsmultiple primary cancers-atomic bomb survivors-radiotherapy

Cardiopulmonary rehabilitation after treatment for lung cancer

Lung cancer is the leading cause of cancer-related death in women and men in the United States. As of 1987, lung cancer deaths in women exceeded deaths caused by breast cancer. Despite years of research and improvements in surgical, chemotherapeutic, and radiation treatments, this fact remains unchanged. Equally dismal is that the expected 5-year survival rate for all patients with lung cancer is 15%. Although hidden in this number is improved survival for many patients who have early disease, it still translates into significant morbidity and early mortality for many patients. Although prevention is key, optimizing the care of these patients with lung cancer is also paramount. Cardiopulmonary rehabilitation programs have been shown to be effective in treating patients with chronic heart and lung diseases, among other illnesses, regardless of prerehabilitation functioning. Not only do morbidity and mortality from cancer hinge directly on premorbid functioning, health, and status, but functional status as a measure of baseline health is a reliable prognostic indicator for patients with lung cancer. As a result, including a program of exercise in any treatment regimen for cancer is sensible. However, rehabilitation in patients with lung cancer has not been studied well. Data on rehabilitation in patients with other cancers and illnesses (eg, chronic obstructive pulmonary disease) are clear in the beneficial effects of supervised exercise on quality of life (QOL). To assess the role of cardiopulmonary rehabilitation in patients with lung cancer undergoing treatment, it is necessary to meld studies regarding patients with noncancerous conditions with studies addressing rehabilitation in patients with cancer. This fusion of information demonstrates that rehabilitation results in significant improvements in QOL in patients who participate, regardless of the disease in question. Although QOL may not always have been an obvious endpoint for treating patients with lung cancer, it is apparent from studies of the patients themselves that an improved QOL is far more important than other goals of therapy.

Zystektomie und Blasenteilresektion in der Behandlung des Harnblasenkarzinoms

87 Patienten mit einem Urothelkarzinom der Harnblase wurden einer offenen Operation unterzogen. Das sind 13.6% aller in diesem Zeitraum behandelten Blasenkarzinome. Bei 37 Patienten wurde eine Blasenteilresektion durchgeführt, bei 50 Patienten eine Zystektomie mit Ileumconduit. Die 5-Jahres-überlebensrate nach Blatsenteilresektion betrug 42% (11/26) und 36% (13/36) nach Zystektomie. Transabdominal operations were performed on 87 patients with urinary bladder carcinoma (13.6% of all cases observed during the same period). Partial bladder resection was performed on 37 patients. The 5-year survival rate was 42% (11/26). Total cystectomy was performed in 50 patients, the 5-year survival rate was 36% (13/36).

Preoperative transcatheter arterial chemo-embolization for locally advanced breast cancer —Application of new thrombotic materials—

The anticancer drugs, Adriamycin and Mitomycin were individually immobilized on absorbable gelatin materials, together with a blood clotting factor, Factor XIII and thrombin, using a special technique. The materials were applied as thrombotic agents in preoperative therapeutic transcatheter arterial embolization for patients with locally advanced breast cancer. This approach to preoperative management proved to be superior to intra-arterial infusion therapy currently applied in various clinics. Key wordsblood clotting factor XIII-transcatheter arterial chemoembolization (TACE)-(locally advanced) breast cancer

Formation of benzo[a]pyrene-DNA adducts in blood monocytes from lung cancer patients with a familial history of lung cancer

The in vitro formation of benzo[a]pyrene-DNA adducts was determined in peripheral blood monocytes of 22 lung cancer patients with at least one first-degree relative with lung cancer and compared to results obtained in 30 healthy controls. In patients, the mean (SEM) adduct formation was 2.8 (0.3) fmol/g DNA as compared to 2.1 (0.1) fmol/g in controls (pKey wordsLung cancer-Genetic predisposition-Familial cancer-Benzo[a]pyrene, DNA adductsThis work was supported by a grant from the German Minister for Research and Technology, BMFT

The Impact of 18-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography on the Staging and Management of Primary Rectal Cancer

Purpose18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) has a role in recurrent colorectal cancer. This study was designed to assess the impact of PET-CT on management of primary rectal cancer.

The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk

This study aimed to determine the relation between methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism and lung cancer risk and the frequency of this polymorphism. The study involved 64 lung cancer patients (the study group) with definitive diagnosis and 61 noncancerous subjects (the control group). MTHFR C677T and A1298C mutation analysis was made using DNA isolated from peripheric blood and multiplex PCR and reverse hybridization strip test. Eighty-four percent of the patients were male. The age, gender, and history of alcohol use of the patients and control group were statistically similar. While MTHFR 677T and 677C allele frequency was 0.33 and 0.67 in the patients respectively, it was 0.29 and 0.71 in the control group. The frequencies of MTHFR 1298C and 1298A were 0.33 and 0.67 in the patients, and it was 0.31 and 0.69 in the control group respectively. When MTHFR 677TT and 677CT genotypes were compared with 677CC genotype, lung cancer risk was 2.4 times higher in the 677TT genotype. When MTHFR 1298AC and 1298CC genotypes were compared with 1298AA genotype, lung cancer risk was 1.5 times higher in 1298CC genotype. According to the results, allele frequency of homozygote T and C was high in lung cancer patients. It was 3.05 and 1.29 times higher in smokers than in non-smokers, and 3.05 and 1.64 times higher in males than in females; 3.0 and 2.44 times higher in those with non-small cell lung cancer than in those with small-cell lung cancer.

Intraarterial Adjuvant Chemotherapy after Pancreaticoduodenectomy for Pancreatic Cancer: Significant Reduction in Occurrence of Liver Metastasis

The clinical benefit of adjuvant chemotherapy in pancreatic cancer patients is still questionable. Phase II studies using radiochemotherapy based on 5-fluorouracil (5-FU) provided evidence of an increase in median survival times. Because palliative chemotherapy by celiac artery infusion (CAI) led to an increase in survival in pancreatic cancer, we treated 24 patients with adjuvant CAI following resection of the head of the pancreas for pancreatic cancer (21 patients with Union Internationale contre le Cancer (UICC) stage III, 2 with UICC stage II, 1 with UICC stage I). Catheters were placed angiographically into the celiac artery and remained there for 5 consecutive days. One cycle of chemotherapy consisted of mitoxantrone, 5-FU, folinic acid, and cisplatinum. This treatment was repeated five times at monthly intervals. CAI was well tolerated, and World Health Organization (WHO) grade III toxicities were observed in 8%; WHO grade IV was seen in none of the treatment cycles. Furthermore, we observed pain reduction in nearly all patients under CAI. Median survival times in patients who received CAI were 23 months for all patients, whereas in patients who did not receive adjuvant treatment the median survival was 10.5 months. With Kaplan-Meier regression analysis of the patients who were curatively resected (R0 resection) and received CAI, the overall 4-year survival was 54%, whereas in patients without CAI the 4-year survival was 9.5%. The occurrence of liver metastases in the CAI group went down to 17%. These results demonstrate that CAI is well tolerated, reduces the risk of liver metastasis, and increases the survival time of pancreatic cancer patients.

In vitro evaluation of the effects of gefitinib on the modulation of cytotoxic activity of selected anticancer agents in a panel of human ovarian cancer cell lines

PurposeThis study was conducted to determine the in vitro optimal combination of selected anticancer agents with gefitinib and evaluate its effect on the expression of correlative biological targets in the cell-signaling pathway. In addition, the effect of gefitinib on the expression of ATP-binding cassette (ABC) transport proteins was evaluated.

DNA repair gene XRCC1 polymorphisms and bladder cancer risk

BackgroundCigarette smoking and chemical occupational exposure are the main known risk factors for bladder transitional cell carcinoma (TCC). Oxidative DNA damage induced by carcinogens present in these exposures requires accurate base excision repair (BER). The XRCC1 protein plays a crucial role in BER by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, we conducted a comprehensive analysis of 14 XRCC1 polymorphisms in a case-control study involving more than 1100 subjects.

Biochemical markers for the detection of bone metastasis in patients with prostate cancer: diagnostic efficacy and the effect of hormonal therapy

In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(−)HT(−)) and 34 patients without bone metastasis on hormonal therapy (BM(−)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procollagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(−)HT(+) group, the BM(+) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(−)HT(−) and BM(−)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(−)HT(−) groups with regard to bone formation and resorption, respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(−)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation. Key words prostate cancer-bone metastasis-biochemical markers of bone turnover-antiandrogen-luteinizing hormone-releasing hormone analogReceived: November 18, 1999 / Accepted: June 12, 2000

Role of CA125 in predicting ovarian cancer survival - a review of the epidemiological literature

CA125 is the gold standard tumor marker in ovarian cancer. Serum level of CA125 is used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients. Thus, it is reasonable to investigate whether CA125 may have utility as a prognostic indicator as well in ovarian cancer. A large number of epidemiological studies have been carried out to this effect. This review summarizes all available epidemiological literature on the association between CA125 levels and survival in ovarian cancer. To place these studies in context, we provide some background information on CA125 and its role in ovarian cancer.

Modified irinotecan plus bolus 5-fluorouracil/L-leucovorin for metastatic colorectal cancer at a single institution in Japan

BackgroundThe modified irinotecan plus bolus 5-fluorouracil/L-leucovorin (IFL) regimen (irinotecan plus bolus 5-fluorouracil/L-leucovorin) used to be one of the standard treatments for metastatic colorectal cancer until approval of oxaliplatin in Japan. We evaluated the efficacy of modified IFL therapy for Japanese patients.

Conservative treatment of breast cancer: Milan experience

BackgroundThe conservative treatment of operable breast cancer has gradually become well-established during the last 20 years as it offers adequate loco-regional control of the disease and saves the brest. Moreover, larger, demolishing operations have not shown to decrease the risk of distant metastases.

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review. Key wordsPancreas-Invasive ductal carcinoma-Intraductal–papillary mucinous neoplasm-Pancreatic intraepithelial neoplasia-Mucinous cystic neoplasm-Mucin

Roles of gastrointestinal hormones in pancreatic cancer

Several gastrointestinal (GI) hormones, such as gastrin, cholecystokinin, and bombesin, have been reported to affect the development of pancreatic cancer. The receptors for these hormones are found in normal and neoplastic pancreatic cells. Activation of these receptors enhances pancreatic carcinogenesis and promotes the growth of established pancreatic carcinoma either in vitro or in vivo. On the other hand, some studies have shown that these GI hormones may have no effect or may play an inhibitory role in the development of pancreatic cancer. The reasons for the apparent discrepancies in the published literature are discussed in this review. In recent years, increasing emphasis has been placed on the effects of GI hormones on cancer invasion and metastasis. As the transition from noninvasion to the invasive state is the crucial event in cancer development, further investigation of the way in which GI hormones affect the invasion and metastasis of pancreatic cancer may be important for the development of new therapeutic approaches with eventual clinical utility. Key words: cholecystokinin-gastrin-bombesin-pancreatic cancer-metastasisReceived for publication on Oct. 23, 1999; accepted on Feb. 2, 2000

The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer

AimRecent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes’ A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion.

Search for residual prostate cancer on pT0 radical prostatectomy after positive biopsy

Reported incidence of no residual prostate cancer (i.e. pathological stage pT0) on radical prostatectomy ranges from 0.07 to 4.2%. The incidence is higher after neoadjuvant endocrine treatment. The aim of this study was to search for residual cancer on radical prostatectomy (RP) specimens when an initial sampling failed to find the cancer in patients with positive biopsy. Our database of 1,328 consecutive patients whose biopsies and RP specimen were both examined at the Polytechnic University-United Hospitals of the Marche Region between March 1995 and June 2006 was reviewed. The radical prostatectomies were grossly completely sampled and examined with the whole mount technique. We identified eight patients (i.e. 0.6%; three untreated and five hormonally treated preoperatively, i.e. 0.3 and 0.8%, respectively, of the total number of RPs included in the study) with positive biopsy and with no residual cancer in the initial routine histological examination of the RP. The RP of this group of eight was subjected to additional sectioning and evaluation of the paraffin blocks of the prostatectomy, also after block-flipping, immunostaining with an antibody against CAM 5.2, p63, PSA, and alpha-methylacyl-CoA racemase, and DNA specimen identity analysis. There were no cases with a false positive biopsy diagnosis, and cancer was not overlooked or missed in the initial routine histological examination of any of the 8 pT0 RPs. A minute focus of cancer (the diameter was always below 2.0mm) was found on the additional sections in five. In particular, cancer was found after block-flipping in one of them. In an additional case, cancer was eventually discovered after immunostaining tissue sections for cytokeratin CAM 5.2, for p63 and PSA. In the remaining two cases (one untreated and the other hormonally treated), cancer was not found (0.15% of the 1,328 RPs included in the study); the review of the description of the macroscopic appearance of the RP and of its slides revealed that part of the peripheral zone corresponding to the site of the positive biopsy was missing, i.e. not removed from the patient at the time of the operation at least in one of the two. DNA specimen analysis confirmed the identity of the biopsy and prostatectomy in both. An extensive search for residual cancer reduces the number of pT0 RPs after a positive biopsy from 0.6 to 0.15%. It is recommended to have the needle biopsy reviewed, carefully look again at the radical prostatectomy, do deeper sections and then flip certain paraffin blocks. In addition, atypical foci should be stained for basal cell markers and often AMACR, especially in hormone-treated cases. If a block is missing part of the peripheral zone (capsular incision), this should be commented on. DNA analysis for tissue identity should be performed when the other steps have been taken without finding cancer. KeywordsProstate cancer-Residual prostate cancer-Vanishing cancer

Role of decay-accelerating factor in regulating survival of human cervical cancer cells

BackgroundDecay-accelerating factor (DAF) is one of the key molecules involved in cell protection against autologous complement, which restricts the action of complement at critical stages of the cascade reaction. The effect of DAF on the survival of human cervical cancer cell (ME180) has not been demonstrated.

Management of paraneoplastic syndromes in lung cancer

Paraneoplastic syndromes are common complications of lung cancer. Although most frequently associated with advanced disease, paraneoplastic syndromes may also occur at early stages. Occasionally, the paraneoplastic syndrome may be the presenting symptom of lung cancer. For most paraneoplastic syndromes, the best treatment is to treat the underlying malignancy. However, in many cases, treatment of moderate efficacy or urgent therapy is required. Specific recommendations for the management of the most common paraneoplastic syndromes, including cachexia, hypercalcemia, and hyponatremia, are provided.

Phase II trial of fludarabine phosphate (F-Ara-AMP) in patients with advanced breast cancer

Eighteen patients with advanced breast cancer were entered into a phase II study of fludarabine phosphate. Fludarabine phosphate was given by continuous infusion for 5 days, at a starting dose of 20 mg/m2 per day for patients previously treated with two or more regimens and 25 mg/m2 per day for minimally treated patients with less than two prior regimens; therapy was repeated every 3–4 weeks. Of the 18 patients, 11 had undergone more than two prior regimens and 7 patients had undergone one prior regimen. One patient achieved a partial response (PR) for 22 months. Myelosuppression was the most common toxicity observed. Four patients developed mild nausea and vomiting and two developed a nonspecific dermatitis that resolved spontaneously. No renal, hepato-, or neurotoxicity was observed. Our study demonstrates that in heavily pretreated patients, fludarabine phosphate given on this schedule has minimal efficacy in treating advanced breast cancer. This drug might possibly have shown more activity in a previously nontreated patient population. However, patients with advanced breast cancer, who have not undergone previous treatment are not often encountered.This paper was presented in part at the 14th International Congress for Cancer Chemotherapy: Kyoto, Japan, 1985

Risk factors of female cancers in Ragusa population (Sicily). 2. Breast cancer

A case-control study on breast, cervix and corpus uteri cancer cases registered in Ragusa between January 1, 1983 and June 30, 1985 has been conducted. Information on risk factors has been obtained by means of a structured questionnaire.Risk factors for breast cancer were: few pregnancies (1–2 vs > 4 OR 2.14, 95%CL 1.13–4.04), few children (for postmenopausal only, chi trend 4.84), previous breast disease (OR 1.97, 95%CL 1.20–3.23), family history (OR 3.57, 95%CL 1.92–6.63), alcohol (OR 1.68, 95%CL 1.12–2.53), high socioeconomical status (1 vs 4 OR 2,93, 95%CL 1.22–70.03). A protective role was evident for: early age at first birth (for premenopausal only, 20 OR 0.11, 95%CL 0.01-0.90), previous ovary disease (OR 0.26, 95%CL 0.08–0.88).

Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio

BackgroundZerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines.

Delayed anastomotic leakage following sphincter-preserving surgery for rectal cancer

PurposeThe aim of the present study was to investigate the characteristics of patients who developed delayed anastomotic leakage (DAL) following sphincter-preserving surgery for rectal cancer. We evaluated the following factors: (1) the incidence of DAL, (2) the clinical features of patients who developed DAL, (3) the risk factors for DAL, and (4) treatment outcomes.

Prophylactic cranial irradiation in lung cancer

Patients with locally advanced lung cancer (non-small cell lung cancer or small cell lung cancer [SCLC]) are threatened by concurrent risks of local, regional, and distant failure. By improving locoregional and systemic control within multimodality protocols, the brain emerges as one of the major relapse sites; therefore, prevention of brain relapse has become a primary focus of attention. Prophylactic cranial irradiation (PCI) has a high potential to reduce the risk of brain metastases. Clear evidence exists from meta-analysis that PCI improves overall and disease-free survival rates for patients with SCLC in complete remission. Long-term toxicities, predominantly neurocognitive impairments, represent potential risks, but within large prospective trials, including adequate control groups, late complications of clinical significance rarely have been observed. PCI is the recommended standard of care for the patients with limited disease SCLC in complete remission. As long as the optimal dose and fractionation remain to be defined in this setting, conventional fractionation with moderate total doses of approximately 30 Gy is preferred. In patients with locally advanced stage III non-small cell lung cancer treated within multimodality protocols, comparable relative risks for cumulative brain relapse have been demonstrated in long-term survivors. Although not the standard of care in this situation, the scientific community should be encouraged to further investigate PCI in these patient subgroups within carefully designed clinical trials, including untreated control arms.

Suprarenal Clostridium septicum Aortitis with Rupture and Simultaneous Colon Cancer

We report a case of combined colon cancer and Clostridium septicum aortitis involving the suprarenal abdominal aorta with rupture. An 82-year-old male presented with fever, abdominal pain, and back pain associated with constipation. He was successfully treated by in situ aortic graft placement with polytetrafluroethylene and concomitant colon resection. Only 20 other cases of C. septicum mycotic aneurysm, aortitis, or aortic dissection have been reported. Concomitant surgical treatment for Clostridium aortitis or mycotic abdominal aortic aneurysm and colon cancer can be accomplished successfully in selected cases when the diagnosis of both conditions is made preoperatively.

Effects of intraoral prosthetics on swallowing in patients with oral cancer

The swallowing patterns of four patients with oral cancer with intraoral palate reshaping/lowering prostheses were studied with and without their prostheses 3 months postoperatively. The prostheses resulted in improved swallow efficiency, increased duration of tongue contact to the pharyngeal wall, and improved speed of movement of the bolus from the valleculae to the pyriform sinus. These results emphasize the effects of the tongue on the pharyngeal as well as oral stage of the swallow. Key wordsIntraoral prosthesis-Oral cancer

Loss of cell-surface receptor EphB2 is important for the growth, migration, and invasiveness of a colon cancer cell line

PurposeIn normal colonic epithelium, the receptor tyrosine kinase, EphB2 interacts with ephrinB1 ligand to maintain the integrity and architecture of the colonic crypt. Loss of EphB2 is seen in most colorectal cancers and correlates with poor prognosis. In this study, we investigated the effects of two levels of EphB2 expression on cell migration and invasion in a colon cancer cell line and on the growth of tumour xenografts.

Hypocholesterolemia in cancer patients may be caused by elevated LDL receptor activities in malignant cells

Several epidemiological studies indicate an inverse relation between plasma cholesterol and the occurrence of cancer. Since we in previous studies have found that certain malignant cell types have an elevated LDL receptor activity, the aim of the present study was to further explore the possibility that an elevated LDL consumption by tumor cells causes hypocholesterolemia. The plasma cholesterol concentrations in patients with acute leukemia were inversely correlated with the rate of receptor-mediated degradation of125I-LDL by the leukemic cells. During chemotherapy, the total plasma and the LDL cholesterol levels increased concomitantly with the reduction in the leukemic cell count in a patient whose leukemic cells exhibited a high rate at receptor-mediated degradation of125I-LDL. In certain patients with inoperable urinary bladder carcinoma, the plasma cholesterol concentration fell as the disease progressed. Studies in breast cancer patients indicate that the number of LDL receptors in the tumor tissue may have prognostic significance. The results are in agreement with the hypothesis that an elevated LDL receptor activity in malignant cells may lead to hypocholesterolemia. Key wordsHypocholesterolemia-LDL-Receptors-Cancer-Cells

Genetic changes at specific stages of breast cancer progression detected by comparative genomic hybridization

Although a simple linear progression model for breast cancer has already been proposed, its validity still remains controversial. Especially, the genetic and molecular features of breast cancer at different stages during the development and progression, as well as their relationship, have rarely been studied under the same experimental conditions simultaneously. According to these limitations in this research area, the current study applied comparative genomic hybridization technique to investigate genomic changes in 15 cases of breast atypical ductal hyperplasia (ADH), 15 cases of ductal carcinomas in situ (DCIS), and 15 cases of invasive ductal carcinomas (IDC) and the relationship among the genetic changes. Thirty commonly altered regions that were identified included known (gains of 1q,8q, 17q,20q,Xq and losses of 8p,13q,16q,17p,22q) and several uncharacterized (gains of 2q,5p, 10p,12q,16p,18q, etc. and losses of 11p13-pter,11q,14q,Xp, etc). The overall frequency of copy number losses was higher in IDC than that in DCIS (P = 0.013). ADH showed more frequent gain of 17q than that in IDC (P = 0.007), and IDC exhibited a higher frequency for the loss of 22q than that in ADH (P = 0.018). On one hand, several common genomic changes shared by ADH, DCIS, and IDC make a linear relationship for these three lesions possible. On the other hand, the heterogeneity has also showed clonal diversification and different pathways of breast cancer progression. The regions of chromosomal copy number alterations may bring new insights into the strategy for tumor progression blocking and the discovery of new potential targets for breast cancer treatment. KeywordsBreast-Breast cancer progression-Chromosome-Comparative genomic hybridization-Molecular cytogenetics

l-Dopa decarboxylase expression profile in human cancer cells

l-Dopa decarboxylase (DDC) catalyses the decarboxylation of l-Dopa. It has been shown that the DDC gene undergoes alternative splicing within its 5′-untranslated region (UTR), in a tissue-specific manner, generating identical protein products. The employment of two alternative 5′UTRs is thought to be responsible for tissue-specific expression of the human DDC mRNA. In this study, we focused on the investigation of the nature of the mRNA expression in human cell lines of neural and non-neural origin. Our results show the expression of a neural-type DDC mRNA splice variant, lacking exon 3 in all cell lines studied. Co-expression of the full length non-neural DDC mRNA and the neural-type DDC splice variant lacking exon 3 was detected in all cell lines. The alternative DDC protein isoform, Alt-DDC, was detected in SH-SY5Y and HeLa cells. Our findings suggest that the human DDC gene undergoes complex processing, leading to the formation of multiple mRNA isoforms. The study of the significance of this phenomenon of multiple DDC mRNA isoforms could provide us with new information leading to the elucidation of the complex biological pathways that the human enzyme is involved in.

Regional pancreatectomy for cancer of the pancreas, ampulla and other related sites

Regional pancreatectomy refers to anen bloc removal of a tumor in or adjacent to the pancreas with an adequate soft tissue margin and with its regional lymphatic draingae. The pancreatic segment of portal vein is part of theen bloc resection with venous reconstruction by end-to-end anastomosis without a graft. This operation, called a Type I regional pancreatectomy, may utilize either a total or subtotal removal of the pancreas. Localized arterial involvement by a neoplasm necessitates adding a segmental resection of the artery with vascular reconstruction, a Type II procedure. Sixty-one patients have had this procedure from 1972 through December 1982. Thirty-four patients had an infiltrating duct adenocarcinoma of the pancreas, 22 had other malignant tumors, 4 were classified as having pancreatitis, and a fifth had a pseudolymphoma. The resectability rate is about 30 per cent. The present operative mortality rate is 4 per cent by 30 days and 8 per cent after 30 days. One-third of the patients are presently alive; 45 per cent of the 22 patients with malignant tumors other than infiltrating duct adenocarcinoma of the pancreas are alive with a median survival time of 39 1/2 months ranging from 3 to 92 months. More than 80 per cent of patients with infiltrating duct adenocarcinoma of the pancreas had advanced stage of the disease (T3 or T4 and Stage II or III cancers); twenty-one per cent are presently alive, 29 per cent died of recurrent disease, and 24 per cent died of other causes. The optimal treatment for patients with cancers in the region of the head of the pancreas is a regional subtotal pancreatectomy Type I or Type II followed by adjuvant chemotherapy. Key Wordsregional pancreatectomy-pancreatectomy-pancreas cancer-portal vein resection-vascular reconstruction

Cell cycle perturbations and radiosensitization effects in a human prostate cancer cell line

Purpose. To test the hypothesis that radiation-induced, transient G2/M arrest could potentially sensitize tumor cells to a subsequent, well-timed radiation dose. Methods. PC-3 human prostate cancer cells were treated using either radiotherapy or 186Re-labeled hydroxyethylidene diphosphonate (186Re-HEDP) treatment in different combinations. The resulting cell cycle shift and clonogenic cell death were analyzed by DNA flow cytometry and colony forming cell assay, respectively. Results. Radiation doses of 4 Gy and 8 Gy induced a transient G2/M arrest, with a maximum after approximately 16 h. The presence of 2 mM pentoxifylline effectively abrogated this radiation-induced G2 M arrest, confirming a cell-cycle checkpoint-mediated effect. A second dose of 4 Gy, timed at the height of the G2/M arrest, significantly increased clonogenic cell-kill compared to delivery after a suboptimal interval (10 h, 20 h or 25 h after the first radiation fraction). Moreover, timed second doses of 2 Gy, 3 Gy or 4 Gy yielded improved normalized treatment effects compared to non-pretreated control. Radionuclide treatment of PC-3 cells, using 186Re-HEDP (0.74 MBq/ml and 1.48 MBq/ml; total dose: 4.1 and 8.2 Gy, respectively) also induced a dose-dependent G2/M accumulation, which sensitized the cells to a subsequent external radiation dose of 2 Gy or 4 Gy. The observed pattern of cell-cycle shift towards a predominance of the G2/M phase is in line with the lack of functional p53 in this cell line. Conclusions. Radiation-induced cell-cycle shift was shown to effectively confer increased radiosensitivity to prostate tumor cells. Optimally timed combination of radiotherapy and radionuclide therapy could thus significantly increase treatment efficacy.

The Accuracy of Sentinel Lymph Node Biopsy in the Treatment of Multicentric Invasive Breast Cancer Using a Subareolar Injection of Tracer

BackgroundThe aim of this study was to evaluate the feasibility and the accuracy of sentinel lymph node biopsy in multicentric breast cancer (MBC) performed by means of a subareolar (SA) injection of both 99Tc-labeled human albumin colloid and lymphazurin.

How Do Cancer Patients Navigate the Public Information Environment? Understanding Patterns and Motivations for Movement Among Information Sources

Little is known about how patients move among information sources to fulfill unmet needs. We interviewed 43 breast, prostate, and colorectal cancer patients. Using a grounded theory approach, we identified patterns and motivations for movement among information sources. Overall, patients reported using one source (e.g., newspaper) followed by the use of another source (e.g., Internet), and five key motivations for such cross-source movement emerged. Patients’ social networks often played a central role in this movement. Understanding how patients navigate an increasingly complex information environment may help clinicians and educators to guide patients to appropriate, high-quality sources.

A simple colostomy implantation model for evaluating colon cancer

PurposeRealistic models of colorectal cancer are necessary to study cancer biology and evaluate therapeutic interventions. Real-time observation and repeated sampling of implanted tumor is difficult to achieve in the current orthotopic animal colorectal cancer model. The aim of this study was to establish a simple colostomy implantation mouse model for evaluating colon cancer.

The importance of KRAS status in managing metastatic colorectal cancer

In the past decade, the standard of care for advanced colorectal cancer has been in a state of flux with the introduction of new agents in the treatment of stage IV disease; however, the 5-year survival rate for advanced disease remains low. Investigators are trying to identify biomarkers that may be predictive and/or prognostic for these agents and thereby improve patient outcomes. This article discusses recent discoveries that have identified the importance of KRAS mutational status in predicting responses to epidermal growth factor receptor-targeting antibodies (cetuximab and panitumumab) in the management of metastatic colon cancer.

Micrometastases in Bone Marrow: Prognostic Indicators for Pancreatic Cancer

Minimal residual disease in patients with operable pancreatic carcinoma is frequently missed by current noninvasive tumour staging. We applied an immunocytochemical cytokeratin assay that allows identification of individual pancreatic carcinoma cells disseminated to bone marrow. Prior to therapy, bone marrow was aspirated from the upper iliac crest of 48 patients with ductal adenocarcinoma of the pancreas at various disease stages and an age-matched control group of 33 noncarcinoma patients. Tumor cells in cytologic bone marrow preparations were detected with monoclonal antibodies (mAbs) CK2, KL1, and A45-B/B3 to epithelial cytokeratins (CK) using the alkaline phosphatase antialkaline phosphatase method. CK-positive cells were found in 14 (48.4%) of 31 cancer patients treated with curative intent and in 10 (58.8%) of 18 patients with extended disease. The overall frequency of these cells was 1 to 83 per 5 × 105 mononuclear cells with no significant differences between patients at different tumor stages and lymph node involvement. After a median follow-up of 22.8 months (range 3–48 months), 6 (40.0%) of 15 patients who underwent complete surgical resection but had tumor cells in bone marrow presented with distant metastasis and 7 (46.7%) had local relapse compared to none of 12 corresponding patients without such cells (p < 0.05). Univariate survival analyses revealed that the presence of CK-positive cells was predictive of reduced overall survival. In conclusion, anticytokeratin mAbs are reliable probes for the immunocytochemical detection of single pancreatic cancer cells disseminated to bone marrow. Thus the described technique may help identify patients with pancreatic cancer and at potentially high risk of early metastatic relapse. The results promise to be of important assistance for determining prognosis and the consequences in therapy of early stage pancreatic cancer.

Phase II trial of sequential paclitaxel and 1?h infusion of bryostatin-1 in patients with advanced esophageal cancer

BackgroundWe sought to determine the response rate and toxicity profile of sequential paclitaxel and bryostatin-1, a novel, selective inhibitor of protein kinase C, in patients with advanced esophageal cancer.

Trastuzumab and gemcitabine as salvage therapy in heavily pre-treated patients with metastatic breast cancer

PurposeIn Her2-postive metastatic breast carcinoma, first-line trastuzumab-based therapy is well established; many centres continue antibody treatment beyond disease progression. In this trial, we evaluated the efficacy and safety of gemcitabine and trastuzumab after earlier exposure to anthracyclines, docetaxel and/or vinorelbine, and trastuzumab.

A personal experience with subtotal and conservation surgery as treatment for laryngeal cancer

A personal technique for laryngeal cancer reconstructive surgery is presented and discussed. The functional and therapeutic purpose of this surgery is to broaden its indications and to improve functional results. In particular, our surgical technique involves removal of the soft internal part of the cricoid cartilage (mucosa, submucosa and perichondrium), which is otherwise conserved. Satisfactory functional results can be achieved by: (a) modeling of two symmetrical pseudoarytenoids; (b) an anterior epiglottiplasty or the use of a Hiranandani base-of-the-tongue flap to close the anterior gap (if present); (c) muscular flap lateral-plasty avoiding a cricoidhyoidpexy.Key wordsLaryngeal cancer-Reconstructive laryngectomy-Cricoid cartilage-Laryngeal functional surgery

Cost-Effectiveness of Colorectal Cancer Screening in the Average Risk Population

Colorectal cancer (CRC) is a leading cause of cancer death in North America and in Israel. Risk of CRC increases exponentially with age starting at the age of 50 years. Therefore, people older than 50 years are being considered as an average risk population for CRC. The objective of this study was to obtain an improved assessment of the cost-effectiveness analysis of screening for CRC in the average risk population by using a more accurate technique, namely the Partially Observed Markov Decision Process (POMDP). We conducted a cost-effectiveness analysis within the specific probability rates and costs in Israel.This study revealed that it is highly cost-effective to screen average-risk asymptomatic individuals.

GM-CSF Gene therapy using adenoviral vector in hamster pancreatic cancer

The aim of this study was to examine the antitumor effect of irradiated granulocyte macrophage-colony-stimulating factor (GM-CSF)-gene-transduced hamster pancreatic cancer cells and its relationship to the amount of GM-CSF produced by transduced tumor cells. Hamster pancreatic adenocarcinoma cells, HPD1NR, which spontaneously secrete 15.0 ± 0.4 pg/106 cells per 24 h of GM-CSF, and HPD2NR cells, which do not secrete GM-CSF, were used. When these cells were infected with recombinant adenovirus harboring the GM-CSF gene, HPD1NR and HPD2NR secreted 624.2 ± 9.9 and 157.8 ± 5.7 pg/106 cells per 24 h, respectively. Vaccination with irradiated GM-CSF-secreting HPD2NR completely protected syngeneic hamsters challenged with live parental cells. On the other hand, vaccination with irradiated HPD1NR protected 60% of hamsters from tumor development after challenge with parental cells. None of the tumor-free hamsters initially vaccinated with irradiated GM-CSF-producing HPD2NR cells developed tumor upon repeated challenge with parental cells during the entire observation period. Irradiated GM-CSF-gene-transduced hamster pancreatic cells are promising as a novel adjuvant cancer therapy after surgery for primary and metastatic pancreatic cancer. The results indicate the necessity for a therapeutic strategy for cancer based on the cytokine status of tumors. Key words:GM-CSF gene-gene therapy-pancreatic cancer-vaccine-adenovirusReceived for publication on Dec. 16, 1999; accepted on April 6, 2000

Second primary esophageal or lung cancer in patients with head and neck carcinoma in Taiwan: incidence and risk in relation to primary index tumor site

BackgroundSecond primary cancer is prevalent in patients with head and neck cancer (HNC), for which esophagus and lung are the most usual sites, associated with an extremely poor prognosis. However, information regarding the actual risk of second primary esophageal or lung cancer in South-east Asia, the betel-quid chewing area, has been restricted to data from single-institutions. We have therefore conducted a population-based study to evaluate the incidence, risk, and developmental time of second esophageal or lung cancer in HNC patients.

Difluorodeoxyuridine plasma concentrations after low-dose gemcitabine during chemoradiation in head and neck cancer patients

PurposeThe aim of this study was to investigate whether relevant plasma levels of dFdU could be detected during concurrent chemoradiation (CRT) with low doses of dFdC administered in patients with head and neck cancer and to assess the toxicity related to dose.

The influence of resilience on fatigue in cancer patients undergoing radiation therapy (RT)

PurposeThe primary goal of the study was to determine if resilience influences fatigue in a consecutive sample of cancer patients treated with radiotherapy (RT) at the beginning and at the end of the treatment.

Fat intake and cancer of the gastrointestinal tract and prostate

The epidemiological evidence for and against the postulated role of dietary fat in the aetiology of human gastrointestinal and prostate cancers is critically reviewed. Evidence for a causal association is inconsistent, and much is of low validity. Several studies of colorectal cancer provide evidence to refute the fat hypothesis, at least in some populations. The expanding interest in precursor adenomas and the possible role of fat in their aetiology has led to case-control studies of colorectal adenomas and clinical preventive trials to see if fat is related to risk, but virtually no results have yet been published. The few studies done in relation to prostate cancer justify further investigation of the role of fat, but there appear to be no putative mechanisms to explain an association. Key wordsDietary fat-Epidemiology-Review-Precursors-International

Fatintake, obesity, and cancer of the breast and endometrium

Many studies indicate that obesity is associated with postmenopausal breast cancer and cancer of the endometrium. The mechanisms by which obesity contributes to cancer risk is not known, although increases in serum estrone from Δ4-androstenedione by the adipose tissue have been implicated in postmenopausal women. Blood estrogens increase with the degree of obesity and aging. In animal experiments the confounding of high fat, low carbohydrate, and high calorie diets needs to be defined. The effects of diet on estrogen metabolism; the relationship of fatty acids from animal, vegetable, and marine sources to tumor formation; and the mechanisms by which energy intake influences cancer risk need to be precisely defined. Any estimate of the contribution of heredity to the burden of human cancer is impossible until we have a better understanding of genetic and environmental interactions. Key wordsFat-Energy-Obesity-Estrogens-Cancer-Breast-Endometrium

Palliative radiotherapy for bleeding from advanced gastric cancer: is a schedule of 30?Gy in 10 fractions adequate?

PurposeTo evaluate the effectiveness of short-course radiotherapy (RT) with 30Gy in 10 fractions for bleeding from advanced gastric cancer.

Efficacy of RNAi targeting of pyruvate kinase M2 combined with cisplatin in a lung cancer model

PurposePyruvate kinase isoenzyme M2 (PKM2) is a key enzyme in aerobic glycolysis; inhibition of PKM2 leads to the tumor growth inhibition. In this study, the effects of combined treatment with cisplatin (DDP) and a plasmid that expresses a short hairpin RNA (shRNA) targeting PKM2 on the growth of human A549 xenograft lung cancer model were investigated.

Treatment of colon cancer in rats with rMuTNF and the interferon-inducer bropirimine

It is well documented that the antitumor activity of tumor necrosis factor (TNF) is improved by interferons (IFN's). Bropirimine (BP) is an immune response modifier which induces IFN. Both TNF and BP have the capacity to inhibit the growth of a transplantable colon tumor (CC 531) in inbred WAG rats. In the present study their combined use was investigated in a one-week assay, with the tumor implanted under the renal capsule. The results indicate that BP, given on days 0 and 1, and 1 g TNF on days 0, 2 and 4 act additively, leading to an almost complete inhibition of tumor growth.

Peritoneal lavage CEA/CA125 is a prognostic factor for gastric cancer patients

BackgroundWe recently found an elevation in the pre-operative peritoneal lavage carcinoembryonic antigen (CEA) level to be associated with an earlier detection of recurrent peritoneal dissemination and a poor prognosis.

Preoperative transcatheter arterial chemo-embolization for locally advanced breast cancer —Application of new thrombotic materials—

The anticancer drugs, Adriamycin and Mitomycin were individually immobilized on absorbable gelatin materials, together with a blood clotting factor, Factor XIII and thrombin, using a special technique. The materials were applied as thrombotic agents in preoperative therapeutic transcatheter arterial embolization for patients with locally advanced breast cancer. This approach to preoperative management proved to be superior to intra-arterial infusion therapy currently applied in various clinics. Key wordsblood clotting factor XIII-transcatheter arterial chemoembolization (TACE)-(locally advanced) breast cancer

The Impact of 18-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography on the Staging and Management of Primary Rectal Cancer

Purpose18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) has a role in recurrent colorectal cancer. This study was designed to assess the impact of PET-CT on management of primary rectal cancer.

Cancer in pregnancy: maternal-fetal conflict

The occurrence of malignancies during pregnancy has increased over the last decades. They complicate approximately 1 per 1000 pregnancies. The most common malignancies associated with pregnancy include malignant melanoma, malignant lymphomas and leukemia, and cancer of the cervix, breast, ovary, colon and thyroid. Since it is impossible for prospective randomized clinical trials to be conducted in this field, relevant data have been generated from case reports and matched historical cohort studies in order to evaluate the treatment outcomes and the issues complicating the management of malignancy in the pregnant patient. There is almost always a conflict between optimal maternal therapy and fetal well-being. The maternal interest is for an immediate treatment of the recently diagnosed tumor. However, the optimal therapy, be it chemotherapy, radiotherapy or surgery, may impose great risks on the fetus. Consequently, either maternal or fetal health, or both, will be compromised. Therefore, both the pregnant patient and her physician are often in a dilemma as to the optimal course. On the basis of the medical facts, we discuss the issues raising potential ethical conflicts and present a practical ethical approach which may help to increase clarity in maternal-fetal conflicts. We review the available data informing the incidence and impact of the most common malignancies during pregnancy and their treatment on both the pregnant woman and her fetus. The optimal therapy for the tragic diagnosis of cancer in pregnancy requires a collaborative and interdisciplinary approach between gynecologists, oncologists, obstetricians, surgeons, neonatologists, psychologists, nursing staff and other disciplines. The purpose of this article is not to answer specific questions or to construct management schemes for specific tumors but to provide a framework for approaching some of these complex issues.

HER-2/neu status and response to CMF: retrospective study in a series of operable breast cancer treated with primary CMF chemotherapy

PurposePrimary chemotherapy brings the opportunity for an early and accurate assessment of response and offers an ideal model to search for new predictors of response. HER-2/neu is one of the most studied genes for this purpose.

Clinicopathological characteristics of triple-negative breast cancers

Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors and HER2. Although patients with TNBC tend to have a poor prognosis, only chemotherapy is expected to be effective because no therapeutic targets have yet been established. DNA microarray analyses have proved that TNBCs are composed of the basal-like subtype and normal breast (or unclassified) subtype, the former being correlated with an aggressive clinical course. Histological types of TNBCs are reported to be common with those of basal-like subtype, comprising high-grade invasive ductal carcinoma, no special type [solid-tubular carcinoma (or atypical medullary carcinoma), invasive ductal carcinoma with a large central acellular zone], typical medullary carcinoma, and metaplastic carcinomas. The basal-like subtype is characterized by the expression of myoepithelial/basal markers and molecular changes including TP53 gene mutations, BRCA1 inactivation, and many chromosomal alterations. New target molecules for the treatment of TNBCs are under extensive investigation, and their clinical application is awaited. KeywordsBasal-like subtype-BRCA1-Histopathology-p53-Triple-negative breast cancer This article is based on a presentation delivered at Symposium 3, “Triple-negative breast cancer,” held on 27 September 2008 at the 16th Annual Meeting of the Japanese Breast Cancer Society in Osaka.

[18F]-fluorodeoxyglucose positron emission tomography in patients with suspected recurrence of breast cancer

Aim. To evaluate the role of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients presenting with a suspicion of breast cancer relapse after primary treatment. Materials and methods. Sixty consecutive female patients with clinical (n=35) or radiological (n=25) suspicion of breast cancer recurrence were evaluated by FDG-PET. Positive PET findings were further evaluated by histological examination or clinical and radiological follow-up. In 25 patients, the serum tumor marker (CA 15-3) status was compared to the PET results. Results. Disease relapse was proven in 40 patients. Additionally, in three patients a second cancer was diagnosed with (n=1), and without (n=2) concomitant disease relapse. PET missed local recurrence in three patients, and was false positive in another four. In patient-based analysis, the overall sensitivity, specificity, and accuracy were 89%, 84%, and 87%, and 100%, 97%, and 98% for locoregional recurrence and distant metastases, respectively. FDG-PET was more sensitive than the serum tumor marker CA 15-3 in detecting relapsed breast cancer. Conclusion. FDG-PET is a valuable tool in the follow-up of patients with breast cancer.

In vitro evaluation of the effects of gefitinib on the modulation of cytotoxic activity of selected anticancer agents in a panel of human ovarian cancer cell lines

PurposeThis study was conducted to determine the in vitro optimal combination of selected anticancer agents with gefitinib and evaluate its effect on the expression of correlative biological targets in the cell-signaling pathway. In addition, the effect of gefitinib on the expression of ATP-binding cassette (ABC) transport proteins was evaluated.

A randomized trial of three cisplatin-containing regimens in advanced non-small-cell lung cancer (NSCLC): a study of the Umbrian Lung Cancer Group

Survival in patients with locally advanced (stage III Mo) and metastatic (M1) non-small-cell lung cancer (NSCLC) is short. Phase II studies have reported objective responses ranging from 20% to 60% using cisplatin-based chemotherapeutic regimens, yet few have shown improvement in median survival. In our phase II pilot studies with cisplatin (CDDP) and etoposide (VP-16), we observed a 26% response rate; with CDDP, VP-16, and mitomycin-C, a 38% response rate was obtained in advanced NSCLC patients. A total of 156 consecutive patients with locally advanced and metastatic NSCLC were randomized to one of three treatment arms to determine whether the chemotherapy protocols had any effect on response rate and median survival in a large, randomized study. Arm 1 consisted of CDDP (120 mg/m2 × 3 weeks); arm 2, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 given i.v. on days 1–3), repeated every 3 weeks; and arm 3, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 on days 1–3) given every 3 weeks, plus mitomycin C (10 mg/m2 on days 1, 21, and 42, then every 6 weeks, for a maximal dose of 100 mg). After 71 patients had been enrolled in the study, we stopped accrual in the CDDP arm due to a lack of response [1 complete response (CR) in 24 patients; 4%] and continued enrollment in the two combination-chemotherapy arms. In the CDDP/VP-16 arm a 30% response rate [1 CR, 18 partial responses (PRs)] was obtained, and in the CDDP/VP-16 mitomycin C arm a 26% response rate (4 CRs, 11 PRs) was seen among a total of 150 evaluable patients. Responses were observed in 31% of patients with favorable performance status (PS) (ECOG 0–1) vs 14% in patients with a poor PS (ECOG 2–3). Of patients with locally advanced disease (III Mo), 17 (33%) obtained an objective response, compared with 20 patients (20%) with metastatic disease. Median survival was 18 weeks in the CDDP arm, 35 weeks in the CDDP/VP-16 arm, and 37 weeks in the CDDP/VP-16/mitomycin C arm. The median survival in the multimodal chemotherapy arms was significantly greater than that obtained with CDDP alone. Toxicity was predominantly myelosuppression in the mitomycin C-containing arm (27%, wtto grade 3–4). Our study shows that combination chemotherapy using CDDP/VP-16 is active and safe in the treatment of advanced NSCLC patients with a good performance status. The addition of mitomycin C did not improve the therapeutic response. Published in part in Seminars in Oncology, suppl., Dec. 88 in the proceedings of the Perugia International Cancer Conference I

Effects of intraoral prosthetics on swallowing in patients with oral cancer

The swallowing patterns of four patients with oral cancer with intraoral palate reshaping/lowering prostheses were studied with and without their prostheses 3 months postoperatively. The prostheses resulted in improved swallow efficiency, increased duration of tongue contact to the pharyngeal wall, and improved speed of movement of the bolus from the valleculae to the pyriform sinus. These results emphasize the effects of the tongue on the pharyngeal as well as oral stage of the swallow. Key wordsIntraoral prosthesis-Oral cancer

Modified irinotecan plus bolus 5-fluorouracil/L-leucovorin for metastatic colorectal cancer at a single institution in Japan

BackgroundThe modified irinotecan plus bolus 5-fluorouracil/L-leucovorin (IFL) regimen (irinotecan plus bolus 5-fluorouracil/L-leucovorin) used to be one of the standard treatments for metastatic colorectal cancer until approval of oxaliplatin in Japan. We evaluated the efficacy of modified IFL therapy for Japanese patients.

Role of decay-accelerating factor in regulating survival of human cervical cancer cells

BackgroundDecay-accelerating factor (DAF) is one of the key molecules involved in cell protection against autologous complement, which restricts the action of complement at critical stages of the cascade reaction. The effect of DAF on the survival of human cervical cancer cell (ME180) has not been demonstrated.

Reduced expression of EphB2 is significantly associated with nodal metastasis in Chinese patients with gastric cancer

AimsEphB2 is a member of the Eph receptor tyrosine kinase family that has been involved in the regulation of cytoskeleton organization and cell migration in various cell types. Its role and regulation in carcinogenesis is controversial, especially in gastric cancer. We detected EphB2 expression and determined its clinical significance and explored its underlying molecular mechanism in gastric cancers.

The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer

AimRecent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes’ A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion.

What implications do the tolerability profiles of antiandrogens and other commonly used prostate cancer treatments have on patient care?

PurposeIncreased awareness of prostate cancer has led to earlier initiation of therapy, and the potential for a longer duration of treatment has led to a stronger emphasis on tolerability. Historically, the mainstay of treatment of hormone-sensitive prostate cancer has been castration-based therapy, but antiandrogens are now emerging as an alternative. This article reviews the tolerability profiles of antiandrogens as well as other existing treatments for prostate cancer and examines their implications on patient care.

Echoendoscopie et cancer de l’?sophage et de l’estomac

L’échoendoscopie est une technique d’examen permettant de réaliser le bilan d’extension des cancers de l’œsophage et de l’estomac et vient en concurrence ou en complément du PET scan. Ses performances sont connues et permettent de prédire le stade T et N dans 85 et 75 % des cas respectivement.

Are There Indications for Palliative Resection in Pancreatic Cancer?

Controversy exists about the indication for a palliative pancreatoduodenectomy. A palliative resection for patients with a pancreatic carcinoma can be performed safely nowadays with low mortality and acceptable morbidity in centers with experience. The early results in terms of mortality and morbidity are not different from resections with curative intent or even after bypass surgery. The procedure seems effective for controlling symptoms of the disease, and the quality of life after a palliative resection is acceptable and not worse than after bypass surgery. It is, however, still doubtful whether the incidence of symptom recurrence, such as jaundice, obstruction, and pain, is lower after resection than after bypass surgery. The longer survival after palliative resection could also be due to patient selection and postoperative treatment. There are no randomized trials to prove the superiority of palliative resection over bypass surgery. The safety of pancreatic resection for cancer has already changed the policy in centers with experience, and surgeons are more willing to perform a resection because the results are better or at least the same as after bypass surgery. There are, however, no results to confirm that a palliative resection should be performed routinely or to justify resection as a debulking procedure.

Who Benefits from Portal Vein Resection during Pancreaticoduodenectomy for Pancreatic Cancer?

Portal vein resection during pancreaticoduodenectomy has recently experienced renewed interest. We describe our results with this procedure over a 20-year period. Among 88 consecutive pancreatectomies for cancer of head of the pancreas, 14 included en bloc removal of the portal vein. There was no hospital mortality. Only 21% were found to have histologically confirmed cancer invasion, and the remainder had inflammatory adherence. Two-year survival was 15% compared to 34% for patients who did not have portal vein resection. There were no 5-year survivors. We discuss our results in light of other recent reports.

Characterization of four novel epithelial ovarian cancer cell lines

These authors contributed equally to this paper.

Recent trends of HER-2 testing and trastuzumab therapy for breast cancer

Molecular-targeted therapy using trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor type-2 (HER-2), is considered to be effective for metastatic as well as primary breast cancer and has already become a worldwide standard therapy for patients with HER-2 protein over-expression and gene amplification. Pretreatment evaluation of HER-2 status is considered to be essential for selection of patients, and according to the generally used algorithm, cases with an immunohistochemistry (IHC) score of 3+ and positivity upon fluorescence in situ hybridization (FISH) are thought to be eligible for trastuzumab therapy. In order to develop an appropriate domestic HER-2 testing system in Japan, the Trastuzumab Pathology Committee was established in 2000 and has been used as a forum for active discussions of policies related to HER-2 testing. After trastuzumab therapy and HER-2 testing had become widely adopted internationally, new guidelines for HER-2 testing were proposed by the ASCO/CAP group in 2007. Since then, these guidelines have gradually become accepted and used in many large-scale clinical studies of HER-2-targeting agents. On the other hand, new ISH methods have been introduced, such as bright-field HER-2 and chromosome 17 centromere double in situ hybridization (BDISH) and dual color-chromogenic in situ hybridization (dc-CISH). These methods make it possible to examine HER-2 gene amplification using only one paraffin section like the dc-FISH method, and to observe grains on the HER-2 gene and centrosome-17 by conventional microscopy. These approaches are considered to be reliable and equally as effective as the dc-FISH method. Accurate evaluation of HER-2 status is thought to be most important for appropriate selection of breast cancer patients who will obtain genuine benefit from trastuzumab treatment. In order to perform effective evaluation of HER-2 status, it is necessary to establish a reliable HER-2 examination system and to maintain its quality at a high level. KeywordsHER-2-Breast cancer-Trasutuzumab-BDISH-SISH-FISH-Immunohistochemistry

Breast cancer in the male: A report of 138 cases

This is a report of 138 male patients with cancer of the breast who were treated at the Hellenic Anticancer Institute from 1937 to 1974. The overall 5-year survival rate for 120 patients followed up was 32.5%. Analysis of the 5-year survival rate in relation to the mode of treatment showed that for radical mastectomy it was 42.9%, for simple mastectomy 40.7%, and for lumpectomy 35%. There were no 5-year survivors among patients treated with a combination of radiotherapy, chemotherapy, and hormonal manipulation. The 5-year survival rate for stage I cancer was 54.6%, for stage II the rate was 48.7%, and for stage III it was 18.5%. There were no 5-year survivors with stage IV cancer. The 5-year survival rate for patients who underwent radical mastectomy with positive axillary lymph nodes was 30.8%, while for those in whom the axillary lymph nodes were negative it was 56.5%. The overall 10-year survival rate was 14.8%. Au Hellenic Anticancer Institute, 138 hommes atteints de cancer du sein ont été traités entre 1937 et 1974. La survie globale à 5 ans, pour 120 malades suivis, est de 32.5%. Elle est de 42.9% après mastectomie radicale, de 40.7% après mastectomie simple, de 35% après exérèse limitée à la tumeur. Il n'y a aucun survivant à 5 ans pour les malades traités par association de radio-, chimio- et hormonothérapie. La survie à 5 ans est de 54.6% pour les cancers au stade I, 48.7% pour les stades II, 18.5% pour les stades III et 0% pour les stades IV. Elle est de 30.8% pour les mastectomies radicales avec ganglions axillaires envahis et de 56.5% lorsque ces ganglions ne sont pas atteints. La survie globale à 10 ans est de 14.8%.

Gene Polymorphisms of Endothelial Nitric Oxide Synthase and Angiotensin-converting Enzyme in Patients with Lung Cancer

The objectives of this study were to examine the possible involvement of endothelial nitric oxide synthase (ecNOS) and angiotensin-converting enzyme (ACE) genes in the genetic basis of lung cancer. Two hundred eighteen patients with lung cancer and 121 healthy subjects were included in this study. The ecNOS and ACE genotypes were determined in all subjects by polymerase chain reaction. The distribution of genotypes of ecNOS gene was significantly different in the lung cancer group than in the control population. ACE genotype distribution was not significantly different in the lung cancer group compared with the control group. These results suggest that polymorphisms of the ecNOS gene, but not the ACE gene, may be associated with the development of lung cancer. Key words: Polymorphism—Endothelial nitric oxide synthase—Angiotensin-converting enzyme—Lung cancer.Accepted for publication: 31 October 2000

The role of the NFκB signalling pathway in cancer

The nuclear factor kappa B (NFκB) signalling pathway regulates the expression of hundreds of genes that are involved in different cellular processes such as cell proliferation, survival, stress responses, cellular immunity and inflammation. Its aberrant regulation is involved in several pathologies, but its relevance in cellular transformation and cancer development has been extensively studied. Mutations in the core components of NFκB as well as in the cellular machinery that regulates its activation have been found in many types of tumours. On the other hand, its role in promoting cell survival is an important obstacle in many cancer therapies. The development of chemical inhibitors that block NFκB activation acting either directly on IKKs or on the proteosome machinery has shown antitumour and proapoptotic activity both in preclinical and clinical studies. Keywordsrel-NFκB-IκB-Bortezomib-IKK Supported by an unrestricted educational grant from Pfizer.

Serum level of arginine-vasopressin influences the prognosis of extensive-disease small-cell lung cancer

PurposeThe purpose of this study is to elucidate the influence of serum arginine-vasopressin (AVP) level on prognosis of extensive-disease small-cell lung cancer (ED-SCLC).

Construction of a lentiviral vector for RNA interference of human VIM gene and its silencing effect in pancreatic cancer cells

ObjectiveTo construct a lentiviral expression vector for RNA interference (RNAi) of human VIM gene; and assess its gene silencing effect in pancreatic cancer cell line Panc-1.

The remote effects of cancer on the nervous system

Key wordsCancer, Remote Effects-Nervous System, Effect of Cancer-Paraneoplastische Syndrome

Cancer of the gallbladder associated with pancreaticobiliary maljunction without bile duct dilatation in a European patient

A rare case of pancreaticobiliary maljunction (PBM) without dilatation of the biliary tract (DBT) associated with gallbladder carcinoma is described herein. A 62-year-old European woman with a long history of right upper abdominal pain was diagnosed as having PBM without DBT by endoscopic retrograde cholangiopancreatography and other examinations. Excision of the gallbladder and biliary duct with a Roux-en-Y hepaticojejunostomy was performed, and subsequent pathological examination of the surgical specimen showed a well differentiated adenocarcinoma of the gallbladder. She had no clinical symptoms for 58 months postoperatively. PBM allows reflux of pancreatic juice into the biliary tract. Recent findings support the idea that epithelial hyperplasia plays an important role in gallbladder carcinogenesis with PBM, and also support the concept that gene mutations are involved in the carcinogenesis of biliary epithelium in patients with PBM. For these reasons, we advocate that resection of the extrahepatic biliary tract in PBM patients without bile duct dilatation, rather than cholecystectomy alone, is the treatment of choice for preventing bile duct carcinoma. Key words: pancreaticobiliary maljunction-gallbladder cancerReceived for publication on Dec. 15, 1999; accepted on Feb. 22, 2000

Recent insights into the role of integrins in cancer metastasis

Integrins have been repeatedly found involved in cancer metastasis. The past two years have seen considerable evolution in our knowledge on the role of these integrins in tumour cells. This includes the elucidation of different signalling pathways by which integrins dictate the anchorage-independent growth, survival and motility of tumour cells. Moreover, integrins may have a more complex role in cancer metastasis as they cooperate with serine proteases and metalloproteases to promote tumour cell invasion and angiogenesis. Finally, integrins favour tumor cell extravasation. Key words. Integrin; cancer; proliferation; apoptosis; invasion; angiogenesis; extravasation; metastasis.

Improving Results of Pancreaticoduodenectomy for Pancreatic Cancer

This report from The Johns Hopkins Hospital reviews the results of pancreaticoduodenal resection during the decade of the 1990s, focusing on two recent publications. The first to be discussed involves a cohort of 650 consecutive patients undergoing pancreaticoduodenectomy (PD), with 443 patients having periampullary adenocarcinomas, 282 of whom had a pathologic diagnosis of pancreatic adenocarcinoma. The second report to be discussed involves the use of adjuvant chemoradiation therapy in a cohort of 174 patients who had successfully undergone PD for pancreatic adenocarcinoma. In both of these cohorts the operative mortality was less than 2%, and the median survival for resected pancreatic adenocarcinoma approximated 20 months.

Sequential vinorelbine–capecitabine followed by docetaxel in advanced breast cancer: long-term results of a pilot phase II trial

PurposeTo evaluate the response rate of the combination of capecitabine (C) and vinorelbine (V) followed by Docetaxel (D) in the 1st line treatment of advanced and metastatic breast cancer patients.

Clinical Outcomes of Self-Expandable Metal Stent and Prognostic Factors for Stent Patency in Gastric Outlet Obstruction Caused by Gastric Cancer

The aim of this study was to assess clinical outcomes of endoscopic stenting for a gastric outlet obstruction caused by gastric cancer and the prognostic factors for stent patency by reviewing medical records. Eighty-one stents were inserted into 75 patients (48 men, average age 66years). The technical and clinical success rates were 98 and 87%, respectively. The median stent patency was 55days (95% CI 40–70days). The median survival was 79days (95% CI 58–123days). Stent reobstruction caused by tumor ingrowth or overgrowth occurred in 25 cases (31%). Cox multivariate regression analysis showed that covered stents (odds ratio 0.29, 95% CI 0.11–0.76; P=0.01) and chemotherapy after stent placement (odds ratio 0.34, 95% CI 0.13–0.91; P=0.03) were significant prognostic factors for stent patency. This study found that endoscopic stenting is a safe and effective palliation treatment for malignant gastric outlet obstruction and a covered stent and chemotherapy are significant prognostic factors for stent patency.

Disseminated Epithelial Tumor Cells in Bone Marrow of Patients with Esophageal Cancer: Detection and Prognostic Significance

p < 0.01). It was concluded that although bone marrow is not a preferential site of overt metastasis of esophageal cancer, the frequent occurrence of isolated tumor cells at this distant site indicates that hematogenous dissemination of viable malignant cells occurs early in tumor progression.

High polymorphism in the trisomic portion of a gastric cancer cell line

BackgroundGenetic instability is a hallmark of malignancy, and microsatellite instability is a widely appreciated mechanism of generating genetic changes. We have recently observed four markers clustered on chromosome 20 that showed the effects of microsatellite instability in the gastric adenocarcinoma cell line SNU-1. Each affected marker had alleles of three different sizes. The aim of this study was to investigate the origin for this high-density polymorphism on a single chromosome.

Phase II study of acivicin as a 72-hr continuous infusion in patients with untreated colorectal cancer. A National Cancer Institute of Canada clinical trials group study

The National Cancer Institute of Canada (NCIC) Clinical Trials Group has carried out a phase II study of acivicin given as a 72-hour continuous infusion in previously untreated patients with measurable metastatic colorectal carcinoma. Toxicity in 24 patients was mild to moderate and consisted primarily of GI symptoms such as nausea, vomiting, diarrhea or CNS changes including drowsiness, lethargy, dizziness. No responses were seen in 23 evaluable patients. We did not find acivicin given as described to be effective in colorectal carcinoma.Key wordsacivicin-colorectal carcinoma

Increase of hepcidin plasma and urine levels is associated with acute proctitis and changes in hemoglobin levels in primary radiotherapy for prostate cancer

PurposeTo analyse hepcidin serum and urine levels during radiotherapy for prostate cancer.

Lack of effect of cisplatin on i. v. L-PAM plasma pharmacokinetics in ovarian cancer patients

Melphalan (L-PAM) pharmacokinetics were investigated in nine ovarian cancer patients before and after cisplatin (DDP) treatment. When L-PAM was given 24 h before DDP, the elimination half-life (t1/2), plasma clearance (Clp), and volume of distribution (Vd) of L-PAM were, respectively: 46.4±6.7 min, 20.5±3.7 l/m2, and 306.8±34.4 ml/min per square meter. When L-PAM was inoculated 24 h after DDP, t1/2, Clp, and Vd were 47.5±6.3 min, 20.4±2.8 l/m2, and 322.0±54.1 ml/min per square meter. Thus, DDP pretreatment does not significantly affect L-PAM pharmacokinetics. Regression analysis showed a significant correlation between the L-PAM elimination rate constant () and renal function assessed by creatinine clearance. One patient who received this sequence of treatment for six courses showed a threefold decrease of L-PAM clp after the last treatment. The reported high myelotoxicity of the combination of DDP and L-PAM when DDP was given 24 h before L-PAM cannot be attributed to DDP-induced changes in L-PAM kinetics but might to some extent be related to a loss of renal function consequent to many courses of treatment.This work was supported by a Grant from the Swiss League against Cancer

Adjuvant Therapy for Pancreatic Cancer

Pancreatic cancer is a major cause of cancer death; and despite advances in the standards of surgery and supportive care, the median and long-term survival rates have not shown similar dramatic improvements. Techniques such as radical surgery alone cannot guarantee a cure. Previous work with conventional chemotherapy and radiotherapy in patients with advanced pancreatic cancer has indicated a role for adjuvant therapy for patients with resectable tumors. The main modalities that have been assessed are based on the Gastrointestinal Tumour Study Group (GITSG) results using 5-fluorouracil chemotherapy, external beam radiation therapy (EBRT), or both. Alternative approaches such as neoadjuvant therapy have been used, which may increase the number of patients suitable for resection; and regional therapy techniques have been used to increase the therapeutic potential by concentrating agents to the tumor bed. The results of single or combination therapy do show some improvement in survival but have been limited in most cases to retrospective nonrandomized series of patients. Therefore the results must be assessed as such. There are several large randomized trials that will deliver definitive answers in the near future as to whether conventional adjuvant therapy is effective. New approaches using novel agents for advanced disease are currently being assessed, and they may eventually identify the most appropriate and effective agents to use for pancreatic cancer in the adjuvant setting.

Detection of bone metastases in patients with prostate cancer by F-18 fluorocholine and F-18 fluoride PET–CT: a comparative study

PurposeThe aim of this prospective study was to compare the potential value of F-18 fluorocholine (FCH) and F-18 fluoride positron emission tomography (PET)–computed tomography (CT) scanning for the detection of bony metastases from prostate cancer.

Photodynamic therapy of cancer. Basic principles and applications

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality approved for clinical treatment of several types of cancer and non-oncological disorders. In PDT, a compound with photosensitising properties (photosensitiser, PS) is selectively accumulated in malignant tissues. The subsequent activation of the PS by visible light, preferentially in the red region of the visible spectrum (λ≥600 nm), where tissues are more permeable to light, generates reactive oxygen species, mainly singlet oxygen (1O2), responsible for cytotoxicity of neoplastic cells and tumour regression. There are three main mechanisms described by which 1O2 contributes to the destruction of tumours by PDT: direct cellular damage, vascular shutdown and activation of immune response against tumour cells. The advantages of PDT over other conventional cancer treatments are its low systemic toxicity and its ability to selectively destroy tumours accessible to light. Therefore, PDT is being used for the treatment of endoscopically accessible tumours such as lung, bladder, gastrointestinal and gynaecological neoplasms, and also in dermatology for the treatment of non-melanoma skin cancers (basal cell carcinoma) and precancerous diseases (actinic keratosis). Photofrin?, ALA and its ester derivatives are the main compounds used in clinical trials, though newer and more efficient PSs are being evaluated nowadays. KeywordsPhotodynamic therapy-Photosensitiser-Reactive oxygen species-Tumour destruction-Cancer Supported by an unrestricted educational grant from Roche Farma S.A.

Environmental effect and genetic influence: a regional cancer predisposition survey in the Zonguldak region of Northwest Turkey

The Cretaceous-Eocene volcano-sedimentary units of the Zonguldak region of the western Black Sea consist of subalkaline andesite and tuff, and sandstone dominated by smectite, kaolinite, accessory chlorite, illite, mordenite, and analcime associated with feldspar, quartz, opal-CT, amphibole, and calcite. Kaolinization, chloritization, sericitization, albitization, Fe–Ti-oxidation, and the presence of zeolite, epidote, and illite in andesitic rocks and tuffaceous materials developed as a result of the degradation of a glass shards matrix, enclosed feldspar, and clinopyroxene-type phenocrysts, due to alteration processes. The association of feldspar and glass with smectite and kaolinite, and the suborientation of feldspar-edged, subparallel kaolinite plates to fracture axes may exhibit an authigenic smectite or kaolinite. Increased alteration degree upward in which Al, Fe, and Ti are gained, and Si, Na, K, and Ca are depleted, is due to the alteration following possible diagenesis and hydrothermal activities. Micromorphologically, fibrous mordenite in the altered units and the presence of needle-type chrysotile in the residential buildings in which cancer cases lived were detected. In addition, the segregation pattern of cancer susceptibility in the region strongly suggested an environmental effect and a genetic influence on the increased cancer incidence in the region. The most likely diagnosis was Li-Fraumeni syndrome, which is one of the hereditary cancer predisposition syndromes; however, no mutations were observed in the p53 gene, which is the major cause of Li-Fraumeni syndrome. The micromorphology observed in the altered units in which cancer cases were detected may have a role in the expression of an unidentified gene, but does not explain alone the occurrence of cancer as a primary cause in the region. KeywordsAlteration minerals-Genetic influence-Geochemistry-Health effects-Mineralogy-Turkey-Volcanosedimentary units-Zonguldak

Incidence of objectively diagnosed thromboembolic disease in cancer patients undergoing cytotoxic chemotherapy and / or hormonal therapy

 From August 1993 to May 1994 there were 1505 inpatient and 2590 outpatient chemotherapy treatment episodes at the Clatterbridge Centre for Oncol- ogy. A total of 21 thromboembolic events, including two arterial events, were recorded among these patients at a median of 8 weeks from the start of treatment (range 0–14 weeks), and 2 episodes occurred at the time of first presentation. The median age of the patients developing thromboembolism was 53 (range 29–75) years, and there were 14 women and 7 men. In all, 13 of the events (62%) occurred in patients receiving inpatient treatment and 8 (38%), in outpatients. The incidence of thrombosis per treatment episode in inpatients was therefore 0.008 as compared with 0.003 in outpatients. The associated malignancies were breast cancer (5), testicular cancer (4), lung cancer (3), ovarian cancer (3) and non-Hodgkin’s lymphoma (2), with bladder, colon, anal and brain cancer providing 1 case each. The following bulky pelvic or para-aortic disease was present in 9 patients: testicular cancer (3), ovarian cancer (3), lymphoma (2) and bladder cancer (1). In all, 20 of the 21 thrombotic episodes were successfully treated, with 1 patient dying from the complications of venous gangrene. Thromboembolic disease is a relatively common and important cause of morbidity and mortality in cancer patients that requires early recognition and treatment. Key words Cancer-Chemotherapy-ThromboembolismReceived: 18 February 1996 / Accepted: 30 September 1996

Treatment of colon cancer in rats with rMuTNF and the interferon-inducer bropirimine

It is well documented that the antitumor activity of tumor necrosis factor (TNF) is improved by interferons (IFN's). Bropirimine (BP) is an immune response modifier which induces IFN. Both TNF and BP have the capacity to inhibit the growth of a transplantable colon tumor (CC 531) in inbred WAG rats. In the present study their combined use was investigated in a one-week assay, with the tumor implanted under the renal capsule. The results indicate that BP, given on days 0 and 1, and 1 g TNF on days 0, 2 and 4 act additively, leading to an almost complete inhibition of tumor growth.

Preoperative dynamic lymphoscintigraphy predicts sentinel lymph node metastasis in patients with early breast cancer

BackgroundPreoperative lymphoscintigraphy is commonly used in sentinel lymph node biopsy (SLNB) for patients with early breast cancer; however, its significance to predict SLN metastasis remains to be determined.

The use of positive core wash cytology to estimate potential risk of needle tract seeding of breast cancer: directional vacuum-assisted biopsy versus automated core needle biopsy

BackgroundA disadvantage of the image-guided core needle biopsy is that needle tract seeding may occur and affect the local recurrence and overall survival rates of patients after breast-conserving surgery, although the chance is small. The purpose of this study was to compare the potential risk of needle tract seeding of breast cancer from ultrasonographically guided needle biopsies that were performed with a directional vacuum-assisted device and an automated core needle gun.

Role of decay-accelerating factor in regulating survival of human cervical cancer cells

BackgroundDecay-accelerating factor (DAF) is one of the key molecules involved in cell protection against autologous complement, which restricts the action of complement at critical stages of the cascade reaction. The effect of DAF on the survival of human cervical cancer cell (ME180) has not been demonstrated.

Bisphenol A may reduce the efficacy of androgen deprivation therapy in prostate cancer

Individuals diagnosed with specific diseases may represent subpopulations with heightened sensitivity to environmental compounds. This may be due to their disease-mediated molecular milieu and/or the interference of environmental compounds with pharmaceutical drug targets. Prostate cancer represents a significant clinical challenge in the United States. If the disease becomes advanced, standard therapies are ineffective, leading to high rate of patient morbidity and mortality. Understanding the complex reasons for therapeutic resistance is critical for improving the life expectancy for patients with this cancer. Recently, it has been identified that common somatically derived genetic mutations that arise following the selective pressure of standard prostate cancer treatments may facilitate sensitivity to environmental contaminants. These somatic mutations within the androgen receptor allow the estrogen mimic, bisphenol A (BPA), to bind and activate the receptor, resulting in increased proliferation and tumor growth in the presence of the traditional therapy regimen for prostate cancer. In an in vivo xenograft model of prostate cancer, low level exposure of BPA was sufficient to reduce the efficacy of treatment. Herein, the possible effect of BPA on prostate cancer treatment and disease management for humans is explored as an example of environmental endocrine disruptor exposure reducing the efficacy of disease management. These data lend support to the hypothesis that environmental exposure to select compounds may interfere with specific therapeutic regimens. KeywordsAndrogen receptor-Bisphenol A-Endocrine disrupting compound-Prostate cancer

Value of Extended Resection and Intraoperative Radiotherapy for Resectable Pancreatic Cancer

Since 1984 intraoperative radiotherapy (IORT) combined with extended resection for pancreatic cancer has been performed in our clinic to prevent local recurrence. Following extended resection, a dose of 30 Gy of 9- to 12-MeV electrons is administered to the operative field, including the paraaortic area from the diaphragm above to the inferior mesenteric artery below. The 5-year survival rate was 15.3% in all 37 cases, 20.2% in patients who had macroscopic tumor clearance, and 16.9% in patients with stage IVa tumor according to the Japanese classification. In autopsies of 10 patients who underwent combined therapy, four had local recurrence enclosed by thick, firm connective tissue. There was no local control recurrence in two patients who underwent noncurative resection. Enhanced local control induced by the combined therapy, however, has only a limited impact on overall survival because of the systemic spread of disease, especially hepatic metastases. At present, as we have no effective treatment for hepatic metastases, it is important to perform an extended resection with IORT on carefully selected patients. The combined therapy may offer the best approach to control local recurrence when dealing with advanced, but not highly advanced, cancer as defined by the stage of tumor. Therefore a combination of IORT and extended resection can have an impact on the results of surgical treatment for pancreatic cancer when anticancer treatment of hepatic metastases is established.