Quality of life in patients with cancers of the upper gastrointestinal tract

Accurate assessment of health-related quality of life in patients with upper gastrointestinal cancers is essential to help determine treatment strategies. Questionnaires may be used to screen for physical and psychosocial morbidity, to evaluate new therapies and there is accumulating evidence to suggest that quality of life scores have prognostic value. There are well validated generic measures of quality of life suitable to use in patients with cancers of the upper gastrointestinal tract, but only two systems (EORTC QLQ-C30 and the FACT-G) have site-specific modules that have been constructed for this patient group. The future use of computer-assisted techniques to collect, analyze and interpret quality of life data will enable the implementation of quality of life results in clinical practice.     

Quality of life in patients with cancers of the upper gastrointestinal tract

Accurate assessment of health-related quality of life in patients with upper gastrointestinal cancers is essential to help determine treatment strategies. Questionnaires may be used to screen for physical and psychosocial morbidity, to evaluate new therapies and there is accumulating evidence to suggest that quality of life scores have prognostic value. There are well validated generic measures of quality of life suitable to use in patients with cancers of the upper gastrointestinal tract, but only two systems (EORTC QLQ-C30 and the FACT-G) have site-specific modules that have been constructed for this patient group. The future use of computer-assisted techniques to collect, analyze and interpret quality of life data will enable the implementation of quality of life results in clinical practice.     

Quality of life during chemotherapy in lung cancer patients: results across different treatment lines

Background:

Most lung cancer patients are diagnosed at an advanced disease stage and predominantly receive palliative treatment, which increasingly consists of several chemotherapy lines. We report on patients'' quality of life (QOL) to gain knowledge on QOL during and across multiple lines of chemotherapy. This includes patients with (neo)adjuvant therapy up to 3rd or above line palliative chemotherapy.

Methods:

Lung cancer patients receiving outpatient chemotherapy at the Kufstein County Hospital completed an electronic version of the EORTC QLQ-C30. Linear mixed models were used for statistical analysis.

Results:

One hundred and eighty seven patients were included in the study. Surprisingly, irrespective of the chemotherapy line patients reported stable QOL scores during treatment. None of the calculated monthly change rates attained clinical significance, referring to established guidelines that classify a small clinical meaningful change as 5 to 10 points. According to treatment line, 3rd or above line palliative chemotherapy was associated with the worst QOL scores, whereas patients undergoing (neo)adjuvant or 1st line palliative chemotherapy reported fairly comparable QOL.

Conclusion:

The essential finding of our study is that all QOL aspects of the EORTC QLQ-C30 questionnaire remained unchanged during each chemotherapy line in an unselected population of lung cancer patients. Between treatment lines pronounced differences were found, indicating that later palliative chemotherapy lines are associated with higher QOL impairments. These changes in QOL may not primarily be related to the treatment, but rather refer to impairments due to disease progression and may be partly due to a consequence of the prior therapies.     

Recent progress and limitations of chemotherapy for pancreatic and biliary tract cancers

Gemcitabine chemotherapy has been the standard for advanced pancreatic cancer for more than a decade. New oral fluoropyrimidines such as S-1 and capecitabine are other key drugs. Gemcitabine plus erlotinib was the only combination therapy that significantly prolonged survival, although the effect was minimal. Little or no improvement in survival with recent molecular-targeted drugs might be attributed to the very high incidence of K-ras gene mutation in pancreatic cancer. Recently, the non-gemcitabine-based-regimen of FOLFIRINOX showed significantly greater overall survival compared with gemcitabine for the first time. For biliary tract cancer, gemcitabine plus cisplatin combination chemotherapy has been proved to significantly prolong survival and will become the standard therapy. Further improvement in survival is expected by the addition of cetuximab.     

Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas

To examine the association between gallstones and cholecystectomy, we conducted a nationwide population-based cohort study in Denmark. Patients with a discharge diagnosis of gallstones from 1977 to 1989 were identified from the Danish National Registry of Patients and followed up for cancer occurrence until death or the end of 1993 by record linkage to the Danish Cancer Registry. Included in the cohort were 60 176 patients, with 471 450 person-years of follow-up. Cancer risks were estimated by standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) stratified by years of follow-up and by cholecystectomy status. Among patients without cholecystectomy, the risks at 5 or more years of follow-up were significantly elevated for cancers of liver (SIR = 2.0, CI = 1.2-3.1) and gallbladder (SIR = 2.7, CI = 1.5-4.4) and near unity for cancers of extrahepatic bile duct (SIR = 1.1), ampulla of Vater (SIR = 1.0) and pancreas (SIR = 1.1). The excess risk of liver cancer was seen only among patients with a history of hepatic disease. Among cholecystectomy patients, the risks at 5 or more years of follow-up declined for cancers of liver (SIR = 1.1) and extrahepatic bile duct (SIR = 0.7), but were elevated for cancers of ampulla of Vater (SIR = 2.0, CI = 1.0-3.7) and pancreas (SIR = 1.3, CI = 1.1-1.6). These findings confirm that gallstone disease increases the risk of gallbladder cancer, whereas cholecystectomy appears to increase the risk of cancers of ampulla of Vater and pancreas. Further research is needed to clarify the carcinogenic risks associated with gallstones and cholecystectomy and to define the mechanisms involved.     

Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer

This phase II study was conducted to determine the efficacy and toxicity of a gemcitabine (GEM) and oxaliplatin (OX) chemotherapy protocol in patients with unresectable biliary tract cancer (BTC). Patients were treated with GEM 1000 mg m-2 (30 min infusion) on days 1, 8, 15, and OX 100 mg m-2 (2 h infusion) on days 1 and 15 (gemcitabine and oxaliplatin (GEMOX-3 protocol), repeated every 28 days. The data were collected according to the Simon 2-stage design for a single centre phase II study (alpha=0.05; beta=0.2). Primary end point was response rate; secondary end points were time-to-progression (TTP), median survival, and safety profile. Thirty-one patients were enrolled in the study between July 2002 and April 2005. Therapeutic responses were as follows: partial response in eight patients (26%, 95% confidence interval (CI) 14-44), stable disease in 14 patients (45%, 95%CI 29-62), resulting in a disease control rate of 71%. Nine patients (29%, 95%CI 16-47) had progressive disease. Median TTP was 6.5 months. Median overall survival was 11 months. Common Toxicity Criteria (CTC) Grade 3-4 toxicities were transient thrombocytopenia (23%), peripheral sensory neuropathy (19%), leucopenia (16%), and anaemia (10%). In conclusion the GEMOX-3 protocol is active and well tolerated in patients with advanced BTC. It can be applied in an outpatient setting with three visits per month only.     

Descriptive epidemiology of subsites of cancers of the liver, biliary tract and pancreas in Japan

Recent time trends (1979-1987) and geographical distributions in mortalities from subsites of cancers of the hepato-biliary-pancreatic system have been investigated on the basis of the vital statistics of Japan. The corrected age-adjusted mortality rates (CAAMRs) were calculated to eliminate the influence of the proportion of subsite-unknown cancers. During the above period, the CAAMR for intrahepatic bile duct cancer increased by a relatively high extent (2.0-fold in males and 1.67-fold in females), and those for cancers of the gallbladder, extrahepatic bile duct and pancreas (head and other parts) increased to a moderate extent (1.2-1.4-fold). The CAAMR for primary liver cancer showed an increasing trend in males and a decreasing trend in females. The CAAMR for cancer of the ampulla Vater changed little during the period. A clear cluster of prefectures with high CAAMRs was observed in the northern part of Japan for cancers of the extrahepatic bile duct and pancreatic head. Clusters of prefectures with high CAAMRs for cancer of the gallbladder and ampulla Vater were observed in the mid-northern part of Japan, especially on the Japan Sea side. The CAAMR for primary liver cancer was high in the Island of Kyushu and some western parts of Japan, and low in the northern part of Honshu Island. No clear clusters of prefectures with high CAAMRs were observed for cancers of the intrahepatic bile duct and pancreas, other than for the pancreatic head.     

Treatment of advanced biliary tract cancers: from chemotherapy to targeted agents

Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage and have a dismal prognosis. The treatment of advanced disease is mainly based on system...     

Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy

Purpose

Prognostic factors for patients with advanced biliary tract cancer receiving chemotherapy are presently not well established. Gallbladder cancer and intra-hepatic cholangiocarcinoma are previously reported prognostic factors of poor prognosis; however, tumor volume has not been analyzed in these previous reports.

Methods

We analyzed 56 consecutive patients with advanced biliary tract cancer who had received gemcitabine and S-1 combination chemotherapy as first-line palliative chemotherapy. Prognostic factors, including the baseline sum longest diameter (BSLD) representing tumor volume in Response Evaluation Criteria in Solid Tumor, were evaluated.

Results

By multivariate analysis, age ??70 (HR 3.01, 95% CI 1.25?C7.31, P?=?0.014) and larger BSLD (HR 1.09, 95% CI 1.01?C1.18, P?=?0.021) were statistically significant independent predictors of poor prognosis. Primary biliary site was not identified as a prognostic factor (P?=?0.728). Median survival times of patients with BSLDs????9.0?cm and BSLDs?>?9.0?cm were 18.7 and 8.8?months, respectively (P?=?0.024).

Conclusions

Age and BSLD were identified as strong prognostic factors for patients with advanced biliary tract cancer receiving chemotherapy. Tumor volume might be more important than primary biliary site for the prognosis of advanced biliary tract cancer.     

Pancreatic and biliary tract cancers]

There are several tumor markers for pancreatic and biliary tract cancers, such as carcinoembryonal antigen, pancreatic enzyme, carbohydrate antigen and tumor associated gene. CA19-9 and SPan-1, which are type I carbohydrate antigens, are especially useful among these tumor markers. Combination assays of these tumor markers improve the positive rate for these cancers. These tumor markers are useful not only in diagnosis but also in assessing the therapeutic efficacy and early detection of recurrence after operation.     

MUC1 peptide vaccination in patients with advanced pancreas or biliary tract cancer

BACKGROUND: To evaluate the immunogenicity of MUC1 peptide vaccine in advanced pancreatic and bile duct cancers, a phase I clinical trial was conducted. MATERIALS AND METHODS: A 100-mer MUC1 peptide consisting of the extracellular tandem repeat domain and incomplete Freund's adjuvant were subcutaneously administered to 6 pancreatic and 3 bile duct cancer patients at weeks 1, 3 and 5 and doses ranging from 300 to 3000 microg. Circulating intracytoplasmic cytokine-positive CD4+ T cells and anti-MUC1 IgG antibodies were measured before and after vaccination. RESULTS: There were no adverse events, except for mild reddening and swelling at the vaccination site. In 8 patients eligible for clinical evaluation, 7 had progressive disease and 1 stable disease with a tendency for increased circulating anti-MUC1 IgG antibody after vaccination. CONCLUSION: This phase I clinical trial revealed the safety of a vaccine containing 100-mer MUC1 peptides and incomplete Freund's adjuvant.     

Preoperative imaging of biliary tract cancers

Many imaging techniques are available for the evaluation of patients with malignant obstructive jaundice. Ultrasonography, in experienced hands, is valuable for evaluating the local extent of the disease, but its usefulness for staging distant metastases is limited. When used properly, CT and MR imaging can provide valuable information about the extent of local tumor involvement and distant metastases. These noninvasive techniques provide images of the bile ducts and vascular images that are comparable in quality to those obtained with more invasive procedures, such as PTC, ERCP, and angiography, and do not have the risk for complications of these invasive techniques.     

Multidisciplinary treatment of biliary tract cancers

Ninety-six patients referred for radiation therapy to Washington University affiliated institutions with tumors of the extrahepatic biliary tree form the basis of this report. Patients were examined with regard to demographic factors, tumor primary site, presenting symptoms, methods of diagnosis, and methods of management. The median survival of all 96 patients in this series was 11 months. There was no significant difference between patients with gallbladder cancer and patients with cancer of the biliary ductal system. There was a statistically significant improvement in survival in those patients undergoing resection as management or as a component of the management of their tumors (P = 0.02). Patients receiving >4,000 cGy of radiation therapy had an improved survival compared to those patients receiving ≤4,000 cGy of radiation therapy (P = 0.003). While surgical resection improved survival for those patients undergoing removal of all gross tumor, this effect was noted especially in patients with gallbladder cancer. © Wiley-Liss, Inc.     

Molecular pathology of biliary tract cancers

The molecular mechanisms underlying the development, growth and metastatic diffusion of biliary tract cancers are still undefined. The increase in worldwide incidence and mortality of cholangiocarcinoma justifies the impellent need to clarify the intracellular mechanisms triggering the malignant transformation of the biliary epithelium and growth of biliary malignancies. A more complete characterization of the molecular pathology of bile duct cancers could lead to the identification of valid targets for the diagnosis and therapy of these devastating malignancies. This review describes the scientific progress made over the past decades with regard to the understanding of the molecular processes of cholangiocarcinogenesis.     

Postoperative infection control in patients with hepatic, biliary tract, and pancreatic cancers]

Postoperative infection occurs more frequently in patients with malignant disease than in patients with benign disease. Postoperative infection control in patients with hepatic cancer, biliary tract cancer and pancreatic cancer is studied. Although in patients with jaundice due to malignancy the rate of positive bacterial culture of the bile collected at the time of PTCD was low, the rate of positive bile culture increased after 10 to 14 days of PTCD. The predominant strain was Enterococcus spp., followed by Klebsiella spp., Enterobacter spp. and E. coli in that order. These bacteria isolated from the bile were considered to be causative organisms of postoperative infection. Prophylactic antibiotics after the operation for jaundice due to malignancy should be chosen based on the results of bile culture. In patients undergoing hepatectomy, which is considered to be an aseptic operation, gram positive cocci such as S. aureus was the most frequently encountered organism. On the other hand, in patients undergoing hepatectomy and intestinal anastomosis, enteric bacteria were frequently isolated from the infectious foci. In this study there were 6 cases of methicillin-resistant S. aureus (MRSA) postoperative infection, 3 cases after pancreatoduodenectomy, and 3 cases after hepatectomy. Even after an aseptic operation, postoperative MRSA infection is likely to occur in patients undergoing a more invasive operation, so hospital infection control should be again emphasized.     

Small cell carcinoma of the pancreas and biliary tract

Four cases of anaplastic carcinoma of the pancreas or biliary tract were studied clinicopathologically and immunohistochemically. All four cases were intermediate cell type and contained a minimum amount of microscopic foci of differentiated glandular adenocarcinoma. Argyrophilic tumor cells were not seen in any of the four tumors. Immunohistochemically, no tumor was positive for hormonal products, but all tumors were positive for epithelial markers. These findings suggest that the anaplastic carcinoma are not derived from argyrophilic cells, but rather from adenocarcinomas which have the potential for anaplastic metaplasia. The long-term survival of one patient emphasized the importance of chemotherapy in the treatment of small cell carcinoma of the pancreas and biliary tract.     

Cellular and molecular biology of biliary tract cancers

Cancer of the biliary tract has been associated with point mutations of K-ras and beta-catenin proto-oncogenes; alterations of p53, p16, APC, and DPC4 tumor suppressor genes by a combination of chromosomal deletion, mutation, or methylation; and infrequently microsatellite instability. The frequencies of these alterations vary by location and race of the patient, tumor subsite, histology, and associated disease. Advances in the understanding of the genetics of this disease will help in diagnosing biliary tract cancer, screening at-risk patients, and developing therapies.