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Toxicity of a 24-hour infusion of gemcitabine in biliary tract and pancreatic cancer: a pilot study.

The antitumor activity of gemcitabine is not dose-response related but schedule-dependent. Based on the results of a published phase I study in patients with nonsmall-cell lung cancer we started a pilot study of a 24-hr infusion of gemcitabine in patients with adenocarcinoma of the pancreas and biliary tract cancer. Twenty-five patients were enrolled and received a 24-hr infusion of gemcitabine once weekly on three consecutive out of 4 weeks. Dose levels of gemcitabine ranged from 100 to 150 mg/m2. One of 13 chemotherapy-naive patients had a partial response. Dose-limiting toxicity (DLT) was thrombocytopenia in pretreated patients and neutropenia in chemotherapy-naive patients. Other toxicities were oral mucositis, fever, flu-like symptoms, and asthenia. Maximum tolerated dose (MTD), especially in pretreated patients, was 100 mg/m2.

Aged↗

Physical activity in the prevention and treatment of other morbid conditions and impairments associated with obesity: current evidence and research issues.

PURPOSE: To evaluate the current status of knowledge concerning the effects of physical activity in the treatment and prevention of obesity- related problems, including cancers of the colon, breast, uterus, and prostate; gallstones; osteoarthritis; back pain; sleep apnea; reproductive abnormalities; and impaired health-related quality of life. DESIGN: A Medline literature search on the effects of physical activity in the above conditions was conducted. Only studies with some measure of weight and a description of the type of physical activity were included. RESULTS: No controlled randomized trials of exercise in the treatment of any of the studied conditions in obese patients were identified. Most of the epidemiologic studies reviewed were beset with severe methodological weaknesses. Most of the 18 studies on physical activity and colon cancer risk showed a protective effect that in some studies appeared to be greater than expected by weight loss alone. Some but not all studies of hormone-dependent cancers and gallstones showed a protective effect for physical activity. There were insufficient data on the role of exercise for the other morbid conditions studied. CONCLUSION: The scarce data available on the role of physical activity in the prevention of obesity-related chronic conditions listed above suggest a protective role that needs to be examined further in studies with improved methodologies. Well-designed intervention trials are needed to assess the role of physical activity in the treatment and long-term outcome of obese patients with these co-morbid conditions.

Back Pain↗

Concomitant adenosquamous carcinoma of the common bile duct and early adenocarcinoma of the gall-bladder.

We report a 59 year old male with obstructive jaundice and a clinical diagnosis of carcinoma of the midportion of the common bile duct. Examination of the surgical specimen revealed a small tumour in the neck of the gall-bladder. Histologic examination revealed the tumour in the common bile duct was an adenosquamous carcinoma whereas that in the gall-bladder was an early papillary adenocarcinoma. Thus, this is a rare case of the simultaneous development of adenosquamous carcinoma and early papillary adenocarcinoma in the biliary tree.

Adenocarcinoma↗

Adenosquamous carcinoma of the gall-bladder with gastric foveolar-type epithelium.

An 80 year old Japanese man had adenosquamous carcinoma of the gall-bladder characterized by an adenocarcinoma (AC) in the gall-bladder lumen and a squamous cell carcinoma (SCC) in the invaded region of the liver. In the AC, the tumor cells consisted of atypical columnar epithelium with pseudostratification, mimicking gastric foveolar epithelium, while atypical signet-ring cells were scattered within the SCC. There was an abrupt transition between the AC and SCC areas. The tumor cells in the AC area were intensely positive for galactose oxidase-Schiff staining, and paradoxical concanavalin A staining revealed these tumor cells to have Class II mucins. Immunohistochemically, the tumor cells in foveolar-type adenocarcinoma were diffusely positive for cathepsin D. Flow cytometrical analysis of DNA content showed the AC area to be diploid and the SCC area to be aneuploid. The S-phase fraction of the SCC area (46.9%) was larger than that of the AC area (19.5%). The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC area (mean 50.627%) was larger than that of the AC area (mean 3.048%, P < 0.01). These results suggest that the AC area of this tumor, histochemically and immunohistochemically, showed gastric foveolar-type characteristics, the SCC component was squamous cell metaplasia of the pre-existing AC, and that the SCC area had a greater proliferating capacity than the AC area.

Aged↗

Differences in c-fos gene product expression in cancers of the gall-bladder and biliary tract.

The c-fos gene encodes a 55 kDa nuclear protein product that complexes to a cellular protein, p39. The pattern of expression of c-fos is particularly complex with increased expression of the protein observed in undifferentiated cultured cells while reduced expression is found during terminal differentiation. The expression of c-fos gene was studied by immunohistochemistry in carcinoma of the gall-bladder (n = 13), biliary tract (n = 5) and ampulla of Vater (n = 9). Non-malignant conditions investigated include chronic cholecystitis (n = 11), gall-bladder dysplasia (n = 3) and adenoma (n = 1), and ampullary carcinoma in situ (n = 3). Strong positive granular cytoplasmic immunostaining for c-fos oncoprotein was present in most gall-bladder adenocarcinomas (n = 11; 85%). The single gall-bladder adenoma and only one of the dysplasia cases were positive. Most of the cases of chronic cholecystitis showed either absent or only focal to patchy and weak to moderate c-fos immunoreactivity in the deeper glands and Rokitansky-Aschoff sinuses but not in the superficial epithelium. None of the biliary tract and ampullary tumors showed immunostaining for c-fos. The difference in c-fos immunoreactivity between gall-bladder carcinoma and chronic cholecystitis was statistically significant (P = 0.0002; chi 2 test with continuity correction). In conclusion, c-fos protein may be important in the development of gall-bladder neoplasia with increased c-fos immunoreactivity in gall-bladder carcinoma but not in chronic cholecystitis, biliary tract and ampullary neoplasms. These findings suggest that gall-bladder carcinoma may arise from a different genetic basis compared to biliary tract and ampullary cancers.

Adenoma↗

Extrahepatic biliary papillomatosis occurring after removal of a dysplastic gall bladder.

A case is presented of a woman who developed obstructive jaundice secondary to dysplastic mucinous papillomatosis two years after she had undergone cholecystectomy and exploration of the common bile duct. The gall bladder was dysplastic. It is suggested that the dysplastic glands removed from the common bile duct at the second operation either represented seedlings from dysplastic areas of the gall bladder or were a manifestation of dysplastic field change.

Bile Duct Neoplasms↗

On the relationship of cholelithiasis to carcinoma of the gall-bladder and on the sex dependency of the carcinoma of the bile ducts. A study based on the autopsy data from 1928 to 1972.

On the basis of the autopsy data from the Pathology Department of the Wilhelminen Hospital, Vienna from 1928 to 1972, it has been shown that gall-stones occur more frequently in conjunction with the carcinoma of the gall-bladder but have not aetiological relationship with the malignancy. It is further shown that the carcinoma of the bile ducts is more common in males and the carcinoma of the gall-bladder more common in females.

Autopsy↗

[Combined intraductal and percutaneous radiotherapy of malignant bile duct obstruction with subsequent prosthetic management].

Radiotherapy of the inoperable malignant bile duct obstruction is performed to prolong the survival time in comparison to the palliative drainage. The preferable method is a combination of intracavitary irradiation via a percutaneous transhepatic drainage (30-40 Gy at a distance of 1 cm) and a moving field technique (30-40 Gy). This combination allows a high local tumor dose and a relatively large treatment volume. After radiotherapy, the PTD is being exchanged by a large-bore biliodigestive prosthesis.

Adenocarcinoma↗