Loss of heterozygosity at microsatellite marker sites for tumour suppressor genes in oesophageal adenocarcinoma.
Morgan RJ. Newcomb PV. Bailey M. Hardwick RH. Alderson D.
University Department of Surgery, Bristol Royal Infirmary, UK.
AIMS: Loss of cell cycle control is an important step in the development of human tumours. A number of tumour suppressor genes are involved in cell cycle control, including p16, p53 and Rb. The aim of this study was to seek evidence of deletions of these genes in oesophageal adenocarcinoma. METHODS: Paired (tumour and normal squamous epithelium) frozen tissue samples from 12 patients were analysed by polymerase chain reaction (PCR) for loss of heterozygosity (LoH) at five microsatellite marker sites (two each for p16 and Rb, one for p53). Aneuploid tumour cell populations were sorted by flow cytometry prior to PCR, to eliminate stromal cell contamination. RESULTS: Of the 12 tumours, 11 (92%) had LoH at one or more loci. LoH at the p53 locus occurred in nine of 12 tumours, at one or both p16 loci in seven of 11 tumours, and at one or both Rb loci in eight of 12 tumours. Five tumours had LoH at two tumour suppressor gene loci, and a further four tumours had LoH at loci for all three genes. CONCLUSIONS: Allelic deletions of p53, p16 and Rb are common in oesophageal adenocarcinoma, and may be important in the development of this disease.
Transforming growth factor alpha immunoreactivity in human gallbladder and extrahepatic biliary tract tumours.
Department of Pathology, University of Melbourne, Australia.
AIMS: Transforming growth factor alpha (TGF-alpha), a protein structurally similar to epidermal growth factor (EGF), is implicated in the development of many human tumours. This study examines the expression of TGF-alpha in gallbladder and extrahepatic biliary tract tumours in which EGFR expression has been previously shown to be important. METHODS: A monoclonal antibody to the TGF-alpha protein was used to investigate the immunohistochemical expression of TGF-alpha in carcinoma of the gallbladder (n = 13), common bile duct (CBD) (n = 6) and ampulla of Vater (n = 8). Tissues from cases of chronic cholecystitis (n = 11), gallbladder dysplasia (n = 3) and adenoma (n = 1), and ampullary carcinoma in situ (CIS) (n = 3) were used as non-malignant controls. These cases were previously studied for EGFR expression. RESULTS: TGF-alpha overexpression, defined as intense immunoreactivity in more than two-thirds of cells immunostained for TGF-alpha, was present in most gallbladder carcinomas (n = 10; 77%) but with no significant differences in expression between different tumour grades. None of the cases of gallbladder dysplasia or chronic cholecystitis had strong TGF-alpha expression and this was significantly different from the carcinomas (P = 0.013 and P = 0.0001, respectively; chi 2 test), although a few cases of chronic cholecystitis showed weak (n = 4), moderate (n = 6) or no (n = 1) immunoreactivity. A few ampullary carcinomas (n = 2; 25%) and CIS (n = 1; 33%), and half of the CBD carcinomas (50%) had strong TGF-alpha immunoreactivity. There was correlation between TGF-alpha and EGFR immunoreactivity in the tumour cases (r = 0.70, r2 = 0.49, P = 0.0001; simple regression analysis), although the rate of EGFR immunoreactivity in CBD and ampullary carcinomas was somewhat higher than that of TGF-alpha. However, no statistically significant correlation between TGF-alpha expression with patient survival or tumour recurrence (r = 0.11, r2 = 0.012, P = 0.65; simple regression analysis) was found. CONCLUSIONS: Increased TGF-alpha expression occurs more frequently in gallbladder carcinoma than in gallbladder dysplasia, chronic cholecystitis, CBD or ampullary tumour, with no specific relationship to tumour grade, suggesting that TGF-alpha overexpression occurs early in the development of gallbladder cancers, and that biliary tract cancers have a different molecular origin. Correlation was found between TGF-alpha and EFGR expression in gallbladder and biliary tract tumours.
Erythrocyte membrane stearic to oleic acid ratio in carcinoma of the gallbladder: a preliminary study.
Pandey M. Khatri AK. Dubey SS. Gautam A. Shukla VK.
Department of Surgery, Banaras Hindu University, Varanasi, India. firstname.lastname@example.org
AIMS: The role of erythrocyte membrane stearic to oleic acid ratio (saturation index) as a marker of malignancy is still unclear, though an association has been found in colorectal carcinoma, bronchogenic carcinoma, leukaemia, lymphoma and in hepatic malignancies. This study aims to investigate the role of the saturation index in primary carcinoma of the gallbladder. METHODS: This paper describes the results of the stearic to oleic acid ratio determination in 26 subjects with either cholelithiasis or carcinoma of the gallbladder, also including a group of age- and sex-matched controls, using gas chromatography. This is the first report of the saturation index in carcinoma of the gallbladder. RESULTS: A significantly lower saturation index was observed in patients with carcinoma of the gallbladder than with cholelithiasis (t = 2.19, P = 0.043, T = 47, P < 0.05, Wilcoxon P < 0.001, F = 2192.23, P < 0.001; 95% CI 18.45-30.44) and controls (t = 2.5, P = 0.024, T = 36, P < 0.05, F = 10904.11, P < 0.001, Wilcoxon P < 0.001; 95% CI 52.42-63.39). Among the carcinoma patients a further lowering was noted in stage IV disease compared with stage III (T = 6, P < 0.05). CONCLUSIONS: These changes are probably due to a marked increase in oleic acid content at the expense of stearic acid. This lowering of the saturation index in carcinoma of the gallbladder is similar to that observed previously in the other malignancies.
Screening for colorectal cancer reduces emergency admissions.
Scholefield JH. Robinson MH. Mangham CM. Hardcastle JD.
Department of General Surgery, University Hospital, Nottingham, UK.
AIMS: Colorectal cancer is common and accounts for over 15,000 deaths annually in England and Wales. Up to 30% of these patients require emergency surgery. Screening for colorectal cancer can reduce the mortality of colorectal cancer. This study addresses the impact of a population-based screening study on emergency admissions with colorectal cancer. METHOD: From 1981 a randomized trial of Faecal Occult Blood (FOB) screening has been undertaken in the Nottingham area, recruiting over 150,000 patients. The present study examined the records of patients enrolled in this study who presented as an emergency with colorectal cancer. RESULTS: Colorectal cancer was identified in 1962 cases, of which 468 (23.9%) presented as emergencies. The overall compliance was 60% (proportion of individuals completing at least one test). There were significantly fewer emergencies in the Screen-detected group compared with the Control group (P = < 0.0001). This group also had a significantly reduced 30-day mortality and a lower stoma rate than the Control group. Conversely the Non-responders had a significantly greater proportion of emergency admissions and a significantly increased stoma rate compared with the Control group. CONCLUSIONS: Screening for colorectal cancer using a faecal occult blood test can significantly reduce the number of emergency presentations with colorectal cancer. It is likely that the introduction of a national programme of screening for colorectal cancer would lead to increased compliance and that this would lead to a significant reduction in the emergency workload on the National Health Service from colorectal cancer.
Appraisal of transplantation for malignant tumours of the liver with special reference to early stage hepatocellular carcinoma.
Pichlmayr R. Weimann A. Oldhafer KJ. Schlitt HJ. Tusch G. Raab R.
Klinik fur Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany.
The enthusiasm to treat or even cure patients with unresectable hepatobiliary malignancy by total hepatectomy and liver transplantation has considerably diminished. Nowadays, due to organ-donor shortage, patients have to be selected with predictable likelihood for long-term survival. According to own experience and a review of the literature, liver transplantation may be considered in unresectable early stage hepatocellular and proximal bile duct carcinoma, the uncommon entities fibrolamellar carcinoma, epithelioid haemangioendothelioma and hepatoblastoma as well as in liver metastases from neuroendocrine tumours. At present, advanced stages of hepatocellular and proximal bile duct carcinoma, as well as intrahepatic bile duct carcinoma, haemangiosarcoma and metastases from nonendocrine tumours, should be excluded from transplantation. In order to cure the cancer-bearing disease, liver transplantation might be the ideal treatment for small but still resectable hepatocellular carcinoma with underlying cirrhosis. Our retrospective comparison of survival after resection and transplantation for early stage hepatocellular carcinoma does not reveal a significant difference. Although a tendency has been observed in favour of transplantation, resection of these tumours is still justifiable, not least because of donor organ shortage.
Huge non-functioning pancreatic cystic neuroendocrine tumour: a case report.
Kotoulas C. Panayiotides J. Antiochos C. Sambaziotis D. Papadopoulos G. Karameris A.
Second Surgical Clinic, 401 Army General Hospital of Athens, Greece.
A case of an 18-cm large cystic, non-functioning endocrine (islet cell) tumour located at the tail of the pancreas in a 29-year-old Caucasian female is reported here. Pre-operative radioimmunoassays for pancreatic peptides were negative, while immunohistochemistry confirmed the neuroendocrine nature of the tumour. This is the largest cystic non-functioning islet-cell tumour so far described.
A histopathological assessment of the response of rectal adenocarcinoma to combination chemo-radiotherapy: relationship to apoptotic activity, p53 and bcl-2 expression.
Scott N. Hale A. Deakin M. Hand P. Adab FA. Hall C. Williams GT. Elder JB.
Department of Histopathology, North Staffordshire NHS Trust, Stoke-on-Trent, UK.
AIMS: To investigate the use of pre-operative chemo-irradiation in downstaging advanced rectal cancer prior to surgical resection. METHODS: We examined the pathological effects of chemo-irradiation on 24 rectal tumours and correlated the efficacy of treatment with the level of apoptosis, mitosis, P53 and bcl-2 protein expression on pre-treatment biopsies. RESULTS: All tumours were resectable following chemo-irradiation. Six cancers showed complete regression with no viable tumour in the resection specimen. A significant correlation was found between spontaneous tumour apoptosis and tumour regression. CONCLUSIONS: Our results suggest that in rectal cancer the apoptotic rate in untreated tumour tissue may predict sensitivity to radiation and cytotoxic agents. No relationship was found between regression and mitotic rate, p53 or bcl-2 expression.
Resection of liver metastases from colorectal cancer: the real impact of the surgical margin.
Elias D. Cavalcanti A. Sabourin JC. Lassau N. Pignon JP. Ducreux M. Coyle C. Lasser P.
Department of Oncological Surgery, Institut Gustave Roussy, Comprehensive Cancer Center, Villejuif, France.
AIMS: The benefit of liver resection for metastatic colorectal cancer is now established. Nevertheless if the surgical margin on pre-operative imaging is considered to be less than 10 mm, this is considered an absolute contraindication to surgery by some, and a relative contraindication by others, so its real impact on prognosis is not clear. METHODS: From 1984 to 1996, 269 patients underwent hepatectomy for liver metastases and were prospectively studied. The only two objectives of this surgery were to be curative (or achieve complete R0 resection), and to avoid mortality. Of the 269, 187 patients had surgical margins inferior to 10 mm. Sixty per cent had multiple liver metastases, and 37% had extrahepatic metastatic sites. Their clinical and pathological factors were specifically studied. RESULTS: The crude 5-year survival of these 187 patients (including the 2% post-operative mortality) was 24.7%, and the disease-free survival was 18.8%. The surgical margin was 0 mm in 60 cases and was histologically invaded in 20 cases. The most important prognostic factor was whether the resection was considered palliative (R1-R2 resection according to UICC criteria) (P < 0.0001). When the cases with invaded margins were excluded, there was not prognostic difference between the 107 patients with a margin of 0-4 mm and the 143 patients with a margin greater than 4 mm. However, a surgical margin greater than 9 mm appears to be a second prognostic factor (P = 0.001), when these 187 patients are compared to others. The reasons behind this are that there is a close relationship between narrow margins and extensive disease (high number of metastases, bilateral localization and extended hepatectomy), and also an increased possibility of microscopic satellite lesions within 10 mm around the metastases. CONCLUSION: The real prognostic impact of the surgical margin must not be overestimated. Hepatectomy for metastases can provide long-term survival in patients with supposed poor prognostic factors. Resection is justified so long as it is complete and with minimal risk. An experienced, specialized centre can be a prognostic determinant.
Treatment of liver metastases from uveal melanoma by combined surgery-chemotherapy.
Salmon RJ. Levy C. Plancher C. Dorval T. Desjardins L. Leyvraz S. Pouillart P. Schlienger P. Servois V. Asselain B.
Department of Surgery, Institut Curie, Paris, France.
AIMS: To investigate sporadic results demonstrating prolonged survival after surgical resection and/or intraarterial chemotherapy (IACH) for liver metastases from uveal melanoma. METHODS: From December 1992 to March 1997 every patient with liver metastases from uveal melanoma was enrolled in a prospective study including: (1) aggressive surgical approach removing as much liver disease as possible; (2) implantation of an intraaterial catheter; (3) intraarterial chemotherapy for 6 months. 75 patients were enrolled: 38 men, 37 women, mean age 51 years (range: 18-72), mean time from initial diagnosis of uveal melanoma to liver metastases 37 months (ranged: 1-168). RESULTS: Disseminated disease in both lobes was present in all but one patient. Macroscopically curative surgery was possible in 27.5%. Significant tumour reduction was performed in 49.3% and a simple biopsy was possible in 23.2%. Eight patients did not receive chemotherapy and died soon after. IACH included Fotemustine and/or DTIC-Platinum for 4-9 cycles. Overall median survival was 9 months; very similar to non-operated historical controls. In the 61 patients receiving complete treatment surgery plus chemotherapy, median survival improved to 10 months. When curative resection was possible, survival increased to 22 months (P < 0.001). CONCLUSIONS: Aggressive surgical resection, when possible, appears to be the best method of improving survival of liver metastases from uveal melanoma. New drug combinations are also required to improve survival.
Port site metastasis from synchronous primaries of the colon and ovary following laparoscopic cholecystectomy.
Rieger N. McIntosh N.
Department of Surgery, Flinders Medical Centre, Bedford Park, Australia.
We report two cases of port site metastasis as the presenting feature of colonic and ovarian carcinoma after laparoscopic cholecystectomy. Cholecystectomy was performed for upper abdominal pain and gallstones. Six and 4 months after the operation the patients presented with nodules at port sites, other than the site of extraction. Biopsy proved both to be adenocarcinoma and further management found these to be from advanced caecal and ovarian carcinomas.
de Jong E. Mulder W. Nooitgedacht E. Taat CW. Bras J.
Department of Surgery of Academic Medical Center, Amsterdam, The Netherlands.
The purpose of this study is to provide an overview of cases of Carney's triad and to discuss the clinical implications of this diagnosis. A search was made of the English-language literature for original articles, reviews and abstracts addressing Carney's triad. A new patient was described and added to the number of known patients. In literature 40 patients were found with a complete or incomplete triad. There exists no agreement on the pathology and possible common origin of these tumours. Directions are given for diagnostics and therapy. The diagnosis of Carney's triad has specific clinical implications that make a good knowledge of this syndrome mandatory.
Localization of monoclonal antibody CC49 in colonic metastasis from renal cell carcinoma.
Avital S. Hitchcock CL. Baratz M. Haddad R. Skornick Y. Schneebaum S.
Department of Surgery A, Tel-Aviv Sourasky Medical Center, Israel.
We report a rare case of solitary metastasis from renal cell carcinoma which manifested as a primary colonic tumour 5 years after nephrectomy. A monoclonal antibody CC49 (anti-TAG-72 antibody), used in Radioimmunoguided Surgery, was found to localize in the tumour. Pathological examination revealed metastasis of renal cell carcinoma in the colon. Immunohistochemistry with CC49 showed moderate staining of the colonic mucosa around the metastasis with no reaction in the tumour itself. Based on this case and other published studies, we conclude that TAG-72, the antigen manifested in many adenocarcinomas, can be up-regulated and expressed in normal colonic mucosa adjacent to another tumour as a result of stimulations, such as cytokine release, in response to this tumour.