A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Effectiveness and cost-effectiveness of colorectal cancer screening: Selecting the ideal strategy

Abstract Colorectal cancer is the second most common cancer killer of Americans. Recently developed and tested methods of screening and surveillance can effectively diagnose and treat the disease in most patients before symptoms develop when the chance of cure is high. It is also possible to prevent colorectal cancer by detecting and resecting premalignant adenomatous polyps. Evidence-based guidelines recommend that the average-risk population greater than age 50 be screened with annual faecal occult blood tests plus periodic flexible sigmoidoscopy. This approach is feasible, efficacious, affordable and cost-effective in a high-risk country such as the US. Widespread compliance with these recommendations could reduce the mortality from this malignancy by more than 50%.     

Short-term outcome analysis of a randomized study comparing laparoscopic vs open colectomy for colon cancer

The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas. The role of laparoscopic techniques in the treatment of colon carcinomas is questionable. Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections. A prospective, randomized study was conducted comparing laparoscopic assisted colectomy (LAC) open colectomy (OC) for colon cancer. We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging. Benefit has been demonstrated with LAC in this setting. Passing flatus, oral intake, and discharge from hospital occurred earlier in LAC- than OC-treated patients The mean operative time was significantly longer in the LAC group than in the OC group. The overall morbidity was significantly lower in the LAC group. No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification. The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer. However, the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome.Presented at the annual meeting of the Society of American Gastrointestinal Surgeons (SAGES), Orlando, FL, USA, 11–14 March 1995     

Treatment of chronic lymphocytic leukemia in early and stable phase of the disease: Long-term results of a randomized trial

Abstract: In 1982 the IGCI CLL cooperative group decided to investigate the usefulness of treating, at diagnosis B-cell chronic lymphocytic leukemia (CLL) in early and stable phase of the disease. From January 1982 to December 1986, 148 patients were randomized either to receive immediate treatment with chlorambucil (CLB) or to defer therapy to the time of progression. The early and stable phase of the disease was defined by a total tumor mass (TTM) score < 9, the absence of anemia or thrombocytopenia and a doubling time > 12 months. The main end-point of the study was survival. At the last evaluation in April 1993, after a median follow-up of 75 months, no significant difference was found in overall survival between early vs. deferred treatment patients from every cause of death as well as from death due to CLL-related causes only. The same results were obtained when the patients in more favorable stages, such as Binet stage A and TTM < 4.5, were considered. Interestingly, the incidence of epithelial cancer was similar in the two groups. Early treatment was associated with a significantly better response and a lower progression rate. From this long-term experience, it can be concluded that immediate chemotherapy with CLB is not beneficial for CLL patients in early and stable phase of the disease in terms of survival.     

Laparoscopy to correctly diagnose and stage metastatic breast cancer mimicking Crohn's disease

We report a case of metastatic lobular breast carcinoma with extrahepatic gastrointestinal disease. On the basis of clinical findings, radiologic investigations, computerized axial tomography, gastrointestinal endoscopy, and gastric biopsy, the diagnosis of gastric and ileal Crohn's disease was made. The correct diagnosis of peritoneal carcinomatosis was made at laparoscopy. This case exemplifies the utility of laparoscopy in establishing the diagnosis and staging for abdominal disease of uncertain etiology.     

Improvement in the Treatment of Childhood Cancer: Analysis of Survival Data from the National Children's Hospital (1965-1987)

Developments in the treatment of childhood cancer have beenevaluated in patients who had been treated in the National Children'sHospital from 1965 to 1987. The total number of patients was867, of which leukemia accounted for 376, malignant lymphoma61, neuroblastoma 174, Wilms' tumor 55, yolk sac tumor 29, rhabdomyosarcoma36 and hepatoblastoma 30. Patients were divided into three timeintervals: the 1960s, 1970s and 1980s. A marked improvementin five-year survival was recognized in Wilms' tumor and yolksac tumor, amounting to 80%, followed by rhabdomyosarcoma, acutelymphoblastic leukemia and malignant lymphoma. There was noimprovement in patients with acute non-lymphoblastic leukemia,neuroblastoma and hepatoblastoma. Prognostic factors for neuroblastomawere further analyzed, and the age of onset and stage of diseasewere found to have remained constant for 23 years. Factors relatingto the improvement of survival were discussed.     

Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer

Summary Genetically determined polymorphisms of N-acetylation and oxidative capacity have been studied using dapsone and metoprolol in 51 Japanese patients with spontaneous bladder cancer and 203 healthy control subjects.The results for N-acetylation pharmacogenetics were against the initial expectation that there would be a preponderance of slow acetylators in the cancer group, as 3 such patients (5.9%) were found as compared to 13 (6.4%) in the healthy group. There was no poor metabolizer (PM) of metoprolol in the cancer group, whereas in the healthy group one (0.5%) was a PM. There were no significant differences between the groups in the frequency of slow acetylator and poor oxidiser phenotypes, or in the frequency distribution profiles of acetylation (monoacetyldapsone/dapsone) and oxidative metabolic ratio (log metoprolol/-hydroxymetoprolol).The results indicate that neither N-acetylation nor the debrisoquine/sparteine-type oxidative phenotype and/or capacity represent a genetic predisposition to spontaneous bladder carcinogenesis in Japanese patients. In the normal Japanese population there is a great predominance of rapid acetylators and extensive oxidisers.     

The Stockholm breast cancer screening trial — 5-year results and stage at discovery

In screening programmes it is important to assess a preliminary effectiveness of the screening method as soon as possible in order to forecast survival figures. In March 1981 a controlled single-view mammographic screening trial for breast cancer was started in the south of Stockholm. The population invited for screening mammography consisted of 40,000 women aged 40–64 years, and 20,000 women served as a well-defined control group. The main aim of the trial was to determine whether repeated mammographic screening could reduce the mortality in the study population (SP) compared to the control population (CP).The cumulative number of advanced mammary carcinomas in the screening and the control populations from the first five years of screening have shown a tendency towards more favourable stages in the screened population aged 40–64 years. A breakdown by age suggests an effect in age group 50–59 years, but not yet in age groups 40–49 and 60–64 years.When comparing the rates of stage II+ cancer, an increased number is found in the study group. As the total rate of breast cancer is higher in SP than in CP, there ought to be a concealed group of stage II+ cancers in the CP which makes the comparison biased. A new approach has been designed, where an estimation of the hidden number of stage II+ cancers in CP is added to the clinically detected cases, and in this respect a comparison has shown a decrease in the cumulative number of advanced cancers in the SP in relation to the CP (p<0.05). According to this it could be important to add the estimated number of undetected, hidden cases in the control group in order to utilize the difference in detection rate in the screening- and control group respectively.     

Intraoperative frozen section examination of axillary sentinel lymph nodes in breast cancer

The study presents the results from intraoperative frozen section assessment of axillary sentinel lymph nodes (SLNs) in breast cancer. Routine histological frozen sections from one level were used, two sections stained with haematoxylin and eosin. Immunohistochemistry for cytokeratins was applied to the permanent SLN paraffin sections only. Axillary dissection was performed on all SLN-positive cases regardless of the size of the metastatic deposits. With a detection rate of 83%, 272 patients entered the study over a period of 46 months. A total of 61 cases were SLN positive by frozen section analysis. The paraffin sections gave an additional 23 SLN-positive cases. The false-negative rate for frozen sections was then 27% (23/84). Micrometastases were found in 28 of 84 cases, and macrometastases in 56. The false-negative rate of frozen sections for micrometastases was 71% (20/28), and for macrometastases 5% (3/56). A total of 73% (61/84) of the patients underwent axillary surgery as a one-step procedure.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.