Lars Bo Svendsen

EFFECT OF CIMETIDINE ON SURVIVAL AFTER GASTRIC CANCER

The effect of cimetidine on survival was investigated in 181 patients with gastric cancer. Immediately after operation or the decision not to operate, the patients were randomised in double-blind fashion to placebo or cimetidine 400 mg twice daily for two years or until death, with review every three months. Median survival in the cimetidine group was 450 days (range 1-1826) and in the placebo group 316 days (1-1653). The relative survival rates (cimetidine/placebo) were 45%/28% at 1 year, 22%/13% at 2 years, 13%/7% at 3 years, 9%/3% at 4 years, and 2%/0% at 5 years. Survival in the cimetidine group was significantly longer than in the placebo group.

Endoscopic Palliation of Inoperable Cancer of the Oesophagus or Cardia by Argon Electrocoagulation

BACKGROUND Cancer of the oesophagus and the cardia tends to present late. Palliation of dysphagia is the prospect of most of the patients. This paper reports the use of argon electrocoagulation in 83 patients with inoperable cancer strictures in the oesophagus and cardia. METHODS The argon electrocoagulation was done by a fibre conducting electricity and argon air to the site of coagulation. After treatment the patients were allowed to take fluids and normal food the same evening or the next morning. After recanalization the patients were treated regularly every 3-4 weeks. RESULTS Recanalization enabling passage for normal food was achieved with 1 treatment in 48 patients (58%), whereas 22 (26%) needed more than 1 treatment. In 13 patients (16%) the ability to eat normal food was not achieved. In these patients dysphagia improved at least one grade. Perforation was seen in seven patients (8%) and in 1% of treatments. Perforations were successfully treated conservatively in six of the seven patients. Sixty-three patients (76%) died during the investigation period, on average 146 days (range, 43-397 days) after diagnosis. CONCLUSION Argon electrocoagulation offers an easy, cheap, and safe alternative to treatment with laser photocoagulation and expandable metal stents.

Cimetidine for Severe Gastroduodenal Haemorrhage: A Randomized Controlled Trial

During a period of 12 months, 88 patients with severe haemorrhage from gastric or duodenal ulcers or from erosive gastritis completed a double-blind trial of either cimetidine or placebo. Only patients needing immediate blood transfusion were admitted to the trial. It was found that in patients with severe bleeding from gastric or duodenal ulcers neither the severity of bleeding nor the incidence of emergency surgery was reduced by cimetidine. Furthermore, the treatment did not improve the mortality rate. It is concluded that patients with severe bleeding from gastric or duodenal ulcers will not benefit from immediate treatment with intravenous cimetidine.

Three-dimensional anal endosonography may improve staging of anal cancer compared with two-dimensional endosonography.

PURPOSEThree-dimensional (3-D) endosonography is a new method of staging anal carcinoma that has not yet been validated in comparison with two-dimensional (2-D) endosonography, the latter using only a single scan plane. The aim of this study was to investigate the differences between the two endosonographic techniques.METHODSThirty patients with an endosonographically detectable anal tumor were examined with a 10 MHz rotating endoprobe. Cross-sectional images of the anal sphincters were stored on a 3-D system during retraction of the endoprobe through the anal canal. Afterwards, any projection could be reconstructed. Cross-sectional images (2-D) were compared with reconstructed projections (3-D) according to five parameters concerning tumor spread and presence of regional lymph nodes. In this study, a scale of 0 to 5 points on critical issues was used; ideally, the results should be identical in 2-D and 3-D endosonography.RESULTSThe 3-D method detected a median of 5 diagnostic findings, compared with a median of 4 findings with the 2-D method (P = 0.001). In eight patients the lateral tumor margin was visualized only by 3-D endosonography. The median number of lymph nodes visualized in 3-D was 1 (range, 0-13), in 2-D the median number was 0 (range, 0-6), P = 0.002.CONCLUSIONSUse of 3-D endosonography in patients with anal carcinoma improves detection of perirectal lymph nodes and may improve that of tumor invasion, compared with 2-D endosonography. This may affect local tumor staging and thus planning of treatment. A study with histopathologic correlation is needed to verify this endosonographic study.

Cimetidine as an adjuvant treatment in colorectal cancer

PURPOSE: To evaluate the influence of a H2 receptor antagonist (cimetidine) on survival in patients with colorectal carcinoma, a randomized, controlled pilot study was performed in three university hospitals in Copenhagen, Denmark. METHODS: A total of 192 patients, who had undergone a resection or an exploratory operation for adenocarcinoma of the colon or rectum between May 1988 and May 1991, were enrolled in the study. After a median observation time of 40 months, outcome was noted for each patient concerning cancer-specific mortality rate. RESULTS: In patients operated with curative intent (n=148), no difference was found in cancer-specific mortality between the two treatments. However, a tendency toward reduction in mortality rate was found in patients with curatively operated Dukes Stage C carcinoma (P=0.11, log-rank test; difference, 29 percent; 90 percent confidence interval, 2 to 57 percent) in the cimetidine-treated group. In patients with disseminated disease no total difference was found between the two treatment groups. CONCLUSIONS: Cimetidine does not seem to reduce mortality in patients with colorectal cancer, but there seems to be a tendency toward a survival benefit in patients undergoing surgery for Dukes Stage C carcinoma. Results seem to justify trials in this patient catagory to reveal a benefit of H2 receptor antagonists in adjuvant therapy of colorectal carcinoma.

Changes in gastric mucosal cell proliferation after antrectomy or vagotomy in man.

The rate of gastric epithelial cell proliferation was studied in peptic ulcer patients treated by partial gastrectomy or proximal gastric vagotomy (PGV). Endoscopic biopsies were incubated in vitro with 3H-thymidine and autoradiographs were prepared. The percentage of DNA-synthesizing cells (labeling index) in the progenitor cell region was estimated. Five patients were studied before and 3 months after antrectomy, whereas six other subjects were studied before and 2 weeks and 2 months after PGV. The results indicate that epithelial cell proliferation in fundic mucosa is accelerated after antrectomy in man and that PGV is followed by an increased rate of cell renewal in fundic and antral mucosa, whereas the kinetic parameters in duodenal mucosa remain unaffected by this operation. It is concluded that the proliferative changes after these operations are most likely caused by the development of gastritis. The study did not support the hypothesis that gastrin exerts a physiological trophic action on human gastric mucosa.

A prospective randomized comparison of curved array and radial echoendoscopy in patients with esophageal cancer

BACKGROUND Both curved array and radial scanning echoendoscopy are used for locoregional staging of cancer arising in the esophagus or cardia. The accuracy of TNM staging of these malignancies by curved array and radial EUS was compared in a prospective, randomized study. METHODS Patients with cancer of the esophagus or cardia were examined by both curved array and radial echoendoscopy in randomized order by the same endosonographer in an unblinded fashion. The staging results and the examination time for the two echoendoscopies were compared and statistically analyzed, and finally compared with surgical and histopathologic staging. RESULTS A total of 104 patients underwent EUS; 36 had surgical resection of the tumor, 26 surgical exploration without resection, and 42 did not undergo surgery. Comparison of the TNM staging results for the two echoendoscopies gave high kappa values (T, 0.77; N, 0.75; M, 0.89), indicating excellent agreement. The accuracy of curved array echoendoscopy and radial echoendoscopy by component of the TNM staging system were, respectively, T, 72% and 73%; N, 70% and 77%; and M, 61% and 57%. Mean procedure time for the curved array and radial examinations was, respectively, 15 and 12 minutes (p<0.01). CONCLUSION There was no clinically relevant difference between curved array and radial echoendoscopy in the staging of cancer of the esophagus or cardia. The choice of echoendoscope for TNM staging in patients with these malignancies is, therefore, a question of personal preference.

Computed Tomography (CT) Perfusion as an Early Predictive Marker for Treatment Response to Neoadjuvant Chemotherapy in Gastroesophageal Junction Cancer and Gastric Cancer - A Prospective Study

Objectives To evaluate whether early reductions in CT perfusion parameters predict response to pre-operative chemotherapy prior to surgery for gastroesophageal junction (GEJ) and gastric cancer. Materials and Methods Twenty-eight patients with adenocarcinoma of the gastro-esophageal junction (GEJ) and stomach were included. Patients received three series of chemotherapy before surgery, each consisting of a 3-week cycle of intravenous epirubicin, cisplatin or oxaliplatin, concomitant with capecitabine peroral. The patients were evaluated with a CT perfusion scan prior to, after the first series of, and after three series of chemotherapy. The CT perfusion scans were performed using a 320-detector row scanner. Tumour volume and perfusion parameters (arterial flow, blood volume and permeability) were computed on a dedicated workstation with a consensus between two radiologists. Response to chemotherapy was evaluated by two measures. Clinical response was defined as a tumour size reduction of more than 50%. Histological response was evaluated based on residual tumour cells in the surgical specimen using the standardized Mandard Score 1 to 5, in which values of 1 and 2 were classified as responders, and 3 to 5 were classified as nonresponders. Results A decrease in tumour permeability after one series of chemotherapy was positively correlated with clinical response after three series of chemotherapy. Significant changes in permeability and tumour volume were apparent after three series of chemotherapy in both clinical and histological responders. A cut-off value of more than 25% reduction in tumour permeability yielded a sensitivity of 69% and a specificity of 58% for predicting clinical response. Conclusion Early decrease in permeability is correlated with the likelihood of clinical response to pre-operative chemotherapy in GEJ and gastric cancer. As a single diagnostic test, CT Perfusion only has moderate sensitivity and specificity in response assessment of pre-operative chemotherapy making it insufficient for clinical decision purposes.

Mandibular Osteomas in Colorectal Cancer

Orthopantomography of the mandible was carried out on 50 patients with colorectal cancer without known familial disposition. Twelve patients (24%) had osteomas, as against 5% in the control group (P less than 0.001). Since an increased occurrence of mandibular osteomas has earlier been demonstrated in cases of familial polyposis coli and the family cancer syndrome, we must conclude that genetic factors are presumably of more importance in the development of colorectal cancer than previously assumed.

Hereditary colon cancer syndromes: an in vitro study

Assays of in vitro biological properties associated with cellular transformation revealed differences in cultured skin cells within the heritable colon cancer syndromes with and without polyposis coli. Such evidence suggested that an in vitro panel of biological assays could be used to recognize genotypes which increase the risk of colon cancer prior to clinical expression and supported the concept, long assumed on clinical differences, of genetic heterogeneity within the heritable colon cancer syndromes.