Biomedical subjects
Publications and source records attributed to J J Bonenkamp.
A patient is presented with massive hematemesis caused by a fistula between the left cardiac atrium and a gastric tube interposition, which was constructed after esophagectomy for esophageal cancer 3 years earlier.
BACKGROUND: Repair of abdominal wall defects in the presence of contamination or infection continues to be a significant problem for surgeons. The loss of tissue warrants reinforcement of the abdominal wall, preferably by autologous material. However, autologous repair often requires extensive operations that carry a high morbidity. Moreover, the lack of sufficient fascia may be so extensive that insertion of a prosthetic material is inevitable. Polypropylene (PP) is the most appropriate material to use under these circumstances, but without coverage, the mesh will wrinkle and ultimately be extruded. The present report describes an alternative technique for repair of heavily contaminated abdominal-wall defects. PATIENTS: Two patients with a very large heavily contaminated abdominal wall defect due to necrotizing fasciitis in one patient and a lion's bite in the other were treated with the omental sandwich technique. After radical debridement, resulting in a full thickness loss of the abdominal wall, the peritoneum was restored using absorbable polyglactin mesh. The fascial defect was bridged with a PP mesh that was fixed to the adjacent myoaponeurosis and covered with a pedicled omental flap. In both patients the omentum was covered with a split skin. RESULTS: Wound healing in both patients was without complications. Both patients had a sufficient abdominal wall, without signs of herniation after a follow up of 4 and 30 months, respectively. CONCLUSION: The omental sandwich technique is an attractive method to repair large abdominal wall defects in the presence of contamination or overt infection.
Hereditary diffuse gastric cancers are rare, accounting for at most 1-3% of gastric cancers. It can be caused by a mutation in the tumour-suppressor gene CDH1. A healthy person carrying a CDH1 mutation has a cumulative risk of developing gastric cancer of 70-80%. In most cases, gastric cancer is detected before the age of 40 years. The effectiveness of screening for hereditary diffuse gastric cancer or early detection with twice-yearly upper GI endoscopy with blind biopsies is highly questionable. Given the poor prognosis of patients with hereditary diffuse gastric cancer, prophylactic gastrectomy can be considered an option for patients with a CDH1 mutation. It is recommended that the supervision, screening and possible preventative gastrectomy for hereditary diffuse gastric cancers are handled by a multidisciplinary team in a specialised centre.
PURPOSE: To assess the occurrence of high-risk epithelial lesions in women of breast cancer families with and without a BRCA mutation. PATIENTS AND METHODS: Prospective study of women at very high risk of breast cancer undergoing prophylactic mastectomy (68 BRCA1 mutation carriers, 14 BRCA2 mutation carriers and 24 non-BRCA mutation carriers). RESULTS: The prevalence of high-risk lesions is equal in women with a BRCA1 or a BRCA2 mutation, but is higher in non-BRCA mutation carriers: all lesions 43% versus 71% (p=0.02), atypical lobular hyperplasia 26% versus 67% (p=0.001), atypical ductal hyperplasia 17% versus 42% (p=0.01), lobular carcinoma-in situ 15% versus 29% (p=0.10) and ductal carcinoma-in situ 9% versus 17% (p=0.25). The presence of high-risk lesions is related to absence of a BRCA mutation and to age over 40 years. CONCLUSION: Women with an autosomal dominant family history for breast cancer, with and without a BRCA mutation are prone to develop high-risk epithelial lesions, especially over 40 years.
PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.
BACKGROUND: Isolated limb infusion (ILI) is a simple yet effective alternative to conventional isolated limb perfusion for the treatment of advanced melanoma of the extremities. PATIENTS AND METHODS: The study group comprised 13 patients with very advanced limb disease who had failed to achieve a satisfactory response to one or more ILIs with melphalan, and in whom amputation was the only other realistic treatment option. The aim of this study was to evaluate the efficacy and toxicity of ILI with fotemustine after systemic chemosensitisation with dacarbazine (DTIC). RESULTS: Complete remission was achieved in four patients and partial remission in eight patients, with a median response duration of 3 months. Limb salvage was achieved in five of 12 assessable patients (42%). Limb toxicity peaked 9 days after ILI; two patients experienced Wieberdink grade IV (severe) toxicity and four patients had grade V toxicity (requiring early amputation). CONCLUSIONS: ILI with fotemustine after DTIC chemosensitisation can be successful when gross limb disease has not been controlled by one or more ILIs with melphalan. However, it cannot be recommended as a routine method of treatment for advanced melanoma of the extremities because of the high incidence of severe limb toxicity.
A 75-year-old woman with Parkinson's disease presented with an amelanotic melanoma on her right lower leg with an inguinal lymph node metastasis. For the previous six years she had been treated with levodopa-carbidopa. The disease disappeared after inguinal lymph node dissection and hyperthermic isolated regional perfusion. It is sometimes thought that levodopa may have an activating effect on melanoma, due to its possible role in the biosynthetic pathway of melanin. However, on the basis of the literature available, such a causal association is unlikely.
Fibrovascular esophageal polyps are rare benign tumors. They can grow to considerable length and cause symptoms such as dysphagia, retrosternal discomfort, vomiting, and even asphyxia. A barium contrast esophageal radiography will show a filling defect compatible with an esophageal mass. Surgical removal through cervical esophagotomy is the preferred treatment, and recurrences after surgery are rare. We describe a patient who developed three recurrent giant fibrovascular esophageal polyp within eight years. A review of the literature is given.
BACKGROUND: Western patients with gastric cancer often present with incurable disease. The role of palliative surgical resection is still debatable. Non-curatively treated patients from the Dutch Gastric Cancer Trial were studied to define more accurately which patients might benefit from palliative resection. METHODS: In the Dutch Gastric Cancer Trial 285 (26 per cent) of the randomized patients were found to have incurable tumours at laparotomy. Four signs of incurability were noted: irresectable tumour (T+), hepatic metastasis (H+), peritoneal metastasis (P+) and distant lymph node metastasis (N4+). Patients had either an explorative laparotomy, a gastroenterostomy, or a resection (partial or total). In the analysis, particular attention was paid to the prognostic factors of age, number of metastatic features, and a combination of these. RESULTS: Overall survival time was greater if a resection was performed (8.1 versus 5.4 months; P < 0.001). For patients aged over 70 years there was still a survival advantage of about 3 months if resection was carried out. Morbidity and perioperative mortality rates in this older age group were, however, high (50 and 20 per cent respectively). For patients with one metastatic site a resection was of significant benefit (survival 10.5 versus 6.7 months; P = 0.034). For patients with two or more metastatic sites resection had no significant survival advantage (5.7 versus 4.6 months; P = 0.084). Combination of these factors indicates that patients aged less than 70 years with one metastatic site will benefit significantly from a palliative resection, in contrast to other combinations of factors. CONCLUSION: Age as well as the number of metastatic sites should be taken into account when a palliative resection is considered. Palliative resection may be beneficial for patients under 70 years of age if the tumour load is restricted to one metastatic site.
We present an immunocompetent man with extensive warts on the hands, refractory to a number of conventional treatment modalities and causing substantial morbidity and impairment of normal function. Isolated limb infusion (regional intra-arterial chemotherapy) with melphalan and actinomycin D was performed, with substantial clearing of the warts within 2 months. Treatment-induced morbidity was limited to mild local erythema and oedema which resolved within 3 weeks. After 9 months' follow up, the patient had only a few residual warts and was able to resume normal activities.
BACKGROUND: Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection, as recommended by the Japanese medical community, or a limited (D1) dissection. We conducted a randomized trial in 80 Dutch hospitals in which we compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery. METHODS: Between August 1989 and July 1993, a total of 996 patients entered the study. Of these patients, 711 (380 in the D1 group and 331 in the D2 group) underwent the randomly assigned treatment with curative intent, and 285 received palliative treatment. The procedures for quality control included instruction and supervision in the operating room and monitoring of the pathological results. RESULTS: Patients in the D2 group had a significantly higher rate of complications than did those in the D1 group (43 percent vs. 25 percent, P<0.001), more postoperative deaths (10 percent vs. 4 percent, P= 0.004), and longer hospital stays (median, 16 vs. 14 days; P<0.001). Five-year survival rates were similar in the two groups: 45 percent for the D1 group and 47 percent for the D2 group (95 percent confidence interval for the difference, -9.6 percent to +5.6 percent). The patients who had R0 resections (i.e., who had no microscopical evidence of remaining disease), excluding those who died postoperatively, had cumulative risks of relapse at five years of 43 percent with D1 dissection and 37 percent with D2 dissection (95 percent confidence interval for the difference, -2.4 percent to +14.4 percent). CONCLUSIONS: Our results in Dutch patients do not support the routine use of D2 lymph-node dissection in patients with gastric cancer.
The five-year survival rate after curative resection for gastric cancer is higher in Japan (62%) than in the Netherlands (30%). In Japan, extensive D2 resection surgery is performed, in the Netherlands D(1) resection in which only the perigastric lymph nodes are removed. In a large prospective randomised trial, surgical departments of 80 Dutch hospitals compared the results of both resection types. A Japanese surgeon gave instruction in the D2 technique. D2 patients suffered more complications than D(1) patients and hospital mortality was 10% as against 4%. Demographic characteristics and concomitant morbidity might explain these differences. A change in current therapy is not advised at present. However, the surgical protocols and standards developed in connection with the trial reduced the overall death rate and morbidity of surgical treatment of gastric cancer in the Netherlands.
The poor prognosis of patients with gastric cancer with free abdominal tumour cells on cytological examination has been described in Japan. In a randomized trial in the Netherlands comparing D1 and D2 lymphadenectomy for gastric cancer, patients were subjected to cytological examination of abdominal washings on an optional basis; findings were of no consequence for scheduled treatment. Cytology results in 535 patients were obtained, in 457 (85.4 per cent) after curative resection and in 78 (14.6 per cent) after palliative operation. There was a clear association of positive cytology results with serosal invasion (12 per cent positive cytology) and lymph node infiltration (7.5 per cent positive cytology). Survival of those with positive cytology results was significantly lower than that of those with negative findings, irrespective of the procedure employed (curative or palliative). Cytological examination of abdominal washings increases the accuracy of staging and improves the selection of patients suitable for curative or palliative resection.
Prognostic value of microscopical resection-line involvement of the proximal and distal resection lines was examined in patients undergoing potentially curative resection in a multicentre trial with strict quality control. Tumour-positive resection lines were seen in 41 of the 699 evaluable patients (5.9%). Resection-line involvement was associated with T stage (P < 0.001), N stage (P = 0.003), tumour location (P < 0.001) and tumour differentiation (P < 0.001). Presence of resection-line involvement was also associated with significantly worse survival. Together with T3 and T4 stage (relative risk (RR) 2.04), N(+) stage (RR 4.02) and tumour differentiation (RR 1.33), resection-line involvement (RR 2.28) was also an independent prognostic factor for survival. Survival in patients with resection-line involvement was comparable with patients with positive cytology. In patients undergoing potentially curative resection for gastric cancer, peri-operative frozen-section examination should be mandatory, especially in those with poorly differentiated, signet ring cell or anaplastic tumours, with tumours covering the entire stomach and T3 or T4 tumours. In case of tumour-positive margin(s) at final histology, re-laparotomy could be considered if achieving tumour-free resection lines seems realistic.
For patients with gastric cancer deemed curable the only treatment option is surgery, but there is disagreement about whether accompanying lymph-node dissection should be limited to the perigastric nodes (D1) or should extend to regional lymph nodes outside the perigastric area (D2). We carried out a multicentre randomised comparison of D1 and D2 dissection. 1078 patients were randomised (539 to each group). 26 allocated D1 and 56 allocated D2 were found not to satisfy eligibility criteria (histologically confirmed adenocarcinoma of the stomach without clinical evidence of distant metastasis). Each of the remainder was attended by one of eleven supervising surgeons who decided whether curative resection was possible and, if so, assisted with the allocated procedure. Among the 711 patients (380 D1, 331 D2) judged to have curable lesions, D2 patients had a higher operative mortality rate than D1 patients (10 vs 4%, p = 0.004) and experienced more complications (43 vs 25%, p < 0.001). They also needed longer postoperative hospital stays (median 25 [range 7-277] vs 18 [7-143] days, p < 0.001). Morbidity and mortality differences persisted in almost all subgroup analyses. While we await survival results, D2 dissection should not be used as standard treatment for western patients.
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PURPOSE: An overview is presented of reports published since 1980, in which postoperative adjuvant chemotherapy is compared with surgery alone for patients with gastric cancer. A MEDLINE literature review yielded 123 reports, 14 of which were relevant randomized trials; data from 11 of these trials were (or became) available for analysis of crude mortality odds. These 11 trials included 2,096 patients. METHODS: Odds ratios were calculated by comparing the adjuvant treatment arm with the observation-only arm. Those odds ratios that could be considered homogeneous yielded an estimated common odds ratio of 0.88 (95% confidence interval [CI], 0.78 to 1.08), which was slightly, but far from significantly, in support of adjuvant treatment. RESULTS: The results confirm the common opinion that the adjuvant chemotherapy regimens prescribed in these trials, although effective in phase II studies, do not improve survival. Furthermore they indicate that postoperative chemotherapy in general offers no additional survival benefit for patients with curatively resected gastric cancer. CONCLUSION: In conclusion, at present, postoperative chemotherapy cannot be considered as standard adjuvant treatment. New trials of adjuvant therapy for gastric cancer must include a no-treatment control arm.
OBJECTIVE: To compare the postoperative course of patients in the Dutch nationwide randomised trial of R1 (conventional) compared with R2 resection (including extended lymph node dissection) in the treatment of gastric cancer. DESIGN: Prospective randomised controlled trial. SETTING: National multicentre trial with 72 participating hospitals in The Netherlands. SUBJECTS: 192 patients who were operated on between August 1989 and May 1990. INTERVENTIONS: 96 patients were randomised for a R1, and 96 for a R2 resection. MAIN OUTCOME MEASURES: Morbidity and mortality among 131 patients (64 R1 and 67 R2) for whom the resection was performed with curative intent. RESULTS: The groups were comparable for age, sex, type of resection, site of tumour and depth of invasion. Complications developed in 23 R1 (36%) and in 29 R2 patients (43%). Seven patients died in the postoperative period. Median hospital stay was significantly longer after R2 (18 days, range 7-122) than after R1 resection (15 days, range 2-63) (p < 0.05). Morbidity and mortality among the patients whose R2 resection was done by the Japanese instructor (n = 34) did not differ significantly from those among patients operated on by the Dutch supervisors (n = 33), but those operated on by the Japanese instructor stayed in hospital significantly longer (20 compared with 16 days, p < 0.05). CONCLUSIONS: If R2 resections are carried out by properly trained surgeons under supervision, they can be done safely. The reported high morbidity after R2 resection in Western countries seems to result from a lack of proper instruction and quality control.