Genetic control of host-vs-graft reactivity after small bowel transplantation with heterotopic and orthotopic placement.
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Publications and source records attributed to J Klempnauer.
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BACKGROUND: Donor-specific blood transfusion prior to transplantation has been demonstrated to prolong allograft survival. This study compared the effect of donor-specific blood transfusion after kidney, heart, pancreas, and skin allotransplantation in congenic rats of reciprocal strain combinations across a major histocompatibility complex barrier. STUDY DESIGN AND METHODS: Whole donor-specific and third-party blood was administered to the prospective graft recipients 14 and 7 days before the transplantation of kidney, heart, pancreas, and skin. Rejection was defined by cessation of organ-specific function (i.e., uremia, cessation of heartbeat, and recurrence of diabetes). The survival of skin grafts was monitored visually. All allografts were histologically assessed immediately after rejection or at the end of a 100-day observation period. RESULTS: Donor-specific blood transfusion leads to permanent acceptance of all renal allografts. LEW.1U heart allografts were accepted by LEW.1A recipients, but they were rejected in the reciprocal situation. Survival of pancreas and skin allografts was not significantly prolonged. Third-party blood had no effect on allograft survival. CONCLUSION: The beneficial effect of donor-specific blood transfusion depends on both the kind of transplanted organ and the genetic incompatibility involved. The precise mechanisms responsible for the remarkable organ-specific differences remain unknown.
PURPOSE: To define the prognostic factors after surgical resection of bile duct carcinomas at the hepatic bifurcation. PATIENTS AND METHODS: The retrospective single-center experience details 151 patients after surgical resection of central bile duct carcinoma performed between 1971 and 1995. Tumor removal was accomplished by resection of the bile duct bifurcation either alone (group I, n = 33), in combination with hepatic resection (group II, n = 77), or combined with hepatic and vascular resection (group III, n = 41). Survival analysis was performed by the Kaplan-Meier method and the relationship between each of the clinicopathologic variables and survival was assessed by the log-rank test. Multivariate results were confirmed using Cox regression. RESULTS: The overall hospital mortality rate was 9.9% and depended on the extent of resection (group 1, 6.1%; group II, 7.8%; group III, 17.1%). After exclusion of hospital deaths, the overall patient survival rate was 28.4% at 5 and 15.5% at 10 years, with a median survival duration of 2.05 +/- 0.23 years. Univariate survival analysis identified tumor size, lymph node metastases, residual tumor stage, and tumor grading as factors with a statistically significant prognostic impact. Survival prognosis was not influenced by the site of the tumor according to the classification of Bismuth and Corlette, extent of resection, International Union Against Cancer (UICC) stage, perineural and vascular invasion, age, or sex. In a multivariate Cox analysis, only lymph node metastases and residual tumor stage proved to be of independent prognostic significance. CONCLUSION: Resection of central bile duct carcinoma is feasible in many patients and a favorable outcome after resection is mainly determined by curative resection and the absence of lymph node metastases.
BACKGROUND: Acute venous mesenteric ischaemia is rare and there is no standard conservative or operative treatment. METHODS: The results of surgical treatment for acute mesentericoportal thrombosis were retrospectively analysed in 31 patients. The thrombotic occlusion affected the superior mesenteric vein in 19 patients, the portal vein in eight and both vessels in four. Surgical treatment comprised venous thrombectomy (nine patients), bowel resection (17), a combination of thrombectomy and bowel resection (two), distal splenorenal shunt (one) and simple laparotomy (two). RESULTS: When the mesentericoportal blood flow was restored, the mortality rate was lower, but not significantly so, than after bowel resection alone (two of nine versus seven of 17). In addition to thrombectomy, local thrombolysis with recombinant tissue plasminogen activator was performed in five patients via a catheter placed into a distal mesenteric vein and all survived. The overall hospital mortality rate was 11 (35 per cent) of 31. CONCLUSION: An active approach should be encouraged in patients with this condition employing thrombectomy in addition to bowel resection. Early results are encouraging and local thrombolysis warrants further study.
Among different treatment modalities for exocrine pancreatic cancer from the surgical point of view the performance of complete tumor resection must be the aim independent any controversies about principles of surgery. Although the overall prognosis is generally poor, therapeutic nihilism is not justified any longer because postoperative mortality could be decreased to less than 5% in the past years. Nevertheless, the rate of long-term survival can only be improved by early diagnosis based on the knowledge of individual risk factors as well as by multimodality strategies including perioperative regimens (chemo- and/or radiotherapy) to increase survival rates even in advanced stages of this tumor with its dismal prognosis.
BACKGROUND: The results of surgical intervention for acute mesenteric ischemia following major cardiac surgery were analysed. EXPERIMENTAL DESIGN: Retrospective investigation. Setting. University Hospital of Hannover Medical School. PATIENTS: Eleven patients (five women and six men) amongst a total of 90 patients operated from 1972 to 1993 because of an acute splanchnic ischemia. This subgroup represented 12%. The causes of splanchnic ischemia were arterial embolism in 55% and nonocclusive disease in 45%. INTERVENTIONS: Surgical intervention comprised embolectomy in one patient (9%), bowel resection in 36% and exploratory laparotomy only in 55%. MEASURES: Hospital mortality, causes of death and long term survival were analysed. RESULTS: The inhospital mortality of the 11 patients was 91% and only one female patient with arterial embolism survived after bowel resection. In the 79 patients without previous cardiac surgery the postoperative mortality of mesenteric ischemia was significantly (p<0.001) lower with 62%. CONCLUSIONS: Following cardiac surgery mesenteric infarction is a rare complication with an incidence of 0.06% and the chance of survival is minimal. Whenever acute abdominal disease occurs after cardiac surgery, the differential diagnosis should include mesenteric ischemia. Only an immediate surgical intervention with revascularisation and/or removal of gangrenous bowel segments may eventually improve the patient's prognosis.
Between 1972 and 1993 a total of 90 patients were operated on for acute mesenteric ischemia at Hanover Medical School, Department of Abdominal- and Transplantation Surgery. As causes of mesenteric ischemia, arterial embolism (23%), arterial thrombosis (30%), venous thrombosis (33%), and non-occlusive disease (14%) were differentiated. The overall hospital mortality was 66%. The hospital mortality after venous thrombosis was 37%, significantly lower than after arterial (79%) and functional (83%) types of mesenteric ischemia. Besides the pathogenesis of mesenteric infarction, a multivariate analysis revealed age and presence of peritonitis and intestinal perforation to be independent prognostic factors of hospital lethality. Patients with venous thrombosis had a mean age of 48 years and were significantly younger than the remaining patients who had an average age of over 60 years. Surgical procedures comprised solitary bowel resection (60%), isolated embolectomy and/or thrombectomy (10%), a combination of embolectomy/thrombectomy and bowel resection (4%), and exploratory laparotomy only (21%). Vascular reconstruction was associated with a significantly better survival rate than bowel resection only. While hospital mortality was dependent on the type of mesenteric ischemia, long-term survival after exclusion of hospital deaths proved independent of the original pathogenesis. Of the patients who survived the acute attack of mesenteric ischemia, 70% were alive 2 years later and 50% 5 years later. The survival probability of these patients was not determined by recurrence of mesenteric ischemia, but was mainly related to their cardiovascular comorbidity and a high incidence and prevalence of malignancies.
This report details nine patients after curative surgical resection of histologically proven mucinous cystadenocarcinoma of the pancreas and compares the prognosis with ductal adenocarcinomas. Cystadenocarcinomas represented 2.1% (10/ 466) of a total of 466 patients who underwent surgical exploration and 5.5%, of all curatively resected carcinomas of the exocrine pancreas at Hanover Medical School from 1971 to 1994. Forty percent of adenocarcinomas and 90% of cystadenocarcinomas were resectable. A curative R0 resection was possible in all patients with cystadenocarcinoma and 85 % with adenocarcinoma. Six of the patients with cystadenocarcinoma were female and three were male. Their median age was 54 +/- 12 years (range: 44 to 81 years). Four cystic neoplasms were located in the head, one in the head and body, three in the tail, and one in the body and tail of the pancreas. There was no hospital mortality in this group. The prognosis after resection of cystadenocarcinomas was significantly better compared to ductal adenocarcinomas of the pancreas. The Kaplan-Meier survival was 89% vs 52% after 1 year, and 56% vs 13% at 5 years. Our results indicate the favourable prognosis of cystadeno- over ductal adenocarcinomas of the pancreas in a cohort of patients with curative tumour resection.
OBJECTIVES: The authors evaluated the experience and results of a single center in surgical treatment of proximal bile duct carcinoma. SUMMARY BACKGROUND DATA: Whenever feasible, surgery is the appropriate treatment in proximal bile duct carcinoma. To improve survival rates and with special regard to liver transplantation, the extent of surgical radicalness remains an open issue. PATIENTS AND METHODS: Retrospective analysis of 249 patients who underwent surgery for proximal bile duct carcinoma via the following procedures: resection (n = 125), liver transplantation (n = 25), and exploratory laparotomy (n = 99). Survival rates were calculated according to the Kaplan-Meier method, uni- and multivariate analysis of prognostic factors, and log rank test (p < 0.05). RESULTS: Survival rates after resection and liver transplantation are correlated with international Union Against Cancer (UICC) tumor stage (resection: overall 5-year, 27.1%; stage I and II, 41.9%; stage IV, 20.7%; liver transplantation: overall 5-year, 17.1%; stage I and II, 37.8%; stage IV, 5.8%). Significant univariate prognostic factors for survival after liver resection were lymph node involvement (N category), tumor stage, tumor-free margins, and vascular invasion; for transplantation, they were local tumor extent, N category, tumor stage, and infiltration of liver parenchyma. For resection and transplantation, a multivariate analysis showed prognostic significance of tumor stage and tumor-free margins. CONCLUSION: Resection remains the treatment of choice in proximal bile duct carcinoma. Whenever possible, decisions about resectability should be made during laparotomy. With regard to the observation of long-term survivors, liver transplantation still can be justified in selected patients with stage II carcinoma. It is unknown whether more radical procedures, such as liver transplantation combined with multivisceral resections, will lead to better outcome in advanced stages. With regard to palliation, surgical drainage of the biliary system performed as hepatojejunostomy can be recommended.
Squamous cell carcinoma of the liver arising from a non-parasitic cyst is a rare entity of a primary liver tumor with an unfavourable prognosis. We report a case of a patient with a cyst in the right lobe leading to upper abdominal symptoms and respiratory discomfort. Malignancy was not suspected from the clinical findings or repeated cytological examination of the cyst fluid. However, the blood stained brown color of the cyst fluid was unusual. Cyst recurrence after six attempts of conservative treatment with sonography guided drainage over a period for more than one year led to laparotomy with cyst unroofing. Because frozen section from the cyst wall revealed the unexpected finding of squamous cell carcinoma right hemihepatectomy was performed during the same operation. The patient is alive more than four years after surgery without cyst or tumor recurrence. The difficulties in establishing diagnosis are confirmed by the review of other reports. In the diagnosis and treatment of symptomatic non-parasitic liver cysts possible malignancy has to be considered. In case of proven carcinoma radical surgery with partial hepatectomy should be performed.
From 1971 to 1995 we have performed 23 liver resections in 22 patients because of hepatic metastases of pancreatic (n = 20) or ampullary (n = 2) carcinomas. In 16 patients the hepatic secondaries were removed synchronously with the pancreatic primary tumour. In 7 cases liver resection was performed for metachronous metastases. Only one patient died after simultaneous resection of liver and pancreas (operative lethality 4,3%). Curative R0-resection was accomplished in 69% of patients with synchronous and 100% with metachronous liver metastases. The median survival time was 8,3 months after synchronous and 5,8 months after metachronous hepatic resection. The one-year survival amounted to 41 and 40% resp. Though distant metastases are a definite sign of a progressed tumour stage, the prognosis of patients with hepatic metastases should not be considered hopeless. In view of a comparatively small operative risk there is a chance for individual patients to gain valuable survival time.
The value of color-coded duplex sonography in the assessment of combined kidney and pancreatic transplantations (KTX/PTX) was studied in 9 patients. In normal graft function the median resistive index (RI) was 0.69 (range 0.60-0.80) for the kidney and 0.61 (range 0.55-0.70) for the pancreas. Ten episodes of graft dysfunction (kidney n = 4; pancreas n = 6) were observed. During renal rejection and hemolytic uremic syndrome the RI was above 0.80. In pancreatic rejection the RI exceeded 0.80 while all other causes of pancreatic dysfunction were not associated with changes in the RI. Color-coded duplex sonography may prove to be a reliable noninvasive diagnostic method in the evaluation of the posttransplant course after combined KTX/PTX, in particular in the diagnosis of pancreatic rejection.
Univariate and multivariate analysis was used to assess the potential and limitations of curative resection in cancer of the pancreas. From 1971 to 1993, we operated 466 patients with cancer of the pancreas, using tumor resection in 192 cases. Among these, 40% required resection of the vessels or neighboring organs allowing RO resection in 85% of the patients. The most valuable prognostic factor was curative resection, followed by tumor grading and tumor size. Non-curative tumor resection did not improve survival over exploratory laparotomy or palliative anastomoses. Operative mortality after resection was lower than for procedures leaving the tumor in situ. Extended resection with vessel resection had no effect unless combined with local curative ablation, but cannot be indicated in cases with synchronous metastases or invasion of the neighboring organs. Preoperative explorations do not provide a precise indication of extension in cancer of the pancreas which can only be evaluated in an open procedure by an experienced surgeon.
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A retrospective analysis of presenting clinical symptoms was performed in 584 patients who were operated on at a surgical university hospital during the last two decades because of carcinoma of the exocrine pancreas or the periampullary region. Patients with carcinoma of the pancreatic head primarily presented with jaundice, those with localisation of the tumour in the pancreatic body and tail with pain. In contrast to the common opinion ampullary carcinomas produced jaundice only in 70% of patients. In our series ampullary carcinomas did not present clinical symptoms at an earlier stage than pancreatic head tumours as it is commonly speculated. At the time of surgery carcinomas of the ampulla and the pancreatic head were found to be in equivalent stages. A NIDDM was significantly associated with carcinomas of the pancreatic body. Diabetes mellitus is more likely a result of carcinomatous destruction of the pancreas rather than a precancerosis. Almost all periampullary tumours could be resected while the resection rate was only 41% in case of exocrine pancreatic tumours. Pancreatic carcinomas which presented with upper abdominal pain, back pain, weight loss, inappentence, and diarrhoea were significantly more often irresectable. Jaundice, however, was more frequent in patients with resectable tumours. Back pain is probably caused by infiltration of the retroperitoneum and the aortic plexus and thus represents the clinical sign of an often occult retroperitoneal tumour spread. The precise knowledge of the presenting symptoms in cancer of the pancreas and ampulla is of primary importance because diagnostic procedures only commences after onset of symptoms and no possibilities of an effective screening can be envisaged.
Resection was performed in 85 patients with ampullary and in 150 with ductal pancreatic head carcinoma. Curative resection was achieved in 98 and 87 per cent respectively. Patient survival at 5 years after exclusion of hospital deaths was 38 versus 16 per cent respectively. The patients were compared retrospectively in a multivariate survival analysis. For patients with pancreatic carcinoma, residual tumour stage, tumour size and grading were independent prognostic factors, but for those with ampullary carcinoma only tumour size was a prognostic factor. Lymph node metastasis impaired prognosis, but this effect was demonstrable for both groups only after univariate analysis. The Union Internacional Contra la Cancrum classification system was not a reliable parameter of prognosis after resection of ampullary carcinoma. Patients with ampullary cancer appear to have a better prognosis intrinsically than those with pancreatic head tumours, and not simply because they present at an earlier stage. The difference in prognosis cannot be explained sufficiently by a differential importance of the various survival variables.
Conventional cytogenetic studies revealed gains and structural aberrations of chromosome 1 to be the most consistent chromosomal aberrations in hepatocellular carcinoma (HCC). We investigated touch preparations of eight HCC, five cholangiocellular carcinomas (CCC), five liver cell adenomas (LCA), four focal nodular hyperplasias (FNH) as well as nine specimens of normal liver tissue using fluorescence in situ hybridization (FISH) with centromere specific probes for chromosomes 1 and 8. Polysomies of chromosome 1, especially trisomy 1, were found in five of eight HCC and four of five CCC but in no normal liver tissue or benign tumour. Only three of seven cases of HCC revealed trisomy 8 whereas the five benign liver tumours and all normal liver tissues examined had disomy 8. Our results confirm conventional cytogenetic findings in terms of chromosome 1 aberrations in HCC although they are not specific for these types of malignant liver tumours. Since alpha-satellite probes were used in our study, only gains or losses including the centromeric regions of the chromosomes 1 and 8 could be detected. Nevertheless, our findings suggest that FISH may help in the differential diagnosis of malignant versus benign neoplasms of the liver.
At Hanover Medical School 466 patients were operated for ductal pancreatic cancer from 1971 to 1993. In 192 cases the pancreatic tumor could be resected, which amounts to a resection rate of 41%. These patients were subjected to uni- und multivariate factorial analysis in order to evaluate factors of significant prognostic value. Extended pancreatic resection because of vascular involvement or invasion of adjacent organs was performed in 40% (n = 77) of the cases. A curative R0 resection was possible in 85% of patients. The operative lethality dropped with time and from 1985 to 1993 was 3.5%. Patient survival at 5 years was 13.4% with a median survival time of 10.9 months. According to the univariate analysis the prognosis deteriorated with increasing tumor size and lymphatic and hematogenic metastases. There was a significant correlation between tumor stage according to the UICC and prognosis. The prognosis after resection was also significantly influenced by the residual tumor state and tumor grading. Extended pancreatic resections, however, had no significant prognostic impact. The multivariate analysis showed that only three factors were of independent significant relevance: residual tumor state, tumor size and tumor grade. The presence or absence of lymphatic and hematogenic metastases had no independent prognostic significance after resection of ductal pancreatic carcinomas.