Hereditary tyrosinemia type I. Self-induced correction of the fumarylacetoacetase defect.

Two Norwegian patients with chronic tyrosinemia type I showed > 50% residual fumarylacetoacetase activity in liver samples obtained during liver transplantation. The enzyme characteristics of both patients were comparable with those of a normal control. Immunohistochemistry on liver sections from these patients and from three other Norwegian tyrosinemia patients revealed a mosaicism of fumarylacetoacetase immunoreactivity corresponding completely or partly to some of the regenerating nodules. This appearance of enzyme protein is presumably induced by the disease process. The mechanism involved remains unclear and could be caused by a genetic alteration, regained translation of messenger RNA, or to enhanced stability of an abnormal enzyme.

Activation of the plasma contact system and hemodynamic changes after graft revascularization in liver transplantation.

In this study, the relation between activation of the plasma contact system and hemodynamic changes during orthotopic liver transplantation was evaluated. Nineteen consecutive courses of OLT in 17 adult patients were investigated. Veno-venous bypass was used in all patients. Blood samples were drawn through all phases of the procedure, and analyzed for the following parameters using functional techniques (chromogenic peptide substrate assays): plasma kallikrein (KK), prekallikrein, functional plasma kallikrein inhibition, C1 inhibitor, and alpha 2-macroglobulin. Plasma high molecular weight kininogen (HK) degradation was evaluated using the immunoblotting technique. An abrupt rise in KK activities occurred within 1 min after portal reperfusion of the liver graft (7-16 U/L, P < 0.05). Simultaneously, proteolytic breakdown of HK was seen. The elevated KK activities were maintained the next 1 1/2 hr. Ten min after graft reperfusion, a significant increase in cardiac output compared with the anhepatic phase (7.2-12.4 L/min, P < 0.05) was found. At the same time, systemic vascular resistance fell significantly (817-408 dynes x sec/cm-5, P < 0.05). The increase in plasma KK activities accompanied by simultaneous degradation of HK seen immediately after reperfusion of the liver graft may be due to contact activation as recipient blood contacts with the underlying basement membrane of injured sinusoidal endothelium in the transplanted liver. We suggest that hemodynamic changes associated with the postreperfusion syndrome seen after revascularization of the liver in OLT could at least be caused in part by bradykinin release due to contact activation.

Alterations in lymphocyte subsets in blood may predict resectability in carcinoma of cardia or oesophagus.

Impaired immune responses in patients with carcinoma of cardia or oesophagus have previously been reported. However, we do not know whether resectability correlates with specific immunological variables. Immunological assessment was performed in 35 such cancer patients including measurement of total T cells (CD3+) and T cell subsets (CD4+ and CD8+), NK cells (CD16+) and B cells (CD19+) in blood. In vitro lymphocyte responses to phytohemagglutinin (PHA) separated from peripheral blood were quantitated. The numbers in peripheral blood of both total T cells (CD3+) and B lymphocytes (CD19+) were significantly lower in the inoperable patients compared to resected patients (P < 0.01). The number of NK cells (CD16+) was, however, not significantly lower in the inoperable patients compared to the patients operated for cure. Lymphocyte responses to PHA in vitro were similar in resectable and non-resectable patients, but significantly lower in inoperable patients compared to the controls (P < 0.01). In conclusion, resectability in carcinoma of cardia or oesophagus is associated with changes in both T (CD3+) and B (CD19+) cell subsets.

p53 accumulation confers prognostic information in resectable adenocarcinomas with ductal but not with intestinal differentiation in the pancreatic head.

The aim of the study was to examine the relation between p53 protein accumulation, clinicopathological variables and prognosis in resectable adenocarcinomas of the pancreatic head. The clinical records and tissue specimens of 82 consecutive patients resected for adenocarcinomas located in the head of the pancreas were reviewed retrospectively. Formalin-fixed and paraffin-embedded specimens from each tumour were stained with the monoclonal antibody DO7, and the nuclear p53 positivity within each tumour was assessed. Histopathological reclassification showed that 60 tumours exhibited ductal differentiation and 22 tumours intestinal differentiation. Twenty-five percent (15/60) of the ductal tumours and 50% (11/22) of the intestinal tumours were positive for p53 accumulation. p53 immunoreactivity was significantly correlated to a worse prognosis in the tumours of ductal differentiation, with median survival 0.76 years for p53 positive and 1.44 years for p53 negative patients. The p53 positivity of tumours with intestinal differentiation showed no such correlation. No correlation was found between p53 accumulation and other known prognostic factors in either the ductal or the intestinal type of tumours. Our results indicate that the tumour biology of ductal adenocarcinomas differs significantly from that of adenocarcinomas of the intestinal type located in the pancreatic head, and that p53 accumulation confers a worse prognosis only of ductal tumours. Subclassification of these tumours based on type of differentiation is therefore suggested since periampullary tumours include ductally as well as intestinally differentiated adenocarcinomas.

Plasma carcinoembryonic antigen concentrations and immunohistochemical patterns of epithelial marker antigens in patients with large bowel carcinoma.

Carcinoembryonic antigen (CEA), secretory component (SC), and epithelial IgA were traced by paired immunofluorescence staining in 102 large bowel carcinomas from 99 patients. The immunohistochemical results were evaluated semiquantitatively in relation to histological tumour grade, clinicopathological stage, and preoperative plasma CEA concentration. CEA expression was significantly increased (p less than 0.05) in the following order: histologically normal colon mucosa, transitional mucosa adjacent to tumours, neoplastic epithelium; the reverse was true for the expression of SC and epithelial IgA (p less than 0.01). CEA was significantly more abundant in the moderately and poorly differentiated tumors than in the well differentiated ones (p less than 0.05), whereas the latter showed better expression of SC (p less than 0.05) and epithelial IgA (p approximately 0.06). In the transitional mucosa, CEA staining tended to be inversely related to histological tumour grade, whereas SC and epithelial IgA were significantly better seen in this zone when the adjacent tumour was well differentiated than when it was moderately or poorly differentiated (p less than 0.01). Furthermore, the expression of SC and epithelial IgA in the transitional mucosa decreased with increasing invasiveness of the tumours, whereas the opposite relation was indicated for CEA expression. Plasma CEA concentrations were not clearly correlated with histological levels than the localised well differentiated tumours tended to be associated with lower levels than the localised moderately differentiated ones (p approximately 0.06). Moreover, the latter variety was associated with lower plasma CEA concentrations than disseminated tumours of comparable differentiation (p less than 0.01).

Surgical treatment as a principle in patients with advanced abdominal carcinoid tumors.

Seventy-five patients with advanced abdominal carcinoid tumors (65 midgut, 10 others) have been examined retrospectively to evaluate the role of surgical treatment as a principle, irrespective of stage of disease. Eighteen of 52 patients (35%) exhibited the carcinoid syndrome. Two or more primaries were found in 39% of patients with midgut lesion, 81% of these patients had regional metastases, 5% of these patients had distant lymph node metastases, and 74% of the patients had liver secondaries. All patients underwent operation, an additional 34% of the patients had a further reoperation, 9% of the patients had a second reoperation, 3% of the patients had a third reoperation, and one patient (2%) had a fourth reoperation. Intraoperative debulking (liver excluded) was performed in 33% of the patients, and 48% of the patients had treatment (resection, hepatic artery ligation, embolization) directed at the liver. The postoperative mortality rate was 2% after the primary operation for midgut lesions. The median survival for midgut tumors was 92 months, compared to 40 months for other lesions (not significant). A significantly higher survival rate was revealed for those patients with midgut lesion who were undergoing intraabdominal debulking procedures (liver excluded); median survival was 139 months versus 69 months without debulking. For those patients with liver metastases, median survival after intervention was 216 months and 48 months without such treatment (p less than 0.001). It is concluded that resection of intraabdominal carcinoid tumor masses can be performed in a high proportion of patients. Despite the retrospective, uncontrolled nature of this study, the difference in survival probabilities in favor of aggressive surgical therapy is so marked that it is not unreasonable to conclude that surgery has played a role in prolonging life in these patients.

Loss of one chromosome #13 during development of a polyposis tumor.

A cell panel from six different familial cancers, where both normal and tumor tissues were available, was examined for genotypic changes with polymorphic DNA probes. Seventeen probes were tested, representing chromosomes #1, #2, #5, #6, #13, #14, #17, and #19. One probe, p7F12 (D13S1, at 13q12-q14) revealed loss of heterozygosity in two tumors: an osteosarcoma from a patient with retinoblastoma that had been included as a control, and one polyposis tumor that had been established in nude mice from a duodenal carcinoma biopsy. Loss of heterozygosity was observed in the first passage of the mouse tumor. Chromosome analysis in later passages revealed loss of one whole chromosome #13 as the single consistent karyotypic change.

Results of hepatic lobectomy for primary epithelial cancer in 31 adults.

Hepatic lobectomy for primary epithelial cancer was performed in 31 adults from 1964 through 1977 in the surgical departments of six Scandinavian hospitals. Twenty-three patients were discharged and had a 2 year survival rate of 62 per cent and a 5 year survival rate of 16 per cent. Alternatives to surgery have not yet emerged. Further progress requires centralization.

A comparative study of the short-term outcome following open and laparoscopic liver resection of colorectal metastases.

BACKGROUND: Laparoscopic resection of liver tumors is feasible, but few studies have compared short-term outcome of the laparoscopic approach to that of a conventional technique. METHODS: Eighteen tumor resections performed during 14 procedures (14 patients) by conventional surgery were compared to 21 similar resections performed laparoscopically during 15 procedures (13 patients). All patients had colorectal liver metastases. RESULTS: No perioperative mortality occurred. Surgical time, peroperative bleeding and blood transfusion requirement were similar in the two groups. The resection margin was involved by tumor tissue in one specimen laparoscopically resected and in two specimens conventionally resected (p = 0.58). Patients operated laparoscopically remained in hospital for median 4 days, while patients operated conventionally stayed median 8.5 days (p <0.001). Patients operated laparoscopically required less opioid medication than patients having conventional surgery (median 1 vs 5 days; p = 0.001). CONCLUSIONS: Short-term outcome of laparoscopic liver resection compares to that of conventional surgery, with the additional benefits derived from minimal invasive therapy.

Laparoscopic resection of the pancreas: a feasibility study of the short-term outcome.

BACKGROUND: Laparoscopic resection is not an established treatment for tumors of the pancreas. We report our preliminary experience with this innovative approach to pancreatic disease. METHODS: Thirty two patients with pancreatic disease were included in the study on an intention-to-treat basis. The preoperative indications for surgery were as follows: neuroendocrine tumors ( n=13), unspecified tumors ( n=11), cysts ( n=2), idiopathic thrombocytopenic purpura with ectopic spleen ( n=2), annular pancreas ( n=1), trauma ( n=1), aneurysm of the splenic artery ( n=1), and adenocarcinoma ( n=1). RESULTS: Enucleations ( n=7) and distal pancreatectomy with ( n=12) and without splenectomy ( n=5) were performed. Three patients underwent laparoscopic exploration only. Four procedures (13%) were converted to an open technique. One resection was converted to a hand-assisted procedure. The mortality rate for patients undergoing laparoscopic resection was 8.3% (two of 24). Complications occurred after resection in nine of 24 procedures (38%). The median hospital stay was 5.5 days (range, 2-22). Postoperatively, opioid medication was given for a median of 2 days (range, 0-13). CONCLUSION: Resection of the pancreas can be performed safely via the laparoscopic approach with all the potential benefits to the patients of minimally invasive surgery.

Liver tumors and minimally invasive surgery: a feasibility study.

Laparoscopic liver resection has not yet been established, although recent reports document that liver resection can be performed safely by the laparoscopic approach. Other interventional procedures like cryoablation have also been introduced in treatment of liver metastases. In this report 11 liver resections performed laparoscopically in eight patients are presented. Six patients had colorectal metastases, one a metastases from a malignant melanoma, and one patient had focal nodular hyperplasia. Two patients received synchronous cryoablation of remaining liver metastases. During follow up, two patients received percutaneous cryoablation of liver recurrences monitored by an open configuration magnetic resonance scanner. All except one of the tumors we attempted to remove had free resection margins (re-resection of new metastasis). No complications occurred except an atelectasis of the left lower pulmonary lobe in one patient. Median postoperative hospital stay was 3 days, and median postoperative opioid-dependent days was 1. The report demonstrates that minimally invasive techniques may safely be combined in hepatic intervention, and that the advantages of minimally invasive surgery, such as reduced hospital stay and less patient discomfort, also applies to liver resections.

Hyperthermia induced polyphosphate changes in Propionibacterium acnes as studied by 31P NMR.

The polyphosphate component in 31P NMR spectra of the Gram-positive Propionibacterium acnes increased after hyperthermia treatment. The cells were exposed to temperatures in the interval from 15 degrees C to 45 degrees C. The amount of polyphosphate increased with increasing temperature. There were no temperature induced changes in the other phosphorous components seen in the spectra with exception of a decrease in ATP for higher temperatures. The increase in polyphosphates was less than that obtained from cells irradiated by near ultra-violet light.

Enzyme activity and protein patterns as premalignant markers in mucosal biopsy specimens from the large intestine.

Total enzyme activity of glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LD) was measured in homogenates of resected biopsy specimens and in endoscopic biopsy specimens. LD isoenzyme patterns were scanned by a laser technique after agarose gel electrophoresis. Examinations were performed in homogenates of premalignant lesions such as ulcerative colitis and adenomas of the colon, with normal mucosa and carcinomas as control material. Additionally, two-dimensional electrophoretic protein patterns were compared for normal mucosa, adenomas, and carcinomas of the large intestine. The mean activity of both G6PD and LD was highest in the presence of dysplasia; however, only G6PD activity seemed independent of inflammatory changes. The percentage of LD isoenzyme M monomers was significantly higher in homogenates of specimens with dysplastic changes than in specimens with only inflammatory changes. A positive correlation was found between total LD isoenzyme M monomers and LD 5 monomers for the whole material and for each of the histological subgroups of ulcerative colitis. A positive correlation between total LD activity and the percentage of LD 5 monomers was seen only for dysplastic, adenomatous, and malignant tissues. The several hundred protein spots seen on two-dimensional protein maps showed that most of the spots were common for normal mucosa, adenomas, and carcinomas, but differences were also seen. Polyps and carcinomas had strikingly similar protein patterns, different from that of normal mucosa. The results of the two-dimensional protein electrophoresis lend further support to the hypothesis that polyps are precursors of carcinomas of the large intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of gastric bypass operation on glucose tolerance in obesity.

A series of variables involved in glucose handling were monitored before and after gastric bypass operation for morbid obesity. Blood glucose, insulin, C-peptide, gastric inhibitory polypeptide (GIP), pancreatic polypeptide (PP), and gastrin were measured basally and after an oral glucose load. Blood glucose, insulin, C-peptide, and PP were also measured after an intravenous glucose load. Adrenocortical function was evaluated by measuring plasma cortisol and urinary excretion of 17-hydroxy-corticosteroids and 17-ketosteroids. Nine subjects were examined before and 3 and 12 months after operation. Glucose tolerance improved postoperatively concomitant with decreased basal levels of C-peptide and insulin, increased hepatic insulin extraction, and evidence of reduced adrenocortical function. Parallel with reduced insulin resistance, support for an increase in both insulin secretion and removal was obtained postoperatively. It is concluded that the considerable endocrine abnormalities seen in morbid obesity can be normalized after gastric bypass operation and weight reduction.

Ancient myth, modern reality: a brief history of transplantation.

From trephination to modern surgical procedures, transplantation is an exciting technology that has evolved over centuries. This article reviews the historical incidences of organ and tissue transplantation among humans and reflects on accomplishments made in general surgery that assisted transplant technology. Following a brief historical overview, the article focuses on modern transplanting issues including: development of immunosuppressive therapy, organ availability, qualifications for donors and recipients, organ procurement, and new transplant technology.