Does seeding of intraluminal tumour cells cause anastomotic recurrence after oesophageal resection?

BACKGROUND: Recurrence at the cervical anastomosis of a tumour of the oesophagogastric junction after resection of the oesophagus with gastric tube reconstruction is a peculiar phenomenon in view of the distance of the primary tumour from the proximal anastomosis. It is hypothesised that contamination with tumour cells from the nasogastric tube or the gastric reconstruction tube could be responsible for this phenomenon. METHOD: Fifteen patients with a tumour of the oesophagus or gastric cardia were included. During the operation the nasogastric tube was left in the resected specimen. Debris from the tube was washed out for cytological examination. Also the gastric reconstruction tube was washed out and the debris examined for malignant cells. RESULTS: In all of the patients with a tumour extending intraluminally malignant cells were found in the nasogastric tube or the gastric reconstruction tube or both. In 92% of these patients malignant cells were found in the nasogastric tube, while 60% of the gastric reconstruction tubes were contaminated with tumour cells. CONCLUSION: The presence of intraluminal malignant cells during oesophageal resection and gastric tube reconstruction is very high, possibly leading to anastomotic recurrence. Measures should be taken to minimise local contamination with tumour cells.

[Two patients with retroperitoneal paragangliomas]. / Twee patiënten met een retroperitoneaal paraganglioom.

A 35-year-old woman and a 36-year-old man presented with abdominal complaints which, in both cases, appeared to be due to an unusual retroperitoneal tumour, namely a paraganglioma. Three years after radical excision the women had no complaints, while the male patient had developed metastatic disease; he was still alive 6 years after excision. Paragangliomas are sporadic tumours. Although well defined, these tumours are not well known, mainly due to the numerous different names used to describe them in the literature. These neuro-endocrine tumours arise from hyperplastic paraganglionic cells and occur in or near the ganglia of the autonomic nervous system. Paragangliomas may produce catecholamines and, on the basis of this, are classed as either functional or non-functional. In the absence of metastases, there are no definitive clinical, histopathological or molecular-biological parameters to predict whether a tumour is benign or malignant. Macroscopic radical surgical excision is therefore the treatment of choice. Five- and ten-year survival rates of a radically excised paraganglioma are 75% and 45%, respectively. In the case of metastatic disease, half the patients will die within 3 years. If a paraganglioma is found, genetic screening for familial neoplastic syndromes is advised.

[Liver transplantation in acute liver insufficiency: definitive replacement or auxiliary liver?]. / Levertransplantatie bij acute leverinsufficiëntie: definitieve vervanging of hulplever?

Orthotopic liver transplantation (OLT) has greatly improved the chances of survival in patients with acute hepatic failure. However, this mode of treatment requires lifelong immunosuppressive medication and negates the potential recovery of the host liver. In theory, auxiliary heterotopic liver transplantation (HLT) offers the diseased host liver a chance to regenerate, so that immunosuppression can be tapered off and eventually stopped. In the University Hospital Rotterdam Dijkzigt OLT and HLT were performed in two patients, with acute and subacute hepatic failure respectively. The patient undergoing OLT recovered quickly but needed a successful re-OLT after a serious rejection episode. The removed diseased liver showed no signs of regeneration at histology. The patient undergoing HLT also recovered well. HIDA scanning as well as liver biopsies of the host liver and the grafted liver 1 and 6 months after transplantation indicated full recovery of the host liver, so that immunosuppression is being tapered off.

[Possibilities and limitations of heterotopic auxiliary liver transplantation]. / Möglichkeiten und Grenzen der heterotopen auxiliären Lebertransplantation.

Although auxiliary heterotopic liver transplantation offers theoretical advantages over orthotopic liver replacement, clinical results have heretofore been dismal. After development of a technique of reduced size liver grafts provided with portal and arterial blood and venous drainage via the suprahepatic V. cava (HLT) in experimental animals, this method was applied in 21 transplantations in 19 patients. 11 of 16 patients with chronic liver insufficiency and one of three patients with fulminant liver failure survived transplantation for at least 1 year. HLT was well tolerated even by high-risk patients. Possibilities and limitations of this novel approach are discussed.

The Lynch syndrome; a high-risk factor for colorectal carcinoma.

Based on the case history of two patients, the problems of suspected familial colon carcinomas are discussed with special reference to screening policy and treatments. Upon identification of hereditary colon cancer (Lynch syndrome). treatment of the patient should consist of extensive resection and, if the patient is younger than 50 years, life-long careful follow-up.

Auxiliary partial liver transplantation for end-stage chronic liver disease.

Auxiliary heterotopic liver transplantation is theoretically attractive because it leaves the recipient's liver in place. The surgical trauma of hepatectomy is avoided, and failure of the graft does not necessarily lead to the death of the patient or a second, emergency transplantation. Another advantage is that matching the body sizes of the donor and the recipient is not mandatory, which increases the number of possible donors. However, previous clinical results of auxiliary liver transplantation have been poor. We performed auxiliary partial liver transplantation in six consecutive patients with end-stage chronic liver disease who were not accepted for orthotopic liver transplantation because they had massive ascites, deficient clotting function, cachexia, or poor pulmonary reserve. The donor liver was transplanted to the right subhepatic region after removal of segments II and III, and it was provided with portal and arterial blood. There were no major changes in hemodynamic measurements during surgery. The mean hospital stay after transplantation was 22.7 days (range, 14 to 29). After a mean follow-up period of 14 months (range, 5 to 23), all patients were alive, with good graft function as demonstrated by scintigraphy, Doppler ultrasonography, and synthesis of clotting factors. From these observations we conclude that auxiliary partial liver transplantation is an attractive alternative to orthotopic liver transplantation in high-risk patients. Its role in other patients who need liver transplants remains to be defined.

Late results of mesocaval interposition shunting for bleeding oesophageal varices.

Survival, encephalopathy and shunt patency were studied in 64 consecutive patients who underwent mesocaval shunting with a wide-calibre Dacron prosthesis. Half of the patients were operated as emergency cases. Operative blood loss in patients who had emergency procedures was significantly higher than during elective operations. Overall, 30-day mortality was 27 per cent. Survival was 61 per cent after 1 year and 39 per cent after 5 years. Serious encephalopathy requiring hospital admission occurred in 5 patients (11 per cent of patients surviving more than 1 month). Shunt patency was assessed by scintisplenoportography and ultrasonography. Cumulative shunt occlusion rate was 16 per cent after 1 year, 33 per cent after 5 years and 52 per cent after 8 years of follow-up. Out of 17 patients with an occluded shunt, 9 had persistent or recurrent bleeding, while 3 patients had recurrent bleeding despite a patent shunt. We conclude that the mesocaval Dacron interposition shunt should not be recommended as the procedure of first choice for portosystemic shunting.

A reproducible model of acute hepatic failure by transient ischemia in the pig.

A model of transient acute hepatic failure has been developed in the pig. Three days after a functional end-to-side portacaval shunt was introduced, 15 ambulant animals underwent total liver ischemia for 4 to 6 h by the closure of a mechanical clamp surrounding the hepatic artery. Four of the eight animals subjected to 4 hr of ischemia survived. All but one of the animals undergoing 6 hr of hepatic ischemia developed grade 4 encephalopathy after 24 to 30 hr and died within 50 hr. Quantitative estimation of liver cell necrosis revealed less than 40% necrosis in the survivors, and approximately 62% (range 49-75%) in animals who died of hepatic coma. As far as the putative toxins are concerned, significant differences were found between animals undergoing 4 and those undergoing 6 hr of ischemia, especially in the plasma ammonia levels and the plasma ratios for tyrosine and phenylalanine. Plasma arginine levels had fallen to zero in both groups at 24 hr and only rose to preischemic values in animals who survived. This large animal model fulfills the accepted criteria of potential reversibility, reproducibility, and death due to hepatic failure.

Hemodynamics and coagulation in experimental auxiliary liver transplantation during fulminant hepatic failure.

In pigs, ischemic liver cell necrosis was induced by 6 hours' occlusion of the hepatic artery and the portal vein 3 days after construction of a side-to-side portacaval shunt and division of the hepatic ligaments. Two thirds of the liver of an MLC-compatible donor was heterotopically transplanted 13 hours (group I), and 3 hours (group II) after induction of liver failure. In group I (N = 11), three animals died of liver failure before or shortly after induction of anesthesia. Of the remaining pigs, two animals survived more than 2 weeks. In group II (N = 10), intraoperative hypotension was prevented by reduction of the interval between liver failure and transplantation and by thermodilution catheter monitored fluid replacement. A significant decrease in cardiac output and an increase of pulmonary and systemic vascular resistance were observed during auxiliary partial liver transplantation (APLT). In the immediate postoperative period, six pigs died of deficiencies in hemostasis that were caused by consumptive coagulopathy related to severe host liver damage rather than fibrinolysis. Two pigs in group II survived in good condition 12 and 42 days after APLT. In the longer surviving pigs of both groups, either the graft or the host liver recovered. Processes that might be responsible for the observed hemodynamic changes and coagulation disorders are discussed. These results indicate that APLT is technically feasible in severely ill pigs with acute hepatic failure.

Rejection and survival of auxiliary partial liver grafts in non-tissue-typed pigs.

A technique for auxiliary heterotopic transplantation of 60% of the liver has been developed in the pig to study acute and chronic rejection. Transplantations were performed in 13 non-tissue-typed donor-recipient combinations without immunosuppressive medication. Three pigs died in the 1st postoperative week from technical problems. In the remaining 10 animals acute rejection of the graft was not found, but signs of chronic rejection developed in 6 animals. It is concluded that auxiliary partial liver transplantation is technically feasible in the pig. Although the auxiliary liver graft is subject to immune attack, long-term graft survival without immunosuppressive medication can be achieved.

Auxiliary transplantation of part of the liver improves survival and provides metabolic support in pigs with acute liver failure.

In pigs subtotal ischemic liver cell necrosis was induced 4 days after auxiliary transplantation of 60% of the liver of an MLC-compatible donor (ATPL group, n = 13). In control animals (n = 14) temporary liver ischemia was preceded by division of the hepatic ligaments and creation of an end-to-side portacaval shunt. In the ATPL group six animals died of gastric hemorrhage, intestinal strangulation, or sepsis. The remaining seven animals survived in excellent condition until sacrifice 26 days after the induction of liver ischemia. Excellent graft function was demonstrated by uptake and excretion of 99mTc-HIDA at cholescintigraphy, ammonia detoxification, synthesis of clotting factors and glucohomeostasis. EEG recordings in the animals that underwent transplantation did not change from preischemic levels. Evidence of hepatic regeneration was found in the transplanted livers but could not be demonstrated in the damaged host livers. The control animals died in coma within 72 hours. These results indicate that auxiliary transplantation of a partial liver provides metabolic support and improves survival in animals with induced acute liver failure.

Long-term survival of auxiliary partial liver grafts in DLA-identical littermate beagles.

Auxiliary heterotopic transplantation of 60% of the liver in the beagle, using a technique in which all requirements for optimal graft survival are met, is described. The autologous liver is left in situ. Transplants were performed in non-tissue-typed and matched donor-recipient combinations. Postoperatively the recipients were treated with a standard schedule of 2 mg azathioprine and 1 mg prednisolone i.v. daily for 75 days--thereafter, the immunosuppressive drugs were gradually withdrawn. HIDA-hepatobiliary scanning proved to be useful for the assessment of graft function. In eight non-tissue-typed donor-recipient combinations, median graft survival was 7 days, most transplants being subject to acute rejection. However, in nine experiments in which donor and recipient were DLA-identical littermates, the median graft survival was 112 days (P less than 0.005). In these animals signs of chronic rejection developed after tapering the immunosuppressive drugs. It is concluded that, in this model, graft survival is improved by histocompatibility matching. The feasibility of partial heterotopic liver transplantation indicates that this method must be reconsidered for clinical application, especially for patients with acute liver failure. For the recipient, it is a relatively minor operation that--by its temporary life sustaining function--may allow for the regeneration or restoration of function of the recipient's own liver.