NK activity during graft-versus-host disease and graft rejection in rats following intestinal semiallogenic and allogenic transplantation with or without mesenteric lymphadenectomy.

Graft-versus-host disease (GVHD) and graft rejection are major problems following intestinal transplantation (IT). Natural killer (NK) cells may be important effector cells in both conditions. In this study, Sprague-Dawley (SD) or SD-Brown Norway (BN) F1 rat intestine was transplanted into BN recipients with and without associated graft mesenteric lymphadenectomy (GML). Cyclosporine (15 mg/kg day) was administered to all animals. Pieces of the intestinal graft were examined 4 days posttransplant and again at death. NK activity calculated using intestinal intraepithelial lymphocytes (IL) was determined utilizing an 18-hr cytotoxic assay assessing 51Cr release and the results are reported as lytic units. YAC-1 cells were used as the target. NK activity was reduced 4 days after IT both in native (8.02 +/- 0.64) and in grafted bowel (3.14 +/- 1.51), with histological evidence of rejection as compared with that of control bowel in ungrafted rats (21.1 +/- 2.14). Survival was increased, on mean, a total of 6 days with the addition of GML in both semiallogenic and allogenic transplanted rats. At the time of death, the NK activity in the native bowel had increased (17.1 +/- 3.02) and histologic evidence of GVHD was present. These data suggest that: (1) NK cells are important in GVHD and (2) both semiallogenic and allogenic transplants survive longer if they are combined with GML (P < or = 0.05 and P < or = 0.01, respectively).

Liver transplantation with vena cava in situ and selective use of temporary portacaval shunt or portal clamping.

BACKGROUND/AIMS: The recipient hepatectomy with vena cava in situ in liver transplantation has overcome the need of venous-venous bypass thanks to temporary porta caval shunt or portal clamping. METHODOLOGY: 150 orthotopic liver transplants in 137 patients were performed and the vena cava in situ technique was used in 142 (venous bypass in 7, temporary porta caval shunt in 49, portal clamping in 87). The suprahepatic cava veins anastomosis was performed with Belghiti in 97 and piggyback techniques in 45. RESULTS: There were no differences in operative and warm ischemia times nor in blood requirements, while a greater stability of body temperature was documented in the vena cava In Situ group: in the latter temporary porta caval shunt preserved the temperature better than portal clamping (P < 0.01). In anhepatic phase mean artery pressure decreased in veno-venous bypass and increased in the vena cava In situ groups (P < 0.01). The venous return and the cardiac performances (anhepatic phase) were better preserved in the vena cava In Situ group. (P < 0.0001). CONCLUSIONS: Temporary portal caval shunt or portal clamping and piggyback or Belgiti Techniques allow a better hemodynamic stability through out the procedure, obviating the need for veno-venous bypass or fluid overload, if selectively used.

[Primary lymphoma of the stomach. Clinical and prognostic analysis of our experience and 20 years' literature]. / Linfoma gastrico primitivo. Analisi clinica e prognostica della nostra esperienza e di 20 anni di letteratura.

Primary gastric lymphoma (PGL) is a comparatively rare cancer. A large series from the literature forms the basis for a review of the clinical aspects, the diagnostic and therapeutic procedures most recently adopted and the long-term results. 1837 cases of PGL have been analysed: in 1196 of them symptomatology was painful, ulcer-like; the diagnosis of a malignant lesion was obtained in 72% of cases by radiography, while oesophagogastroduodenoscopy with biopsy produced a diagnosis of gastric lymphoma in 47.6% of cases. 1634 patients were subjected to surgical therapy with a resection index of 66.5% and postoperative mortality between 0 and 22.25%. Back-up treatment for the various stages of the disease is not well codified but is indicated by most authors. The prognosis of PGL is comparatively good compared to that of other intestinal lymphomas with total survival, independently of the stage, of 44.3% at 5 years. Surgical therapy is the intervention of choice in cases in which there is a possibility of resection in advanced stages also. Overviews are required so as to quantify the role of radiotherapy and chemotherapy in both initial and advanced stages.

[Efficacy of immunomodulating treatment in patients with different degrees of immunosuppression]. / Efficacia del trattamento immuno-modulante nei soggetti con diverso grado di immunodepressione.

Immunodepression is a common condition in patients undergoing elective operations and it constitutes a high risk for the onset of postoperative infective complications. The use of immunomodulatory drugs has proved useful in the prophylaxis of these complications, although the precise indications for each drug have not yet been clearly codified. The present study aimed to assess the effects of thymostimulin in patients with different degrees of immunodepression, by evaluating both the incidence of postoperative infections and the changes induced in various immunological parameters. The results obtained indicated that those subjects with the highest degree of immunodepression (hypo-anergic) benefited most from drug therapy in comparison to those with a lesser degree of immunodepression (relatively hypo-ergic). The advantages were evident in hypo-anergic subjects both with regard to the frequency of early postoperative infections, and with regard to immunological parameters. On the other hand, in relatively hypo-ergic subjects, benefits were limited to the improvement of some immunological parameters. In our opinion, the use of thymostimulin is of particular use only in those subjects with marked immunodepression since the incidence of post-operative sepsis is highest in this group.

Liver resection for hepatocellular carcinoma in cirrhotic patients.

The results of a multicentric retrospective analysis of 265 liver resections for hepatocellular carcinoma in cirrhotic patients have been collected and assessed. Overall operative mortality was 9.1%. The actuarial 3-year survival was 46.5%. Better results were obtained in patients with encapsulated lesions and alphafetoprotein levels less than 400 ng/dl. Tumoral recurrence, which was the main cause of late death, was related to alphafetoprotein higher levels and to the type of surgery performed: tumor resection with short tumour free margin had the highest recurrence rate. Results were significantly better in those centers where intraoperative ultrasonography was systematically employed.

Effect of ursodeoxycholic acid administration on bile duct proliferation and cholestasis in bile duct ligated rat.

The origin, mechanism, and significance of the bile duct proliferation (BDP) associated with cholestasis remain unexplained. This study examined the effect of oral administration of ursodeoxycholic acid (UDCA) on both BDP and cholestasis in the rat. After bile duct ligation, male Sprague-Dawley rats were treated for 30 days with either UDCA (5 mg/day) (group A) or saline solution (group B). Animals were sacrificed at day 30. The serum activity of aminotransferase (ALT, AST), alkaline phosphatase, and gamma-glutamyltransferase (GGT) was significantly lower (P < 0.01) in the UDCA-treated rats. Total serum bilirubin and total serum bile acids were lower (P < 0.001) in group A. Moreover, the control of BA in bile was reduced also (P < 0.02). Conversely, serum cholesterol levels were not different between the two groups. Histological examination showed that the number of ductular cells in the portal areas was significantly (P < 0.001) reduced in UDCA-treated as compared to saline-treated rats. The replication activity, assessed as the number of bromodeoxyuridine-positive cells, was also significantly lower in treated animals (33 +/- 11 vs 64 +/- 22 per 1000 cells; P < 0.001). Lobular bile ductules were three times larger in group B, and extrahepatic duct measurements confirmed this increase in size of the larger biliary ducts (P < 0.001). These findings demonstrate that UDCA reduces BDP in response to BD ligation. Although the mechanism(s) of this effect is still hypothetical, UDCA may reduce the level of irritating bile salts such as chenodeoxycholic acid and lithocolate and increase periductular bile acid recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of transarterial chemoembolization before liver resection for hepatocarcinoma.

The aim of this study was to clarify whether chemoembolization (TACE) before liver resection (LR) can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve disease-free and overall survival. Eighty-nine patients with tumor-stage (TNM) I-II HCC were evaluated for LR. Patients were prospectively allocated to LR alone or TACE plus LR based on their place of residence. Twenty nonlocal patients (24%) were selected for LR, while 69 (77.5%) local patients were selected for TACE plus LR. Following TACE, the tumor stage could be confirmed in only 20 patients (29%) who then underwent LR. Operative mortality was 0%, but in the TACE-LR group, 3 patients died of liver failure between 2 and 5 months after surgery. Early recurrence (<24 months) was 59% for LR versus 20% for TACE plus LR (P <.05). Late recurrence was 18% for LR versus 10% for TACE plus LR (P = not significant [NS]). The overall recurrence rate was 76% for LR versus 30% for TACE plus LR (P <.02). Death due to HCC recurrence was 70% for LR versus 15% for TACE plus LR (P <.05). The overall 1- and 5-year survival rates did not differ significantly (71% to 38% for LR v 85% to 43% for TACE + LR; P = NS), whereas the difference in 1- and 5-year disease-free survival was highly significant (64% to 21% for LR v 82% to 57% for TACE + LR; P <.02). TACE was able to improve the HCC staging process and significantly reduce the incidence of early and overall HCC recurrence and related death after LR; it improved the disease-free interval, but not the overall survival, due to an increase in liver failure in the first 5 months.

Laparoscopic surgery after orthotopic liver transplantation.

Laparoscopic surgery is currently a widely accepted approach to several surgical fields because of its advantages in terms of postoperative pain reduction and easy patient recovery. This approach may be useful even in solid-organ transplantation surgery as a diagnostic or treatment procedure in some surgical complications. From July 1991 to December 1998, we performed 142 liver transplantations on 129 patients. During the postoperative period, many complications occurred. Here we report two cases of intestinal occlusion caused by adhesions and three cases of lymphocele, all approached with laparoscopic surgery. In all cases but one, we were able to complete the surgery by laparoscopic means; in one of the two occlusions, the procedure was switched to laparotomy because of a choledochojejunal anastomosis lesion. The three cases of lymphocele must be considered in a particular manner because such cases, to our knowledge, have never been described in the literature. They always presented with a late-onset right pleural effusion and were located in the retrohepatic, retrogastric, and left paracaval areas, close to the esophageal hiatus. In conclusion, we believe a laparoscopic approach is a useful strategy to solve some surgical complications in patients who underwent orthotopic liver transplantation; however, the use of laparoscopic surgery in this field is strictly connected to the surgeon's experience and versatility.

Epstein-Barr virus-associated post-transplant lympho-proliferative disease of donor origin in liver transplant recipients.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disease, a potential complication of solid organ transplantation, occurs in about 3% of orthotopic liver transplant recipients. We report the genetic and virological characterization of two cases of post-transplant lymphoproliferative disease that occurred early (4 and 6 months) after orthotopic liver transplant as large-cell non-Hodgkin's lymphomas located at the hepatic hilum. METHODS: Lymphomatous tissues were analyzed for clonality and presence of Epstein-Barr virus (EBV) sequences by Southern blot, polymerase chain reaction, and in situ hybridization techniques. RESULTS: The tumors in both cases were sustained by a clonal proliferation of B lymphocytes containing type A EBV DNA. Moreover, in situ hybridization with a digoxigenin-labeled EBV-specific probe evidenced a strong nuclear signal in most of the neoplastic cells. DNA microsatellite analysis at three different loci detected alleles of donor origin in both tumor samples, suggesting that the neoplastic B cells were of donor origin. CONCLUSIONS: EBV-infected donor B lymphocytes might be responsible for intragraft post-transplant lymphoproliferative disease in orthotopic liver transplant recipients. As 20 to 30% of post-transplant lymphomas involve the graft itself, donor-derived post-transplant lymphoproliferative disease might be more frequent than presently appreciated. Prospective studies are needed to assess its real incidence and identify possible risk factors.