THE ROLE OF SURGERY IN A PATIENT WITH CARCINOID SYNDROME, COMPLICATED BY CARCINOID HEART DISEASE.

A 55-year-old female patient was admitted for flushing and abdominal pain in the right upper quadrant. Her past medical history revealed high blood pressure and a recent echocardiography showed thickened appearance of tricuspid valve with coaptation defect and grade II tricuspid regurgitation. Contrast enhanced abdominal CT scan and MRI were subsequently performed and revealed a large macronodular liver mass, as well as other micronodular lesions disseminated in the liver parenchyma. CT guided biopsy from the main liver mass revealed neuroendocrine tumor of unknown origin (probably GI) with Ki-67 of 8%. Surgical exploration was decided. During laparotomy, the primary tumor was found in the proximal ileum and the patient underwent segmental enterectomy. Non-anatomical hepatectomy was also performed to remove the bulk of the tumor burden (more than 90%). Postoperative course was uneventful and the carcinoid syndrome relieved. At present, 15 months postoperatively, the patient is under treatment with somatostatin analogue for its antiproliferative effect, with good clinical, biochemical and tumoral control and stable heart disease. In patients with neuroendocrine liver metastases from unknown primary, surgical exploration could allow detection (and resection) of the primary tumor and surgical debulking of liver metastases to control carcinoid syndrome and carcinoid heart disease.

PROGNOSTIC FACTORS IN PATIENTS WITH SURGICAL RESECTION OF PANCREATIC NEUROENDOCRINE TUMOURS.

CONTEXT: Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. OBJECTIVE: The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. SUBJECTS AND METHODS: The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. RESULTS: Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. CONCLUSIONS: Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%.

Optimal Solution Volume for Luminal Preservation: A Preclinical Study in Porcine Intestinal Preservation.

BACKGROUND: Rodent studies suggest that luminal solutions alleviate the mucosal injury and prolong intestinal preservation but concerns exist that excessive volumes of luminal fluid may promote tissue edema. Differences in size, structure, and metabolism between rats and humans require studies in large animals before clinical use. METHODS: Intestinal procurement was performed in 7 pigs. After perfusion with histidine-tryptophan-ketoglutarate (HTK), 40-cm-long segments were cut and filled with 13.5% polyethylene glycol (PEG) 3350 solution as follows: V0 (controls, none), V1 (0.5 mL/cm), V2 (1 mL/cm), V3 (1.5 mL/cm), and V4 (2 mL/cm). Tissue and luminal solutions were sampled after 8, 14, and 24 hours of cold storage (CS). Preservation injury (Chiu score), the apical membrane (ZO-1, brush-border maltase activity), and the electrolyte content in the luminal solution were studied. RESULTS: In control intestines, 8-hour CS in HTK solution resulted in minimal mucosal changes (grade 1) that progressed to significant subepithelial edema (grade 3) by 24 hours. During this time, a gradual loss in ZO-1 was recorded, whereas maltase activity remained unaltered. Moreover, variable degrees of submucosal edema were observed. Luminal introduction of high volumes (2 mL/mL) of PEG solution accelerated the development of the subepithelial edema and submucosal edema, leading to worse histology. However, ZO-1 was preserved better over time than in control intestines (no luminal solution). Maltase activity was reduced in intestines receiving luminal preservation. Luminal sodium content decreased in time and did not differ between groups. CONCLUSIONS: This PEG solution protects the apical membrane and the tight-junction proteins but may favor water absorption and tissue (submucosal) edema, and luminal volumes >2 mL/cm may result in worse intestinal morphology.

Liver transplantation in a patient with unresectable colorectal liver metastases -- a case report.

BACKGROUND: Due to the lower survival rates achieved, in the early period of liver transplantation era, in patients with colorectal liver metastases, and because of the organ shortage,in the last two decades colorectal liver metastases are considered a contraindication for liver transplantation. However, the increasing number of marginal donors, and the improvements in posttransplant immunossuppresion, chemotherapy and methods to assess the extrahepatic disseminationof colorectal cancer, opened the perspective of liver transplantation to certain patients with malignancies (such as HCC beyond Milan criteria, and selected patients with cholangiocarcinomaor liver metastases from neuroendocrine tumors).Since some of these patients experienced favorable outcomes,in the last years, there were authors that considered a rationalerevisitation of the benefits of liver transplantation in patients with unresectable colorectal liver metastases. Thus, in 2006, a Norwegian group started a study which aims to assess the results of liver transplantation in patients with unresectable colorect alliver metastases. Their results were unexpectedly favorable, revealing that 5-year overall survival rate was 60%, and the quality of life was excellent in the first year following transplantation.However, all the patients presented relapse of the disease in the first two years following transplantation. In the present paper we present the clinico-pathologic characteristics,the pre- and postoperative management and the outcome of a patient with unresectable colorectal liver metastases who underwent liver transplantation in a very advanced state of the disease (when he developed subacute liver failure due to insufficient functional liver parenchyma and toxicity of chemotherapy).We consider useful to present such observations,because collecting the data presented by different centers maybe contributive to identification of a selected group of patients who could benefit from liver transplantation. CASE REPORT: A 42-year old male patient, it was diagnosed with upper rectum cancer and multiple bilobar liver metastases in April 2009. Chemotherapy was started (in another hospital),and because the disease was stable after 7 cycles of FOLFOX and Bevacizumab, the patient was reffered to surgery (for a "two stage" liver resection). In October 2009 it was performed primary tumor resection associated with left lateral section ectomy and segment 4 metastasectomy. Because in November 2009 CT scan re-evaluation revealed progression of liver metastases, the second stage hepatectomy was precluded. Subsequent therapy consisted in radio embolization, multiple lines of chemotherapy,and targeted therapies. After more than 2 years, the liver metastases progressed and the patient developed progressive cholestatic subacute liver failure due to insufficient functional liver parenchyma and chemotherapy toxicity. In this state of the disease, he was admitted in our hospital, being dependant by liver dialysis and plasma exchange procedures. Due to the patients' age, and because the MDCT scan revealed the absence of extrahepatic disease (after almost three years of disease progression), and he could not benefited from any type of antineoplastic treatment due to progressive cholestatic subacute liver failure, liver transplantation with an organ from amarginal donor was considered and performed in January 2012.The postoperative course was uneventful, and the quality of his life improved (being fully reinserted social and professional).The immunosuppressive regimen consisted in Sirolimus and Mycophenolate mofetil, and the adjuvant chemotherapy started two months following liver transplantation. However,the patient developed extrahepatic relapse of the disease (lung metastases and retroperitoneal recurrence), but now, at morethan 20 months following transplantation, he is still alive in agood clinical condition. CONCLUSIONS: In patients with multiple unresectable liver onlycolorectal metastases, liver transplantation may improve overallsurvival and quality of life, by using marginal grafts whichcannot be allocated to the patients with standard indicationsfor liver transplantation. The advent of MDCT and PET CT scan and the use of m-TOR inhibitors may improve the resultsachieved by liver transplantation in patients with CLMs.Further studies could be useful in an attempt to disclosewhether a selected group of patients with unresectable liveronly colorectal metastases could become acceptable candidatesfor liver transplantation.

Intrahepatic cholangiocarcinoma--a rare indication for liver transplantation. Case report and review of the literature.

BACKGROUND: While hepatocellular carcinoma is a common indication for liver transplantation, intrahepatic cholangiocarcinoma represents a controversial indication for this procedure, due to lower disease-free and overall survival rates achieved by liver transplantation in such patients. Hence, in the last years, few centers reported satisfactory survival rates after liver transplantation for cholangiocarcinoma, in highly selected groups of patients. Herein we present the clinicopathological characteristics, the pre- and postoperative management and the favorable outcome of a patient undergoing liver transplantation for an unresectable intrahepatic cholangiocarcinoma. We consider that reporting the patients with such favorable outcomes is useful, since collecting the data presented by different centers may contribute to identification of a selected group of patients with cholangiocarcinoma who may benefit from liver transplantation. CASE REPORT: A 62-year old female patient with a primary liver tumor developed on HBV liver cirrhosis, was admitted in our center for therapeutical management. Since preoperative work-up suggested that the tumor is an unresectable hepatocellular carcinoma (due to its location and underlying liver disease), we decided to perform liver transplantation. The pathological examination of the explanted liver revealed that the tumor was a stage I intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and in present, 15 months after transplantation, the patient is alive, without recurrence. CONCLUSIONS: Liver transplantation may represent a valid therapeutical option in selected patients with intrahepatic cholangiocarcinoma. Patients with early stage intrahepatic cholangiocarcinomas unresectable due to the underlying liver cirrhosis seem to benefit mostly by liver transplantation. Further studies are needed to identify the favorable prognostic factors in order to select the most appropriate candidates for liver transplantation. The most suitable immunosuppressive and (radio)chemotherapic regimens should be identified in the future, in order to improve the disease-free and overall survival rates of the patients undergoing liver transplantation for intrahepatic cholangiocarcinoma.

[Current treatment of hepatocellular carcinoma. Analysis of a series of 123 cases over a 5-year period]. / Tratamentul multimodal al carcinomului hepatocelular. Analiza unei experiente clinice de 123 de cazuri în 5 ani.

We analyze a 123-cases experience over a 5-year period in the treatment of hepatocellular carcinoma (HCC). Liver resection, transplantation and hyperthermic ablation of the tumor were used according to the indication and patient selection. Systemic chemotherapy followed resection in 18 cases and hyperthermic ablation in 5 cases. Chemo-embolisation was performed in patients to be transplanted and in other two patients with tumor destruction. A number of 86 liver resections were performed in 84 patients (2 re- resections in 1 patient, subsequently transplanted) - 43 on normal liver and 41 on cirrhotic liver. Postoperative mortality was 4.7% in non-cirrhotic and 4.9% in cirrhotic patients. Survival in non-cirrhotic patients was 77% at 1 year, 65% at 2 years, and constant - 45% at 3 and 4 years, whereas in cirrhotic patients it was 60%, 56%, 56% and 36% (Kaplan-Meyer actuarial survival rates). Nine patients underwent liver transplantation (4 OLTs, 3 living donor LT, 1 split LT and 1 "domino" LT); postoperative mortality was 11% (1 patient). At present five patients are alive and well. One patient died by peritoneal carcinomatosis at 10 months; another patient died at 6 months by severe cholestatic recurrent C virus hepatitis and one patient was discharged with permanent severe neurologic disturbances. In 31 patients hyperthermic ablation of the tumor was used with zero mortality. Actuarial survival rates were 75% at one year and 67% at 2 years. In conclusion, in non-cirrhotic patients with HCC resection is the treatment of choice. In cirrhotic patients limited resections should be preferred and liver transplantation is the best solution in selected cases; local ablative methods may be used for some unresectable tumors. The role of adjuvant chemotherapy has to be determined in future comparative studies.