Neuroendocrine tumors of pancreas: how can we apply the 2006 TNM proposal?

BACKGROUND/AIMS: In 2006, a TNM system for foregut neuroendocrine tumors has been proposed. Our study aimed to present the management of neuroendocrine tumors of pancreas according to this classification and to highlight some of its limitations. METHODOLOGY: Clinical, biochemical, radiological, surgical and pathological data were retrospectively collected on 22 consecutives patients, who underwent surgery for neuroendocrine tumors of pancreas between November, 1991 and September, 2005. These data were used to set the TNM. RESULTS: After excluding 5 patients, the remaining 17 patients were analyzed. In 9 patients, with a mean age of 39 years, tumors were benign with a mean size of 1.8 cm, classed at stage I-IIa, whereas for 8 patients with a mean age of 57 years, tumors were malignant with a mean size of 6cm and were classed at stage IIb-IV. There were 3 deaths in stage IIb-IV, and none in stage I-IIa. CONCLUSION: TNM may be considered as a useful tool for prognostic stratification, but true benign tumors need to be excluded in order to improve the classification. Size and age appeared as variables affecting malignant behavior and the prognosis.

Randomized controlled trial comparing somatostatin with octreotide in the prevention of complications after pancreatectomy.

BACKGROUND/AIMS: The postoperative morbidity following pancreaticoduodenectomy (PD) remains very high. Somatostatin or octreotide are indicated in the prevention of pancreatic stump-related complications. The aim of this study is to compare the efficacy of somatostatin and octreotide after PD. METHODOLOGY: Between November 2000 and December 2003 we collected prospectively clinical and biological data from patients with a benign or malignant pancreatic tumor requiring a PD. Fifty patients were randomized into two groups, 25 treated with somatostatin (group S) and 25 with octreotide (group O). RESULTS: There was no postoperative death. Complications occurred in 20 patients (40%), 11 in group S, 9 in group O (NS). General complications occurred in 7 patients in group S, and 5 patients in group O. Local complications related to the pancreatic stump were found in 4 patients in both groups. At the end of the period of administration of the two study drugs, 2 patients (8%) had a pancreatic fistula in group S and 3 in group O (12%) (p=0.52). A trend of more rapid decreased level of amylase and lipase concentrations in surgical drainage was observed in group S but it is not statistically significant (p=0.29). CONCLUSIONS: In patients requiring PD for pancreatic tumor, somatostatin and octreotide seem to behave similarly in the postoperative period.

Prediction of postoperative complications after urgent laparotomy by intraperitoneal microdialysis: A pilot study.

OBJECTIVE: The aim of the present study was to investigate the role of intraperitoneal microdialysis (IPM) techniques in monitoring the evolution of postoperative critically ill patients requiring urgent laparotomy. SUMMARY BACKGROUND DATA: Postoperative intraabdominal sepsis is associated with an important degree of morbidity and mortality in acutely ill patients. Early diagnosis is critical to improve outcomes. METHODS: : The study included 25 consecutive patients admitted to the intensive care unit (ICU) after urgent laparotomy. Measurements of microdialysate fluid were performed through a microdialysis catheter, positioned intraperitoneally, during the first 5 postoperative days and lactate/pyruvate (L/P) ratios calculated. Patients were followed until hospital discharge. RESULTS: Ten patients had a complicated postoperative course, including 4 deaths (3 refractory shock, 1 mesenteric ischemia), 3 reinterventions (1 necrotic collection, 1 mesenteric ischemia, 1 biliary leak), 2 secondary peritonitis, and 1 intraabdominal collection. The IPM L/P ratio in these patients was already significantly higher during the first 24 postoperative hours compared with patients who had no complications (35 +/- 21 vs. 18 +/- 6, P < 0.01). An IPM L/P ratio above 22 on postoperative day 1 had a sensitivity of 0.64 and a specificity of 0.79 for complications. There were no significant differences between the two groups in pH, lactate, white blood cell count, or subcutaneous L/P ratio. No complication was associated with the technique. CONCLUSIONS: IPM is safe and reliable and provides valuable information after urgent laparotomy. Persistently high L/P values should raise the possibility of serious postoperative complications.

Early immunosuppression withdrawal after living donor liver transplantation and donor stem cell infusion.

Long-term results of organ transplantation are still limited by serious side effects of immunosuppressive drugs. A major issue, therefore, is to elaborate novel therapeutic protocols allowing withdrawal or minimization of immunosuppressive therapy after transplantation. We report on 3 patients prospectively enrolled in an original protocol designed to promote graft acceptance in living donor liver transplantation, using posttransplant conditioning with high doses of antithymocyte globulin followed by injection of donor-derived stem cells. In 2 patients, early immunosuppression withdrawal was possible, without subsequent graft deterioration. In these 2 cases, in vitro studies showed indices of immunological tolerance as assessed by specific hyporesponsiveness to donor alloantigens in mixed lymphocytes culture. In the third patient, acute rejection rapidly occurred after discontinuation of immunosuppression, and minimal immunosuppression has to be maintained during long-term follow-up. In this case, a clearly distinct immunoreactive profile was observed as compared to tolerant patients, as no specific modulation of the antidonor response was observed in vitro. Of note, no macrochimerism could be detected in any of the 3 patients during the follow-up. In conclusion, these clinical observations demonstrated that, despite the absence of macrochimerism, donor stem cells infusion combined with recipient conditioning may allow early immunosuppression withdrawal or minimization after liver transplantation.

Evaluation of da Vinci Nissen fundoplication clinical results and cost minimization.

BACKGROUND: A new technical tool was developed and introduced into the therapeutic field of videoscopic surgery-robotic telemanipulation surgery. The aim of this study is to investigate in a prospective randomized trial the feasibility of the Nissen procedure using the da Vinci and to evaluate the benefits and the costs of this new technique compared with the conventional laparoscopic approach. MATERIALS AND METHODS: Twenty patients with gastro-esophageal reflux disease (GERD) were randomized into laparoscopic Nissen versus robot-assisted Nissen fundoplication. All the patients signed an informed consent document. The time data of the procedure, the efficacy of the instruments, the intra-operative incidents, postoperative morbidity, and cost minimization are presented. RESULTS: Nine patients were assigned to the robot, and 11 to the laparoscopic procedure. Both groups were similar in age, male/female ratio, and body mass index. The robot procedure time was significantly longer. The hospital stay and the alimentation day were similar. The number of postoperative complaints was similar after the 1st, 6th, and 12th postoperative months. However, on the 3rd postoperative month, the number of complaints was significantly higher in the robot group. The robot procedure was more expensive with regard to the instrumentation and reusable material, the nursing costs, the investment costs, and the maintenance costs. CONCLUSIONS: No clear advantage of using robotics in the Nissen procedure was observed. The procedure seems to be feasible and safe. The technique is limited because of unadapted instruments. The disadvantages are the high costs and prolonged operative time.

Donor stem cell infusion after non-myeloablative conditioning for tolerance induction to HLA mismatched adult living-donor liver graft.

BACKGROUND AND AIM OF THE STUDY: The induction of transplantation tolerance, defined as the survival of a functioning allograft in the absence of continuing immunosuppressive therapy, would be a major advance. Clinical and experimental data have shown that transplantation tolerance could be induced by pre-transplant myeloconditioning and infusion of donor hematopoietic cells. We investigated the feasibility and safety of a protocol to induce tolerance to HLA mismatched living-donor liver graft by pre-transplant non-myeloablative conditioning followed by donor stem cells (SC) infusion, in patients with advanced liver cancers. PATIENTS AND METHODS: Two patients with intrahepatic cancers who did not fulfill criteria for cadaver liver transplantation were included in the study. Preparative regimen consisted in cyclophosphamide and anti-thymocyte globulin, followed by infusion of purified donor CD34(+) stem cells. Living-donor liver transplantation (LDLT) using the liver right lobe was performed after hematological reconstitution, respectively 40 and 55 days after donor stem cell infusion. Immunosuppressive therapies were discontinued when liver graft function returned to normal. RESULTS: The procedure could be completed in the two patients. No severe toxicity of the preparative regimen was observed. Neither patient presented graft versus host reaction after donor stem cell infusion. A transient macrochimerism was observed in the first case, while no chimerism could be detected in the second. Immunosuppression was discontinued, respectively 90 and 28 days, after liver transplantation, without subsequent rejection episode. In the two cases, liver function remained normal for the study period. In both patients, the period of immune reconstitution was prolonged, as illustrated by persisting low CD4(+) cell counts. Mixed lymphocyte cultures, performed after immunosuppression withdrawal, demonstrated donor specific hyporesponsiveness in the first case, but in a context of global hyporeactivity in the two patients. The first patient died from tumor recurrence 370 days after liver transplantation. The second patient is alive, 270 days after liver transplantation, but with a suspicion of tumor relapse as indicated by the reappearance of tumor marker in blood. CONCLUSION: In the two cases, acceptance of HLA mismatched living-donor liver graft was obtained after non-myeloablative conditioning and donor stem cell infusion. Improving the rate of immune reconstitution appears as a priority to reduce the risk of tumor recurrence in such patients.

[Acute intestinal bleeding due to Taenia solium infection]. / Emorragia intestinale acuta da Taenia solium. Caso clinico.

Parasite infections of the digestive tract are a rare cause of acute haemorrhage in Western countries. We report here on a case of acute intestinal bleeding due to Taenia solium infection diagnosed at surgery. A 79-year-old white female patient was admitted to our institution for instable angina and severe anaemia secondary to acute intestinal bleeding. The patient's medical history was positive for long-standing microcytic anaemia. A recent diagnostic work-up had revealed the presence of chronic erosive antral gastritis and colonic diverticular disease without acute bleeding. On admission to our department the patient underwent antegrade bowel endoscopy which showed a bleeding site 120 cm caudad to the Treitz ligament in the absence of ulcers and/or neoplastic lesions. The patient was eventually referred to surgery for suspected intestinal angiodysplasia. At surgery no gross lesions of the stomach, bowel or colon were observed. We then performed a custom enterotomy 120 cm caudad to the Treitz ligament and discovered a 250-cm-long tapeworm. The parasite was removed with the aid of a second enterotomy 60 cm cephalad to the previous one and the entire bowel was explored with an intraoperative fiberoptic endoscope. Histology of the parasite revealed a T. solium species. The postoperative course was uneventful and the patient was discharged on postoperative day 10 with a prescription of 2 g/day niclosamide. No recurrent digestive bleeding has so far been reported after a follow-up of 8 months. T. solium infection is a common cause of chronic microcytic anaemia in tropical and subtropical areas. In Western countries intestinal parasite infections are rarely taken into account in the diagnostic work-up of patients affected with chronic anaemia and/or acute digestive bleeding. The mechanisms responsible for acute intestinal bleeding in tapeworm infections are poorly understood and could be related to parasite-induced erosions of the bowel wall or be secondary to manipulations occurring during diagnostic manoeuvres.

Aminopyrine breath test compared to the MELD and Child-Pugh scores for predicting mortality among cirrhotic patients awaiting liver transplantation.

Better tools for predicting the risk of death while awaiting transplantation are urgently needed because organ shortage is increasing the numbers on transplantation waiting lists. The aminopyrine breath test (ABT), model for end-stage liver disease (MELD), and Child-Pugh (C-P) score were compared as predictors of this risk in 137 cirrhotic candidates for liver transplantation. Eighty-three were transplanted within 3 months of registration, 35 others survived, 13 died before transplantation, and 6 were removed from the list. By univariate analysis, the continuous variables significantly associated with death while awaiting transplantation were: history of infected ascites, C-P score, ABT, and international normalized ratio or prothrombin time. Receiver operating characteristic curves for quantitative variables showed that the area under the curve was greatest for ABT (0.858 +/- 0.067). By Youden curve analysis, the best cut-off points for identifying cirrhotic patients at high risk of death while on the waiting list were: > 10, > 16, and < 0.7% for the C-P score, MELD score, and ABT, respectively. These results show that ABT is as good as the MELD and C-P scores, or better, as a predictor of death among cirrhotic patients awaiting liver transplantation.

New considerations for an overall approach to treat hepatocellular carcinoma in cirrhotic patients.

BACKGROUND: Increasing numbers of cases and organ shortage justify reconsidering the global therapeutic approach for hepatocelluar carcinoma in cirrhotic patients. METHODS: Recent literature was reviewed, focused on new therapeutic technologies such as radiofrequency. RESULTS: For small tumors, liver transplantation offers theoretically the best chance for cure. However, organ shortage may eliminate this advantage, because of tumor progression while waiting for a graft. For small tumors, arising on compensated cirrhosis, resection or radiofrequency ablation may provide efficient local tumor control without precluding subsequent transplantation in case of tumor recurrence and/or cirrhosis decompensation. CONCLUSIONS: For small tumors and compensated cirrhosis, resection or radiofrequency could represent acceptable first line treatments. In addition to permit safe and immediate tumor control, this strategy would allow a preferential redistribution of grafts to patients with decompensated cirrhosis in whom transplantation is the only possibility.

Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study.

PURPOSE: The addition of radiation to adjuvant 5-fluorouracil for the treatment of pancreatic cancer has not yet shown any definite benefit. Gemcitabine (GEM) has potential activity in advanced pancreatic cancer and is a powerful radiosensitizer. We evaluated the feasibility of postoperative administration of GEM alone, followed by concurrent GEM and irradiation (RT) after curative resection for pancreatic adenocarcinoma. METHODS AND MATERIALS: GEM 1000 mg/m(2) on Days 1 and 8 every 21 days for three courses was given within 8 weeks after surgery and was followed by GEM 300 mg/m(2) weekly +40 Gy in a split course. Twenty-two patients (median age 59 years, range 39-74, Performance Status 0-1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included. RESULTS: For GEM alone, all patients received the three planned courses, with dose reductions in 7 (32%) of 22 patients. All patients, except two, completed full chemoradiation; one received only 20 Gy because of both World Health Organization Grade 4 vomiting and thrombopenia and the other stopped RT after 32 Gy because of early disease progression. No reduction in GEM during RT was necessary; no toxic death was noted; and World Health Organization Grade 3-4 hematologic and nonhematologic toxicities occurred in 8 (36%) and 7 (nausea, vomiting) (32%) of 22 patients respectively. No late toxicity developed. After a median follow-up of 15 months, 11 patients were alive, and 2 patients had died of causes unrelated to their disease or toxicity, The median disease-free survival and overall survival was 6 and 15 months, respectively. CONCLUSION: This adjuvant regimen was well tolerated and can be easily administered after curative surgery for pancreatic cancer. Its intensification with continuous RT is currently being investigated.

Preconditioning of donors with interleukin-10 reduces hepatic ischemia-reperfusion injury after liver transplantation in pigs.

BACKGROUND: Graft ischemia-reperfusion injury (IRI) resulting from postreperfusion inflammatory reaction remains a major cause of complications after liver transplantation. In this article, the authors investigated the effect of anti-inflammatory cytokine interleukin (IL)-10 on IRI, in a preclinical model of liver transplantation in pigs. METHODS: Donor pigs received IL-10 or saline at the start of liver graft harvesting. After 5 hr of cold ischemia, liver grafts were transplanted into untreated recipient pigs. IRI severity was measured in recipients by transaminase release and by cellular infiltration and necrosis on liver biopsy specimens. RESULTS: Donor IL-10 administration attenuated IRI, as indicated by significant reduction of mean peak of transaminase in recipients of grafts from IL-10-treated donors. In contrast, no significant differences in cell infiltration or amount of necrosis were observed on liver biopsy specimens between groups. CONCLUSIONS: Donor preconditioning with IL-10 may constitute an interesting pharmacologic approach to reduce IRI severity after liver transplantation.

Cholangitis caused by Roux-en-Y hepaticojejunostomy obstruction by a biliary stone after liver transplantation.

Biliary stones may occur after liver transplantation, mostly in relation with biliary strictures. We describe an unusual case of biliary stone developing 18 years after liver transplantation and biliary-enteric anastomosis for biliary atresia, responsible for an acute cholangitis caused by obstruction of the jejunal loop. Surgical exploration allowed the removal of the stone and did not reveal any enteric stricture. Both biliary and enteric anastomosis were patent. An hepatobiliary scintigraphy performed 2 weeks after surgery demonstrated a delayed bile excretion through the jejunal limb and a focal accumulation of the tracer at the level where the stone was found. In conclusion, biliary stone formation could develop after liver transplantation and biliary-enteric anastomosis, in the absence of mechanical stricture, secondarily to bile stasis caused by functional disorder of the efferent jejunal loop. Hepatobiliary scintigraphy plays a central role in the diagnosis and comprehension of such a disorder.

[F-18] fluorodeoxyglucose positron emission tomography as a tool for early recognition of incomplete tumor destruction after radiofrequency ablation for liver metastases.

BACKGROUND AND OBJECTIVES: To assess the value of FDG positron emission tomography (PET) for early detection of incomplete tumor destruction after radiofrequency ablation (RFA) for liver metastasis. METHODS: Twenty-eight unresectable liver metastases in 17 patients were treated by RFA. Patients underwent computed tomography (CT) and FDG-PET preoperatively, at 1 week, 1 month, and 3 months postoperatively. Postoperative CT and FDG-PET at 1 week and 1 month were analyzed to identify hypervascular and hypermetabolic residual tumors at the RFA site. These results were correlated with follow-up CT and, in case of reintervention, with pathologic results. RESULTS: In 24/28 of RFA-treated metastases, CT and FDG-PET at 1 week and 1 month showed no tumor residues. During follow-up, none of these 13 patients developed local recurrence at RFA site. In four patients, FDG-PET at 1 week and 1 month showed peripheral hypermetabolic residue after RFA, whereas CT did not revealed residual tumor. In three patients, local persistence of viable tumor cells was biopsy-proven at reintervention. In the fourth, follow-up CT showed subsequent development of a local recurrence. CONCLUSIONS: FDG-PET accurately monitors the local efficacy of RFA for treatment of liver metastases, as it early recognizes incomplete tumor ablation, not detectable on CT.

Squamous cell carcinoma of the esophagus: multimodal therapy in locally advanced disease.

The aim of this prospective study is to report our experience in the multimodal management of locally advanced esophageal squamous cell carcinoma (LAESC; stage III cTNM), focusing on the results of chemoradiotherapy followed by surgery. These findings were compared to the results of a standard group of patients with locally advanced esophageal carcinoma (LAEC; stage III pTNM) treated in our center with surgery alone. Sixty-one patients with LAESC underwent preoperative chemoradiotherapy (5-fluorouracil + cisplatin) with concomitant 45 Gray radiotherapy in a 5-week course. Transthoracic esophagectomy was performed 4 to 5 weeks after the end of the neoadjuvant therapy. Thirty-eight patients underwent surgery, and 37 of them had resections (resectability: 97% in the multimodal group; 84% in the standard surgical series; p = 0.07). The R0 (complete) resection rate was 78% compared to 56% in the standard surgical group (p <0.03). Eleven patients had no residual tumor in the resected specimen (pathologic complete response: pCR: 30%). The operative mortality rate was 19% compared with 8.8% in the standard series. The overall median survival of the resected patients was 21 months, with a 5-year survival rate of 11% (14% in the surgical group; NS). The 3-year and 5-year survival rates were 34% for the pCR group and respectively 5% and 0% for the group with pathologic incomplete response (pIR; p <0.05). The median survival was 28 months for the pCR patients and 19 months for the pIR group. In this non-randomized trial, preoperative chemoradiotherapy in LAESC seems to increase the resectability and R0 resection rates, to allow a higher pCR rate and a longer survival only in the pCR group, at the expense of an inadequate increase in operative mortality. This multimodal treatment cannot be proposed as a standard procedure unless less toxic regimens are developed, increasing the benefits with better local and distant failure control and decreasing operative mortality.