The incidence of over-the-counter medication use in patients with midgut neuroendocrine tumors.

Recent increases in the use of over-the-counter (OTC) medicines and the underreporting of the use of these medications to physicians have sparked interest in the number and types of "supportive" therapies used by patients with neuroendocrine tumors (NETS). Patients with NETS are of special interest as a result of the potential interactions/interferences between tumor-associated peptide and amine production and OTC supplements. A prospective analysis of patients with primary small bowel NETS between 1998 and 2012 was conducted to define and catalog each patient's prescription and OTC medication use at each clinic visit. The most recently recorded patient medications were used for this analysis. Three hundred sixty-two patients with small bowel primary NETS were studied. One hundred eighty-seven patients (51.6%) were taking nutritional supplements. Of these taking supplements, the per cent of patients taking one, two, three, or more than three supplements was 28.3, 24.1, 22.5, and 25.1 per cent, respectively. Females (n = 109) were more likely to take supplements in comparison to males (n = 78; P = 0.037). Fifty one patients (14.1%) took proton pump inhibitors and 31 patients (8.6%) took loperamide. OTC supplements were used by 50 per cent of patients with primary small bowel NETS in this study. Over one-third of our patients reported using three or more OTC medicines daily. These medicines have the potential to interact with the metabolism of prescribed medicines, modify ability to clot during surgery, exacerbate NET symptoms, and alter NET markers. Given the prevalence of OTC medications and their potential actions, it is important to carefully catalog their use.

IN VITRO CHEMOTHERAPY PROFILING OF WELL-DIFFERENTIATED MIDGUT NEUROENDOCRINE TUMORS (NETS) BASED ON INDIVIDUAL PATIENT TUMOR BIOMARKERS ANALYSIS.

BACKGROUND: Midgut neuroendocrine tumors (NETs) are rare malignancies with indolent clinical courses. In general, they are well-differentiated with most tumor cells in the G0 phase of the cell cycle, consistent with the poor response rate of NETs to chemotherapy in vivo. We hypothesize that insults, such as surgery, can drive NET cells from G0 into S phase and that biomarker analysis of individual patient tumors harvested and grown in the lab will provide useful practical guide for future intra and post-operative adjuvant therapy. METHODS: 97 well-differentiated midgut NET patients underwent cytoreductive surgery at our institution between May/2012 and October/2012. 148 surgical specimens were collected and submitted to a single commercial lab for processing. Primary tumors, lymph nodes and liver metastases were harvested and cultured. Their ribonucleic acids (RNA) were then extracted to analyze the expressivity, a total of 88 different biomarkers. Based on our patients' specific tumor biomarker expressivity and known correlations between 36 anti-neoplastic agents with their linked biomarkers, recommendations were reported as clinically beneficial or non-beneficial. RESULTS: A total of 148 specimens from 97 patients were tested. In four of the 97 patients, no clinically beneficial chemotherapy agent could be identified. Among the remaining 93 patients, the top three agents that are most likely to be clinically beneficial are: fluorouracil, cisplatin and carboplatin. These were reported to be clinically beneficial in 135/148 (91.2%), 103/148 (69.6%), and 103/148 (69.6%) patients respectively. CONCLUSIONS: Midgut NETs are slow growing tumors which are chemotherapeutically inert owing to the fact that most of the tumor cells are in G0 cell cycle. Surgical insult drives NET cells into active synthetic phase where they begin to express biomarkers specific to their tumor cells. Analysis of these biomarkers guides further potential beneficial therapy based on the current known associations among biomarkers and chemotherapy agents. These results must then be compared and confirmed against a direct in-vitro chemo sensitivity assessment conducted simultaneously on the same patients.

A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation.

Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n = 82), (2) recipients switched to FK506 for antirejection or rescue therapy (n = 61), and (3) recipients converted to FK506 for other reasons (n = 11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% > or = 2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P = 0.04); for PTA recipients, 84% versus 66% (P = n.s.); and for PAK recipients, 80% versus 14% (P = 0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV-positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P = n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.

The risks, benefits, and costs of expanding donor criteria. A collaborative prospective three-year study.

The study purpose was to identify risks, benefits and costs associated with an expanded donor protocol. The protocol design evaluated organs rescued using expanded donor criteria and weighed all costs associated with doing so. Costs were measured against conditions experienced with expanded and traditional criteria and recipient outcome. Traditional donors were between 5 and 55, with negative serologies, and no history of hypertension or diabetes. "Expanded donors" were between 55 and 75 or less than 5, with a history of hypertension, diabetes and/or sero-positive for Hepatitis C. During this study 73 donors met criteria from which 200 organs were transplanted. Defined costs and outcomes for recipients were tracked. Using expanded criteria: costs averaged 20% more per organ; OPO personnel spent an average of 6 hours more time on-site; an additional 12-14 hours in placement activity; and average organs per donor decreased. Heart patient and graft survival rates for traditional and expanded donor organs were comparable. Kidney patients transplanted from this pool experienced a decrease in patient (P = .14) and a significant decrease in graft (P = .02) survival rates. Patient (P = .05) and graft (P = .01) survival rates were significantly lower in liver patients transplanted with expanded donor organs. Two hundred transplants occurred using expanded donor criteria. Costs for the OPO increased appreciably. Heart and kidney utilization from these donors seems justified. It is thought that liver recipients' results were due to utilizing them in sicker patients. Recovery of organs from donors using expanded criteria appears to be a reasonable way of increasing organ supply.

Left gastric artery as an alternative for arterial reconstruction in orthotopic liver transplantation.

The hepatic arterial blood supply is indispensable for the survival of the graft during liver transplantation. Inadequacies in the recipient hepatic artery mandate arterial reconstruction different from the preferred method of direct anastomosis. We report the use of the left gastric artery as an attractive alternative for reconstructing the arterial blood supply of a transplanted liver.

Nodular regenerative hyperplasia: a controversial indication for orthotopic liver transplantation.

Nodular regenerative hyperplasia of the liver is an uncommon cause of portal hypertension. Patients with nodular regenerative hyperplasia have signs and symptoms of portal hypertension, without evidence of hepatocellular failure or encephalopathy. We report the case of a 44-year-old woman with recurrent esophageal bleeding and refractory ascites who had a history of hemosiderosis, hepatitis C, and chronic renal allograft rejection. Our preoperative diagnosis was cirrhotic end-stage liver disease and end-stage renal disease for which the patient underwent combined hepatic and renal transplantation. Her portal hypertension symptoms resolved, and her renal function has been normal for 18 months of follow-up. Histologic examination of the liver revealed nodular regenerative hyperplasia, and a review of the literature regarding the surgical management of patients with nodular regenerative hyperplasia revealed that various shunting procedures are generally recommended. After the failure of medical management in patients with nodular regenerative hyperplasia, portosystemic shunting may be indicated before proceeding to hepatic transplantation.

Protocol Doppler color flow imaging immediately after kidney transplantation.

Doppler color flow imaging has been used to identify obstruction, rejection, and nonfunctioning renal allografts. When done in the immediate posttransplant period on poorly functioning kidneys, it allows early and accurate detection of surgically correctable changes such as arterial or venous thrombosis or early obstruction by blood, urine, or lymph. Further, it determines changes in intrarenal flow patterns that may indicate early transplant dysfunction, such as acute tubular necrosis and/or acute rejection as well as obstruction. Additionally, baseline values can be obtained in uncomplicated cases for serial follow-up. Between July 1980 and February 1991, 20 transplant patients had Doppler color flow imaging in the immediate posttransplant period. The kidney contour, perirenal collections, vessel flow patterns, and resistive indexes were assessed. In two patients, immediate surgical intervention salvaged the allograft. In several other patients with primary nonfunctioning kidneys, the study distinguished between acute tubular necrosis and obstruction due to external compression. We concluded that protocol Doppler color flow imaging is valuable in the immediate posttransplant period for determining surgically correctable complications.

Improved zipper closure of the abdominal wall in patients requiring multiple intra-abdominal operations.

Optimal management of pancreatic abscess and septic complications of acute pancreatitis remains controversial. With the "open packing" approach, repeated closure of the midline fascia is complicated by loss of tissue integrity and suture strength. An improved zipper closure of the abdominal wall in six patients with pancreatic abscess is presented. Improvements included: (1) using a separating jacket-type zipper to allow maximal intraoperative exposure; (2) employing a removable tuck for expansion of the patch covering the wound; (3) substituting a nonmeshed polytetrafluoroethylene material for the polypropylene mesh to prevent adherence to the underlying viscera; and (4) creating a flap underneath the zipper teeth to protect the underlying tissue from injury. Satisfactory results were achieved with the improved zipper technique.

Modified vascular reconstruction for pancreaticoduodenal allograft.

The simultaneous recovery of the cadaveric liver and pancreaticoduodenal allograft is well established. The current technique for procurement enables the retrieval of both organs in most multiorgan donor operations. Vascular complications may account for 45 percent of pancreatic graft failures, most of which are thromboses of the portal vein caused by low flow in the entire pancreatic vasculature, a twisted venous anastomosis or an acutely angled arterial reconstruction that can contribute to the thrombosis and, thereby, to graft failure. Because a diabetic recipient may have severely atherosclerotic vessels, an interposition autograft of the internal iliac artery of the recipient is not recommended. Our modified vascular reconstruction prevents compromised arterial blood supply when donor arterial grafts (iliac, carotid or femoral) are not available and when direct splenic to SMA reconstruction is not feasible.

Liver transplantation in patients with situs inversus.

Situs inversus has been considered an absolute contraindication to liver transplantation due to technical difficulties. Associated vascular malformation and distorted anatomy may make the procedure even more complicated or impossible. Only three cases of patients with abdominal situs inversus who underwent successful liver transplantation have been reported in the English literature. We describe two additional patients with situs inversus who suffered from biliary atresia and underwent successful liver transplantation. The preoperative evaluation and the operative procedure are presented, and technical difficulties are discussed. Since biliary atresia is associated with polysplenia syndrome, including vascular malformation and visceral malposition, we suggest that each case be extensively evaluated preoperatively to determine the size requirement for the donor liver and the feasibility of reconstruction.

Salvage of hemodialysis access in infected arteriovenous fistulas.

Infection combined with additional complications of arteriovenous fistulas is a serious threat to access in patients with upper-extremity polytef (polytetrafluoroethylene) grafts. We present three cases of infected access grafts that were treated with systemic antibiotics, excision of the grafts, and primary anastomosis of the arterialized vein to artery for access salvage. The new arteriovenous fistulas were used immediately, preventing interruptions in hemodialysis regimens. This technique of immediate reconstruction allows the surgeon to utilize the arterialized outflow vein and save other sites of access for future use.

Pancreas transplantation. A new program.

Sixteen pancreatico-duodenal transplants were performed on 15 insulin-dependent diabetics, aged 25-46, during a 20-month period beginning May 1, 1988. Fourteen patients received a combined cadaveric pancreas/renal transplant with bladder drainage. One patient received a second pancreas transplant 24 hours after the first pancreas graft failed due to portal vein thrombosis. One patient received a pancreas graft 3 years after kidney transplantation. Complications included five cases of hematuria, two bladder leaks, two wound infections, one cytomegalovirus pneumonia, three cases of graft pancreatitis, one pseudocyst, one urine reflux pancreatitis requiring conversion to pancreatico-enterostomy, and two late deaths. Average time to discharge was 17 days following transplant, with 2.9 re-hospitalizations per patient and an average of 38 in-hospital days during the first 6-12 months. Seventeen rejection episodes occurred in 12 patients, diagnosed by declining urine amylase and pH and/or finding of rejection on kidney biopsy. Patient and kidney graft survival is 87 per cent. Pancreas graft survival is 81 per cent (1-20 months follow-up). All patients are insulin-independent and normoglycemic. Mean glycosylated hemoglobin concentration is 4.0 +/- 0.9 post-transplant vs. 7.5 +/- 0.6 pretransplant. Mean serum creatinine is 1.4 +/- 0.7 mg/dl. A new program of pancreas transplantation can be successful in carefully selected diabetic patients, with special attention to avoidance of preservation injury to the pancreas during multiorgan donor procurement. Combined pancreatic/renal transplantation is believed to be the therapeutic treatment of choice in Type I diabetic patients who have impaired renal function and have no significant cardiovascular disease.