Understanding pancreatic exocrine insufficiency and replacement therapy in pancreatic cancer.

Pancreatic exocrine insufficiency (PEI) is highly prevalent in patients with pancreatic cancer, and has substantial implications for quality of life and survival. Post resection, PEI is associated with increased post-operative complications, longer hospital stays and higher costs. Treatment with pancreatic enzyme replacement therapy (PERT) improves quality of life and confers significant survival advantages. Despite this many patients with pancreatic cancer do not currently receive PERT. The nutritional consequences of PEI are extensive and even more relevant in the elderly owing to age related gastrointestinal tract and pancreatic changes that predispose to malnutrition.

A case report of an angiomyxoma in the liver.

Angiomyxomas are uncommon myxoid tumours arising most commonly from the pelvis. A 46-year-old woman with a history of polycystic kidney disease presented asymptomatically for surveillance ultrasonography; changes were noted in the size and morphology of her liver cysts. Subsequent radiological assessment displayed features suspicious of malignancy and a right hemihepatectomy was performed with curative intent. Pathological examination of the resected specimen found histology consistent with an angiomyxoma arising primarily from the liver parenchyma. Follow-up review of the patient has been uneventful with annual imaging showing no evidence of recurrence. Angiomyxomas do not characteristically invade other tissues. However, any liver lesion displaying suspicious features of malignancy should be resected in the absence of disseminated disease.

Recurrent acute pancreatitis in bowel malrotation.

OBJECTIVE: Recurrent acute pancreatitis is an uncommon diagnosis in teenagers. Excluded alcohol and biliary stones, more prevalent aetiologies in these group of patients are genetic pancreatitis, pancreatic duct system abnormalities, neoplasia, traumas and congenital abnormalities of the duodenum such as duodenal duplication or diverticulum. Two reported cases of recurrent pancreatitis associated to midgut malrotation were described in English literature. Bowel malrotation is a difficult diagnosis in a teenager or a young adult and a common delay is documented. Ladd's procedure is largely recognized to be the standard treatment for a symptomatic malrotation. CASE REPORT: Our Report describes in details a case of recurrent pancreatitis, where a late diagnosis of midgut malrotation was obtained and an endoscopic management was attempted. A literature review and an analysis of two previously reported cases were performed to explore a possible aetiopathogenesis of the recurrent acute pancreatitis in patients with midgut malrotation. RESULTS: 24 months of follow-up showed an asymptomatic patient on a free diet, with a mild deranged Liver Functional Tests and a normal Amylase and Lipase. The recurrence of acute pancreatitis has not been observed until the present day. CONCLUSIONS: Recurrent episodes of acute pancreatitis in young adults, without a history of alcohol abuse or evidence of gallstones, might be an atypical presentation of midgut malrotation and it should be in the differential diagnosis. In this case, a Ladd's operation is beneficial and an endoscopic procedure does not obtain advantages.

Amantadine monotherapy is ineffective in the treatment of hepatitis C virus recurrence in the post-liver transplantation setting.

BACKGROUND: Recurrent hepatitis C virus (HCV) infection is universal after liver transplantation (LT), yet no effective therapy is available. Amantadine (Am) is currently under evaluation. The aim of this study was to assess the safety and the effectiveness of Am monotherapy in LT patients with HCV recurrence. METHODS: Twelve patients who underwent transplantation 1-4 years earlier were included when there was detectable serum HCV-RNA and histological signs of liver damage with evidence of progressive hepatic fibrosis. Basal Ishak's scores were 2.1 +/- 1.3 and 5.1 +/- 2.7, respectively. Exclusion criteria were histological cirrhosis and comorbidities. All patients were receiving cyclosporine, with or without azathioprine. Amantadine was given orally (200 mg/d) for 3 months. RESULTS: Eight (67%) patients completed a 3-month treatment course without dose adjustments. Am was reduced to 100 mg/d in 3 cases and withdrawn in 1 due to side effects, namely, insomnia (n = 7; 58%), tremor (n = 4; 33%), headache (n = 2; 17%), asthenia (n = 2; 17%), and dermatitis, diarrhea, and increased creatinine (each n = 1; 8%). Serum HCV-RNA levels decreased in 3 patients, increased in 3, and remained unchanged in the others. Alanine aminotransferase (ALT) remained abnormal in all cases. Liver function test results did not improve. CONCLUSIONS: Short-term Am monotherapy was ineffective to treat post-LT HCV relapse and was associated with significant side effects.

Use of mycophenolate mofetil in liver transplantation: a literature review.

Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary immunosuppressive therapy after orthotopic liver transplantation (OLT) is based on a calcineurin-inhibitor (CNI): cyclosporine or tacrolimus. Renal failure with arterial hypertension, due to CNI side-effects, is a major cause of morbidity and mortality after OLT. Several studies have shown the efficacy of MMF to improve CNI-induced nephrotoxicity, blood pressure, and uric acid concentration in liver transplant patients with concomitant reduction or withdrawal of CNI. Predose plasma mycophenolic acid concentrations (MPA) are related to adverse events, drug dose, and clinical status. Blood level values outside the suggested MPA therapeutic range are associated with acute rejection episodes and side effects, which have been described in about half of the patients treated with MMF. Most authors have described gastrointestinal and hematological side-effects, whereas these appear usually dose related, responding quickly to reduction. MMF is potent and safe immunosuppressive agent, and replacement of CNI by MMF in liver transplant patients with renal dysfunction may improve not only kidney function but also other CNI-associated side-effects, such as hypertension and hyperuricemia, with a low risk of rejection.

Digital histology quantification of intra-hepatic fat in patients undergoing liver resection.

BACKGROUND: High intra-hepatic fat (IHF) content is associated with insulin resistance, visceral adiposity, and increased morbidity and mortality following liver resection. However, in clinical practice, IHF is assessed indirectly by pre-operative imaging [for example, chemical-shift magnetic resonance (CS-MR)]. We used the opportunity in patients undergoing liver resection to quantify IHF by digital histology (D-IHF) and relate this to CT-derived anthropometrics, insulin-related serum biomarkers, and IHF estimated by CS-MR. METHODS: A reproducible method for quantification of D-IHF using 7 histology slides (inter- and intra-rater concordance: 0.97 and 0.98) was developed. In 35 patients undergoing resection for colorectal cancer metastases, we measured: CT-derived subcutaneous and visceral adipose tissue volumes, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), fasting serum adiponectin, leptin and fetuin-A. We estimated relative IHF using CS-MR and developed prediction models for IHF using a factor-clustered approach. RESULTS: The multivariate linear regression models showed that D-IHF was best predicted by HOMA-IR (Beta coefficient(per doubling): 2.410, 95% CI: 1.093, 5.313) and adiponectin (ß(per doubling): 0.197, 95% CI: 0.058, 0.667), but not by anthropometrics. MR-derived IHF correlated with D-IHF (rho: 0.626; p = 0.0001), but levels of agreement deviated in upper range values (CS-MR over-estimated IHF: regression versus zero, p = 0.009); this could be adjusted for by a correction factor (CF: 0.7816). CONCLUSIONS: Our findings show IHF is associated with measures of insulin resistance, but not measures of visceral adiposity. CS-MR over-estimated IHF in the upper range. Larger studies are indicated to test whether a correction of imaging-derived IHF estimates is valid.

Screening for predictors of adverse outcome in onco-geriatric surgical patients: A multicenter prospective cohort study.

AIMS: The aim of this study was to investigate the predictive ability of screening tools regarding the occurrence of major postoperative complications in onco-geriatric surgical patients and to propose a scoring system. METHODS: 328 patients ≥ 70 years undergoing surgery for solid tumors were prospectively recruited. Preoperatively, twelve screening tools were administered. Primary endpoint was the incidence of major complications within 30 days. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. A scoring system was derived from multivariate logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was applied to evaluate model performance. RESULTS: At a median age of 76 years, 61 patients (18.6%) experienced major complications. In multivariate analysis, Timed Up and Go (TUG), ASA-classification and Nutritional Risk Screening (NRS) were predictors of major complications (TUG>20 OR 3.1, 95% CI 1.1-8.6; ASA ≥ 3 OR 2.8, 95% CI 1.2-6.3; NRS impaired OR 3.3, 95% CI 1.6-6.8). The scoring system, including TUG, ASA, NRS, gender and type of surgery, showed good accuracy (AUC: 0.81, 95% CI 0.75-0.86). The negative predictive value with a cut-off point >8 was 93.8% and the positive predictive value was 40.3%. CONCLUSIONS: A substantial number of patients experience major postoperative complications. TUG, ASA and NRS are screening tools predictive of the occurrence of major postoperative complications and, together with gender and type of surgery, compose a good scoring system.

Marginal donors in liver transplantation.

Marginal liver donor criteria included the following: obesity (weight >100 Kg or BMI >27), age >50 years; macrovesicular steatosis >50%; intensive care unit stay >4 days; prolonged hypotensive episodes of >1 hour, and <60 mm Hg with high inotropic drug use (dopamine, [DPM] > 14 microg/kg per minute); cold ischemia time >14 hours, peak serum sodium >155 mEq/L; sepsis, viral infections, and alcoholism; high levels of bilirubin, ALT, and AST, or extrahepatic neoplasia. Between August 1992 and May 2003, we performed 251 liver transplants in 241 patients of whom 155 are presently alive. We used 124 (49.4%) standard donors and 127 (50.6%) marginal donors. Among the group that received a standard donor, 81 (65.3%) are still alive. Among recipients of organs from marginal donors. 81 (63.8%) are still alive. We also assessed the quality of donors according to the severity of recipient disease. For standard donors these outcomes were 61.5% for UNOS 1, 37.5% for UNOS 2A, 73.2% for UNOS 2B, and 80% for UNOS 3 for marginal donors they were 46.1% for UNOS 1, 53.6% for UNOS 2A, 70.7% for UNOS 2B, and 63.6% for UNOS 3. Among the patients who received a liver from a donor >60 years old, there were no survivors in UNOS 1 and 2A, but there were good results in groups 2B and 3. These results suggest there is no difference between marginal and standard donors, even in sick patients, with the exception of donor age.

Sentinel lymphadenectomy in cutaneous melanoma.

AIMS AND BACKGROUND: In the last ten years validation of the sentinel lymph node (SLN) concept has led to modification of the surgical approach for patients with intermediate-risk cutaneous melanoma. METHODS AND STUDY DESIGN: Forty-eight patients affected by cutaneous melanoma with a Breslow thickness between 0.65 and 4 mm were enrolled in the study. Approximately 2 mCi of radiotracer and 1 mL of vital blue dye were injected in each patient around the site of the primary lesion. Lymphoscintigraphy was performed until the lymphatic basin and the respective SLN were localized. The whole surgical procedure consisted of enlargement of the surgical margins followed by localization and excision of the SLN(s) by using both radiotracer and vital dye. Whenever the SLN proved to be histologically positive for metastasis, complete regional lymphadenectomy was performed. RESULTS: Within 15 minutes of radiotracer administration the lymphatic basin was localized in all 4 patients by lymphoscintigraphy. Vital dye and radiotracer successfully allowed SLN localization and excision in 46 of 48 patients (97%); in one case the SLN was detected by radiotracer alone. The SLN proved to be metastatic in six (13%) of 46 evaluable patients; interestingly, in three of them the presence of metastatic cells was revealed only by immunohistochemistry. All patients with tumor-positive SLNs had primary lesions with a Breslow thickness = 2 mm. CONCLUSIONS: Sentinel lymphadenectomy is able to identify lymph node involvement in patients with cutaneous melanoma with a Breslow thickness > 1 mm, thus avoiding the risks associated with radical regional lymphadenectomy. Lymphoscintigraphy proved to be an important tool to obtain correct preoperative localization of the drainage basin, especially for melanomas located on the face and trunk.

A comparison of diagnostic imaging modalities for colorectal liver metastases.

AIMS: The aims of this study were to compare the diagnostic performance of CT scan, MR liver, PET-CT and intra-operative ultrasound (IOUS) for the detection of liver metastases against the histopathological findings, and to compare PET-CT with CT for the detection of distant disease in metastatic colorectal cancer patients eligible for surgical treatment. METHODS: A prospective study was performed that measured concordance between the number and stage of metastatic lesions identified with various preoperative imaging modalities and histology of patients undergoing surgical treatment for CRLM. RESULTS: Compared with histopathology, concordance for the number of metastatic liver lesions was moderate for CT scan (K = 0.477, 95% CI: 0.28-0.66), moderate for MR scan (K = 0.574, 95% CI: 0.39-0.75), good for FDG PET-CT (K = 0.703, 95% CI: 0.52-0.87) and very good for IOUS (K = 0.904, 95% CI: 0.81-0.99). Additional CRLM were identified intraoperatively in six patients (9.1%) with IOUS and in 7.5% of the cases surgical strategy was changed according to the new intraoperative findings. The diagnosis of intra abdominal lymph node metastatic disease was made with PET-CT only in nine patients (13.6%) DISCUSSION: Our study supports the recent recommendations of the Oncosurg Multidisciplinary International Consensus regarding the importance of high quality CT and MR in the staging of CRLM but provides further evidence for the added value of PET-CT, especially in detecting extrahepatic intra-abdominal metastatic disease that may be amenable to potentially curative resection. Despite these advances in preoperative staging, there still remains a role for IOUS in detecting additional metastases at the time of surgery.

Surgical management of hepatocellular carcinoma: is the jury still out?

INTRODUCTION: Hepatocellular carcinoma (HCC) is currently the fifth most common neoplasm worldwide. The only therapies which are capable of providing cure are hepatic resection and liver transplantation. Results from either resection or transplantation show 5-year survival rates of up to 70% in selected patients. Patient assessment is key to selecting candidates for surgery be it resection or transplantation. METHODS: A search was performed of the English Medline database for the period 1997-2006 using the MeSH headings: hepatocellular carcinoma, liver resection, and liver transplantation, with the main analysis concentrated on survival data for all patients undergoing resection or transplantation. RESULTS: There is a large variation in the mortality and recurrence rate following resection/transplantation due to differences in definition in different series. The median perioperative (30 day/in-hospital) mortality rate following resection was a median of 4.7%. The median 1, 3 and 5 year overall survival rates were 80.1%, 55% and 37.1%, respectively. The disease-free survivals at identical time intervals were 64%, 38% and 27%. The median 30 day mortality following liver transplant was 4.7% and the median 3-month mortality was 13.3%. The median overall 1, 3, and 5-year survival rates were 80.9%, 70.2% and 62%, respectively, whilst the disease-free survivals at identical time intervals were 79%, 62.5% and 54.5%. Several risk factors for overall and/or disease-free survival following resection and transplantation were found in those papers where a multivariate analysis was included. DISCUSSION: A possible algorithm would be to perform resection for patients with preserved liver function and offer transplantation to those of Child-Pugh status B or C who fit within Milan criteria. If recurrence occurred after resection or underlying liver disease progresses, salvage transplants may be performed. CONCLUSION: The current evidence base for resection and transplantation in the treatment of HCC is inadequate to provide a definite answer as to which is optimal therapy and a randomised controlled trial to compare the outcomes of resection and transplantation is now required.

Perioperative use of the LiMON method of indocyanine green elimination measurement for the prediction and early detection of post-hepatectomy liver failure.

INTRODUCTION: A non-invasive liver function monitoring system, the LiMON, has been developed that measures indocyanine green (ICG) elimination by pulse spectrophotometry. The aim was to assess the relationship between pre and post-operative ICG plasma disappearance rate (ICG PDR %/min) values and the onset of post-hepatectomy liver dysfunction. METHODS: 37 patients scheduled for major liver resections were selected. None had chronic liver disease. IGC PDR was measured preoperatively and on days 1, five and 10 postoperatively. On the same day, serum liver function tests were measured. RESULTS: The median preoperative and post-operative day 1 ICG PDR for the patients who developed liver dysfunction was significantly lower compared to those who did not (p=0.044, p=0.014). Significant correlation was found between ICG PDR measurement taken on postoperative day 1 and bilirubin level on day 1 (p=0.002), 5 (p=<0.001) and 10 (p=0.001). The same was true for ICG PDR on post-operative day 1 and albumin level on day 5 and 10 (p=0.003, p<0.001). DISCUSSION: LiMON ICG PDR measured by pulse spectophotometry is a quick, non-invasive and reliable liver function test in patients undergoing liver resection that aids in the prediction and early detection of post-hepatectomy liver dysfunction.

Liver transplantation in primary hepatic carcinoid tumor: case report and literature review.

Ninety percent of all carcinoid tumors develop in the gastrointestinal tract. Although the liver is a usual site for metastases, primary hepatic carcinoid tumors (PHCTs) are extremely rare. The diagnosis is based on histopathologic characteristics and on exclusion of a nonhepatic primary tumor. While liver transplantation (OLT) is a well-established surgical treatment in selected cases of unresectable metastatic carcinoid tumor, its use in PHCT has not been widely described. We report the case of a 50-year-old woman with unresectable PHCT treated with OLT. After 64 months, disease recurred in the liver and mesentery. Laparotomy with multiple radiofrequency ablations of liver lesions and resection of peritoneal deposits was performed; however, in the postoperative period, a fatal myocardial infarct occurred. Our case is the fourth one reported in literature. It confirms long-term survival after OLT in patients with unresectable PHTCs.