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Background: Laparoscopic liver resection has been increasingly adopted worldwide as a result of the rapid advancement in surgical techniques and equipment. This study aims to determine the factors associated with and outcomes of open conversion after laparoscopic minor hepatectomy (LMH) based on a single center multi-surgeon experience., Methods: This is a retrospective review of the first 147 consecutive LMH performed between 2006 and April 2014 at a single institution. Data on patient demographics, pathology results, perioperative outcomes, and operative results were collected. Factors associated with open conversion were analyzed via univariate analysis and a P value <.05 was considered statistically significant., Results: LMH was performed for malignancy in 114 (77.6%) patients of which hepatocellular carcinoma (n = 82) and colorectal metastases (n = 16) were the most common pathologies. Forty-one (27.9%) patients had cirrhotic livers and 18 (15.7%) had fibrotic livers. Fifty patients (44%) had concomitant surgery in addition to LMH. Twenty (13.6%) procedures required open conversion and the most common reason was for bleeding (n = 12). Twenty-five patients (17%) experienced postoperative complications. Univariate analyses demonstrated that only individual surgeon volume (n ≤ 10 cases) [15 (24.2%) vs 5 (5.9%), P = .001] and institution volume (n ≤ 25 cases) [8 (32%) vs 12 (9.8%), P = .003] were factors associated with open conversion. Open conversion was significantly associated with increased intra-operative blood loss, increased intra-operative blood transfusion, increased postoperative morbidity, and longer postoperative stay., Conclusions: Individual surgeon and institution volumes were important factors associated with open conversion after LMH. Open conversion after LMH resulted in poorer outcomes compared to procedures that were successfully completed laparoscopically.

Background and Aims: Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER) Score, to predict outcomes of HCC patients who have undergone surgical resection., Methods: Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992-2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis., Results: A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities., Conclusion: The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.

Background: The Sendai Consensus Guidelines (SCG) were formulated in 2006 to guide the management of mucinous cystic lesions of the pancreas (CLPs) and were updated in 2012 (International Consensus Guidelines, ICG 2012). This study aims to evaluate the clinical utility of the ICG 2012 with the SCG based on initial cross-sectional imaging findings., Methods: One hundred fourteen patients with mucinous CLPs were reviewed and classified according to the ICG 2012 as high risk (HR(ICG2012)), worrisome (W(ICG2012)), and low risk (LR(ICG2012)), and according to the SCG as high risk (HR(SCG)) and low risk (LR(SCG))., Results: On univariate analysis, the presence of symptoms, obstructive jaundice, elevated serum carcinoembryonic antigen (CEA)/carbohydrate antigen (CA)19-9, solid component, main pancreatic duct ≥ 10 mm, and main pancreatic duct ≥ 5 mm was associated with high grade dysplasia/invasive carcinoma in all mucinous CLPs. Increasing number of HR(SCG) or HR(ICG2012) features was associated with a significantly increased likelihood of malignancy. The positive predictive value of HR(SCG) and HR(ICG2012) for high grade dysplasia/invasive carcinoma was 46% and 62.5% respectively. The negative predictive value of both LR(SCG) and LR(ICG2012) was 100%., Conclusion: Both the guidelines were useful in the initial cross-sectional imaging evaluation of mucinous CLPs. The ICG 2012 guidelines were superior to the SCG guidelines., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Presently, the role of liver resection (LR) for multifocal hepatocellular carcinoma (HCC) remains controversial. However, in many regions worldwide, LR remains the only treatment modality available to such patients which offers the possibility of long-term cure. The aim of this study is to determine the outcomes and prognostic factors of patients with multifocal HCC after LR., Methods: This is a retrospective analysis of 110 patients who underwent potentially curative LR for pathologically proven multifocal HCC between 2000 and 2011., Results: The median age was 64 (range, 18-84) years, and there were 88 males (80.0 %). Sixty-one patients underwent a major hepatectomy, and the overall postoperative mortality was 1.8 %. Sixty-eight patients had liver cirrhosis, of which, 58 were child's A and 10 were child's B. The 1- and 5-year overall survival (OS) was 82 and 44 %, respectively. The corresponding 1- and 5-year recurrence-free survival (RFS) was 57 and 19 %, respectively. Multivariate analysis demonstrated that the number of nodules (>3) and presence of microvascular invasion were associated with RFS. Number of nodules (>3), margin positivity, Child-Pugh status, and presence of microvascular invasion were independent prognostic factors of OS., Conclusions: LR followed by treatment of recurrences may result in reasonable long-term survival and should be considered in a selected group of patients with multifocal HCC. Number of nodules (>3), margin positivity, Child-Pugh status, and presence of microvascular invasion, but not tumor size, were independent negative predictors of OS. These findings have potential implications on the AJCC staging for multifocal HCC.

Background: The Sendai Consensus Guidelines (SCG) were formulated in 2006 and updated in Fukuoka in 2012 (FCG) to guide management of cystic mucinous neoplasms of the pancreas. This study aims to evaluate the clinical utility of the SCG and FCG in the initial triage of all suspected pancreatic cystic neoplasms., Study Design: Overall, 317 surgically-treated patients with a suspected pancreatic cystic neoplasm were classified according to the SCG as high risk (HR(SCG)) and low risk (LR(SCG)), and according to the FCG as high risk (HR(FCG)), worrisome (W(FCG)), and low risk (LR(FCG)). Cystic lesions of the pancreas (CLP) were classified as potentially malignant/malignant or benign according to the final pathology., Results: The presence of symptoms, proximal lesions with obstructive jaundice, elevated serum carcinoembryonic antigen/carbohydrate antigen 19-9 (CEA/CA 19-9), size ≥3 cm, presence of solid component, main pancreatic duct dilatation, thickened enhancing walls, and change in ductal caliber with distal atrophy were predictive of a potentially malignant/malignant CLP on univariate analyses. The positive predictive value (PPV) and negative predictive value (NPV) of HR(SCG) and HR(ICG2012) for a potentially malignant/malignant lesion was 67 and 88 %, and 88 and 92.5 %, respectively. There were no malignant lesions in both LR groups but some potentially malignant lesions such as cystic pancreatic neuroendocrine neoplasms with uncertain behavior were classified as LR., Conclusion: The updated FCG was superior to the SCG for the initial triage of all suspected pancreatic cystic neoplasms. CLP in the LR(FCG) group can be safely managed conservatively, and those in the HR(FCG) group should undergo resection.

The impact of different carcinogenic exposures on the specific patterns of somatic mutation in human tumors remains unclear. To address this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by infection with the liver fluke Opisthorchis viverrini and 101 cases caused by non-O. viverrini-related etiologies. Whole-exome sequencing (n = 15) and prevalence screening (n = 194) identified recurrent somatic mutations in BAP1 and ARID1A, neither of which, to our knowledge, has previously been reported to be mutated in CCA. Comparisons between intrahepatic O. viverrini-related and non-O. viverrini-related CCAs demonstrated statistically significant differences in mutation patterns: BAP1, IDH1 and IDH2 were more frequently mutated in non-O. viverrini CCAs, whereas TP53 mutations showed the reciprocal pattern. Functional studies demonstrated tumor suppressive functions for BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations, even within the same tumor type.

Background: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC)., Methods: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong., Results: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography., Conclusions: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

Management of Neuroendocrine liver metastases (NELM) is challenging. The presence of NELM worsens survival outcome and almost 10% of all liver metastases are neuroendocrine in origin. There is no firm consensus on the optimal treatment strategy for NELM. A systematic search of the PubMed database was performed from 1995-2010, to collate the current evidence and formulate a sound management algorithm. There are 22 case series with a total of 793 patients who had undergone surgery for NELM. The overall survival ranges from 46-86% at 5 years, 35-79% at 10 years, and the median survival ranges from 52-123 months. After successful cytoreductive surgery, the mean duration of symptom reduction is between 16-26 months, and the 5-year recurrence/progression rate ranges from 59-76%. Five studies evaluated the efficacy of a combination cytoreductive strategy reporting survival rate of ranging from 83% at 3 years to 50% at 10 years. To date, there is no level 1 evidence comparing surgery versus other liver-directed treatment options for NELM. An aggressive surgical approach, including combination with additional liver-directed procedures is recommended as it leads to long-term survival, significant long-term palliation, and a good quality of life. A multidisciplinary approach should be established as the platform for decision making.

Objective: To compare microvascular invasion (McVI) with parameters defined by the Milan criteria in predicting tumor recurrence and overall survival (OS) in patients with surgical resection (SR) for hepatocellular carcinoma (HCC)., Summary Background Data: Although the Milan criteria is discriminatory for selecting patients with good outcomes in liver transplantation and SR for HCC, it neither adequately predict tumor recurrence nor explain differences in survival for patients with good liver function. McVI is a strong indicator of intrahepatic metastasis in HCC, but its relative significance for predicting clinical outcomes compared to the Milan criteria is unclear., Methods: Patients undergoing SR with curative intent from January 2000 to March 2009 at the Singapore General Hospital were followed up for long-term outcomes till January 1, 2010. They were stratified first by the Milan criteria and then by the presence of McVI and compared relative to OS., Results: Altogether, 454 of the 515 patients received curative SR. There were stratified into 4 groups (Milan+, McVI-), (Milan+, McVI+), (Milan-, McVI-), and (Milan-, McVI+). All pair-wise comparisons between groups relative to OS were significant except (Milan+, McVI-) (OS, 90%, 73%, and 60% at 1, 3, and 5 years) with (Milan-, McVI-) (OS, 86%, 71%, and 61% at 1, 3, 5 years) and (Milan+, McVI+) with (Milan-, McVI+). Multivariate Cox regression analysis showed that McVI was predictive of OS, after which Milan status did not add additional discriminative information., Conclusions: McVI is a better predictor of tumor recurrence and OS than the Milan criteria after SR for HCC. Assessment of McVI should aid in patient selection for adjuvant treatments to improve outcomes after SR.

Introduction: This study aims to determine if the quantitative method of region-of-interest (ROI) analysis of lesion attenuation on CT may be a useful adjunct to the conventional approach of diagnosis by visual assessment in assessing tracer wash-out in hepatocellular carcinomas., Materials and Methods: From a surgical database of 289 patients from 2 institutions, all patients with complete surgical, pathological and preoperative multiphasic CT scans available for review were selected. For each phase of scanning, HU readings of lesion obtained (Lesion(arterial), Lesion(PV) and Lesion(equilibrium)) were analysed using receiver operating curves (ROC) to determine the optimal method and cut-off value for quantitative assessment of tumour wash-out (Lesion(arterial - equilibrium), Lesion(PV - equilibrium) or Lesion(peak - equilibrium))., Results: Ninety-four patients with one lesion each met the inclusion criteria. The area under the curve (AUC) values for Lesion(arterial - equilibrium) (0.941) was higher than the AUC for Lesion(pv - equilibrium) (0.484) and for Lesion(peak - equilibrium) (0.667). Based on ROC analysis, a cut-off of 10HU value for Lesion(arterial - equilibrium) would yield sensitivity and specificity of 91.5% and 80.9%, respectively. ROI analysis detected 9/21 (42.9%) of lesions missed by visual analysis. Combined ROI and visual analysis yields a sensitivity of 82/94 (87.2%) compared to 73/94 (77.7%) for visual analysis alone., Conclusion: Using a cut-off of 10 HU attenuation difference between the arterial and equilibrium phases is a simple and objective method that can be included as an adjunct to visual assessment to improve sensitivity for determining lesion wash-out on CT.

We report a case of combined heart and liver transplantation for familial amyloid polyneuropathy. This is the first such combined transplant performed in Asia, and differs from previously described cases, in that cardiopulmonary bypass was continued at partial flow during liver transplantation in our case. This was done in order to provide haemodynamic support to the cardiac graft and to protect it from the impending reperfusion insult that frequently accompanies liver transplantation. The utility of this management course is discussed, along with its actual and potential complications. We also describe the impact of a lung-protective ventilation strategy employed during cardiac transplantation.

Background: Presently, several systems for the prognostication of pancreatic endocrine neoplasms (PENs) exist and the most appropriate classification system has not been clearly defined. This study aims to validate the performance of the 2004 World Health Organization (WHO), European Neuroendocrine Tumor Society (ENETS), Memorial Sloan-Kettering Cancer Center (MSKCC), American Joint Committee for Cancer (AJCC) TNM staging and Bilimoria criteria in a cohort of patients with PENs who underwent surgery at a single institution., Methods: This study is a retrospective review of 61 consecutive patients who underwent surgical treatment for PEN. Actuarial disease-specific survival (DSS) of all 61 patients and recurrence-free survival (RFS) of 53 patients who had curative resection were analysed., Results: On univariate analyses, tumour size ≥50 mm, non-curative resection, lymph node involvement, presence of distant metastases, presence of necrosis, mitotic count ≥2/10 hpf and poor differentiation were associated with decreased DSS. Tumour size ≥50 mm, lymph node involvement, lymphovascular invasion, presence of necrosis and mitotic count ≥2/10 hpf were associated with decreased actuarial RFS. All five staging systems were useful in stratifying the 61 patients according to actuarial DSS. However, the MSKCC grading and ENETS grading systems were not statistically significant in stratifying DSS in the 61 patients. In the 53 patients who underwent curative resection, the WHO, ENETS, MSKCC, AJCC staging and the MSKCC grading systems were successful in stratifying the patients according to actuarial RFS. However, the Bilimoria scoring and ENETS grading systems were not useful in prognosticating these 53 patients., Conclusion: All five classification systems were useful for the prognostication of surgically treated PENs in our patient cohort., (© 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.)

Cholangiocarcinoma (CC) and hepatocellularcarcinoma (HCC) are two main forms of liver malignancies, which exhibit differences in drug response and prognosis. Immunohistotochemical staining for cytokeratin markers has been used to some success in the differential diagnosis of CC from HCC. However, there remains a need for additional markers for increased sensitivity and specificity of diagnosis. In this study, we have identified a p38 MAP kinase, p38delta (also known as MAPK13 or SAPK4) as a protein that is upregulated in CC relative to HCC and to normal biliary tract tissues. We performed microarray gene expression profiling on 17 cases of CC, 12 cases of adjacent normal liver tissue, and three case of normal bile duct tissue. p38delta was upregulated in 16 out of 17 cases of CC relative to normal tissue. We subsequently performed immunohistochemical staining of p38delta in 54 cases of CC and 54 cases of HCC. p38delta staining distinguished CC from HCC with a sensitivity of 92.6% and a specificity of 90.7%. To explore the possible functional significance of p38delta expression in CC, we examined the effects of overexpression and knockdown of p38delta expression in human CC cell lines. Our results indicate that p38delta is important for motility and invasion of CC cells, suggesting that p38delta may play an important role in CC metastasis. In summary, p38delta may serve as a novel diagnostic marker for CC and may also serve as a new target for molecular based therapy of this disease.

Introduction: Presently, the need for and choice of preoperative localization tests for insulinomas remain controversial. We report the results from a single institution experience whereby the management policy adopted was that of accurate preoperative localization before surgical exploration., Materials and Methods: From 1990 to 2008, 17 patients with a clinical and biochemical diagnosis of an insulinoma who underwent surgery were retrospectively reviewed. The diagnosis of all insulinomas were confirmed pathologically., Results: All tumors were localized preoperatively and an average of 2.2 preoperative localization studies including 1.4 noninvasive studies and 0.8 invasive studies were utilized per patient. Invasive localization modalities were more sensitive (92%) than noninvasive modalities in localizing insulinomas (71%). Intra-arterial calcium stimulation with hepatic venous sampling was the most sensitive invasive modality (100%), whereas magnetic resonance imaging was the most sensitive noninvasive modality (63%). Fifteen of 17 tumors (88%) were localized intraoperatively via inspection/palpation and/or intraoperative ultrasonography. Both insulinomas which were not localized intraoperatively were localized correctly to the distal pancreas via preoperative transhepatic portal venous sampling. None of the patients required a blind resection or surgical reexploration for failed localization. All 17 patients underwent complete surgical resection which included eight enucleations and nine distal pancreatectomies with a cure rate of 94% (16/17) at a median follow-up of 35 (range, 1-217) months. The postoperative morbidity and long-term outcome of enucleation was similar to distal pancreatectomy despite a higher rate of microscopic margin involvement., Conclusion: Accurate preoperative localization of insulinomas is useful as it eliminates the need for blind distal pancreatectomy and avoids reoperation. Complete surgical resection is the treatment of choice, and whenever possible, a pancreas-sparing approach such as enucleation should be adopted.

Introduction: Splenectomy is routinely performed in conventional distal pancreatectomies. Spleen removal with its possible sequelae of infections and haematological complications has prompted the development of spleen-preserving techniques. This study aimed to evaluate the safety and clinical outcomes of distal pancreatectomy with preservation of the spleen., Methods: A retrospective review of 24 consecutive patients who underwent spleen-preserving distal pancreatectomy in a tertiary care hospital was conducted., Results: There were 17 female and seven male patients, and the mean age was 47 (range 14-77) years. Median American Society of Anesthesiologists score was II (range I-III) . The indications were as follows : mucinous cystadenoma (n = 7), serous cystadenoma (n = 6), insulinoma (n = 3), intraductal papillary mucinous tumour (n = 2), pseudocyst (n = 3), papillary cystic adenoma (n = 1), neuroendocrine neoplasm (n = 1), and metastatic carcinoma of the thyroid (n = 1). Two patients developed postoperative pancreatic fistula and another two patients developed postoperative ileus with spontaneous resolution. Mean operative time was 172 (range 105-250) minutes. Mean length of postoperative hospital stay was 6.7 (range 5-11) days. There was no perioperative mortality in this series., Conclusion: Spleen-preserving distal pancreatectomy can be safely performed with low morbidity, and should be considered in the surgical management of distal pancreatic disease.

Objective: To critically analyze a large single-institution experience with distal pancreatectomy (DP), with particular attention to the risk factors, outcome, and management of the postoperative pancreatic fistula (PF)., Design: Retrospective study., Setting: Tertiary referral center., Patients: A total of 232 consecutive patients with pancreatic or extrapancreatic disease necessitating DP over 21 years., Interventions: Twenty-one patients underwent spleen-preserving DP, 117 underwent DP with splenectomy, and 94 underwent DP with multiorgan resection., Main Outcome Measures: The perioperative and postoperative data of patients who underwent DP were analyzed. This included factors associated with postoperative morbidity with particular attention to the PF (defined by the International Study Group of Pancreatic Fistula) and changing trends in operative and perioperative data during the study period., Results: The overall operative morbidity and mortality were 47% (107 patients) and 3% (7 patients), respectively. During the study period, the rates of resection increased from 3 cases to 23 per year, and increasingly these were performed for smaller and incidental lesions. The morbidity rate remained unchanged, but there was a decline in postoperative stay and the need for care in the intensive care unit. Pancreatic fistulas occurred in 72 patients (31%); 41 (18%) were grade A, 13 (6%) grade B, and 18 (8%) grade C. Increased weight, higher American Society of Anesthesiologists score, blood loss greater than 1 L, increased operation time, decreased albumin level, and sutured closure of the stump without main duct ligation were associated with a postoperative PF on univariate analysis. A DP with splenectomy was associated with a higher incidence of grade B or C PF and non-PF-related complications. Ninety-two percent of PFs were successfully managed nonoperatively. Clinical outcomes correlated well with PF grading, as evidenced by the progressive increase in outcome measures such as postoperative stay, readmissions, reoperations, radiologic interventions, and non-PF-related complications from grade A to C PFs., Conclusions: Pancreatic fistula is the most common complication after DP and its incidence varies depending on the definition applied. Several risk factors for developing a PF were identified. Splenic preservation after DP is safe. The grade of a PF correlates well with clinical outcomes, and most PFs may be managed nonoperatively.

Background: Pancreaticoduodenectomy (PD) for locally advanced stomach cancer involving duodenum or/and pancreatic head was controversial and rarely carried out. It was mainly reported from the Japanese institutions., Methods: A review of prospective database from January 2003 to December 2006 of patients who had locally advanced stomach cancer involving duodenum or/and head of pancreas that precluded curative subtotal gastrectomy who underwent diagnostic laparoscopy or exploratory laparotomy to exclude peritoneal metastatic disease. Patients were advised to undergo neoadjuvant chemotherapy before PD., Results: Seven patients underwent PD during the above-mentioned period. Only four patients had neoadjuvant chemotherapy before PD. The median operative time was 8 h (range 6-9 h). Five patients had combined tranverse colectomy done. There was no 30-day operative mortality or re-operation. Three patients developed controlled pancreatic leaks and fistulas that were successfully treated with conservative measures. The length of hospital stay was 10-53 days (median 15 days). Median survival was 13 months and 2-year survival rate was 60%. Patients who received neoadjuvant chemotherapy seemed to have better survival rate (P = 0.039)., Conclusion: Our initial experience has shown that with careful and stringent patients selection, PD for locally advanced stomach cancer can be carried out with acceptable morbidity and mortality. Early results for patients who received neoadjuvant chemotherapy showed trend towards prolonged survival. However, longer follow up and further patient recruitment are needed to confirm our initial optimistic findings.

Objectives: To determine the outcome of patients undergoing distal pancreatectomy for pancreatic adenocarcinoma., Methods: A retrospective review of 39 patients undergoing distal pancreatectomy for adenocarcinoma., Results: Thirty patients underwent surgery for ductal adenocarcinoma, 5 for malignant intraductal papillary mucinous neoplasm and 4 for mucinous cystadenocarcinoma. Malignant cystic neoplasms were significantly less likely to demonstrate perineural invasion, more likely to be well-differentiated, of lower T stage and of lower AJCC staging compared to ductal adenocarcinoma. These had a longer median disease-specific survival (42 (3-144) vs. 15 (14-16) months, p = 0.002). Eight patients underwent extended resections. These were associated with longer operating times compared to standard resections but there was no difference in surgical morbidity or mortality, blood transfusions, length of hospitalization or long-term survival. Univariate analysis demonstrated that R2 resection, size >30 mm, lymph node involvement, need for perioperative blood transfusion, serum albumin <40 g/l and platelet count <200/microl were predictors of survival for ductal adenocarcinoma., Conclusions: Malignant cystic neoplasms have less aggressive behavior and more favorable outcome compared to ductal adenocarcinoma. R2 resection, larger tumor size, lymph node involvement, perioperative transfusion, decreased serum albumin and low platelet count are factors associated with decreased survival in patients with ductal adenocarcinoma undergoing distal pancreatectomy.

Background: This study aims to determine the use of preoperative clinical, biochemical, and cross-sectional imaging features for predicting malignancy in cystic lesions of the pancreas (CLP)., Study Design: Two hundred twenty patients who underwent operations for CLP or suspected CLP were reviewed. Patients were divided into two groups, patients undergoing operations for pseudocysts and patients undergoing operations for suspected cystic neoplasms. The predictive effect of various preoperative factors on the malignant potential of CLP was evaluated., Results: Forty-four patients with a preoperative diagnosis of pseudocysts underwent operations for complications of pseudocyst. Forty-two were confirmed pathologically to have pseudocysts, but two were found, unexpectedly, to harbor malignant lesions. One hundred seventy-six patients underwent operations for suspected pancreatic cystic neoplasms. There were 70 benign, 51 potentially malignant, and 55 malignant CLP. On multivariate analysis, three factors, ie, elevated serum carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9; cyst size > 3 cm; and presence of one or more of three morphologic features, such as solid component; peripheral calcification; and main duct dilation on cross-sectional imaging were independent predictors of malignancy. Presence of two or three of these factors had a positive predictive value of 88% in predicting a premalignant or malignant CLP., Conclusions: Most pancreatic pseudocysts can be accurately diagnosed preoperatively. In patients with suspected pancreatic cystic neoplasms, elevated serum CEA or carbohydrate antigen 19-9, cyst size > 3 cm, and presence of suspicious morphologic features on imaging are predictors of potentially malignant or malignant CLP. Patients with a high likelihood of a potentially malignant or malignant lesion based on these three factors should undergo operation without additional investigations.

Introduction: The aim of this study is to report an update of the surgical experience at a single institution with these unusual tumors., Methods: Sixteen consecutive patients who underwent surgery for a pathologically confirmed solid pseudopapillary neoplasm (SPPN) were retrospectively reviewed., Results: Fifteen of the patients were female and the median age at diagnosis was 30 years (range, 14-53 years). Abdominal and back pain were the most common presenting symptoms. The tumors appeared on cross-sectional imaging as solid and cystic (n = 14) or cystic (n = 2) masses. The median tumor size was 9.5 cm (range, 5.0-24.0 cm). All 16 patients had curative resections including 3 pancreaticoduodenectomies and 13 distal pancreatectomies. Three patients required extended resections including pancreaticoduodenectomy with portal vein resection, distal pancreatectomy with tranverse colectomy, and distal pancreactomy with omentectomy. Two of the resections were R1 whereas 14 were R0. All patients were alive and disease-free at a median follow-up of 43 months (range, 3-186 months)., Conclusion: SPPNs should be considered in young women presenting with a large solid-cystic pancreatic mass. Aggressive en bloc resection should always be attempted including resection of concomitant metastases as patients demonstrate excellent long-term survival even in the presence of distant spread., (Copyright 2007 Wiley-Liss, Inc.)

Background: Currently, the management strategy of pancreatic cyst (PC) remains controversial because of the inability to diagnose this type of cyst accurately and the limited knowledge of its natural history. Previously, many clinicians have advocated an aggressive resectional policy. This approach is no longer appropriate, and the number of PCs detected incidentally has increased. This study reviews the present literature and attempts to provide a management algorithm of pancreatic cysts based on currently available evidence., Methods: A Medline search was conducted to identify studies investigating PC, with particular emphasis placed on studies addressing its diagnosis and management. Additional articles were obtained from the reference lists of key articles and recent reviews., Comments: Based on current evidence, the optimal management of PC remains an art and should be individualized based on the risk-benefit ratio of surgery, which is influenced by multiple factors, such as the patient's potential life expectancy, surgical risk; and malignant potential of the cyst. Our proposed management algorithm is based on an individual's predicted risk-benefit ratio of surgery. Prospective evaluation of the algorithm is needed to determine its integrity.

Liver resection is commonly performed for solitary hepatocellular carcinoma (HCC) in well-compensated cirrhotic and noncirrhotic patients. Data concerning exacerbation of chronic hepatitis B (ECHB) post-liver resection are scant. To determine the incidence, risk factors, and clinical outcomes of ECHB in patients who underwent hepatic resection for HCC. The methods consisted of a retrospective review of consecutive patients with chronic hepatitis B virus (HBV) infection who had undergone liver resection for HCC from January 2002 to December 2004. Seventy-seven patients underwent 82 liver resections; the mean age was 58.0 +/- 12.1 years; 87% male; 20% hepatitis B e-antigen positive. Incidence of all causes of postoperative hepatitis was 25.6% (n = 21), and ECHB was 8.5% (n = 7). Both groups had their peak alanine aminotransferases, 231.0 IU/L (74-1,400) and 312 IU/L (147-1,400), respectively, observed at day 84 postresection. Three patients died as a result of ECHB within 4 months postsurgery. One- and 2-year survival rates were poorest for the ECHB group at 42.9 and 21.4%, compared with those with postoperative hepatitis due to other causes at 60.3 and 45.2% and those without postoperative hepatitis at 87.7 and 73.5% (p < 0.001). Liver resection for HCC in patients with chronic HBV infection carries a risk for ECHB, and affected patients have poorer clinical outcomes. There is a need for close monitoring of these patients preoperatively and in the early postoperative period.

The purpose of the study was to reliably identify an early stage of diabetic polyneuropathy (DPN) by measuring injury to epidermal nerve fibers. We compared intraepidermal nerve fiber density (IENFD) at the ankle and thigh of 29 diabetic subjects who had no clinical or electrophysiological evidence of small- or large-fiber neuropathy to that of 84 healthy controls. The mean ankle IENFD of diabetic subjects was 9.1+/-5.0 mm and that of controls, 13.0+/-4.8 mm (P<0.001). The thigh IENFD did not differ significantly. The IENFD ratio (thigh IENFD divided by ankle IENFD) was 2.39+/-1.30 in diabetic subjects and 1.77+/-0.58 in controls (P<0.001), indicating a length-dependent reduction of IENFD in diabetics. Ankle IENFD remained significantly lower and the IENFD ratio higher in diabetic subjects after adjusting for age. Two subjects had parasympathetic dysfunction, two had retinopathy, and two early nephropathy. Age, height, weight, duration of diabetes, and average HbA1c did not influence IENFD among diabetic subjects. We used receiver operating characteristic (ROC) curves to describe and compare the utility of various threshold values of ankle IENFD and IENFD ratio for the diagnosis of early DPN. The sensitivity and specificity of diagnosing DPN using ankle IENFD of less than 10 mm were 72.4% and 76.2%, respectively. Thus, asymptomatic diabetics have a measurable, length-dependent reduction of distal epidermal nerves. Analogous to microalbuminuria in diabetic nephropathy, reliable identification and quantitation of nascent diabetic neuropathy may have potential therapeutic implications.

Hepatocellular carcinoma (HCC) is the commonest primary liver tumour. Recurrences are common in the liver although extrahepatic metastases can occur and frequently involve the adrenals. When this occurs in the right adrenal gland, it can be confused with an exophytic HCC arising from the posterior surface of the liver. The distinction between a primary HCC and a metastasis is important but can be difficult in this clinical setting. We report a 52-year-old man with recurrent HCC presenting as an "exophytic" posterior liver surface lesion that was actually a right adrenal metastasis. Although right-sided adrenal metastases of HCC can be difficult to distinguish from intrahepatic recurrences, even with modern diagnostic imaging, management either way involves surgical exploration and resection whenever possible.

Introduction: Despite formal definitions of mucinous cystic neoplasms (MCNs) and intraductal papillary neoplasms (IPMNs) by the World Health Organization (WHO) and Armed Forces Institute of Pathology (AFIP), several controversies with regard to MCNs remain. The aim of this review was to determine the clinicopathological features of MCNs defined by ovarian-type stroma (OS) as proposed by the WHO and AFIP and to compare them with MCNs defined by less stringent criteria., Methods: A MEDLINE search was conducted to identify English-language articles on pancreatic MCNs from 1996 to 2005. Twenty-five studies were identified. The studies were divided into 2 groups: group A included 10 studies with 344 patients whereby the presence of OS was a criteria for the diagnosis of MCNs, and group B, included 15 studies comprising 761 patients whereby the presence of OS was not mandatory for the diagnosis of MCNs., Results: Patients in group A (MCNs as defined by OS) were almost always female (99.7%), with a mean age of 47 (range, 18-95) years. MCNs were located predominantly in the body or tail of the pancreas (94.6%) and had a mean size of 8.7 cm (range, 0.6-35 cm); 76% were symptomatic, 6.8% demonstrated ductal communication, and 27% were malignant. At a mean follow-up of 57.5 (range, 1-264) months and 43 (range, 2-257) months after surgery, 97.9% of benign and 61.9% of malignant neoplasms were disease free, respectively. Patients in group B were older and had a higher proportion of males. Neoplasms were more evenly distributed in the pancreas, were smaller, communicated more frequently with the pancreatic duct, and were composed of a higher proportion of malignant tumors compared with group A. Their clinicopathological features were intermediate between those of group A and patients with IPMN., Conclusion: Pancreatic MCNs with OS have unique and distinct clinicopathological features. MCNs should be defined by the presence of OS, as it is the most reliable way of distinguishing MCNs from IPMN. Adoption of "looser" criteria will result in misclassification of some IPMNs as MCNs.

Background: Although an aggressive resectional approach toward pancreatic cysts has been advocated in the past, many clinicians now deem this therapeutic strategy impractical given the rapidly increasing incidence of incidentally detected pancreatic cystic lesions. The aim of this study was to review the aggressive resectional policy toward pancreatic cysts adopted at our institution during the past 15 years., Methods: One hundred nine consecutive patients who underwent surgical resection of a cystic lesion of the pancreas during a 15-year period were retrospectively reviewed. To determine subsets of patients at lower risk of having a malignant cyst, the clinicopathologic features (in particular, the malignant potential) of these patients were compared as a function of 3 variables, ie, presence of symptoms, patient age, and cyst size, using univariate analyses. Results were expressed as median and range and P < .05 was considered statistically significant., Results: Forty-three (39%) of 109 patients were asymptomatic. Incidental cysts were smaller (28 [10 to 240] vs 59 [10 to 200] mm, P < .001) and were found in older patients (55.0 [18 to 77] vs 45.5 [14 to 82] years, P = .003). Overall, 14% of asymptomatic cysts, versus 35% of symptomatic cysts, were malignant (P = .016). Incidental cysts were also less likely to be premalignant or malignant compared with symptomatic cysts (47% vs 70%, P = .015). Twenty (18%) patients were elderly (73.0 [70 to 82] years old). Elderly patients had a more equal sex distribution (45% vs 76% female, P = .005) and had smaller cysts (26 [10 to 200] vs 55 [10 to 240] mm, P = .003) that involved the head of the pancreas more frequently (8 [40%] vs 17 [19%], P = .045) compared with their younger counterparts. The cohort of elderly patients also had a higher median American Society of Anesthesiologists score (2 [1 to 3] vs 1 [1 to 3], P < .001), and a higher proportion had undergone a "more" major procedure (Whipple's or total pancreatectomy) (55% vs 18%, P < .001). Not unexpectedly, surgical morbidity in the elderly was significantly higher (10 [50%] vs 24 [27%], P = .045). The operative mortality in both groups was not significantly different (1 [5%] vs 1 [1%], P = .324). The proportion of premalignant or malignant lesions in elderly patients was also similar to that in younger patients (11 [55%] vs 55 [62%], P = .574). The size of a cyst in asymptomatic patients had no correlation with its potential for malignancy., Conclusions: Reliance on preoperative characteristics alone such as the presence of symptoms, cyst size, and patient age are not sufficiently reliable in determining the malignant potential and thus management approach toward pancreatic cysts.

Introduction: The preoperative distinction between serous cystic neoplasms (SCNs) and mucinous cystic neoplasms (MCNs) is essential, as all MCNs are considered malignant or potentially malignant and should be surgically resected, whereas SCNs are almost always benign. However, the radiologic distinction between SCNs and MCNs is frequently difficult especially with serous oligocystic adenoma (SOA), a morphologic variant of SCN, as both SOA and MCN appear on cross-sectional imaging as a solitary macrocystic lesion in the pancreas. We reviewed all SOAs managed at our institution to determine if any clinicopathologic features would prove useful for establishing a preoperative diagnosis., Methods: Over a 15-year period, 64 patients with a pathologically confirmed diagnosis of a pancreatic cystadenoma or cystadenocarcinoma treated at Singapore General Hospital were retrospectively reviewed. There were 27 MCNs and 37 SCNs including 12 SOAs. In addition, 40 cases of SOA previously reported in the literature were reviewed and analyzed together with the 12 patients, making this a series of 52 SOAs., Results: In our experience, SOAs comprised 32.4% of the SCNs, and females predominated (7/12). The median age of the patients was 42.5 years (range 22-74 years), and only 4 of the 12 patients were symptomatic. Most of the cysts were located in the body or tail of the pancreas (9/12), and the median cyst size was 52.5 mm (range 10-190 mm). When the clinicopathologic features of SOAs and serous microcystic adenomas (SMAs) were compared, there was no difference between the patients with SOAs and SMAs in terms of age, sex, presence of symptoms, cyst size, or site of the lesion. However, SOAs occurred in the women less frequently (67.3% vs. 96.3%, P=0.004), were smaller [40 mm (range 10-190 mm) vs. 95 mm (range 25-180 mm), P<0.001], and occurred more commonly in the head of the pancreas [25 (48.1%) vs. 2(7.4%)] compared to MCNs. None of the SOAs were frankly malignant compared to the 29.6% of MCNs that were., Conclusions: SOAs and SMAs have similar clinicopathologic features. On the other hand, SOAs differ from MCNs by their relatively higher male/female ratio, higher frequency of tumors occurring in the head of the pancreas, and smaller cyst size. Knowledge of these distinguishing clinical features when used in combination with other diagnostic modalities such as endoscopic ultrasonography/fine-needle aspiration will enable clinicians to better differentiate these two pathologic entities preoperatively.

Background: The role of metastectomy for colorectal and neuroendocrine liver secondaries is well established. Significant palliation and survival have been reported after aggressive surgical resection. However, the role of liver resection for secondaries from other primary tumours is less well defined. In this study, we aim to describe our experience, including indications and selection criteria, operative strategy and clinical outcome of liver resection, for non-colorectal, non-neuroendocrine liver metastases., Methods: A review of prospectively collected operative database was conducted and patients who underwent liver resection of secondaries from non-colorectal, non-neuroendocrine primary tumours were studied. Eighteen patients were included in the study. There were 4 men and 14 women with a median age of 48 years (range, 37-78 years)., Results: Liver resection was carried out either for cure or for palliation of debilitating symptoms. Selection criteria included: (i) absence of extrahepatic disease and (ii) functional status of the liver and volume of remnant liver after hepatectomy. The median follow up was 24 months (range, 7-81 months) for 17 patients, excluding the one who defaulted after surgery. Cancer-specific survival and recurrence-free interval was calculated from the date of hepatectomy. Liver resection was considered curative in 13 patients. There was no 30-day mortality in this cohort of patients. The median recurrence-free survival time was 13 months (95% confidence interval (CI), 8-18 months). The median follow-up time for the 12 patients was 23.5 months (range, 7-35 months). Only five patients died due to cancer-specific causes and one died from acute myocardial infarction. The median cancer-specific survival time was 30 months (95% CI, 25-35 months). The 2-year survival rate was 77.1% (95% CI, 48.9-100%)., Conclusion: The results are encouraging and suggest that with appropriate selection criteria, there is a role for metastectomy of non-colorectal, non-neuroendocrine liver secondaries.

Background: Spontaneous rupture of hepatocellular carcinoma (HCC) is a catastrophic surgical emergency with high mortality rates. The aim of this study is to determine the factors associated with the prognosis and to assess the outcome of different management strategies., Methods: A retrospective study of 34 consecutive patients with spontaneous rupture of HCC was conducted from January 1996 to January 2004. Clinical, biochemical and operative factors influencing 30-day mortality were analysed., Results: In our study, 30-day mortality rate was 32% (n = 11). Presence of cirrhosis, Child's C status, shock on admission, higher blood transfusion requirement, raised alpha-fetoprotein, raised alkaline phosphatase, raised aspartate transaminase, and raised indocyanine green at 15 min were all associated with increased risk of 30-day mortality on univariate analysis (P < 0.05). On multivariate analysis, only shock on admission (P = 0.001) and higher blood transfusion requirement (P = 0.01) were significant independent factors affecting early mortality. Surgical intervention was associated with a better 30-day survival as compared with medical therapy or transarterial embolization. The median survival time of patients undergoing curative resection was significantly longer than that of patients who had surgery for haemostasis only (420 vs 205 days). The overall median survival was 161 days., Conclusions: Spontaneous rupture of HCC is a potentially salvageable complication of HCC. Poor prognosis is associated with poor liver reserve, advanced disease and severity of haemorrhage. Shock and blood transfusion requirement are the only independent factors affecting early mortality.

Aim: Pancreatic endocrine neoplasms (PENs) may occasionally manifest as cystic lesions of the pancreas. The aim of this study is to report our experience with cystic PENs and to compare their clinico-pathological features with their solid counterparts., Materials and Methods: From 1990 to 2004, 38 patients with PENs were reviewed. Six of these tumours appeared on radiological imaging as a cystic lesion of the pancreas., Results: Of the 38 patients with a PEN, 21 of the patients were female and with a median age of 54.5 (range, 33-83) years. Sixteen patients had functional endocrine tumours of which insulinoma was the most common. The six patients with cystic PEN had a median age of 55.5 (range, 41-70) years and half were female. Cystic PENs were significantly larger [48 (range, 25-170) mm vs 19 (range, 3-120) mm, P = 0.013] and were less likely to be benign (0 vs 50%, P = 0.017) compared to their solid counterparts. There was no difference between cystic and solid PENs in terms of age, sex, presence of symptoms, proportion of functioning tumours and location of tumours within the pancreas., Conclusion: Cystic PENs share many clinico-pathological features with solid PENs. These differ only in the cystic appearance and tend to be of a larger size. Hence, these findings suggest that cystic and solid PENs are unlikely to be distinct pathological entities but are likely to be morphological variants of the same entity.

Background/aims: The occurrence of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary neoplasm (IPMN) of the pancreas has rarely been reported. We describe our experience with 3 patients with this association and review the existing literature., Methods: From 1990 to 2005, 65 patients who underwent surgery for a PEN or IPMN were retrospectively reviewed. Forty-three patients had a PEN, 19 had an IPMN and 3 had both an IPMN and PEN. The 3 patients with concomitant IPMN and PEN are the focus of the current study and their clinicopathological features are reported together with 7 patients previously reported in the literature., Results: There were 10 patients with a median age of 62 years (range 40-73). The male:female ratio was equal. Seven of 10 patients were symptomatic and the most common symptoms were abdominal pain (n = 5), jaundice (n = 2) and loss of weight (n = 2). The median size of the endocrine neoplasms was 14 mm (range 2-30) and they occurred in the head (n = 3), body (n = 2) and tail (n = 5). Seven of the PENs were classified as benign, 2 were potentially malignant, and 1 was frankly malignant with lymph node involvement. None of the endocrine neoplasms were functioning. The IPMNs were found in the tail (n = 4), head (n = 3), head and body (n = 1), body (n = 1) and the entire pancreas (n = 1). Five of these neoplasms were benign, 2 were borderline and 3 were malignant (1 carcinoma in situ)., Conclusion: The occurrence of concomitant IPMN and PEN is more frequent than would be expected. However, it is difficult in the present analysis to determine if this association is more than just fortuitous., (Copyright 2006 S. Karger AG, Basel and IAP.)

Aim: To compare the clinico-pathological features of intraductal papillary mucinous cystic tumours (IPMT) and mucinous cystic tumours (MCT) of the pancreas., Methods: Eighteen patients with IPMT and 18 with MCT who underwent surgical resection between 1990 and 2004 were retrospectively reviewed. Their clinico-pathological features were compared using univariate analysis. Statistical analyses of potential predictive factors of malignancy for each of these two groups were also conducted., Results: Patients with IPMT were found to be older (64+/-10 vs 43+/-18 years, p<0.001) and were predominantly male (male:female ratio, 5:4 vs 1:17, p=0.003) as compared to patients with MCT. MCTs were found in the body-tail region (100%) whereas IPMTs were more evenly distributed (50% in the head) (p=0.001). Pathologically, IPMT was distinct from MCT in terms of size (3.8+/-3.2 vs 9.1+/-4.4 cm, p=0.001), association with secondary pancreatitis (50 vs 0%, p=0.011), communication with the pancreatic duct (94 vs 0%, p<0.001), presence of a dilated main pancreatic duct (61 vs 0%, p<0.001) and the presence of ovarian-type stroma (0 vs 44%, p=0.003)., Conclusion: IPMT and MCT are distinct clinico-pathological entities. This distinction is important as management and outcome of these entities may differ.

Objective: To determine whether first-line treatment with percutaneous or surgical drainage of liver abscesses larger than 5 cm results in better clinical outcome., Summary Background Data: Pyogenic liver abscesses larger than 5 cm are currently treated by intravenous antibiotics and either percutaneous (PD) or surgical drainage (SD). Percutaneous techniques have been increasingly performed in place of open drainage as first-line treatment. This paradigm shift has been fueled by the drive for low-risk and less-invasive procedures and the surgical option being reserved for percutaneous failures. Yet there is a lack of data to support percutaneous drainage over open surgical drainage as first-line treatment., Methods: Over a 3-year period, 80 patients with liver abscesses larger than 5 cm amenable to PD and SD were included in the study. This situation was possible as 1 team of surgeons favored the use of PD and 1 team favored the use of SD as first-line treatment. The treatment outcomes in both groups were compared, and clinical end-points included time to defervescence of fever, failure of treatment, secondary procedures, hospital stay, morbidity, and mortality., Results: PD was performed in 36 patients and SD in 44 patients as first-line treatment. Clinical, laboratory, and abscess parameters were comparable in both groups. Sixty-four of 80 patients (80%) had multiloculated abscess. The time to defervescence of fever was not statistically significant (PD versus SD, 4.85 versus 4.38 days; P = 0.09). However, SD had less treatment failures (3 versus 10, P = 0.013), less requirement for secondary procedures (5 versus 13, P = 0.01), and shorter length of hospital stay (8 versus 11 days, P = 0.03). There was no difference in morbidity or mortality rates., Conclusions: The results of our study show that for large liver abscesses more than 5 cm, SD provides better clinical outcomes than PD in terms of treatment success, number of secondary procedures, and hospital stay with comparable morbidity and mortality rates. SD should be considered as first-line treatment of large liver abscesses.

This pictorial essay aims to show the clinical mimicry of hepatocellular carcinoma (HCC) and its diagnostic difficulty, and to create awareness among clinicians and radiologists of potential diagnostic pitfalls. A selected consecutive series of hepatectomies with proven HCC over a three-year period, identifying clinical presentation, blood results and imaging of patients with difficult preoperative diagnosis, was reviewed. The imaging of the focal liver lesions is presented pictorially with pathological correlation. Six patients out of 34 cases of resected HCC were diagnosed to have benign (three liver abscesses) and neoplastic (one Klatskin tumour, one colorectal liver metastasis, one gallbladder cancer) conditions. Compared to the rest in the series, all six patients had normal serum alpha fetoprotein levels. On computed tomography, the mosaic appearance of HCC mimicked locules of liver abscess while HCC with pseudocapsule (rim enhancement) was misdiagnosed as unilocular abscess or metastatic lesion. Arterial enhancement on contrast-enhanced triphasic computed tomography was useful in diagnosis of HCC. In summary, HCC can mimic benign and neoplastic clinical syndromes. The diagnosis of liver abscess can delay subsequent diagnosis of HCC and potentially complicate the treatment plan. Contrast-enhanced triphasic computed tomography or magnetic resonance imaging is useful to resolve difficult diagnosis, especially when the serum alpha fetoprotein level is not raised.