Early Prediction of Post-hepatectomy Liver Failure in Patients Undergoing Major Hepatectomy Using a PHLF Prognostic Nomogram.

BACKGROUND: Liver resection (LR) is the main modality of treatment for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). Post-hepatectomy liver failure (PHLF) remains the most dreaded complication. We aim to create a prognostic score for early risk stratification of patients undergoing LR. METHODOLOGY: Clinical and operative data of 472 patients between 2000 and 2016 with HCC or CRLM undergoing major hepatectomy were extracted and analysed from a prospectively maintained database. PHLF was defined using the 50-50 criteria. RESULTS: Liver cirrhosis and fatty liver were histologically confirmed in 35.6% and 53% of patients. 4.7% (n = 22) of patients had PHLF. A 90-day mortality was 5.1% (n = 24). Pre-operative albumin-bilirubin score (p = 0.0385), prothrombin time (p < 0.0001) and the natural logarithm of the ratio of post-operative day 1 to pre-operative serum bilirubin (SB) (ln(POD1Bil/pre-opBil); p < 0.0001) were significantly independent predictors of PHLF. The PHLF prognostic nomogram was developed using these factors with receiver operating curve showing area under curve of 0.88. Excellent sensitivity (94.7%) and specificity (95.7%) for the prediction of PHLF (50-50 criteria) were achieved at cut-offs of 9 and 11 points on this model. This score was also predictive of PHLF according to PeakBil > 7 and International Study Group for Liver Surgery criteria, intensive care unit admissions, length of stay, all complications, major complications, re-admissions and mortality (p < 0.05). CONCLUSIONS: The PHLF nomogram ( https://tinyurl.com/SGH-PHLF-Risk-Calculator ) can serve as a useful tool for early identification of patients at high risk of PHLF before the 'point of no return'. This allows enforcement of closer monitoring, timely intervention and mitigation of adverse outcomes.

Outcome of distal pancreatectomy for pancreatic adenocarcinoma.

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.

Predictors of post-hepatectomy liver failure in patients undergoing extensive liver resections for hepatocellular carcinoma.

BACKGROUNDS/AIMS: To determine the prevalence of post-hepatectomy liver failure/insufficiency (PHLF/I) in patients undergoing extensive hepatic resections for hepatocellular carcinoma (HCC) and to assess the predictive value of preoperative factors for post-hepatectomy liver failure or insufficiency (PHLF/I). METHODS: A retrospective review of patients who underwent liver resections for HCC between 2001 and 2013 was conducted. Preoperative parameters were assessed and analyzed for their predictive value of PHLF/I. Definitions used included the 50-50, International Study Group of Liver Surgery (ISGLS) and Memorial Sloan Kettering Cancer Centre (MSKCC) criteria. RESULTS: Among the 848 patients who underwent liver resections for HCC between 2001 and 2013, 157 underwent right hepatectomy (RH) and extended right hepatectomy (ERH). The prevalence of PHLF/I was 7%, 41% and 28% based on the 50-50, ISGLS and MSKCC criteria, respectively. There were no significant differences in PHLF/I between RH and ERH. Model for End-Stage Liver Disease (MELD) score and bilirubin were the strongest independent predictors of PHLF/I based on the 50-50 and ISGLS/MSKCC criteria, respectively. Predictive models were developed for each of the criteria with multiple logistic regression. CONCLUSIONS: MELD score, bilirubin, alpha-fetoprotein and platelet count showed significant predictive value for PHLF/I (all p<0.05). A composite score based on these factors serves as guideline for physicians to better select patients undergoing extensive resections to minimize PHLF.

Positron emission tomography with 2-deoxy-2-[18f] fluoro-D-glucose in the detection of malignancy in intraductal papillary mucinous neoplasms of the pancreas.

A 79-year-old Indian male was admitted with upper abdominal discomfort of 1-year duration which was associated with loss of weight and appetite. Serum tumor markers, including carcinoembryonic antigen and carbohydrate antigen 19-9, were within normal limits. A computed tomographic scan demonstrated a cystically dilated and tortuous pancreatic duct measuring 1.9 cm, suggestive of an intraductal papillary mucinous neoplasm. Fusion positron emission tomography/computed tomography with 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography (FDG-PET/CT) which was subsequently performed confirmed a metabolically active focus within the pancreatic head mass with a standard uptake value (SUVmax) of 3.5 compatible with carcinoma. A total pancreatectomy was performed and the final histology demonstrated a main-duct type intraductal papillary mucinous neoplasm with a focus of high-grade dysplasia compatible with carcinoma-in-situ. These images illustrate the emerging utility of FDG-PET/CT in the preoperative detection of malignancy in intraductal papillary mucinous neoplasm.

Follicular dendritic cell sarcoma of the liver with metachronous small bowel and splenic metastases: a case report and literature review.

Follicular dendritic cell sarcoma (FDCS) of the liver is an extremely rare disease, accounting for a mere 0.4% of all soft tissue sarcomas. FDCS most commonly involves lymph nodes but also affects extranodal sites such as the gastrointestinal system, oral cavity, liver, spleen and pancreas, albeit less commonly. It is widely considered a low-to-intermediate grade malignancy. We report a case of FDCS with metachronous involvement of the liver, small intestines and spleen, its imaging, histological findings and its management.

Cystic lesions of the pancreas: an appraisal of an aggressive resectional policy adopted at a single institution during 15 years.

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.

Utility of fusion CT-PET in the diagnosis of small pancreatic carcinoma.

Pancreatic carcinoma has a poor prognosis and early detection is essential for potentially curative resection. Despite the wide array of diagnostic tools, preoperative detection of small pancreatic carcinomas remains difficult. We report a case of small pancreatic carcinoma of the head of pancreas with indeterminate findings on US, ERCP, MRI and EUS which was successfully diagnosed via fusion CT-PET. This case illustrates the utility of CT-PET in the diagnosis of patients with small pancreatic carcinoma with equivocal findings on conventional diagnostic modalities.

On developing a pragmatic strategy for clinical trials: A case study of hepatocellular carcinoma.

Randomised controlled trials (RCTs) with sufficiently high statistical power are not always feasible for patients when the administration of the treatment is burdensome. Nevertheless, useful information concerning the relative effectiveness of the Test and Standard therapies, may be gleaned from under powered trials, non-randomised comparative studies and/or clinician's beliefs: the latter possibly additionally providing some suggestion of the strength of evidence required in order to adopt the Test therapy into clinical practice. In such circumstances, a Bayesian synthesis may be useful in quantifying the evidence of treatment effectiveness. In this article, we aim to present a Bayesian approach for synthesizing the cumulative evidence of the use of adjuvant hepatic intra-arterial iodine-131-lipiodol (I131L) following curative resection in hepatocellular carcinoma (HCC) patients. We constructed a posterior distribution using the information from two small RCTs, three non-randomised comparative studies, three single arm studies and the views of investigators on the use of I131L. This distribution enables calculation of the probability that the Test therapy is more effective than the Standard by a pre-stipulated amount. If this is very high, then for example, one may conclude the Test may replace the Standard therapy. If it is not, then the Standard would be retained for clinical use. Despite a strong early indication of the effectiveness of I131L, the evolving evidence over a 10-year period became more sceptical of its value. Although highly recommended, difficulties of implementing a Bayesian approach in this context are highlighted.

Biliary-enteric transanastomotic stenting with Intestofix.

BACKGROUND: Biliary-enteric transanastomotic stenting is useful under adverse local conditions or when small-calibre bile ducts are encountered. METHODS: A commercially available feeding jejunostomy kit, Intestofix, was inserted transjejunally through the blind loop of a Roux-en-Y hepatico-jejunostomy. CONCLUSIONS: The stent splinted the anastomosis to reduce biliary leaks and may help to prevent subsequent stricture formation.

Rectal arterio-portal fistula: an unusual cause of persistent bleeding per rectum following a proximal spleno-renal shunt.

Gastrointestinal arterio-venous malformations are a known cause of gastrointestinal bleeding. We present a rare case of persistent rectal bleeding due to a rectal arterio-portal venous fistula in the setting of portal hypertension secondary to portal vein thrombosis. The portal hypertension was initially surgically treated with splenectomy and a proximal splenorenal shunt. However, rectal bleeding persisted even after surgery, presenting us with a diagnostic dilemma. The patient was re-evaluated with a computed tomography mesenteric angiogram which revealed a rectal arterio-portal fistula. Arterio-portal fistulas are a known but rare cause of portal hypertension, and possibly the underlying cause of continued rectal bleeding in this case. This was successfully treated using angiographic localization and super-selective embolization of the rectal arterio-portal venous fistula via the right internal iliac artery.The patient subsequently went on to have a full term pregnancy. Through this case report, we hope to highlight awareness of this unusual condition, discuss the diagnostic workup and our management approach.

Ampullary carcinoma: effect of preoperative biliary drainage on surgical outcome.

AIM: To evaluate the influence of preoperative biliary drainage on morbidity and mortality after surgical resection for ampullary carcinoma. METHODS: We analyzed retrospectively data for 82 patients who underwent potentially curative surgery for ampullary carcinoma between September 1993 and July 2007 at the Singapore General Hospital, a tertiary referral hospital. Diagnosis of ampullary carcinoma was confirmed histologically. Thirty-five patients underwent preoperative biliary drainage (PBD group), and 47 were not drained (non-PBD group). The mode of biliary drainage was endoscopic retrograde cholangiopancreatography (n = 33) or percutaneous biliary drainage (n = 2). The following parameters were analyzed: wound infection, intra-abdominal abscess, intra-abdominal or gastrointestinal bleeding, septicemia, biliary or pancreatic leakage, pancreatitis, gastroparesis, and re-operation rate. Mortality was assessed at 30 d (hospital mortality) and also long-term. The statistical endpoint of this study was patient survival after surgery. RESULTS: The groups were well matched for demographic criteria, clinical presentation and operative characteristics, except for lower hemoglobin in the non-PBD group (10.9 +/- 1.6 vs 11.8 +/- 1.6 in the PBD group). Of the parameters assessing postoperative morbidity, incidence of wound infection was significantly less in the PBD than the non-PBD group [1 (2.9%) vs 12 (25.5%)]. However, the rest of the parameters did not differ significantly between the groups, i.e. sepsis [10 (28.6%) vs 14 (29.8%)], intra-abdominal bleeding [1 (2.9%) vs 5 (10.6%)], intra-abdominal abscess [1 (2.9%) vs 8 (17%)], gastrointestinal bleeding [3 (8.6%) vs 5 (10.6%)], pancreatic leakage [2 (5.7%) vs 3 (6.4%)], biliary leakage [2 (5.7%) vs 3 (6.4%)], pancreatitis [2 (5.7%) vs 2 (4.3%)], gastroparesis [6 (17.1%) vs 10 (21.3%)], need for blood transfusion [10 (28.6%) vs 17 (36.2%)] and re-operation rate [1 (2.9%) vs 5 (10.6%)]. There was no early mortality in either group. Median survival was 44 mo (95% CI: 34.2-53.8) in the PBD group and 41 mo (95% CI: 27.7-54.3; P = 0.86) in the non-PBD group. CONCLUSION: Biliary drainage before surgery for ampullary cancer significantly reduced postoperative wound infection. Overall mortality was not influenced by preoperative drainage.

How useful are clinical, biochemical, and cross-sectional imaging features in predicting potentially malignant or malignant cystic lesions of the pancreas? Results from a single institution experience with 220 surgically treated patients.

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.

Critical appraisal of 232 consecutive distal pancreatectomies with emphasis on risk factors, outcome, and management of the postoperative pancreatic fistula: a 21-year experience at a single institution.

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.

Pancreatic cysts: a proposed management algorithm based on current evidence.

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.

Clinicopathological features of patients with concomitant intraductal papillary mucinous neoplasm of the pancreas and pancreatic endocrine neoplasm.

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.

Pancreatic serous oligocystic adenomas: clinicopathologic features and a comparison with serous microcystic adenomas and mucinous cystic neoplasms.

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.