Andrew M. Smith

Pancreatic Lesions in von Hippel–Lindau Disease? A Systematic Review and Meta-synthesis of the Literature

Backgroundvon Hippel–Lindau (vHL) disease is a rare condition that leads to characteristic lesions within many different body systems. Pancreatic manifestations of vHL cover a wide spectrum of pathologies, and thus, accurate characterization and management is critical.MethodsA comprehensive and systematic text word and MeSH search of the medical literature was performed to identify studies where information regarding the prevalence, clinical characteristics, and management recommendations could be extracted.ResultsEleven studies were identified but 2 studies utilized the same data set. Of the 10 remaining studies, a total of 1,442 patients with vHL were available for analysis. Four hundred and twenty patients were examined for any type of pancreatic lesion, 362 for simple cysts or serous cystadenomas (SCAs), and 1,442 for neuroendocrine tumors (NETs). Of the 420 assessed for any pancreatic manifestation of vHL, 252 (60%) had a pancreatic lesion identified. Simple cysts that present as the sole manifestation of pancreatic disease were common and found in 169 of 362 (47%) patients. These are usually asymptomatic and do not normally require intervention. SCAs were reported in 39 of 362 (11%) patients and followed a similar benign course; resection is acceptable in symptomatic patients. NETs were identified in 211 of 1,442 (15%) patients, and 27 of 1,442 (2%) lesions behaved malignantly. Management of NETs depends on size, doubling time, and underlying genetics. Renal cell carcinoma is a characteristic in vHL, but there were no cases of pancreatic metastases identified from the included studies. Adenocarcinomas of the pancreas are not pathogenically linked to vHL.ConclusionsThis review highlights the wide spectrum and high prevalence of pancreatic lesions in vHL. Simple cysts and SCAs are benign, but NETs require careful observation due to their malignant potential.

The Prognostic Value of the Neutrophil–Lymphocyte Ratio (NLR) in Acute Pancreatitis: Identification of an Optimal NLR

IntroductionThe neutrophil–lymphocyte ratio (NLR), calculated from the white cell differential count, provides a rapid indication of the extent of an inflammatory process. The aim of this study was to investigate the prognostic value of the NLR in acute pancreatitis (AP) and determine an optimal ratio for severity prediction.Materials and MethodsNLRs were calculated on days 0, 1, and 2, and correlated with severity. Severity was defined using the Atlanta classification.ResultsOne hundred forty-six consecutive patients managed were included, 22 with severe acute pancreatitis (SAP). NLR in SAP was significantly higher than in the favorable prognosis group on all 3xa0days (day 0, 15.5 vs. 10.5; day 1, 13.3 vs. 9.8; day 2, 10.8 vs. 7.6). The optimal cut-offs from ROC curves were 10.6 (day 0), 8.1 (day 1), and 4.8 (day 2) giving sensitivities of 63–90xa0%, specificities of 50–57xa0%, negative predictive value of 89.5–96.4xa0%, positive predictive values of 21.2–31.1xa0%, and accuracies of 57.7–60xa0%.ConclusionsElevation of the NLR during the first 48xa0h of admission is significantly associated with severe acute pancreatitis and is an independent negative prognostic indicator in AP.

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review.

BACKGROUNDnA post-operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality.nnnMETHODnAn electronic search was performed of Medline (1946-2014) and EMBASE (1996-2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool.nnnRESULTSnSix eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre-operatively whereas 1 score included intra-operative and two studies post-operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16-50).nnnCONCLUSIONnThese scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed.

A matched-pair analysis of laparoscopic versus open pancreaticoduodenectomy: oncological outcomes using Leeds Pathology Protocol

BACKGROUNDnLaparoscopic pancreaticoduodenectomy (LPD) is a safe procedure. Oncological safety of LPD is still a matter for debate. This study aimed to compare the oncological outcomes, in terms of adequacy of resection and recurrence rate following LPD and open pancreaticoduodenectomy (OPD).nnnMETHODSnBetween November 2005 and April 2009, 12 LPDs (9 ampullary and 3 distal common bile duct tumors) were performed. A cohort of 12 OPDs were matched for age, gender, body mass index (BMI) and American Society of Anesthesiologists (ASA) score and tumor site.nnnRESULTSnMean tumor size LPD vs OPD (19.8 vs 19.2 mm, P=0.870). R0 resection was achieved in 9 LPD vs 8 OPD (P=1.000). The mean number of metastatic lymph nodes and total number resected for LPD vs OPD were 1.1 vs 2.1 (P=0.140) and 20.7 vs 18.5 (P=0.534) respectively. Clavien complications grade I/II (5 vs 8), III/IV (2 vs 6) and pancreatic leak (2 vs 1) were statistically not significant (LPD vs OPD). The mean high dependency unit (HDU) stay was longer in OPD (3.7 vs 1.4 days, P<0.001). There were 2 recurrences each in LPD and OPD (log-rank, P=0.983). Overall mortality for LPD vs OPD was 3 vs 6 (log-rank, P=0.283) and recurrence-related mortality was 2 vs 1. There was one death within 30 days in the OPD group secondary to severe sepsis and none in the LPD group.nnnCONCLUSIONSnCompared to open procedure, LPD achieved a similar rate of R0 resection, lymph node harvest and long-term recurrence for tumors less than 2 cm. Though technically challenging, LPD is safe and does not compromise oncological outcome.

Elevated pre-operative neutrophil to lymphocyte ratio predicts disease free survival following pancreatic resection for periampullary carcinomas

BACKGROUNDnThe pre-operative neutrophil-to-lymphocyte ratio (NLR), when ≥5 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, its prognostic value in patients with periampullary tumour has not been reported to date.nnnOBJECTIVESnTo determine the prognostic value of pre-operative NLR in terms of survival and recurrence of resected periampullary carcinomas.nnnMETHODSnThis was a retrospective cohort study of consecutive patients undergoing pancreatoduodenectomy (PD) for periampullary carcinoma (pancreatic, ampullary, cholangiocarcinoma) identified from a departmental database. The effect of NLR upon survival and recurrence was explored.nnnRESULTSnOverall median survival amongst 228 patients was 24 months (inter-quartile range [IQR]: 12-43). The median survival for those whose NLR was <5 was not significantly greater than those patients whose NLR was ≥5 (24 months [IQR: 14-42] versus 13 months [IQR: 8-48], respectively; pxa0=xa00.234). However, for those that developed recurrence, survival was greater in those with an NLR <5 at (20 months [IQR: 12-27] versus 11 months [IQR: 7-22], respectively; pxa0=xa00.038). This effect was most marked in those patients with cholangiocarcinoma (pxa0=xa00.019) whilst a trend to worse survival was seen in those with pancreatic adenocarcinoma. No effect was seen in patients with ampullary carcinoma (pxa0=xa00.516).nnnCONCLUSIONSnThis study provides further evidence that pre-operative NLR offers important prognostic information regarding disease-free survival. This effect, however, is dependent upon the tumour type amongst patients undergoing PD.

PANasta Trial; Cattell Warren versus Blumgart techniques of panreatico- jejunostomy following pancreato- duodenectomy: Study protocol for a randomized controlled trial

BackgroundFailure of the pancreatic remnant anastomosis to heal following pancreato-duodenectomy is a major cause of significant and life-threatening complications, notably a post-operative pancreatic fistula. Recently, non-randomized trials have shown superiority of a most intuitive anastomosis (Blumgart technique), which involves both a duct-to-mucosa and a full-thickness pancreatic “U” stitch, in effect a mattress stitch, over a standard duct-mucosa technique (Cattell-Warren). The aim of this study is to examine if these findings remain within a randomized setting.Methods/DesignThe PANasta trial is a randomized, double-blinded multi-center study, whose primary aim is to assess whether a Blumgart pancreatic anastomosis (trial intervention) is superior to a Cattell-Warren pancreatic anastomosis (control intervention), in terms of pancreatic fistula rates. Patients with suspected malignancy of the pancreatic head, in whom a pancreato-duodenectomy is recommended, would be recruited from several UK specialist regional centers. The hypothesis to be tested is that a Blumgart anastomosis will reduce fistula rate from 20 to 10 %. Subjects will be stratified by research site, pancreatic consistency and diameter of pancreatic duct; giving a sample size of 253 per group. The primary outcome measure is fistula rate at the pancreatico-jejunostomy. Secondary outcome measures are: entry into adjuvant therapy, mortality, surgical complications, non-surgical complications, hospital stay, cancer-specific quality of life and health economic assessments. Enrolled patients will undergo pancreatic resection and be randomized immediately prior to pancreatic reconstruction. The operation note will only record “anastomosis constructed as per PANasta trial randomization,” thus the other members of the trial team and patient are blinded. An inbuilt internal pilot study will assess the ability to randomize patients, while the construction of an operative manual and review of operative photographs will maintain standardization of techniques.DiscussionThe PANasta trial will be the first multi-center randomized controlled trial (RCT) comparing two types of duct-to-mucosa pancreatic anastomosis with surgical quality assurance.Trial registrationISRCTN52263879. Date of registration 15 January 2015.

Obstructive Jaundice Due to a Pancreatic Mass: A Rare Presentation of Acute Lymphoblastic Leukaemia in an Adult

CONTEXTnTo highlight a rare presentation of acute lymphoblastic leukaemia.nnnCASE REPORTnA 39-year-old man presented with a 4 month history of weight loss and a 6 week history of upper abdominal pain radiating to the back with nausea and vomiting. Liver function tests showed an obstructive picture, full blood count was normal and on computerised tomography there was diffuse enlargement of the pancreas, with dilatation of the common bile duct and intra hepatic biliary radicles. Four weeks after presenting, the white cell count became elevated with blasts on the blood film and bone marrow biopsy revealed a precursor B cell acute lymphoblastic leukaemia. After induction chemotherapy his jaundice resolved, the pancreatic mass reduced in size and he is now in a complete remission.nnnCONCLUSIONnAcute lymphoblastic leukaemia may mimic common causes of a pancreatic mass such as adenocarcinoma and should be considered as part of the differential diagnosis when atypical features are present.

PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer

BACKGROUNDnPancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer.nnnOBJECTIVEnTo determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer.nnnDESIGNnA multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy.nnnPARTICIPANTSnPatients with suspected pancreatic malignancy.nnnINTERVENTIONSnAll patients to undergo PET/CT following standard diagnostic work-up.nnnMAIN OUTCOME MEASURESnThe primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours.nnnRESULTSnBetween 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUVmax.) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity (pu2009=u20090.01) and specificity (pu2009=u20090.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios (pu2009<u20090.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients (pu2009=u20090.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval -0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable.nnnCONCLUSIONnPET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer.nnnSTUDY REGISTRATIONnCurrent Controlled Trials ISRCTN73852054 and UKCRN 8166.nnnFUNDINGnThe National Institute for Health Research Health Technology Assessment programme.

Prognostic value of the lymph node ratio after resection of periampullary carcinomas

BACKGROUNDnData have indicated that the lymph node ratio (LNR) may be a better prognostic indicator than lymph node status in pancreatic cancer.nnnOBJECTIVESnTo analyse the value of the LNR in patients undergoing resection for periampullary carcinomas.nnnMETHODSnA cut off value of 0.2 was assigned to the LNR in accordance with published studies. The impact of histopathological factors including a LNR was analysed using Kaplan-Meier and Cox regression methods.nnnRESULTSnIn total, 551 patients undergoing a resection (January 2000 to December 2010) were analysed. The median lymph node yield was 15, and 198 (34%) patients had a LNR > 0.2. In patients with a LNR of > 0.2, the median overall survival (OS) was 18 versus 33 months in patients with an LNR < 0.2 (P < 0.001). Univariate analysis demonstrated a LNR > 0.2, T and N stage, vascular or perineural invasion, grade and resection margin status to be significantly associated with OS. On multivariate analysis, only a LNR > 0.2, vascular or perineural invasion and margin positivity remained significant. In N1 disease, a LNR was able to distinguish survival in patients with a similar lymph node burden, and correlated with more aggressive tumour pathological variables.nnnCONCLUSIONnA LNR > 0.2, and not lymph note status, is an independent prognostic factor for OS indicating the LNR should be utilized in outcome stratification.

Lymphoepithelial cysts of the pancreas:a management dilemma.

Pancreatic lymphoepithelial cysts (LECs) are rare, benign lesions that are typically unexpected post-operative pathological findings. We aimed to review clinical, radiological and pathological features of LECs that may allow their pre-operative diagnosis. Histopathology databases of two large pancreatic units were searched to identify LECs and notes reviewed to determine patient demographic details, mode of presentation, investigations, treatment and outcome. Five male and one female patients were identified. Their median age was 60 years. Lesions were identified on computed tomography performed for abdominal pain in two patients, and were incidentally observed in four patients. Five LECs were located in the tail and one in the body of the pancreas, with a median cyst size of 5 cm. Obtaining cyst fluid was difficult and a largely acellular aspirate was yielded. The pre-operative diagnosis was mucinous cystic neoplasm in all patients. This series of patients were treated distal pancreatectomy and splenectomy. A retrospective review of radiological examinations suggested that LECs have a relatively low signal on T2 imaging and a high signal intensity on T1 weighted images. LECs appear more common in elderly males, and are typically incidental, large, unilocular cysts. Close attention to signal intensity on MRI may allow pre-operative diagnosis of these lesions.