Christopher B. Nahm

Focal nodular hyperplasia--a review of myths and truths.

BackgroundFocal nodular hyperplasia (FNH) is a benign hyperplastic lesion of the liver with no known malignant potential. It has generated much interest due to the frequency with which it presents with atypical features on radiological imaging. Often resulting in misdiagnosis. Moreover, the understanding of particular subtypes of this lesion at a molecular level has changed in recent years. This may have implications on how certain subtypes should be managed.PurposeThis review aims to analyse current literature pertaining to FNH and to provide clinically relevant advice regarding diagnosis and management.

Circulating and disseminated tumor cells in pancreatic cancer and their role in patient prognosis: a systematic review and meta-analysis

Background Disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) have been postulated to seed metastases and contribute to poorer patient outcomes in many types of solid cancer. To date, no systematic reviews have examined the role of both DTCs and CTCs in pancreatic cancer. We aimed to determine the prognostic value of DTCs/CTCs in pancreatic cancer using a systematic review and meta-analysis. Materials and Methods A comprehensive literature search identified studies examining DTCs and CTCs in the bone marrow and blood of pancreatic cancer patients at diagnosis with follow-up to determine disease-free/progression-free survival (DFS/PFS) and overall survival (OS). Statistical analyses were performed to determine the hazard ratio (HR) of DTCs/CTCs on DFS/PFS and OS. Results The literature search identified 16 articles meeting the inclusion criteria. The meta-analysis demonstrated statistically significant HR differences in DFS/PFS (HR = 1.93, 95% CI 1.19–3.11, P = 0.007) and OS (HR = 1.84, 95% CI 1.37–2.45, P =< 0.0001), indicating patients with detectable DTCs/CTCs at diagnosis have worse prognoses. Subgroup analyses suggested CTCs in the peripheral blood (HR =2.03) were more indicative of poor OS prognosis than DTCs in the bone marrow (HR = 1.91), although the difference between these was not statistically significant. Positivity of the CellSearch detection method for DTC/CTC had the highest correlation with decreased OS (HR = 2.79) while immunodetection (HR = 1.91) and RT-PCR (HR = 1.25) were less effective in determining prognosis. Conclusion The detection of DTCs/CTCs at diagnosis is associated with poorer DFS/PFS and OS in pancreatic cancer.

Cholecystostomy: Indications and Subsequent Management

Cholecystostomy is a safe, simple and effective tool as an alternative to laparoscopic cholecystectomy in the treatment of acute cholecystitis in high-risk patients. Although cholecystectomy is considered the definitive treatment, it is associated with a risk of mortality and peri-operative complications in patients with significant comorbidity. As an alternative, cholecystostomy is a relatively rapid, minimally invasive procedure which can often be performed under local anaesthesia.

ATRX loss is an independent predictor of poor survival in pancreatic neuroendocrine tumours

Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms accounting for 1% to 2% of all pancreatic tumors. The biological behavior of PanNETs is heterogeneous and unpredictable, adding to the difficulties of clinical management. The DAXX (death domain associated protein) and ATRX (α-thalassemia/mental retardation syndrome X-linked) genes encode proteins involved in SWI/SNF-like chromatin remodeling. Somatic inactivating mutations in DAXX and ATRX are frequent in PanNETs, mutually exclusive, and associated with telomere dysfunction, resulting in genomic instability and alternate lengthening of telomeres. We sought to assess the clinical significance of the loss of the ATRX and DAXX proteins as determined by immunohistochemistry (IHC) in patients with PanNET. From an unselected cohort of 105 patients, we found ATRX loss in 10 tumors (9.5%) and DAXX loss in 16 (15.2%). DAXX and ATRX losses were confirmed mutually exclusive and associated with other adverse clinicopathological variables and poor survival in univariate analysis. In addition, ATRX loss was also associated with higher AJCC stage and infiltrative tumor borders. However, only ATRX loss, lymphovascular invasion, and perineural spread were independent predictors of poor overall survival in multivariate analysis. In conclusion, loss of expression of ATRX as determined by IHC is a useful independent predictor of poor overall survival in PanNETs. Given its relative availability, ATRX loss as determined by IHC may have a role in routine clinical practice to refine prognostication in patients with PanNET.

Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: A multi-institutional cohort study

BACKGROUND Up to 60% of patients who undergo curative-intent pancreatic ductal adenocarcinoma (PDAC) resection experience disease recurrence within six months. We recently published a systematic review of prognostic immunohistochemical biomarkers in PDAC and shortlisted a panel of those reported with the highest level of evidence, including p53, p16, Ca-125, S100A4, FOXC1, EGFR, mesothelin, CD24 and UPAR. This study aims to discover and validate the prognostic significance of a combinatorial panel of tumor biomarkers in patients with resected PDAC. METHODS Patients who underwent PDAC resection were included from a single institution discovery cohort and a multi-institutional validation cohort. Tumors in the discovery cohort were stained immunohistochemically for all nine shortlisted biomarkers. Biomarkers significantly associated with overall survival (OS) were reevaluated as a combinatorial panel in both discovery and validation cohorts for its prognostic significance. RESULTS 224 and 191 patients were included in the discovery and validation cohorts, respectively. In both cohorts, S100A4, Ca-125 and mesothelin expression were associated with shorter OS. In both cohorts, the number of these biomarkers expressed was significantly associated with OS (discovery cohort 36.8 vs. 26.4 vs 16.3 vs 12.8 months, P < 0.001; validation cohort 25.2 vs 18.3 vs 13.6 vs 11.9 months, P = 0.008 for expression of zero, one, two and three biomarkers, respectively). On multivariable analysis, expression of at least one of three biomarkers was independently associated with shorter OS. CONCLUSION Combinations of S100A4, Ca-125 and mesothelin expression stratify survival after resection of localized PDAC. Co-expression of all three biomarkers is associated with the poorest prognostic outcome.

Postoperative pancreatic fistula: a review of traditional and emerging concepts

Postoperative pancreatic fistula (POPF) remains the major cause of morbidity after pancreatic resection, affecting up to 41% of cases. With the recent development of a consensus definition of POPF, there has been a large number of reports examining various risk factors, prediction models, and mitigation strategies for this costly complication. Despite these strategies, the rates of POPF have not significantly diminished. Here, we review the literature and evidence regarding both traditional and emerging concepts in POPF prediction, prevention, and management. In particular, we review the evidence for the association between postoperative pancreatitis and POPF, and present a novel proposed mechanism for the development of POPF.

Pancreatic hamartoma: a sheep in wolf's clothing: Images for surgeons

A 42-year-old woman presented with a 3-month history of generalized abdominal pain. She had no history of pancreatitis. The examination of the abdomen was unremarkable. Tumour markers (Ca19-9 and CEA) were within normal range. Three-phase computed tomography (CT) of the abdomen revealed a circumscribed ovoid mass in the neck of the pancreas measuring 28 mm in maximal diameter, heterogeneously hypodense relative to pancreas on pre-contrast imaging and associated with small foci of cystic change (Fig. 1). There was mild heterogeneous enhancement, with the lesion predominantly hyperdense on venous phase. There was no proximal pancreatic duct dilatation. Based on the finding of a mixed density pancreatic neck mass, a radiological diagnosis of solid pseudopapillary tumour was given. Endoscopic ultrasound confirmed these findings and supported the diagnosis of solid pseudopapillary tumour. A central pancreatectomy was performed and concomitant vascular resection was not required. At 8 months of follow-up, the patient has no evidence of recurrence or abdominal pain and has returned to normal activities. Macroscopically, the tumour was a well-circumscribed tan lesion with focal cystic areas. Microscopically, the tumour demonstrated a pushing margin beneath a thin fibrous capsule. The tumour comprised disordered pancreatic ducts lined by cuboidal to low columnar epithelium embedded in an inflammatory fibroblast-rich stroma with admixed mature fat (Fig. 2). Some pancreatic acini were seen at the periphery of the tumour, but discrete endocrine islets were lacking. No cytological atypia was seen and there was no abnormality in the surrounding pancreatic parenchyma. The tumour was completely excised. Elastic staining (Verhoeff-Van Gieson) demonstrated a lack of concentric elastic fibres in the walls of the pancreatic duct, but preserved in the pancreas surrounding the tumour. S100 immunohistochemistry demonstrated a lack of peripheral nerves in the tumour but highlighted mature fat within the tumour. The fibrous stroma was diffusely positive for CD34, and chromogranin was negative (Fig. 3). Based on the lack of normal components of the pancreas (i.e. concentric elastic fibres in the duct walls, peripheral nerves and well-formed islets of Langerhans), chronic pancreatitis was ruled out as a diagnosis, and confirmed the diagnosis of a pancreatic hamartoma (PH). PH is a rare benign lesion most commonly in the head of the pancreas, but has also been described in the body and tail. The tumour affects patients of a broad age spectrum, ranging from neonates to the elderly, with no gender predilection. Due to the rising prevalence of cross-sectional abdominal imaging, an increasing number of PH are being diagnosed incidentally. However, larger lesions may present with abdominal pain, an abdominal mass and/or weight loss. Tumour marker levels (Ca19-9, CEA, Ca-125, Chromogranin A) remain unelevated in the presence of PH. Fig. 1. Axial computed tomography images demonstrating the pancreatic hamartoma in the neck of the pancreas (green arrow). Panel (a) demonstrates a hypodense lesion on non-contrast phase. Panel (b) demonstrates a heterogeneously enhancing lesion on arterial phase. Panel (c) demonstrates the peak of contrast enhancement in venous/delayed phase with focal cystic change.