Andrei Manilchuk

Predictors of Pancreatic Cancer–Associated Weight Loss and Nutritional Interventions

Objectives Pancreatic ductal adenocarcinoma (PDAC) is often accompanied by weight loss. We sought to characterize factors associated with weight loss and observed nutritional interventions, as well as define the effect of weight loss on survival. Methods Consecutive subjects diagnosed with PDAC (N = 123) were retrospectively evaluated. Univariate analysis was used to compare subjects with and without substantial (>5%) weight loss. Multivariate logistic regression was performed to identify factors associated with weight loss, and survival analyses were performed using Kaplan-Meier curves and Cox survival models. Results Substantial weight loss at diagnosis was present in 71.5% of subjects and was independently associated with higher baseline body mass index, longer symptom duration, and increased tumor size. Recommendations for nutrition consultation and pancreatic enzyme replacement therapy occurred in 27.6% and 36.9% of subjects, respectively. Weight loss (>5%) was not associated with worse survival on multivariate analysis (hazard ratio, 1.32; 95% confidence interval, 0.76–2.30), unless a higher threshold (>10%) was used (hazard ratio, 1.77; 95% confidence interval, 1.09–2.87). Conclusions Despite the high prevalence of weight loss at PDAC diagnosis, there are low observed rates of nutritional interventions. Weight loss based on current criteria for cancer cachexia is not associated with poor survival in PDAC.

In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study

AIM To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs). METHODS In a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively. RESULTS A total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a “fern pattern” of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology. CONCLUSION In vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs.

Prognostic value of microRNA expression levels in pancreatic adenocarcinoma: a review of the literature

Background Clinical and pathologic markers of prognosis and patterns of failure help guide clinicians in selecting patients for adjuvant therapy after surgical resection for pancreatic adenocarcinoma (PDAC). Recent studies have reported the prognostic utility of microRNA profiling in numerous malignancies. Here, we review and summarize the current literature regarding associations between microRNA expression and overall survival in PDAC patients. Materials and Methods We conducted a systematic search in the PubMed database to identify all primary research studies reporting prognostic associations between tumor and/or serum microRNA expression and overall survival in PDAC patients. Eligible articles were reviewed by the authors and relevant findings are summarized below. Results We found 53 publications that fit our search criteria. In total, 23 up-regulated and 49 down-regulated miRNAs have been associated with worse overall survival. MiR-21 is the most commonly reported miRNA, appearing in 19 publications, all of which report aberrant over-expression and association with shorter survival in PDAC. Other miRNAs that appear in multiple publications include miR-10b, −21, −34a, −155, −196a, −198, −200c, −203, −210, −218, −222, and −328. We summarize the preclinical and clinical data implicating these miRNAs in various molecular signaling pathways and cellular functions. Conclusions There is growing evidence that miRNA expression profiles have the potential to provide tumor-specific prognostic information to assist clinicians in more appropriately selecting patients for adjuvant therapy. These molecules are often aberrantly expressed and exhibit oncogenic and/or tumor suppressor functions in PDAC. Additional efforts to develop prognostic and predictive molecular signatures, and further elucidate miRNA mechanisms of action, are warranted.

The spectrum of confocal endomicroscopy findings in a cystic neuroendocrine tumor of the pancreas

A 60-year-old man was found to have an incidental pancreatic cystic lesion during surveillancemagnetic resonance imaging (MRI) for a known left renal lesion. Endoscopic ultrasound (EUS) revealed a cystic lesion (2.6 ×2.0 cm) with a single thick septum in the pancreatic tail (▶Video1). Needle-based confocal laser endomicroscopy (nCLE) of this lesion was performed with an AQ-Flex-19 miniprobe (Cellvizio; Mauna Kea Technologies Inc., Paris, France). This demonstrated nests of cells surrounded by fibrous septa and vascularity, suggestive of a cystic pancreatic neuroendocrine tumor (PNET) (▶Fig. 1). A pattern of vacuolization was also observed (▶Fig. 2 a; ▶Video1). Fine needle aspiration (FNA) with immunostaining of the sample obtained confirmed the diagnosis of a well-differentiated PNET. The patient underwent distal pancreatectomy and splenectomy. Histopathology of the surgical specimen showed a well-circumscribed mixed solid–cystic lesion (▶Fig. 3 a); synaptophysin immunostaining was reactive and chromatin demonstrated a salt-and-pepper pattern, consistent with a well-differentiated PNET (▶Fig. 3 b). Additionally, the tumor cells contained hyaline globules of varying sizes within the cytoplasm (▶Fig. 2 b). This finding correlated with the vacuolization image pattern seen on nCLE. The presence of these globules has been described in PNETs and solid pseudopapillary tumors, with the descriptive appearance of cytoplasmic vacuolization [1, 2]. A similar pattern has been attributed to the presence of cytoplasmic lipid, which is more common in cystic NETs [3]. Napoleon et al. first described the nCLE criteria of cystic PNETs, which have been validated in resected ex vivo lesions and by independent external observers [4]. The EUS-nCLE findings so far described in cystic PNETs include a trabecular network of dark cells with surrounding fibrosis and vascularity [4, 5]. This case presents a unique recurring feature of vacuolization that correlated with a comparable histopathological pattern. This spectrum of nCLE image patterns for cystic NETs can further assist in the differentiation of pancreatic cystic lesions.