MAP17 Expression in Colorectal Cancer Is a Prognostic Factor for Disease Recurrence and Dismal Prognosis Already in Early Stage Disease.

BACKGROUND: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. PATIENTS AND METHODS: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. RESULTS: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056-0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049-0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. CONCLUSIONS: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality.

BACKGROUND: Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assessed its prognostic significance in colorectal cancer. METHODS: One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. RESULTS: Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate to high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250-12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401-8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. CONCLUSIONS: High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.

Nestin and CD34 expression in colorectal cancer predicts improved overall survival.

BACKGROUND: Nestin, a class VI intermediate filament protein of the cytoskeleton, and CD34, a transmembrane phosphoglycoprotein, are markers of progenitor cells. This study aimed to evaluate their expression and clinical significance in colorectal cancer. METHODS: A clinically annotated tissue microarray, including 599 patients with colorectal cancer, was analyzed by immunohistochemistry. Furthermore, nestin and CD34 correlations with HIF-1a and a panel of cytokines and chemokines were assessed using quantitative reverse transcription PCR and The Cancer Genome Atlas dataset. RESULTS: Expression of nestin and CD34 was observed only in the tumor stroma. Patients displaying high expression of nestin and CD34 demonstrated higher rates of T1 and T2 tumors (p = .020), lower vascular invasion (p < .001) and improved 5-year overall survival (65%; 95% CI = 55-73 vs 45%; 95% CI = 37-53) after adjusting for clinicopathological characteristics (HR: 0.67; 95% CI = 0.46-0.96). A moderate to strong correlation (r = 0.37-0.78, p < .03) of nestin and CD34 was demonstrated for the following markers; HIF-1α, CD4, CD8, FOXP3, IRF1, GATA3, CCL2, CCL3, CXCL12 and CCL21. CONCLUSIONS: Combined expression of nestin and CD34 expression is associated with better overall survival possibly by modulating a favorable immune response.

Evaluation of molecular and genetic predisposing parameters at diverticular disease of the colon.

BACKGROUND: Diverticular disease (DD) refers to the presence of diverticula throughout the gastrointestinal (GI) tract, mainly along colon. DD might evolve into diverticulitis that is accompanied by severe clinical presentation, which includes abscess formation, perforation, stricture, obstruction and/or fistula. AIM: The aim of the present review is to summarize the role of molecular and genetic factors in DD development, as well as their possible contribution towards new prognostic indicators, diagnostic algorithms and new therapeutic approaches. METHODS AND RESULTS: Except from common predisposing parameters, several genetic mutations, immune factors, neurotransmitters, hormones and protein dysfunctions have been associated to the early onset of DD symptoms, pathogenesis and prognosis of the disease. Specific structural changes in the colonic wall, altered matrix composition and compromised motility have been verified as possible pathogenic factors for the development of DD. Dysregulation in peristaltic activity and reduced ability of the longitudinal muscle to relax following contraction has been also associated with DD evolution. In addition, it has been suspected that genetic defects combined with alterations in intestinal microbiota might play an important role in diverticulitis presentation.

The Impact of Cirrhosis on Pancreatic Cancer Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Cirrhosis has been considered a contraindication to major abdominal surgeries, due to increased risk for postoperative morbidity and mortality. The aim of this study was to assess the safety of pancreatectomy in cirrhotic versus non-cirrhotic patients. METHODS: The present systematic review and meta-analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. All meta-analyses were performed using the random effects model. RESULTS: Eight studies were eventually included, enrolling 1229 patients (cirrhotics: 722; and Child-Pugh A: 593; Child-Pugh B/C: 129) who underwent surgery for pancreatic cancer. The overall postoperative morbidity rate was 66% (51%-80%). Infections (26%) and ascites formation/worsening (23%) were the most common postoperative complications, followed by anastomotic leak/fistula (17%). Non-cirrhotic patients were less likely to suffer from anastomotic leak/fistula (OR: 0.39; 95% CI: 0.23-0.65) and infections (OR: 0.41; 95% CI: 0.25-0.67). Postoperative mortality rate was statistically significantly lower in non-cirrhotic versus cirrhotic patients (OR: 0.18; 95% CI:0.18-0.39). The odds ratios of 1 year (OR: 0.62; 95% CI: 0.30-1.30), 2 year (OR: 0.67; 95% CI: 0.25-1.83) and 3 year all-cause mortality (OR: 0.32; 95% CI: 20.03-2.99) were not significantly different between cirrhotic versus non-cirrhotic patients. CONCLUSION: This study demonstrated that non-cirrhotic patients were less likely to undergo any type of re-intervention and had statistically significant lower postoperative mortality rates compared to patients with cirrhosis.

Presentation and surgical management of xanthogranulomatous cholecystitis.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a rare benign chronic inflammatory disease of the gallbladder that often presents as cholecystitis and most of the times requires surgical management. In addition, distinguishing XGC from gallbladder cancer preoperatively is still a challenge. The aim of the present systematic review was to outline the clinical presentation and surgical approach of XGC. DATA SOURCES: The present systematic review was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases from inception until June 2020. RESULTS: The laparoscopic cholecystectomy rate (34%) was almost equal to the open cholecystectomy rate (47%) for XGC. An important conversion rate (35%) was observed as well. The XGC cases treated by surgery were associated with low mortality (0.3%), limited intraoperative blood loss (58-270 mL), low complication rates (2%-6%), along with extended operative time (82.6-120 minutes for laparoscopic and 59.6-240 minutes for open cholecystectomy) and hospital stay (3-9 days after laparoscopic and 8.3-18 days after open cholecystectomy). Intraoperative findings during cholecystectomies for XGC included empyema or Mirizzi syndrome. In addition, complex surgical procedures, like wedge hepatic resections and bile duct excision were required during operations for XGC. CONCLUSIONS: XGC seemed to be a rare, benign inflammatory disease that presents similar features as gallbladder cancer. The mortality and complication rates of XGC were low, despite the complex surgical procedures that might be required in some cases.

Combinatorial Treatment of Tinzaparin and Chemotherapy Can Induce a Significant Antitumor Effect in Pancreatic Cancer.

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.

Combined hepatocellular-cholangiocarcinoma: An update on epidemiology, classification, diagnosis and management.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare subtype of primary hepatic malignancies, with variably reported incidence between 0.4%-14.2% of primary liver cancer cases. This study aimed to systematically review the epidemiological, clinicopathological, diagnostic and therapeutic data for this rare entity. DATA SOURCES: We reviewed the literature of diagnostic approach of CHC with special reference to its clinical, molecular and histopathological characteristics. Additional analysis of the recent literature in order to evaluate the results of surgical and systemic treatment of this entity has been accomplished. RESULTS: The median age at CHC's diagnosis appears to be between 50 and 75 years. Evaluation of tumor markers [alpha fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)] along with imaging patterns provides better opportunities for CHC's preoperative diagnosis. Reported clinicopathologic prognostic parameters possibly correlated with increased tumor recurrence and grimmer survival odds include advanced age, tumor size, nodal and distal metastases, vascular and regional organ invasion, multifocality, decreased capsule formation, stem-cell features verification and increased GGT as well as CA19-9 and CEA levels. In case of inoperable or recurrent disease, combinations of cholangiocarcinoma-directed systemic agents display superior results over sorafenib. Liver-directed methods, such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), hepatic arterial infusion chemotherapy (HAIC), radioembolization and ablative therapies, demonstrate inferior efficacy than in cases of hepatocellular carcinoma (HCC) due to CHC's common hypovascularity. CONCLUSIONS: CHC demonstrates an overlapping clinical and biological pattern between its malignant ingredients. Natural history of the disease seems to be determined by the predominant tumor element. Gold standard for diagnosis is histology of surgical specimens. Regarding therapeutic interventions, major hepatectomy is acknowledged as the cornerstone of treatment whereas minor hepatectomy and liver transplantation may be applied in patients with advanced cirrhosis. Despite all therapeutic attempts, prognosis of CHC remains dismal.

Systematic Review of Surgical and Percutaneous Irreversible Electroporation in the Treatment of Locally Advanced Pancreatic Cancer.

OBJECTIVE: The aim of the present systematic review was to collect, analyze, and critically evaluate the role of irreversible electroporation (IRE) in locally advanced pancreatic cancer (LAPC). Furthermore, we sought to analyze the different approaches of IRE (open, laparoscopic, and percutaneous) and assess the relative outcomes. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using the MEDLINE (1966-2018), Scopus (2004-2018), Google Scholar (2004-2018) and ClinicalTrials.gov databases, eligible articles published up to August 2018 were included. The following keywords were applied: 'irreversible electroporation', 'IRE', 'LAPC', 'unresectable pancreatic cancer', 'palliative treatment', 'locally advanced pancreatic cancer', 'ablation' and 'ablative treatment'. RESULTS: IRE for LAPC was feasible and safe; however, it was associated with morbidity in approximately one in three patients, some of whom experienced serious complications, particularly after surgical IRE. In addition, while mortality following IRE was uncommon, it did occur in 2% of patients. While some studies suggested a survival benefit, others failed to note an improvement in long-term outcomes following IRE compared with other therapies. CONCLUSIONS: Providers and patients need to be aware of the potential morbidity and mortality associated with IRE. In addition, based on the literature to date, the survival benefit of IRE for LAPC remains to be elucidated. Conclusive and definitive evidence to support a survival benefit of IRE does not currently exist. Future multicenter, randomized, prospective trials are needed to clarify the role of IRE in patients with LAPC.

A type of neoplasia deadlier than gastric adenocarcinoma? Report of a case of primary gastric squamous cell carcinoma.

BACKGROUND: Primary gastric squamous cell carcinoma is an extremely rare malignancy with few case reports reported so far in the current medical literature. Its incidence varies between 0.04 and 0.07% of all gastric malignancies with a male predominance in the sixth decade of life. It has been found that this type of malignancy has a more aggressive behavior and associated poorer prognosis, when compared to gastric adenocarcinoma. Thus, the most appropriate management of this kind of neoplasia is still debatable due to the small number of reported cases. CASE PRESENTATION: We report the case of a 66-year-old man who underwent total gastrectomy with D2 lymphadenectomy for an ulcerative lesion in the fundus of the stomach that turned out to be primary gastric squamous cell carcinoma. CONCLUSIONS: Upon confirmation of this specific malignancy, the affected patients should be enrolled in strict follow-up protocols after curative surgery, since the risk for metastasis is high. Physicians should maintain high clinical suspicion in order to diagnose these tumors at an early stage, along with the need to rule out any other possible primary sites of squamous malignancy.

Irreversible electroporation in a case of pancreatic leiomyosarcoma: a novel weapon versus a rare malignancy?

BACKGROUND: Primary pancreatic leiomyosarcoma is an extremely rare entity that needs high clinical suspicion in order to diagnose it at an early stage. Clinical characteristics, diagnosis, and management still remain challenging and controversial, especially in advanced stages, when tumor invades adjacent vessels and organs or gives distant metastases. CASE PRESENTATION: Herein, we describe a case of a 57-year-old woman suffering from advanced pancreatic leiomyosarcoma with thrombosis of the superior mesenteric vein, as well as liver lesions which were suspicious for metastasis. Multidisciplinary team decided for upfront chemotherapy to assess tumor response. Follow-up imaging after the completion of chemotherapy led tumor board to decide for subsequent surgical exploration. The patient underwent exploratory laparotomy and irreversible electroporation ablation of the pancreatic tumor. Postoperative course was uneventful, and she was discharged 10 days later with a plan to receive adjuvant therapy. To the best of our knowledge, this is the first case of pancreatic leiomyosarcoma ever reported, treated with this novel technique of irreversible electroporation that could be an alternative and feasible way for the management of these rare malignancies. CONCLUSIONS: In conclusion, primary pancreatic leiomyosarcoma is a rare and highly malignant tumor associated with poor prognosis. Nowadays, R0 surgical resection remains the cornerstone treatment, combined with adjuvant and/or neoadjuvant chemotherapy prior to resection. In the advanced setting, when major vessel invasion and distant metastases occur, chemotherapy along with irreversible electroporation ablation could be a helpful and possibly effective modality for the management of this highly aggressive tumor.

Hepatic progenitor cells in metastatic liver carcinomas.

AIMS: Hepatic progenitor cells (HPCs) are activated in various liver diseases, but their role in the carcinomatous environment remains unknown. We aimed to identify the possible presence and topography of HPCs in liver metastases. METHODS AND RESULTS: We examined 14 liver resection specimens for colorectal adenocarcinoma (n = 13) and anal squamous cell carcinoma (n = 1) metastases. Immunohistochemical markers of colonic origin (keratin 20 and CDX2) and squamous cell origin (p63), HPC [keratin 19 (K19) and CD56] and stem cell (CD44) markers, and the biliary marker keratin 7 (K7), which may also highlight HPCs, were applied on routinely processed tissue sections. Double immunohistochemistry/immunofluorescence (K7/CDX2) and confocal microscopy were used on selected sections. K7-positive, Κ19-positive and CD56-positive ductular structures were encountered within the metastatic tumour (tumour interior and periphery), and in the immediate peritumoral area. Hybrid structures composed of HPCs and metastatic adenocarcinoma cells were recognised and confirmed by double immunostaining (K7/CDX2). Carcinoma cells were also observed singly or in groups within the epithelium of interlobular bile ducts and/or ductules in portal tracts without evidence of carcinomatous infiltration and at a distance from the metastatic foci. CONCLUSIONS: HPCs are observed at the periphery and in the interior of liver metastatic carcinomas. Bile ductules and small interlobular bile ducts may attract carcinoma cells serving as a potential 'metastatic niche', in line with their recognised role as HPC niches in non-neoplastic liver.

Neutrophils to lymphocytes ratio as a useful prognosticator for stage II colorectal cancer patients.

BACKGROUND: The incidence of colorectal cancer (CRC) is expected to increase by 80% in year 2035. Even though advantages in treatment of CRC have being made over the last decades, the outcome remains poor. Recently, several inflammatory markers including pretreatment neutrophil to lymphocyte ratio (NLR), have being used as prognostic factors, since host inflammatory response to cancer is believed to determine disease progression. The aim of this study is to evaluate the prognostic significance of pretreatment NLR, in terms of overall survival (OS), 5-year survival, disease-free survival (DFS) and recurrence, in CRC patients who underwent curative resection. METHODS: We retrospectively reviewed 296 patients, who were submitted to elective surgery as first therapeutic option in curative intent, between January 2010 and December 2015. Pretreatment NLR, as well as demographics, clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS, 5-year survival, DFS and recurrence. RESULTS: The cutoff point of NLR was calculated with Kaplan-Meier curves and log-rank test to 4.7. Univariate and multivariate analyses disclosed elevated NLR as a significant dismal prognostic factor for DFS (HR 1.88; 95% CI 1.01-3.52; p = 0.048), 5-year survival (HR 2.14; 95% CI 1.12-4.10; p = 0.021) and OS (HR 2.11; 95% CI 1.11-4.03; p = 0.023). In a subgroup analysis, in patients with stage II CRC, NLR > 4.7 was a stronger poor predictor for DFS (HR 2.76; 95% CI 1.07-7.13; p = 0.036), 5-year survival (HR 3.84; 95% CI 1.39-10.63; p = 0.01) and OS (HR 3.62; 95% CI 1.33-4.82; p = 0.012). After adjusting stage for gender, age, location of the primary tumor, differentiation, as well as the presence of perineural, vascular, and lymphovascular invasion, the significance of NLR > 4.7 became more prominent for DFS (HR 2.85; 95% CI 1.21-6.73; p = 0.0176), 5-year survival (HR 4.06; 95% CI 1.66-9.93; p = 0.002) and OS (HR 4.07; 95% CI 1.69-9.91; p = 0.002) in stage II patients. CONCLUSION: Pretreatment NLR > 4.7 is a poor prognostic factor for DFS, 5-year survival and OS in CRC patients undergoing curative resection. The dismal prognostic effect of NRL is magnified in Stage II CRC patients.

Operative Results and Oncologic Outcomes of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Versus Two-Stage Hepatectomy (TSH) in Patients with Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-Analysis.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently emerged as a treatment choice for patients with colorectal liver metastases (CLM) and inadequate future liver remnant (FLR). The aim of this study was to define the results of ALPPS compared with two-stage hepatectomy (TSH) for patients with CLM. MATERIALS AND METHODS: A meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Identification of eligible studies was performed using three distinct databases through February 2017; Medline, ClinicalTrials.gov and Cochrane library-Cochrane Central Register of Controlled Trials using a syntax including medical subject headings terms "portal vein ligation," "PVE," "staged hepatectomy," "staged liver resection," "liver resection," "two-stage hepatectomy," "TSH," "in situ liver transection with portal vein ligation," "associating liver partition and portal vein ligation for staged hepatectomy" and "ALPPS". RESULTS: Among the 634 records identified, 9 studies comparing ALPPS with TSH met the inclusion criteria. These studies included 657 patients with unresectable CLM (ALPPS, n = 186 vs TSH, n = 471). There was no difference in final postoperative FLR between ALPPS versus TSH (mean difference: 31.72, 95% CI: -27.33 to 90.77, p = 0.29). The kinetic growth rate was faster with the ALPPS versus TSH (mean difference 19.07 ml/day, 95% CI 8.12-30.02, p = 0.0006). TSH had a lower overall and major morbidity versus ALPPS (overall morbidity: RR: 1.39, 95% CI: 1.07-1.8, p = 0.01; I 2: 58%, p = 0.01; major morbidity: RR: 1.57, 95% CI: 1.18-2.08, p = 0.002; I 2: 0%, p = 0.44). Overall survival was comparable following ALPPS versus TSH. CONCLUSION: While ALPPS may be a suitable approach for patients, the higher morbidity and mortality should be considered when determining the operative approach for patients with extensive CLM.

High versus low ligation of inferior mesenteric vessels in rectal cancer surgery: A retrospective cohort study.

PURPOSE: To retrospectively evaluate the short-term and the long-term oncological outcome between two groups of patients who had undergone either high or low ligation of inferior mesenteric vessels (IMV) in rectal cancer surgery. METHODS: Between January 2009 and December 2014, 120 patients with rectosigmoid and rectal adenocarcinoma were operated with curative intent as first therapeutic option. Patients were divided in two groups depending on the level of the inferior mesenteric artery (IMA) ligation. High ligation was defined as the division of the IMA less than 2cm from the aorta followed by the ligation of the inferior mesenteric vein at its origin from the lower border of the pancreas (n=76), while low ligation was defined as the division of IMA immediately distal to the origin of the left colic artery (n=44). RESULTS: The median follow up was 51 months. Univariate analyses disclosed that low ligation was related to a higher postoperative complications rate, mainly related to the higher rate of urinary dysfunction but it was also related to a favorable 5-year overall survival (OS) rate. However, multivariate analyses among factors which might influence the short- and long-term outcomes did not disclose the level of ligation as a factor influencing the postoperative course, the recurrence, the disease free survival (DFS) and the 1-, 3- and 5-year OS rates. CONCLUSIONS: The present study disclosed no differences in surgical, histological, short-term and long-term oncological outcomes between patients treated with either high or low ligation of IMA.

Liver transplantation for unresectable colorectal liver metastases: A systematic review.

The use of liver transplantation (LT) for liver metastases attempted in the early 1990's was associated with poor perioperative outcomes and unacceptably low overall survival. Recently, there has been renewed interest in LT as a treatment option for colorectal liver metastases (CLM) in countries where organ supply is high. To date, no meticulous analysis about the efficacy, safety and outcomes of LT in CLM patients has been published. We present the first systematic review on the subject.

Total robotic pancreaticoduodenectomy: a systematic review of the literature.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex operation with high perioperative morbidity and mortality, even in the highest volume centers. Since the development of the robotic platform, the number of reports on robotic-assisted pancreatic surgery has been on the rise. This article reviews the current state of completely robotic PD. MATERIALS AND METHODS: A systematic literature search was performed including studies published between January 2000 and July 2016 reporting PDs in which all procedural steps (dissection, resection and reconstruction) were performed robotically. RESULTS: Thirteen studies met the inclusion criteria, including a total of 738 patients. Data regarding perioperative outcomes such as operative time, blood loss, mortality, morbidity, conversion and oncologic outcomes were analyzed. No major differences were observed in mortality, morbidity and oncologic parameters, between robotic and non-robotic approaches. However, operative time was longer in robotic PD, whereas the estimated blood loss was lower. The conversion rate to laparotomy was 6.5-7.8%. CONCLUSIONS: Robotic PD is feasible and safe in high-volume institutions, where surgeons are experienced and medical staff are appropriately trained. Randomized controlled trials are required to further investigate outcomes of robotic PD. Additionally, cost analysis and data on long-term oncologic outcomes are needed to evaluate cost-effectiveness of the robotic approach in comparison with the open technique.

Report of a case combining solitary Peutz-Jeghers polyp, colitis cystica profunda, and high-grade dysplasia of the epithelium of the colon.

BACKGROUND: Colitis cystica profunda is a rare nonneoplastic disease defined by the presence of intramural cysts that contain mucus, usually situated in the rectosigmoid area, which can mimic various malignant lesions and polyps. Its etiology still remains not fully elucidated, and several mechanisms such as congenital, post-traumatic, and infectious have been implicated in the development of this rare entity. CASE PRESENTATION: Herein, we describe a unique case of colitis cystica profunda in the setting of Peutz-Jeghers-type polyp of the sigmoid colon, associated with high-grade dysplasia of the overlying epithelium in a 48-year-old female patient, who presented to the emergency room with signs of intestinal obstruction. To the best of our insight, this is the first manifestation ever reported in the literature regarding the coexistence of solitary Peutz-Jeghers-type polyp, colitis cystica profunda, and high-grade dysplasia of the epithelium of the colon. CONCLUSIONS: The purpose of this case report is to highlight colitis cystica profunda and its clinical significance. An uncommon nonneoplastic entity, many times masquerading as malignant lesion of the rectosigmoid area of the colon. Clinicians and pathologists should be aware of this benign condition that is found incidentally postoperatively in patients undergoing colectomies, leading to unnecessary increase of morbidity and mortality in these patients, who otherwise could have been cured with conservative treatment only.

From Clinical Standards to Translating Next-Generation Sequencing Research into Patient Care Improvement for Hepatobiliary and Pancreatic Cancers.

Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic.