Primary pancreatic lymphoma:A case report and review of literature

BACKGROUND Primary pancreatic lymphoma(PPL)is a rare tumor that mimics pancreatic adenocarcinoma,leading to diagnostic and therapeutic challenges.PPL accounts for 0.2%of all pancreatic tumors and is typically treated with chemotherapy.However,the long-term survival rates for PPL with chemotherapy and radiotherapy alone are unsatisfactory.Due to the improvements in pancreatic surgery,there is a need to reevaluate the treatment strategies for PPL.CASE SUMMARY A 62-year-old male presented to our clinic.A biopsy was unsuccessful,and the imaging was suggestive of pancreatic adenocarcinoma.Therefore,subtotal splenopancreatectomy was performed and histopathology was performed.He was then diagnosed with primary pancreatic diffuse large B-cell lymphoma.He received adjuvant chemotherapy and radiotherapy.Currently,the patient is alive with no evidence of disease 36 months after surgery.CONCLUSION The potential role of surgery in the treatment of PPL should be emphasized and added in the management protocol of early stage lymphoma.

Portal hypertension in patients with nonalcoholic fatty liver disease:Current knowledge and challenges

Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.

Constipation and colonoscopy

Constipation is a significant sociomedical problem,which can be caused by various reasons.In the diagnostic approach to patients with constipation,the following data are usually sufficient:History,complete physical examination(including rectal examination),and additional diagnostic tests.A colonoscopy is not a necessary diagnostic method for all patients with constipation.However,if patients have alarm symptoms/signs,that suggest an organic reason for constipation,a colonoscopy is necessary.The most important alarm symptoms/signs are age>50 years,gastrointestinal bleeding,new-onset constipation,a palpable mass in the abdomen and rectum,weight loss,anemia,inflammatory bowel disease,and family history positive for colorectal cancer.Most endoscopists do not like to deal with patients with constipation.There are two reasons for this,namely the difficulty of endoscopy and the adequacy of preparation.Both are adversely affected by constipation.To improve the quality of colonoscopy in these patients,good examination techniques and often more extensive preparation are necessary.Good colonoscopy technique implies adequate psychological preparation of the patient,careful insertion of the endoscope with minimal insufflation,and early detection and resolution of loops.Bowel preparation for colonoscopy often requires prolonged preparation and sometimes the addition of other laxatives.

Non-invasive assessment of liver fibrosis in chronic liver diseases:Implementation in clinical practice and decisional algorithms

Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.

内镜超声引导下Trucut活检与细针穿刺的比较

内镜超声（endoscopic ultrasonography，EUS）及其引导下的细针穿刺（EUS-guided fine needle aspiration，EUSFNA）对于诊断胃肠道内外肿瘤和判断肠道周围（peri-intestinal）淋巴结的良恶性是一种非常敏感的方法，尤其适用于胃肠道恶性肿瘤的TNM分期和胰腺良恶性病变的诊断。依据不同部位，EUSFNA的诊断准确率为60％～90％，而判断淋巴结良恶性的准确率则大于90％。但EUSFNA技术本身仍存在一定缺陷。如操作过程中需细胞病理学医师在场进行细胞快速固定、HE染色和病理学诊断。

Role of Helicobacter pylori infection in gastric carcinogenesis:Current knowledge and future directions

Helicobacter pylori(H. pylori) plays a role in the patho-genesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence:(1) eradication of the already present infection; and(2) immunization(prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available.

Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

Hepatitis C virus and type 2 diabetes

This review focuses on the relationship between hepatitis C virus(HCV) infection and glucose metabolism derangements.Cross-sectional and longitudinal studies have shown that the chronic HCV infection is associated with an increased risk of developing insulin resistance(IR) and type 2 diabetes(T2D).The direct effect of HCV on the insulin signaling has been analyzed in experimental models.Although currently available data should be considered as preliminary,HCV seems to affect glucose metabolism via mechanisms that involve cellular pathways that have been implicated in the host innate immune response.IR and T2D not only accelerate the histological and clinical progression of chronic hepatitis C,but also reduce the early and sustained virological response to interferon-alpha-based therapy.Thus,a detailed knowledge of the mechanisms underlying the HCV-associated glucose metabolism derangements is warranted,in order to improve the clinical management of chronic hepatitis C patients.

Measurement of calprotectin in ascitic fluid to identify elevated polymorphonuclear cell count

AIM: To evaluate the diagnostic capability of calprotectin in ascitic fluid for detecting a polymorphonuclear (PMN) cell count > 250/μL ascites. METHODS: In this prospective observational study, a total of 130 ascites samples were analysed from 71 consecutive patients referred for paracentesis. Total and differential leukocyte cell counts were determined manually with a Neubauer chamber and gentianviolet stain. Calprotectin was measured in 1 mL ascetic fluid by enzyme-linked immunosorbent assay (ELISA) and a point-of-care (POC) lateral flow assay with the Quantum Blue Reader (Bühlmann Laboratories). All measurements were carried out in a central laboratory by senior personnel blinded to patient history. A PMN count > 250/μL was the primary endpoint of the study. The diagnostic value of ascitic calprotectin measurement was assessed by comparing to the final diagnosis of each patient that had been adjudicated by investigators blinded to calprotectin values. RESULTS: The PMN count was > 250/μL in 19 samples (14.6%) from 15 patients (21.1%) and varied widely among the study population (range 10-19 800/mL and 1-17 820/mL, respectively). Spontaneous bacterial peritonitis (SBP) was the final diagnosis in four patients (5.6%). All patients with PMN ≤ 250/μL had negative bacterial culture. PMN count was elevated in five patients with peritoneal carcinomatosis, three with lymphoma, one with neuroendocrine carcinoma, and two with secondary peritonitis due to abdominal perforation. PMN cell counts correlated with ascitic calprotectin values (Spearman's rho; r = 0.457 for ELISA, r = 0.473 for POC). A considerable range of ascitic calprotectin concentrations was detected by ELISA [median 0.43 μg/mL, interquartile range (IQR) 0.23-1.23 (range 0.10-14.93)] and POC [median 0.38 μg/mL, IQR 0.38-0.56 (range 0.38-13.31)]. Ascitic calprotectin levels were higher in samples with PMN > 250/μL, by both ELISA [median (IQR) 2.48 μg/mL (1.61-3.65) vs 0.10 μg/mL (0.10-0.36), P < 0.001] and POC [2.78 μg/mL (2.05-5.37) vs 0.38 μg/mL (0.38-0.41), P < 0.001]. The area under the receiver operating characteristics curve for identifying an elevated PMN count was 0.977 (95%CI: 0.933 to 0.995) for ELISA and 0.982 (95%CI: 0.942 to 0.997) for POC (P = 0.246 vs ELISA). Using the optimal cut-off value for ELISA (0.63 μg/mL), ascitic calprotectin had 94.8% sensitivity, 89.2% specificity, positive and negative likelihood ratios of 8.76 and 0.06 respectively, positive and negative predictive values of 60.0% and 99.0% respectively, and 90.0% overall accuracy. Using the optimal cut-off value for POC (0.51 μg/mL), the respective values were 100.0%, 84.7%, 6.53, 0.00, 52.8%, 100% and 87.7%. Correlation between ELISA and POC was excellent (r = 0.873, P < 0.001). The mean ± SD of the difference was -0.11 ± 0.48 μg/mL with limits of agreement of + 0.8 μg/mL (95%CI: 0.69 to 0.98) and -1.1 μg/mL (95%CI: -1.19 to -0.91). CONCLUSION: Ascitic calprotectin reliably predicts PMN count > 250/μL, which may prove useful in the diagnosis of SBP, especially with a readily available bedside testing device.

Personalized medicine in functional gastrointestinal disorders:Understanding pathogenesis to increase diagnostic and treatment efficacy

There is overwhelming evidence that functional gastrointestinal disorders(FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in patients presenting with functional upper gastrointestinal symptoms(UGI Sx). Among patients with UGI Sx, approximately equal proportions(25%) of patients have delayed gastric emptying(GE), reduced gastric accommodation(GA), both impaired GE and GA,or neither, presumably due to increased gastric or duodenal sensitivity.Treatments targeted to the underlying pathophysiology utilize prokinetics,gastric relaxants, or central neuromodulators. Similarly, specific mechanisms in patients presenting with functional lower gastrointestinal symptoms, especially with diarrhea or constipation, are recognized, including at least 30% of patients with functional constipation pelvic floor dyssynergia and 5% has colonic inertia(with neural or interstitial cells of Cajal loss in myenteric plexus); 25% of patients with diarrhea-predominant irritable bowel syndrome(IBSD) has evidence of bile acid diarrhea; and, depending on ethnicity, a varying proportion of patients has disaccharidase deficiency, and less often sucrose-isomaltase deficiency. Among patients with predominant pain or bloating, the role of fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be considered. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2 D6, 2 C19 and 3 A4 in the use of drugs for treatment of patients with FGIDs. Single mutations or multiple genetic variants are relatively rare, with limited impact to date on the understanding or treatment of FGIDs. The role of mucosal gene expression in FGIDs, particularly in IBS-D, is the subject of ongoing research. In summary, the time for personalization of FGIDs, based on deep phenotyping, is here;pharmacogenomics is relevant in the use of central neuromodulators. There is still unclear impact of the role of genetics in the management of FGIDs.

Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis

AIM:To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis.METHODS:We conducted a study of 63 patients with liver cirrhosis.A control group comprised of 30 age and gender-matched healthy persons.Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made.Estimated glomerular filtration rate from serum creatinine(GFRCr)and cystatin C(GFRCys)was calculated.RESULTS:We confirmed significant differences in val-ues of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh(P=0.01),and a significant correlation with model of end stage liver disease(MELD)score(rs=0.527,P<0.001).More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr(P<0.001).Significantly higher renal resistive index was noted in Child-Pugh C than in A(P<0.001)and B stage(P=0.001).Also,a significant correlation between renal resistive index and MELD score was observed(rs=0.607,P<0.001).Renal resistive index correlated significantly with cystatin C(rs=0.283,P=0.028)and showed a negative correlation with GFRCys(rs=-0.31,P=0.016).CONCLUSION:Cystatin C may be a more reliable marker for assessment of liver insufficiency.Additionally,cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.

Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

AIM:To determine the effect of non-selective cyclooxygenase (COX) inhibitors,selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis.METHODS:Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle,aspirin (ASA) (a nonselective COX inhibitor),celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days.The area of colonic lesions,colonic blood flow (CBF),myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2,inducible form of nitric oxide synthase (iNOS),IL-1β and tumor necrosis factor (TNF)-α were assessed.The effects of glyceryl trinitrate (GTN),a NO donor,and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide,onopotassium salt (carboxy-PTIO),a NO scavenger,administered without and with ASA or NO-ASA,and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined.RESULTS:Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF,a significant rise in colonic weight,MPO activity and plasma IL-1β and TNF-α levels.These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)3-(trifluoromethyl)-1H-pyrazole (SC-560),but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E 2 (PGE 2) analog.Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NO x content and CBF,suppression of MPO and downregulation of COX-2,iNOS,IL-1β and TNF-α mRNAs.Treatment with GTN,the NO donor,significantly inhibited the ASA-induced colonic lesions and increased CBF,while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF.These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals.CONCLUSION:NO-releasing ASA,in contrast to ASA,COX-1 inhibitors,and SC-560,accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP.

Mechanism of diarrhea in microscopic colitis

AIM： To search the pathophysiological mechanism of diarrhea based on daily stool weights, fecal electrolytes, osmotic gap and pH. METHODS： Seventy-six patients were included： 51 with microscopic colitis （MC） [40 with lymphocytic colitis （LC）; 11 with collagenous colitis （CC）], 7 with MC without diarrhea and 18 as a control group （CG）. They collected stool for 3 d. Sodium and potassium concentration were determined by flame photometry and chloride concentration by titration method of Schales. Fecal osmotic gap was calculated from the difference of osmolarity of fecal fluid and double sum of sodium and potassium concentration. RESULTS： Fecal fluid sodium concentration was significantly increased in LC 58.11±5.38 mmol/L （P〈0.01） and CC 54.14±8.42 mmol/L （P〈0.05） than in CG 34.28±2.98 mmol/L. Potassium concentration in LC 74.65±5.29 mmol/L （P〈0.01） and CC 75.53±8.78 mmol/L （P〈0.05） was significantly less compared to CG 92.67±2.99 mmol/L. Chloride concentration in CC 36.07±7.29 mmol/L was significantly higher than in CG 24.11±2.05 mmol/L（P〈0.05）. Forty-four （86.7%） patients had a secretory diarrhea compared to fecal osmotic gap. Seven （13.3%） patients had osmotic diarrhea. CONCLUSION： Diarrhea in MC mostly belongs to thesecretory type. The major pathophysiological mechanism in LC could be explained by a decrease of active sodium absorption. In CC, decreased CI/HCO3 exchange rate and increased chloride secretion are coexistent pathways.

Pravastatin:A potential cause for acute pancreatitis

Acute pancreatitis （AP） secondary to drugs is uncommon, with an incidence ranging from 0.3% to 2.0% of AP cases. Drug-induced AP due to statins is rare, and only 12 cases have thus far been reported. In this case report, we report a case of a 50-year-old female on pravastatin therapy for 3 d prior to developing symptoms of AP. The common etiological factors for AP were all excluded. The patient was admitted to the intensive care unit secondary to respiratory distress, though she subsequently improved and was discharged 14 d after admission. Although the incidence of drug-induced AP is low, clinicians should have a high index of suspicion for it in patients with AP due to an unknown etiology. Clinicians should be aware of the association of statins with AR If a patient taking a statin develops abdominal pain, clinicians should consider the diagnosis of AP and conduct the appropriate laboratory and diagnostic evaluation if indicated.

Drain amylase value as an early predictor of pancreatic fistula after cephalic duodenopancreatectomy

AIM: To determine predictors of clinically relevant pancreatic fistulas (CRPF) by measuring drain fluid amylase (DFA) in the early postoperative period.

Systematic mechanism-orientated approach to chronic pancreatitis pain

Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.

HFE gene in primary and secondary hepatic iron overload

Distinct from hereditary haemochromatosis, hepatic iron overload is a common finding in several chronic liver diseases. Many studies have investigated the prevalence, distribution and possible contributory role of excess hepatic iron in non-haemochromatotic chronic liver diseases. Indeed, some authors have proposed iron removal in liver diseases other than hereditary haemochromatosis. However, the pathogenesis of secondary iron overload remains unclear. The High Fe （HFE） gene has been implicated, but the reported data are controversial. In this article, we summarise current concepts regarding the cellular role of the HFE protein in iron homeostasis. We review the current status of the literature regarding the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C, hepatitis B, alcoholic and non- alcoholic fatty liver diseases and porphyria cutanea tarda. We discuss the evidence regarding the role of HFE gene mutations in these liver diseases. Finally, we summarize the common and specific features of iron overload in liver diseases other than haemochromatosis.

Primary retroperitoneal mucinous cystadenoma:A case report

Primary retroperitoneal mucinous cystic tumors are extremely rare.These tumors can be classified as a primary retroperitoneal mucinous cystadenoma with or without borderline malignancy or primary retroperitoneal mucinous cystadenocarcinoma.The most common of these is primary retroperitoneal mucinous cystadenoma,which almost always occurs in female patients;only ten cases have been reported in males.The most common clinical findings for this tumor type include nonspecific abdominal pain and a palpable abdominal mass.A definitive diagnosis is usually obtained from histopathology after surgical excision.Here,we report the case of a 60-year-old female patient who complained of abdominal pain that had been present for 3 mo and presented with a palpable abdominal mass.Multidetector computed tomography scanning revealed a large,unilocular cystic mass in the left retroperitoneal space.Surgical intervention was performed and the tumor was completely removed.Histopathologic examination confirmed that the tumor was a primary retroperitoneal mucinous cystadenoma.Two years after surgery,the patient remains disease free.

Perineural invasion as a prognostic factor in patients with stage Ⅰ-Ⅲ rectal cancer –5-year follow up

BACKGROUND Rectal cancer(RC)is one of the most common diagnosed cancers,and one of the major causes of cancer-related death nowadays.Majority of the current guidelines rely on TNM classification regarding therapy regiments,however recent studies suggest that additional histopathological findings could affect the disease course.AIM To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival(OS)of RC patients.METHODS A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic,Clinical Center of Serbia,between the years of 2014–2016.All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification.In addition,the patient’s demographics,surgical details,postoperative pathological details,differentiation degree and their correlation with OS was investigated.RESULTS Of 245 included patients with stage Ⅰ-Ⅲ RC,lymphovascular invasion(LVI)was identified in 92 patients(38%),whereas perineural invasion(PNI)was present in 46 patients(19%).Using Kaplan-Meier analysis for overall survival rate,we have found that both LVI and PNI were associated with lower survival rates(P<0.01).Moreover when Cox multiple regression model was used,LVI,PNI,older age,male gender were predictors of poor prognosis(HR=5.49;95%CI:2.889-10.429;P<0.05).CONCLUSION LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients,hence more aggressive therapy should be reserved for these patients after curative resection.

Double common bile duct: A case report

Double common bile duct （DCBD） is a rare congenital anomaly in which two common bile ducts exist. One usually has normal drainage into the papilla duodeni major and the other usually named accessory common bile duct （ACBD） opens in different parts of upper gastrointestinal tract （stomach, duodenum, ductus pancreaticus or septum）. This anomaly is of great importance since it is often associated with biliary lithiasis, choledochal cyst, anomalous pancreaticobiliary junction （APBJ） and upper gastrointestinal tract malignancies. We recently recognized a rare case of DCBD associated with APB3 with lithiasis in better developed common bile duct. The opening site of ACBD was in the pancreatic duct. The anomaly was suspected by transabdominal ultrasonography and finally confirmed by endoscopic retrograde cholangiopancreatography （ERCP） followed by endoscopic sphincterotomy and stone extraction. According to the literature, the existence of DCBD with the opening of ACBD in the pancreatic duct is most frequently associated with APB3 and gallbladder carcinoma. In case of DCBD, the opening site of ACBD is of greatest clinical importance because of its close implications with concomitant pathology. The adequate diagnosis of this rare anomaly is significant since the operative complications may occur in cases with DCBD which is not recognized prior to surgical treatment.