Carcinosarcoma of the breast:Facing the challenge of a rare nosologic entity

Carcinosarcoma(CS),also known as metaplastic breast carcinoma with mesenchymal differentiation,is one of the five distinct subtypes of metaplastic breast cancer.It is considered as a mixed,biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition zone.Although cellular origin of this neoplasm remains controversial,most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic differentiation.Despite recent research on the therapeutic strategies against CS neoplastic disorders,surgical resection appears the only potentially curative approach.Since CS metastasize by the lymphatic route,axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always implemented.Nevertheless,the tumor also presents a hematogenous metastatic pattern including pleural,pulmonary,liver,brain and less commonly bone metastases.Thus,surgical removal of breast CS does not necessarily ensure patient’s long-term recovery.Moreover,alternative therapies,such as radio-and chemotherapy proved insufficient and 5-year survival rate is limited.Nevertheless,there is evidence that following surgery,the combination of radio and chemotherapy is associated with a better prognosis than either treatment alone.The aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological spread.Clinical features,histogenesis,morphological and immunochemical findings are discussed,while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

Portopulmonary hypertension and serum endothelin levels in hospitalized patients with cirrhosis

BACKGROUND:Cirrhosis is associated with several extrahepatic manifestations including portopulmonary hypertension (PPHT).Recent data suggest that endothelins (ETs) are related to the pathophysiology of PPHT.The study aimed to measure serum ET levels in hospitalized cirrhotic patients and to determine their association with PPHT and patient outcome.METHODS:Fifty-seven cirrhotic patients [43 males;median age 58 (28-87) years] underwent Doppler echocardiography.Patients with systolic pulmonary arterial pressure ≥40 mmHg and pulmonary acceleration time <100 ms were deemed to have PPHT.ET-1,2,and 3 serum levels were measured with an ELISA assay.All-cause mortality was recorded over a median period of 24 months.RESULTS:Nine out of 57 patients (15.8%) had PPHT.Among various clinical variables,only autoimmune hepatitis was associated with PPHT (OR=11.5;95% CI,1.58-83.4;P=0.01).ET-1 levels [9.1 (1.6-20.7) vs 2.5 (1.4-9.2) pg/mL,P=0.02] and the ET-1/ET-3 ratio [4.73 (0.9-22.4) vs 1.6 (0.3-10.7),P=0.02] were significantly higher in patients with PPHT than in those without.ET-2 and ET-3 levels did not differ between the two groups.There was no difference in survival between the two groups,although ET-1 levels were associated with an adverse outcome in Cox regression analysis (HR=1.11;95% CI,1.02-1.22;P=0.02 per unit increase in ET-1).CONCLUSION:Our data suggest that ET-1 and the ET-1/ET-3 ratio are elevated in patients with PPHT and that ET-1 is associated with a poor outcome irrespective of PPHT.

“Oligometastatic pancreatic cancer”definition:The first step

Pancreatic ductal adenocarcinoma(PDAC)is nowadays the fourth leading cause of cancer-related death worldwide,but according to recent estimations it will become the second leading cause of cancer-related deaths in the USA up to 2030,following lung cancer.The implementation of neoadjuvant chemotherapy during recent years led to an increase of overall survival at 35 months in PDAC after R0 resection[1].However,pancreatic cancer has a particularity that makes it a real challenge for clinicians:only 20%of patients are diagnosed early enough to have a resectable pancreatic cancer,whereas 40%of patients present with locally advanced or non-resectable disease,while the rest present with distant metastases[2].Systemic chemotherapy plays the main role in metastatic PDAC treatment:polychemotherapy regimens such as FOLFIRINOX(folinic acid,5-fluorouracil,irinotecan and oxaliplatin)or combination of gemcitabine/nab-paclitaxel seemed to improve median overall survival from 6.8 to 11.1 months and 6.7 to 8.5 months,respectively[3].

Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance?

Metastasis is the principal cause of cancer mortality, with the lymphatic system being the first route of tumor dissemination. The glycoproteins VEGF-C and VEGF-D are members of the vascular endothelial growth factor (VEGF) family, whose role has been recently recognized as lymphatic system regulators during embryogenesis and in pathological processes such as inflammation, lymphatic system disorders and malignant tumor metastasis. They are ligands for the VEGFR-3 receptor on the membrane of the lymphatic endothelial cell, resulting in dilatation of existing lymphatic vessels as well as in vegetation of new ones (lymphangiogenesis). Their determination is feasible in the circulating blood by immunoabsorption and in the tissue specimen by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Experimental and clinicopathological studies have linked the VEGF-C, VEGF-D/VEGFR3 axis to lymphatic spread as well as to the clinical outcome in several human solid tumors. The majority of these data are derived from surgical specimens and malignant cell series, rendering their clinical application questionable, due to subjectivity factors and post-treatment quantification. In an effort to overcome these drawbacks, an alternative method of immunodetection of the circulating levels of these molecules has been used in studies on gastric, esophageal and colorectal cancer. Their results denotethat quantification of VEGF-C and VEGF-D in blood samples could serve as lymph node metastasis predictive biomarkers and contribute to preoperative staging of gastrointestinal malignancies.

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.

Insights on augmenter of liver regeneration cloning and function

Hepatic stimulator substance （HSS） has been referred to as a liver-specific but species non-specific growth factor. Gradient purification and sequence analysis of HSS protein indicated that it contained the augmenter of liver regeneration （ALR）, also known as hepatopoietin （HPO）. ALR, acting as a hepatotrophic growth factor, specifically stimulated proliferation of cultured hepatocytes as well as hepatoma cells in vitro, promoted liver regeneration and recovery of damaged hepatocytes and rescued acute hepatic failure in vivo. ALR belongs to the new Erv1/Alr protein family, members of which are found in lower and higher eukaryotes from yeast to man and even in some double-stranded DNA viruses. The present review article focuses on the molecular biology of ALR, examining the ALR gene and its expression from yeast to man and the biological function of ALR protein. ALR protein seems to be non-liver-specific as was previously believed, increasing the necessity to extend research on mammalian ALR protein in different tissues, organs and developmental stages in conditions of normal and abnormal cellular growth.

Laparoscopic splenectomy:Current concepts

Since early 1990's,when it was inaugurally introduced,laparoscopic splenectomy has been performed with excellent results in terms of intraoperative and postoperative complications.Nowadays laparoscopic splenectomy is the approach of choice for both benign and malignant diseases of the spleen.However some contraindications still apply.The evolution of the technology has allowed though,cases which were considered to be absolute contraindications for performing a minimal invasive procedure to be treated with modified laparoscopic approaches.Moreover,the introduction of advanced laparoscopic tools for ligation resulted in less intraoperative complications.Today,laparoscopic splenectomy is considered safe,with better outcomes in comparison to open splenectomy,and the increased experience of surgeons allows operative times comparable to those of an open splenectomy.In this review we discuss the indications and the contraindications of laparoscopic splenectomy.Moreover we analyze the standard and modified surgical approaches,and we evaluate the short-term and long-term outcomes.

Malignant carcinoid tumor of the cystic duct:a rare cause of bile duct obstruction

BACKGROUND:Carcinoid tumors of the extrahepatic biliary tree are extremely rare malignancies,accounting for 0.2%-2%of all gastrointestinal carcinoid tumors,while carcinoids of the cystic duct are an uncommon entity and an extremely unusual cause of bile duct obstruction.METHODS:After an extensive literature review,we retrospectively analysed 61 cases of carcinoid tumor of the biliary tree as well as one additional case of a 60-yearold female with symptoms and laboratory/imaging examination findings compatible with those of a malignant biliary tract obstruction.At laparotomy,resection of the gallbladder and common bile duct was performed.Histological study revealed a well-differentiated neuroendocrine carcinoma of the cystic duct.The patient remained disease-free at 16 months.RESULTS:Our presentation is the seventh case reported in the world literature.Compared to cholangiocarcinoma,analysis of the reviewed group indicates an increased incidence of extrahepatic carcinoid tumors in younger persons along with a slight female predominance.Statistically,the most common anatomic location is the common bile duct,followed by the perihilar region and the cystic duct.Jaundice is the most common finding.Curative surgery was realized in the majority of cases and longterm disease-free survival was achieved when surgery was curative.CONCLUSIONS:Carcinoid tumors obstructing the biliary tree are extremely difficult to diagnose preoperatively,and nearly impossible to differentiate from non-neuroendocrine tumors.As surgery offers the only potential cure for both biliary carcinoids and cholangiocarcinoma,we recommend aggressive surgical therapy as the treatment of choice in every case of potentially resectable biliary tumor.

Markers of bacterial translocation in end-stage liver disease

Bacterial translocation(BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence.BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT.

Circulating autoantibodies to endogenous erythropoietin are associated with chronic hepatitis C virus infection-related anemia

BACKGROUND： Chronic hepatitis C virus （HCV） infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin （anti-EPO） have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in pa- tients with chronic HCV infection and investigate its possible association with anemia. METHODS： Ninety-three consecutive patients （62 males and 31 females） with chronic HCV infection, who had never re- ceived antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load t and genotype sequencing were also performed. RESULTS： Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia （19.4% vs 5.3%, P=0.040） compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia （70.0% vs 34.9%, P=0.030）, lower EPO concentrations （median 16.35 vs 30.65 mU/mL, P=0.005）, and higher HCV RNA viral load （median 891.5x103 vs 367.5x 103 IU/mL, P=0.016）. In multivariate regression anal- ysis the presence of anti-EPO remained an independent predictor of anemia （adjusted OR： 14.303, 95% CI： 1.417-36.580, P=0.024）. EPO response to anemia was less prominent among anti-EPO positive patients （P=0.001）. CONCLUSIONS： Circulating anti-EPO are detected in a significant proportion of treatment-naive HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.

Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy

AIM To highlight the potential mechanisms of regeneration in the Associating Liver Partition and Portal vein ligation for Stage hepatectomy models(clinical and experimental) that could unlock the myth behind the extraordinary capability of the liver for regeneration,which would help in designing new therapeutic options for the regenerative drive in difficult setup,such as chronic liver diseases. Associating Liver Partition and Portal vein ligation for Stage hepatectomy has been recently advocated to induce rapid future liver remnant hypertrophy that significantly shortens the time for the second stage hepatectomy. The introduction of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in the surgical armamentarium of therapeutic tools for liver surgeons represented a real breakthrough in the history of liver surgery. METHODS A comprehensive literature review of Associating Liver Partition and Portal vein ligation for Stage hepatectomy and its utility in liver regeneration is performed. RESULTS Liver regeneration after Associating Liver Partition and Portal vein ligation for Stage hepatectomy is a combination of portal flow changes and parenchymal transection that generate a systematic response inducing hepatocyte proliferation and remodeling. CONCLUSION Associating Liver Partition and Portal vein ligation for Stage hepatectomy represents a real breakthrough in the history of liver surgery because it offers rapid liver regeneration potential that facilitate resection of liver tumors that were previously though unresectable. The jury is still out though in terms of safety,efficacy and oncological outcomes. As far as Associating Liver Partition and Portal vein ligation for Stage hepatectomy-induced liver regeneration is concerned,further research on the field should focus on the role of nonparenchymal cells in liver regeneration as well as on the effect of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in liver regeneration in the setup of parenchymal liver disease.

Concept of histone deacetylases in cancer:Reflections on esophageal carcinogenesis and treatment

Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type world-wide, though, a continuous increase in esophageal adenocarcinomas has been noted in the past decades. Common risk factors associated with EC include smoking, alcohol consumption, gastroesophageal reflux disease, Barrett's esophagus and obesity. In an effort to overcome chemotherapy resistance in oncology, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Based on this knowledge, histone acetylation was addressed as a potential novel chemotherapy drug target to repress cancer cell proliferation. There are four classes of histone deacetylases (HDACs) inhibitors with a variety of different mechanisms of actions that render them possible anticancer drugs. They arrest the cell cycle, inhibit differentiation and angiogenesis and induce apoptosis. They do not necessarily act on histone proteins, since they can also exert indirect anti-cancer effects, by modifying various cellular proteins.In addition,HDACs have also been associated with increased chemotherapy resistance.Based on the literature,HDACs have been associated with EC,with surveys revealing that increased expression of certain HDACs correlates with advanced TNM stages,tumor grade,metastatic potential and decreased 5-year overall and disease-free survival.The aim of this survey is to elucidate the molecular identity and mechanism of action of HDAC inhibitors as well as verify their potential utility as anti-cancer agents in esophageal cancer.

Effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats: What we know so far?

To the editor:We read with great interest the article entitled "Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats" by Ulmer et al.[1].The aim of this study was to analyse the impact of terlipressin ver-

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 m L),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.

Synchronous resection of esophageal cancer and other organ malignancies: A systematic review

BACKGROUND Neoplasms arising in the esophagus may coexist with other solid organ or gastrointestinal tract neoplasms in 6%to 15%of patients.Resection of both tumors synchronously or in a staged procedure provides the best chances for long-term survival.Synchronous resection of both esophageal and second primary malignancy may be feasible in a subset of patients;however,literature on this topic remains rather scarce.AIM To analyze the operative techniques employed in esophageal resections combined with gastric,pancreatic,lung,colorectal,kidney and liver resections and define postoperative outcomes in each case.METHODS We conducted a systematic review according to PRISMA guidelines.We searched the Medline database for cases of patients with esophageal tumors coexisting with a second primary tumor located in another organ that underwent synchronous resection of both neoplasms.All English language articles deemed eligible for inclusion were accessed in full text.Exclusion criteria included:(1)Hematological malignancies;(2)Head/neck/pharyngeal neoplasms;(3)Second primary neoplasms in the esophagus or the gastroesophageal junction;(4)Second primary neoplasms not surgically excised;and(5)Preclinical studies.Data regarding the operative strategy employed,perioperative outcomes and longterm outcomes were extracted and analyzed using descriptive statistics.RESULTS The systematic literature search yielded 23 eligible studies incorporating a total of 117 patients.Of these patients,71%had a second primary neoplasm in the stomach.Those who underwent total gastrectomy had a reconstruction using either a colonic(n=23)or a jejunal(n=3)conduit while for those who underwent gastric preserving resections(i.e.,non-anatomic/wedge/distal gastrectomies)a conventional gastric pull-up was employed.Likewise,in cases of patients who underwent esophagectomy combined with pancreaticoduodenectomy(15%of the cohort),the decision to preserve part of the stomach or not dictated the reconstruction method(whether by a gastric pullup or a colonic/jejunal limb).For the remaining patients with coexisting lung/colorectal/kidney/liver neoplasms(14%of the entire patient population)the types of resections and operative techniques employed were identical to those used when treating each malignancy separately.CONCLUSION Despite the poor quality of available evidence and the great interstudy heterogeneity,combined procedures may be feasible with acceptable safety and satisfactory oncologic outcomes on individual basis.

Histone deacetylase inhibitors as a novel therapeutic approach for pheochromocytomas and paragangliomas

Epigenetic mechanisms,such as DNA methylation and histone modifications(e.g.,acetylation and deacetylation),are strongly implicated in the carcinogenesis of various malignancies.During transcription,the expression and functionality of coding gene products are altered following the histone acetylation and deacetylation.These processes are regulated by histone acetyltransferases(HATs)and histone deacetylases(HDACs),respectively.HDAC inhibitors(HDACis)have been developed as promising therapeutic agents,to limit exposure to traditional and toxic chemotherapies and offer more alternatives for some specific malignant diseases with limited options.Mechanistically,these agents affect many intracellular pathways,including cell cycle arrest,apoptosis and differentiation,and their mechanism of action mainly depends on the type of cancer.Currently,five HDACis have been approved for the treatment of several hematological malignancies(e.g.,T-cell lymphoma subtypes and multiple myeloma);while,many of them are tested for further therapeutic indications in solid tumors(e.g.,colorectal,thyroid,breast,lung and pancreatic cancer).Herein,we review the literature and gather all available evidence,from in vitro and in vivo data to clinical trial results,that recognizes the antitumor activity of HDACis on pheochromocytomas and paragangliomas;and supports their clinical implementation in the treatment of these rare neuroendocrine tumors at metastatic setting.

Oxidative imbalance increases the risk for colonic polyp and colorectal cancer development

BACKGROUND The role of oxidative stress in the pathogenesis of colorectal carcinoma(CRC)has garnered considerable interest recently.Specific oxidative factors have been implicated in the pathogenesis of adenomatous polyps and ultimately adenocarcinoma.AIM To evaluate the effect of oxidative imbalance as quantified by specific serological markers in the development of sporadic colon adenocarcinoma.METHODS A total of 170 patients that underwent endoscopy of the lower gastrointestinal tract in a tertiary center within 3 years were included in the study.They were allocated in three groups;those with sporadic colon adenocarcinoma(n=56,32.9%),those with colonic polyps(n=33,19.4%)and healthy controls(n=81,47.7%).All patients were evaluated for oxidant activity and antioxidant capacity with serum measurements of specific markers such as vitamins A,25(OH)D3,E,C,B12,folic acid,glutathione,selenium(Se),zinc(Zn),free iron(Fe^(2+)),and malondialdehyde and results were compared between groups.RESULTS Serum levels of vitamins C,E,D,Se,Zn,vitamin B12 and total antioxidant capacity were significantly lower in the combined neoplasia/polyp group than in the control group(P=0.002,P=0.009,P<0.001,P<0.001,P<0.001,P=0.020 and P<0.001,correspondingly).Increased levels of vitamin E(P=0.004),vitamin D(P<0.001),Se(P<0.001)and Zn(P<0.001)seem to bestow a protective effect on the development of CRC.For vitamin D(P<0.001)and Zn(P=0.036),this effect seems to extend to the development of colon polyps as well.On the other hand,elevated serum levels of malondialdehyde are associated with a higher risk of CRC(OR=2.09 compared to controls,P=0.004).Regarding colonic polyp development,increased concentrations of vitaminΑand Fe^(2+) are associated with a higher risk,whereas lower levels of malondialdehyde with a lower risk.CONCLUSION Increased oxidative stress may play an important role in the pathogenesis and progression of CRC.Antioxidants’presence may exert a protective effect in the very early stages of colon carcinogenesis.

Trimodality treatment in gastric and gastroesophageal junction cancers:Current approach and future perspectives

Gastric and gastroesophageal junction(GEJ)cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage,with an increasing incidence both in Asia and in Western countries.These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses.Accordingly,the understanding of phenotypic and genotypic correlations/classifications has been improved.Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone,with the incorporation of other treatment modalities,such as radiation and chemotherapy(including biologics).Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival.Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate,which is associated with improved long-term outcomes.Several studies have defined various chemotherapy regimens to accompany radiation(before and after surgery).Recently,addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval.Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results.The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers,highlight the remaining questions and present the current research effort addressing them.

Acute esophageal necrosis: A systematic review and pooled analysis

BACKGROUND Acute esophageal necrosis(AEN)is a rare entity with multifactorial etiology,usually presenting with signs of upper gastrointestinal bleeding.AIM To systematically review all available data on demographics,clinical features,outcomes and management of this medical condition.METHODS A systematic literature search was performed with respect to the PRISMA statement(end-of-search date:October 24,2018).Data on the study design,interventions,participants and outcomes were extracted by two independent reviewers.RESULTS Seventy-nine studies were included in this review.Overall,114 patients with AEN were identified,of whom 83 were males and 31 females.Mean patient age was 62.1±16.1.The most common presenting symptoms were melena,hematemesis or other manifestations of gastric bleeding(85%).The lower esophagus was most commonly involved(92.9%).The most widely implemented treatment modality was conservative treatment(75.4%),while surgical or endoscopic intervention was required in 24.6%of the cases.Mean overall followup was 66.2±101.8 d.Overall 29.9%of patients died either during the initial hospital stay or during the follow-up period.Gastrointestinal symptoms on presentation[Odds ratio 3.50(1.09-11.30),P=0.03]and need for surgical or endoscopic treatment[surgical:Odds ratio 1.25(1.03-1.51),P=0.02;endoscopic:Odds ratio 1.4(1.17-1.66),P<0.01]were associated with increased odds of complications.A sub-analysis separating early versus late cases(after 2006)revealed a significantly increased frequency of surgical or endoscopic intervention(9.7%vs 30.1%respectively,P=0.04)CONCLUSION AEN is a rare condition with controversial pathogenesis and unclear optimal management.Although the frequency of surgical and endoscopic intervention has increased in recent years,outcomes have remained the same.Therefore,further research work is needed to better understand how to best treat this potentially lethal disease.

Serum Calprotectin and Prealbumin Levels among Ovarian Cancer Patients Aged 30 - 45 Years

Purpose: Serum calprotectin and prealbumin have been previously linked with ovarian cancer. However, to date, their effectiveness in the diagnosis of the disease remains uncertain. The purpose of the present study is to determine whether serum prealbumin and calprotectin correlate with the stage and type of histologic diagnosis. Materials-Methods: In the present study, we included 80 women aged 30 - 45 years that had either primary ovarian cancer (Stages 1 and 2) with elevated levels of CA-125 (n = 40) or were healthy (n = 40). Serum calprotectin and prealbumin levels were assessed using ELISA kits. Statistical analysis was performed with SPSS v.20.0 statistical software. Results: Both plasma prealbumin and calprotectin levels were significantly different in patients with ovarian cancer compared to healthy controls. Specifically, serum prealbumin levels showed a level towards decreasing as the stage of the disease advanced (21.2 (15.5 - 30.6) in healthy controls, 12.8 (6.9 - 16) for patients with stage 1 disease and 9.9 (4.0 - 15.5) for patients with stage 2 disease p p Conclusions: Both prealbumin and calprotectin seem to be useful markers for the identification of patients suffering from ovarian cancer.