T-regulatory lymphocytes in peripheral blood of gastric and colorectal cancer patients

AIM: To assess the absolute number of T-regulatory cells (Tregs; CD4+CD25+Foxp3+) in the peripheral blood of gastric and colorectal cancer patients. METHODS: We enrolled 70 cancer patients (33 gastric cancer, 37 colorectal cancer) and 17 healthy volunteers. The CD3+CD4+ lymphocytes and CD4+CD25+Foxp3+ Tregs in the peripheral blood were analyzed with flow cytometry. The absolute numbers of Tregs were calculated based on the CD4+CD25+Foxp3+ cells percent-age of CD3+CD4+ cells and the absolute numbers of CD3+CD4+ cells per microliter. RESULTS: The mean number of CD4+CD25+Foxp3+ cells per microliter in colorectal cancer patients was 15.7 (SD: 21.8), for gastric cancer patients 12.2 (SD: 14.3), and for controls 17.5 (SD: 11.4). The absolute number of Tregs was significantly lower in gastric cancer patients than in controls (P = 0.026). There was no statistically significant difference for gastric vs colorectal cancer or colorectal cancer vs controls. The absolute number of Tregs was also significantly depressed in N+ vs Ncancer patients [22.0 (27.7) vs 10.1 (9.0), P = 0.013], and in the subgroup of gastric cancer patients [30.3 (27.6) vs 9.6 (8.0), P = 0.003]. No statistical difference was observed in the proportion of Tregs in the CD4+ population between the groups. CONCLUSION: The absolute number of Tregs in peripheral blood of gastric cancer but not colorectal cancer patients was significantly decreased in comparison with that in healthy controls.

Large symptomatic gastric diverticula:Two case reports and a brief review of literature

Gastric diverticula are rare and uncommon conditions.Most gastric diverticula are asymptomatic.When symptoms arise,they are most commonly upper abdominal pain,nausea and emesis,while dyspepsia and vomiting are less common.Occasionally,patients with gastric diverticula can have dramatic presentations related to massive bleeding or perforation.The diagnosis may be difficult,as symptoms can be caused by more common gastrointestinal pathologies and only aggravated by diverticula.The appropriate management of diverticula depends mainly on the symptom pattern and as well as diverticulum size.There is no specific therapeutic strategy for an asymptomatic diverticulum.Although some authors support conservative therapy with antacids,this provides only temporary symptom relief since it is not able to resolve the underlying pathology.Surgical resection is the mainstay of treatment when the diverticulum is large,symptomatic or complicated by bleeding,perforation or malignancy,with over two-thirds of patients remaining symptom-free after surgery,while laparoscopic resection,combined with intraoperative endoscopy,is a safe and feasible approach with excellent outcomes.Here,we present two cases of uncommon large symptomatic gastric diverticula with a discussion of the cornerstones in management and report a minimally invasive solution,with a brief review of the literature.

Transoral surgery for morbid obesity

Obesity is a serious health problem in the United States.Although laparoscopic surgical procedures are effective in achieving weight loss and improving obesity-related co-morbidities,they are not without their limitations and consequently there is a growing demand for less invasive approaches.Transoral techniques,as both primary and revisional procedures,are promising in this regard as they may provide a safer and more cost-effective means of achieving meaningful weight loss.The aim of this paper is to review the currently available transoral approaches to weight loss,with a particular focus on those applied in human trials.

Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region

AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%).Accordingly,the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7(42.9%) vs 2 of 49(4.1%),P < 0.05].Of the pathological characteristics,only an infiltrative pattern of macroscopic tumor type significantly correlated with the presence of HPV DNA in ESCC samples [20 of 27(74.1%) vs 8 of 29(27.6%) for ulcerative or protruding macroscopic type,P < 0.05].The occurrence of total HPV DNA and both HPV high or low risk phenotypes did not significantly differ with regard to particular grades of cellular differentiation,phases in depth of tumor infiltration,grades of nodal involvement and stages of tumor progression.CONCLUSION:Low risk HPV phenotypes could be one of the co-activators or/and co-carcinogens in complex,progressive,multifactorial and multistep esophageal carcinogenesis.

Clinical management of advanced gastric cancer: The role of new molecular drugs

Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual &#x0201c;scenario&#x0201d; of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice.

Prevalence of bile reflux in gastroesophageal reflux disease patients not responsive to proton pump inhibitors

AIM:To determine the prevalence and characteristics of bile reflux in gastroesophageal reflux disease(GERD) patients with persistent symptoms who are non-responsive to medical therapy.METHODS:Sixty-five patients(40 male,25 female;mean age,50 ± 7.8 years) who continued to report symptoms after 8 wk of high-dose proton pump inhibitor(PPI) therapy,as well as 18 patients with Barrett's esophagus,were studied.All patients filled out symptom questionnaires and underwent endoscopy,manometry and combined pH-metry and bilimetry.RESULTS:There were 4 groups of patients:22(26.5%) without esophagitis,24(28.9%) grade A-B esophagitis,19(22.8%) grade C-D and 18(21.6%) Barrett's esophagus.Heartburn was present in 71 patients(85.5%) and regurgitation in 55(66.2%),with 44(53%) reporting simultaneous heartburn and regurgitation.The prevalence of pathologic acid reflux in the groups without esophagitis and with grades A-B and C-D esophagitis was 45.4%,66.6% and 73.6%,respectively.The prevalence of pathologic bilirubin exposure in these 3 groups was 53.3%,75% and 78.9%,respectively.The overall prevalence of bile reflux in non-responsive patients was 68.7%.Pathologic acid and bile reflux was observed in 22.7% and 58.1% of non-esophagitic patients and esophagitic patients,respectively.CONCLUSION:The high percentage of patients poorly responsive to PPI therapy may result from poor control of duodenogastroesophageal reflux.Many patients without esophagitis have simultaneous acid and bile reflux,which increases with increasing esophagitis grade.

Laparoscopic calibrated total vs partial fundoplication following Heller myotomy for oesophageal achalasia

AIM:To compare the mid-term outcomes of laparoscopic calibrated Nissen-Rossetti fundoplication with Dor fundoplication performed after Heller myotomy for oesophageal achalasia.METHODS:Fifty-six patients(26 men,30 women;mean age 42.8±14.7 years)presenting for minimally invasive surgery for oesophageal achalasia,were enrolled.All patients underwent laparoscopic Heller myotomy followed by a 180°anterior partial fundoplication in 30 cases(group 1)and calibrated NissenRossetti fundoplication in 26(group 2).Intraoperative endoscopy and manometry were used to calibrate the myotomy and fundoplication.A 6-mo follow-up period with symptomatic evaluation and barium swallow was undertaken.One and two years after surgery,the patients underwent symptom questionnaires,endoscopy,oesophageal manometry and 24 h oesophago-gastric pH monitoring.RESULTS:At the 2-year follow-up,no significant difference in the median symptom score was observed between the 2 groups(P=0.66;Mann-WhitneyU-test).The median percentage time with oesophageal pH< 4 was significantly higher in the Dor group compared to the Nissen-Rossetti group(2;range 0.8-10 vs 0.35;range 0-2)(P<0.0001;Mann-WhitneyU-test).CONCLUSION:Laparoscopic Dor and calibrated Nissen-Rossetti fundoplication achieved similar results in the resolution of dysphagia.Nissen-Rossetti fundoplication seems to be more effective in suppressing oesophageal acid exposure.

Role of laryngeal mask airway in laparoscopic cholecystectomy

Laparoscopic cholecystectomy is one of the most commonly performed surgical procedures and the laryngeal mask airway(LMA) is the most common supraglottic airway device used by the anesthesiologists to manage airway during general anesthesia. Use of LMA has some advantages when compared to endotracheal intubation, such as quick and ease of placement, a lesser requirement for neuromuscular blockade and a lower incidence of postoperative morbididy. However, the use of the LMA in laparoscopy is controversial, based on a concern about increased risk of regurgitation and pulmonary aspiration. The ability of these devices to provide optimal ventilation during laparoscopic procedures has been also questioned. The most important parameter to secure an adequate ventilation and oxygenation for the LMA under pneumoperitoneum condition is its seal pressure of airway. A good sealing pressure, not only state correct patient ventilation, but it reduces the potential risk of aspiration due to the better seal of airway. In addition, the LMAs incorporating a gastric access, permitting a safe anesthesia based on these commented points. We did a literature search to clarify if the use of LMA in preference to intubation provides inadequate ventilation or increase the risk of aspiration in patients undergoing laparoscopic cholecystectomy. We found evidence stating that LMA with drain channel achieves adequate ventilation for these procedures. Limited evidence was found to consider these devices completely safe against aspiration. However, we observed that the incidence of regurgitation and aspiration associated with the use of the LMA in laparoscopic surgery is very low.

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP).

Outcomes of inpatient cholecystectomy among adults with cystic fibrosis in the United States

BACKGROUND Symptomatic biliary and gallbladder disorders are common in adults with cystic fibrosis(CF)and the prevalence may rise with increasing CF transmembrane conductance regulator modulator use.Cholecystectomy may be considered,but the outcomes of cholecystectomy are not well described among modern patients with CF.AIM To determine the risk profile of inpatient cholecystectomy in patients with CF.METHODS The Nationwide Inpatient Sample was queried from 2002 until 2014 to investigate outcomes of cholecystectomy among hospitalized adults with CF compared to controls without CF.A propensity weighted sample was selected that closely matched patient demographics,patient’s individual comorbidities,and hospital characteristics.The propensity weighted sample was used to compare outcomes among patients who underwent laparoscopic cholecystectomy.Hospital outcomes of open and laparoscopic cholecystectomy were compared among adults with CF.RESULTS A total of 1239 inpatient cholecystectomies were performed in patients with CF,of which 78.6%were performed laparoscopically.Mortality was<0.81%,similar to those without CF(P=0.719).In the propensity weighted analysis of laparoscopic cholecystectomy,there was no difference in mortality,or pulmonary or surgical complications between patients with CF and controls.After adjusting for significant covariates among patients with CF,open cholecystectomy was independently associated with a 4.8 d longer length of stay(P=0.018)and an$18449 increase in hospital costs(P=0.005)compared to laparoscopic cholecystectomy.CONCLUSION Patients with CF have a very low mortality after cholecystectomy that is similar to the general population.Among patients with CF,laparoscopic approach reduces resource utilization and minimizes post-operative complications.

Normothermic Ex-vivo Liver Perfusion and the Clinical Implications for Liver Transplantation

Despite significant improvements in outcomes after liver trans-plantation,many patients continue to die on the waiting list,while awaiting an available organ for transplantation.Organ shortage is not only due to an inadequate number of available organs,but also the inability to adequately assess and evaluate these organs prior to transplantation.Over the last few decades,ex-vivo perfusion of the liver has emerged as a useful technique for both improved organ preservation and assessment of organs prior to transplantation.Large animal studies have shown the superiority of ex-vivo perfusion over cold static storage.However,these studies have not,necessa-rily,been translatable to human livers.Small animal studies have been essential in understanding and improving this tech-nology.Similarly,these results have yet to be translated into clinical use.A few Phase 1 clinical trials have shown promise and confirmed the viability of this technology.However,more robust studies are needed before ex-vivo liver perfusion can be widely accepted as the new clinical standard of organ preser-vation.Here,we aimed to review al relevant large and smal animal research,as well as human liver studies on normother-mic ex-vivo perfusion,and to identify areas of deficiency and opportunities for future research endeavors.

Anatomy of the perirectal fascia at the level of rectosacral fascia revisited

Background:The relative anatomical understanding of the perirectal fasciae is of paramount importance for the proper performance of total mesorectal excision(TME).This study was to demonstrate the planes of TME and validates the intraoperative findings using cadaveric observations.Methods:In this combined retrospective and prospective study,bilateral attachment of the rectosacral fascia(RSF)was observed in 28 cadaveric specimens(male,n=14;female,n=14).From January 2018 to December 2019,surgical videos of 67 patients who underwent laparoscopic TME at the Affiliated Union Hospital of Fujian Medical University(Fuzhou,China)were reviewed and interpreted with the cadaveric findings.Results:The RSF(synonym:Waldeyer’s fascia)is the end of the pre-hypogastric fascia at the level of S4 and comprises two layers(upper and lower).These two layers provide double fascial protection for the venous sacral plexus.It inserts into the fascia propria of the rectum along a broad horizontal arc that merges anterolaterally in an oblique downward direction until it meets the posterolateral merge of Denonvilliers’fascia at the lateral rectal ligament(LRL).This ligament does not look like a true ligament but is more likely to be a fascial combination that cushions the rectal innervation and middle rectal vessels.Conclusions:Understanding the lateral attachment of RSF and its contribution to LRL provides invaluable surgical guidance to dissect this critical area.Therefore,lateral dissection is proposed from the anterior to the posterior direction to find the correct plane that guarantees an intact mesorectal envelope to protect the important nearby nerve structures.

Detection of circulating tumor cells in blood of pancreatic ductal adenocarcinoma patients

Aim:Previous studies suggest that circulating tumor cells(CTC)are present at very low frequencies in blood of pancreatic cancer(PC)patients.However,no technique has proven efficient for their detection,in part due to the lack of accurate tumor markers.Here,we evaluated the potential utility of two marker candidates-Mucin 16(MUC16)and Tetraspanin 1(TSPAN1)-identified through a detailed review of the literature.Methods:To evaluate the pattern of expression of both markers in pancreatic tumor cells vs.normal blood,we used cell lines derived from pancreatic cancer patients and blood from healthy adults.Results:Antibodies against both MUC16 and TSPAN1 showed expression in three pancreatic cancer(PC)cell lines while they were absent in blood cells.To evaluate the efficiency of isolating tumor cells from blood,PC cell lines were spiked at different frequencies in blood,sequentially stained with biotin-conjugated TSPAN1 and MUC16 antibodies and a streptavidin ferrofluids,followed by immunomagnetic enrichment.The recovery of spiked TSPAN1+tumor cells was high with limited contamination by leukocytes.In contrast,no PC cells were isolated when the biotin MUC16 reagent was used because the biotin-conjugated clone did not recognize PC cells.Conclusion:The combination of MUC16,TSPAN1,and epithelial cell adhesion molecule(EpCAM)antibodies will likely increase the efficiency of capturing circulating tumor cell in blood of pancreatic ductal adenocarcinoma.To further develop a protocol for isolation of circulating tumor cell in blood of PC patients,high amounts of antibodies(5-10 mg)against EpCAM,MUC16,and TSPAN1 will be needed.