Evaluation of bacterial contamination and medium-term oncological outcomes of intracorporeal anastomosis for colon cancer:A propensity score matching analysis

BACKGROUND Although intracorporeal anastomosis(IA)for colon cancer requires longer operative time than extracorporeal anastomosis(EA),its short-term postoperative results,such as early recovery of bowel movement,have been reported to be equal or better.As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum,there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells.However,intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified.abdominal cavity in IA.METHODS Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020,75 underwent EA(EA group),and 52 underwent IA(IA group).After propensity score matching,the primary endpoint was 3-year disease-free survival rates,and secondary endpoints were 3-year overall survival rates,type of recurrence,surgical site infection(SSI)incidence,number of days on antibiotics,and postoperative biological responses.RESULTS Three-year disease-free survival rates did not significantly differ between the IA and EA groups(87.2%and 82.7%,respectively,P=0.4473).The 3-year overall survival rates also did not significantly differ between the IA and EA groups(94.7%and 94.7%,respectively;P=0.9891).There was no difference in the type of recurrence between the two groups.In addition,there were no significant differences in SSI incidence or the number of days on antibiotics;however,postoperative biological responses,such as the white blood cell count(10200 vs 8650/mm^(3),P=0.0068),C-reactive protein(6.8 vs 4.5 mg/dL,P=0.0011),and body temperature(37.7 vs 37.5℃,P=0.0079),were significantly higher in the IA group.CONCLUSION IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.

Establishment of a surveillance program for anal cancer in Crohn's disease

This letter discusses the incidence of anal cancer among Crohn's disease(CD)-related malignancies.Patients with CD have been demonstrated to be at a higher risk of developing small bowel and colorectal cancers than healthy individuals.Although CD-associated anal cancer is relatively rare,patients with CD accom-panied by anal or perianal lesions are at increased risk of anal cancer.Addi-tionally,compared to ulcerative colitis,which is also an inflammatory disease,CD-related anal cancer is often detected at an advanced stage owing to the complexity of CD and is associated with a poor prognosis with frequent local recurrences.Therefore,the detection of early-stage cancer is crucial for improving the prognosis.However,the surveillance methods recommended for CD-related malignancies in the United States and Europe are similar to those for ulcerative colitis.They are not appropriate for detecting CD-related malignancies in the recto-anal region.Therefore,there is an urgent need for surveillance programs aimed at the early detection of malignant anorectal lesions in patients with CD.

Machine learning algorithms able to predict the prognosis of gastric cancer patients treated with immune checkpoint inhibitors

BACKGROUND Although immune checkpoint inhibitors(ICIs)have demonstrated significant survival benefits in some patients diagnosed with gastric cancer(GC),existing prognostic markers are not universally applicable to all patients with advanced GC.AIM To investigate biomarkers that predict prognosis in GC patients treated with ICIs and develop accurate predictive models.METHODS Data from 273 patients diagnosed with GC and distant metastasis,who un-derwent≥1 cycle(s)of ICIs therapy were included in this study.Patients were randomly divided into training and test sets at a ratio of 7:3.Training set data were used to develop the machine learning models,and the test set was used to validate their predictive ability.Shapley additive explanations were used to provide insights into the best model.RESULTS Among the 273 patients with GC treated with ICIs in this study,112 died within 1 year,and 129 progressed within the same timeframe.Five features related to overall survival and 4 related to progression-free survival were identified and used to construct eXtreme Gradient Boosting(XGBoost),logistic regression,and decision tree.After comprehensive evaluation,XGBoost demonstrated good accuracy in predicting overall survival and progression-free survival.CONCLUSION The XGBoost model aided in identifying patients with GC who were more likely to benefit from ICIs therapy.Patient nutritional status may,to some extent,reflect prognosis.

Goblet cell carcinoid of the appendix:Six case reports

BACKGROUND Goblet cell carcinoid(GCC)of the appendix is a rare tumor characterized by neuroendocrine and adenocarcinoma features.Accurate preoperative diagnosis is very difficult,with most patients complaining mainly of abdominal pain.Computed tomography shows swelling of the appendix,so diagnosis is usually made incidentally after appendectomy based on a preoperative diagnosis of appendicitis.Even if a patient undergoes preoperative colonoscopy,accurate endoscopic diagnosis is very difficult because GCC shows a submucosal growth pattern with invasion of the appendiceal wall.CASE SUMMARY Between 2017 and 2022,6 patients with GCC were treated in our hospital.The presenting complaint for 5 of these 6 patients was abdominal pain.All 5 patients underwent appendectomy,including 4 for a preoperative diagnosis of appendicitis and the other for diagnosis and treatment of an appendiceal tumor.The sixth patient presented with vomiting and underwent ileocecal resection for GCC diagnosed from preoperative biopsy.Although 2 patients with GCC underwent colonoscopy,no neoplastic changes were identified.Two of the six patients showed lymph node metastasis on pathological examination.As of the last followup(median:15 mo),all cases remained alive without recurrence.CONCLUSION As preoperative diagnosis of GCC is difficult,this possibility must be considered during surgical treatments for presumptive appendicitis.

Distal margin distance in radical resection of locally advanced rectal cancer after neoadjuvant therapy

Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse.Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function.However, there is currently no consensus on the specific distance of distal resection margin.

Significance of regenerating islet-derived type Ⅳ gene expression in gastroenterological cancers

The regenerating islet-derived members （Reg）, a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers, functioning as trophic or antiapoptotic factors. Regenerat- ing islet-derived type Ⅳ （RegⅣ）, a member of the Reg gene family, has been reported to be overexpressed in gastroenterological cancers. RegIV overexpression in tumor cells has been associated with carcinogen- esis, cell growth, survival and resistance to apoptosis. Cancer tissue expressing RegIV is generally associated with more malignant characteristics than that with- out such expression, and RegⅣ is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers. We previously investigated the expression levels of RegⅣ mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegⅣ gene expression was a significant independent predictor of colorec- tal cancer. The biologic functions of RegⅣ protein in cancer tissue, associated with carcinogenesis, anti- apoptosis and invasiveness, are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegIV, and the feasibility of antibody therapy targeting RegIV is being assessed. These studies may lead to novel therapeutic strate- gies for gastroenterological cancers expressing RegⅣ. This review article summarizes the current information related to biological functions as well as clinical impor- tance of RegⅣ gene to clarify the significance of Reg~ expression in gastroenterological cancers.

possible role of soluble fibrin monomer complex after gastroenterological surgery

AIM To examine the role of soluble fibrin monomer complex(SFMC) in the prediction of hypercoagulable state after gastroenterological surgery.METHODS We collected data on the clinical risk factors and fibrin-related makers from patients who underwent gastroenterological surgery at Hiroshima University Hospital between April 1, 2014 and March 31, 2015. We investigated the clinical significance of SFMC, which is known to reflect the early plasmatic activation of coagulation, in the view of these fibrin related markers.RESULTS A total of 123 patients were included in the present study. There were no patients with symptomatic VTE. Thirty-five(28%) patients received postoperative anticoagulant therapy. In the multivariate analysis, a high SFMC level on POD 1 was independently associated with D-dimer elevation on POD 7(OR = 4.31, 95%CI: 1.10-18.30, P = 0.03). The cutoff SFMC level was 3.8 μg/ml(AUC = 0.78, sensitivity, 63%, specificity, 89%). The D-dimer level on POD 7 was significantly reduced in high-SFMC patients who received anticoagulant therapy in comparison to highSFMC patients who did not.CONCLUSION The SFMC on POD 1 strongly predicted the hypercoagulable state after gastroenterological surgery than the clinical risk factors and the other fibrin related markers.

Current status and future perspectives for the treatment of resectable locally advanced esophagogastric junction cancer:A narrative review

Incidence rates for esophagogastric junction cancer are rising rapidly worldwide possibly due to the economic development and demographic changes.Therefore,increased attention has been paid to the prevention,diagnosis,and the treatment of esophagogastric junction cancer.Although there are discrepancies in the treatment strategy between Asian and Western countries,surgery remains the mainstay of treatment for esophagogastric junction cancer.Recent developments of perioperative multidisciplinary treatment may lead to better therapeutic effect,higher complete resection rate,and better control of the residual diseases,thus result in prolonged prognosis.In this review,we will focus on the treatment of locally advanced resectable esophagogastric junction cancer,and discuss the current status and future perspectives of the perioperative treatment including chemotherapy,radiation therapy,and immunotherapy,as well as the surgical strategy.Better understanding of the latest treatment strategy and future overlook may enable to standardize and individualize the treatment for esophagogastric junction cancer,thus leading to better prognosis for those patients.

Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection(ESD)for early-stage gastrointestinal tumors.The rate of post-ESD bleeding for gastric cancer is higher(around 5%-8%)than that for esophagus,duodenum and colon cancer(around 2%-4%).Although investigations into the risk factors for post-ESD bleeding have identified several procedure-,lesion-,physician-and patient-related factors,use of antithrombotic drugs,especially anticoagulants[direct oral anticoagulants(DOACs)and warfarin],is thought to be the biggest risk factor for post-ESD bleeding.In fact,the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%,which is higher than that in patients not receiving anticoagulants.However,because clinical guidelines for management of ESD in patients receiving DOACs differ among countries,it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice.Given that the pharmacokinetics(e.g.,plasma DOAC level at both trough and T_(max))and pharmacodynamics(e.g.,anti-factor Xa activity)of DOACs are related to risk of major bleeding,plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

Oncologic impact of colonic stents for obstructive left-sided colon cancer

Colonic stenting has had a significant positive impact on the management of obstructive left-sided colon cancer(OLCC) in terms of both palliative treatment and bridge-to-surgery(BTS). Notably, many studies have convincingly demonstrated the effectiveness of stenting as a BTS, resulting in improvements in shortterm outcomes and quality of life, safety, and efficacy in subsequent curative surgery, and increased cost-effectiveness, whereas the safety of chemotherapy after stenting and the long-term outcomes of stenting as a BTS are controversial. Several studies have suggested an increased risk of perforation in patients receiving bevacizumab chemotherapy after colonic stenting. In addition, several pathological analyses have suggested a negative oncological impact of colonic stenting. In contrast, many recent studies have demonstrated that colonic stenting for OLCC does not negatively impact the safety of chemotherapy or long-term oncological outcomes. The updated version of the European Society of Gastrointestinal Endoscopy guidelines released in 2020 included colonic stenting as a BTS for OLCC as a recommended treatment. It should be noted that the experience of endoscopists is involved in determining technical and clinical success rates and possibly oncological outcomes. This review discusses the positive and negative impacts of colonic stenting on OLCC treatment, particularly in terms of oncology.

Optimal resection of gastric bronchogenic cysts based on anatomical continuity with adherent gastric muscular layer: A case report

BACKGROUND Bronchogenic cysts are congenital lesions requiring radical resection because of malignant potential.However,a method for the optimal resection of these cysts has not been completely elucidated.CASE SUMMARY Herein,we presented three patients with bronchogenic cysts that were located adjacent to the gastric wall and resected laparoscopically.The cysts were detected incidentally with no symptoms and the preoperative diagnosis was challenging to obtain via radiological examinations.Based on laparoscopic findings,the cyst was attached firmly to the gastric wall and the boundary between the gastric and cyst walls was difficult to identify.Consequently,resection of cysts alone caused cystic wall injury in Patient 1.Meanwhile,the cyst was resected completely along with a part of the gastric wall in Patient 2.Histopathological examination revealed the final diagnosis of bronchogenic cyst and revealed that the cyst wall shared the muscular layer with the gastric wall in Patients 1 and 2.In Patient 3,the cyst was located adjacent to the gastric wall but histopathologically originated from diaphragm rather than stomach.All the patients were free from recurrence.CONCLUSION The findings of this study state that a safe and complete resection of bronchogenic cysts required the adherent gastric muscular layer or full-thickness dissection,if bronchogenic cysts are suspected via pre-and/or intraoperative findings.

Current approach for Boerhaaves syndrome:A systematic review of case reports

There is no consensus on the appropriate therapeutic strategy for Boerhaave syndrome due to its rarity and changing therapeutic approaches.We conducted a systematic review of case reports documenting Boerhaave syndrome.AIM To assess the therapeutic methods and clinical outcomes and discuss the current trends in the management of Boerhaave syndrome.METHODS We searched PubMed,Google scholar,MEDLINE,and The Cochrane Library for studies concerning Boerhaave syndrome published between 2017 and 2022.RESULTS Of the included studies,49 were case reports,including a total of 56 cases.The mean age was 55.8±16 years old.Initial conservative treatment was performed in 25 cases,while operation was performed in 31 cases.The rate of conservative treatment was significantly higher than that of operation in cases of shock vital on admission(9.7%vs 44.0%;P=0.005).Seventeen out of 25 conservative cases(68.0%)were initially treated endoscopic esophageal stenting;2 of those 17 cases subsequently underwent operation due to poor infection control.Twelve cases developed postoperative leakage(38.7%),and 4 of those 12 cases underwent endoscopic esophageal stenting to stop the leakage.The length of the hospital stay was not significantly different between the conservative treatment and operation cases(operation vs conservation:33.52±22.69 vs 38.81±35.28 days;P=0.553).CONCLUSION In the treatment of Boerhaave syndrome,it is most important to diagnose the issue immediately.Primary repair with reinforcement is the gold-standard procedure.The indication of endoscopic esophageal stenting or endoluminal vacuum-assisted therapy should always be considered for patients in a poor general condition and who continue to have leakage after repair.

Implantation of hydrogel-liposome nanoplatform inhibits glioblastoma relapse by inducing ferroptosis

Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Adenylate cyclase activates the cAMP signalling pathway to enhance platelet-rich plasma-treated Achilles tendon disease,a theoretical bioinformatics-based study

The effectiveness of platelet-rich plasma(PRP)for the treatment of Achilles tendon disorders still needs to be evaluated through a series of prospective studies,but genomic analysis can reveal the existence of complementary PRP treatment options.Based on the 96 platelet activation-related genes in the Kyoto Encyclopedia of Genes and Genomes(KEGG)database,we performed Gene Ontology functional enrichment analysis and KEGG enrichment analysis,pathway correlation analysis,and enrichment mapping to determine the enrichment results of the gene set enrichment analysis and found that the cAMP signalling pathway may be the key to enhancing the effectiveness of PRP treatment.The cAMP signalling pathway interacts with the Rap1 signalling pathway and cGMPPKG signalling pathway to mediate the entire pathophy-siological process of Achilles tendon disease.Moreover,ADCY1-9 may be the key to the activation of the cAMP signalling network.Further based on the data in the Gene Expression Omnibus database,it was found that ADCY4 and ADCY7 may be the players that play a major role,associated with the STAT4-ADCY4-LAMA5 axis and the GRbeta-ADCY7-SEMA3C axis,which is expected to be a complementary target for enhancing the efficacy of PRP in the treatment of Achilles tendon disease.

How secure can we expect the surveillance policies to be after the implementation in T1 polyps with carcinoma?

Approximately 7%of the polyps resected endoscopically have an adenocarcinoma focus,with no previous endoscopic evidence of malignancy.This raises the question of whether endoscopic resection has been curative.Furthermore,there is no consensus on what the endoscopic and histological criteria for good prognosis are,the appropriate follow-up strategy and what are the long-term results.The aim of the retrospective study by Fábián et al was to evaluate the occurrence of local relapse or distant metastasis in those tumors that were resected endoscopically compared to those that underwent oncologic surgery.They concluded that,regardless of the treatment strategy chosen,there was a higher recurrence rate than described in the literature and that adherence to follow-up was poor.The management approach for an endoscopically benign polyp histologically confirmed as adenocarcinoma depends on the presence of any of the previously described poor prognostic histological factors.If none of these factors are present and the polyp has been completely resected en bloc(R0),active surveillance is considered appropriate as endoscopic resection is deemed curative.These results highlight,once again,the need for further multicentric clinical practice studies to obtain more evidence for the purpose of establishing appropriate treatment and follow-up strategies.

Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis

AIM： To examine the effects of anti-high mobility group box 1 （HIGB1） neutralizing antibody in experimental severe acute pancreatitis （SAP）. METHODS： SAP was induced by creating closed duodenal loop inC3H/HeN mice. SAP was induced immediately after intrapedtoneal injection of anti-HMGB1 neutralizing antibody （200 pg）. Sevedty of pancreatitis, organ injury （liver, kidney and lung）, and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS： Anti-HHGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HHGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HHGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION： Blockade of HHGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HHGB1 may act as a key mediator for inflammatory response and organ injury in SAR

Biomarkers for the early diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.

Long-lasting discussion: Adverse effects of intraoperative blood loss and allogeneic transfusion on prognosis of patients with gastric cancer

Gastrectomy with radical lymph node dissection is the most promising treatment avenue for patients with gastric cancer. However, this procedure sometimes induces excessive intraoperative blood loss and requires perioperative allogeneic blood transfusion. There are lasting discussions and controversies about whether intraoperative blood loss or perioperative blood transfusion has adverse effects on the prognosis in patients with gastric cancer. We reviewed laboratory and clinical evidence of these associations in patients with gastric cancer. A large amount of clinical evidence supports the correlation between excessive intraoperative blood loss and adverse effects on the prognosis. The laboratory evidence revealed three possible causes of such adverse effects: anti-tumor immunosuppression, unfavorable postoperative conditions, and peritoneal recurrence by spillage of cancer cells into the pelvis. Several systematic reviews and meta-analyses have suggested the adverse effects of perioperative blood transfusions on prognostic parameters such as all-cause mortality, recurrence, and postoperative complications. There are two possible causes of adverse effects of blood transfusions on the prognosis: Anti-tumor immunosuppression and patient-related confounding factors (e.g., preoperative anemia). These factors are associated with a worse prognosis and higher requirement for perioperative blood transfusions. Surgeons should make efforts to minimize intraoperative blood loss and transfusions during gastric cancer surgery to improve patients’ prognosis.

Small sphincterotomy combined with endoscopic papillary large balloon dilation vs sphincterotomy alone for removal of common bile duct stones

AIM: To evaluate the efficacy and safety of endoscopic papillary large diameter balloon dilation (EPLBD) following limited endoscopic sphincterotomy (EST) and EST alone for removal of large common bile duct (CBD) stones.