Molecular mechanisms of peritoneal dissemination in gastric cancer

Peritoneal dissemination represents a devastating form of gastric cancer(GC) progression with a dismal prognosis. There is no effective therapy for this condition. The 5-year survival rate of patients with peritoneal dissemination is 2%, even including patients with only microscopic free cancer cells without macroscopic peritoneal nodules. The mechanism of peritoneal dissemination of GC involves several steps: detachment of cancer cells from the primary tumor, survival in the free abdominal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space and proliferation with angiogenesis. These steps are not mutually exclusive, and combinations of different molecular mechanisms can occur in each process of peritoneal dissemination. A comprehensive understanding of the molecular events involved in peritoneal dissemination is important and should be systematically pursued. It is crucial to identify novel strategies for the prevention of this condition and for identification of markers of prognosis and the development of molecular-targeted therapies. In this review, we provide an overview of recently published articles addressing the molecular mechanisms of peritoneal dissemination of GC to provide an update on what is currently known in this field and to propose novel promising candidates for use in diagnosis and as therapeutic targets.

Recent advances in the molecular diagnostics of gastric cancer

Gastric cancer(GC) is the third most common cause of cancer-related death in the world,representing a major global health issue. Although the incidence of GC is declining,the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC,including serum carcinoembryonic antigen and carbohydrate antigen 19-9,are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules,including oncogenes,tumor suppressor genes,micro RNAs and long non-coding RNAs,and DNA methylation,as novel molecular markers,although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review,the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized,and certain highlighted papers are examined.

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.

Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCCrelated genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition,no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC.

Clinical utility of the platelet-lymphocyte ratio as a predictor of postoperative complications after radical gastrectomy for clinical T2-4 gastric cancer

AIMTo identify simple and sensitive markers for postoperative complications after gastrectomy, the predictive values were compared among candidate preoperative factors.METHODSThree-hundred and twelve patients with previously untreated clinical T2-4 gastric cancer who underwent a D2 standard gastrectomy (distal gastrectomy or total gastrectomy) were included in the analysis. Correlations between 21 parameters that can be determined by preoperative routine blood tests and clinically relevant postoperative complications (grade II or higher according to the Clavien-Dindo classification) were evaluated. The optimal cutoff values and clinical significance of the selected markers were further evaluated by subgroup analyses according to age, body mass index, operative procedure and clinical disease stage.RESULTSSixty-six patients (21.1%) experienced grade II or higher postoperative complications. The platelet-lymphocyte ratio (PLR, total lymphocyte count/platelet count × 100) exhibited the highest area under the curve value (0.639) for predicting postoperative complications among the 21 parameters, and the optimal cutoff value was determined to be 0.71 (sensitivity = 70%, specificity = 56%). In the univariate analysis, the odds ratio of a low PLR for the occurrence of postoperative complications was 2.94 (95%CI: 1.66-5.35, P < 0.001), and a multivariate binomial logistic analysis involving other potential risk factors identified a low PLR as an independent risk factor for postoperative complications (OR = 3.32, 95%CI: 1.82-6.25, P < 0.001). In subgroups classified according to age, body mass index, operative procedure and clinical disease stage, the low PLR group exhibited an increased incidence of postoperative complications.CONCLUSIONThe preoperative PLR is a simple and useful predictor of complications after curative gastrectomy in patients with clinical T2-4 gastric cancer.

Chemotherapy as a component of multimodal therapy for gastric carcinoma

Prognosis of locally advanced gastric cancer remains poor, and several multimodality strategies involving surgery, chemotherapy, and radiation have been tested in clinical trials. Phase Ⅲ trial testing the benefit of postoperative adjuvant chemotherapy over treatment with surgery alone have revealed little impact on survival, with the exception of some small trials in Western nations. A large trial from the United States exploring postoperative chemoradiation was the first major success in this category. Results from Japanese trials suggest that moderate chemotherapy with oral fluoropyrimidines may be effective against less-advanced （T2-stage） cancer, although another confirmative trial is needed to prove this point. Investigators have recently turned to neoadjuvant chemotherapy, and some promising results have been reported from phase Ⅱ trials using active drug combinations. In 2005, a large phase Ⅲ trial testing preand postoperative chemotherapy has proven its survival benefit for resectable gastric cancer. Since the rate of pathologic complete response is considered to affect treatment results of this strategy, neoadjuvant chemoradiation that further increases the incidence of pathologic complete response could be a breakthrough, and phase Ⅲ studies testing this strategy may be warranted in the near future.

Prognostic significance of perioperative tumor marker levels in stage Ⅱ/Ⅲ gastric cancer

AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9) levels in stage Ⅱ/Ⅲ gastric cancer.METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage Ⅱ/Ⅲ gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival.Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy.

Follow-up after gastrectomy for cancer:results of an international web round table

Oncological follow-up after radical gastrectomy for cancer still represents a discrepancy in the field, with many retrospective series demonstrating that early diagnosis of recurrence does not result in an improvement in patient survival; yet, many centers with high quality of care still provide routine patient follow-up after surgery by clinical and instrumental controls. This was the topic for a web round table entitled “Rationale and limits of oncological follow-up after gastrectomy for cancer” that was launched one year before the 10th International Gastric Cancer Congress. Authors having specific expertise were invited to comment on their previous publications to provide the subject for an open debate. During a three-month-long discussion, 32 authors from 12 countries participated, and 2299 people visited the dedicated web page. Substantial differences emerged between the participants: authors from Japan, South Korea, Italy, Brazil, Germany and France currently engage in instrumental follow-up, whereas authors from Eastern Europe, Peru and India do not, and British and American surgeons practice it in a rather limited manner or in the context of experimental studies. Although endoscopy is still considered useful by most authors, all the authors recognized that computed tomography scanning is the method of choice to detect recurrence; however, many limit follow-up to clinical and biochemical examinations, and acknowledge the lack of improved survival with early detection.

Factors affecting the quality of life of patients after gastrectomy as assessed using the newly developed PGSAS-45 scale: A nationwide multi-institutional study

AIM To identify certain clinical factors other than the type of gastrectomy which affect the postoperative quality of life(QOL) of patients after gastrectomy.METHODS The postgastrectomy syndrome assessment scale(PGSAS)-45 was designed to assess the severity of symptoms, the living status and the QOL of gastrectomized patients. It consists of 45 items, of which 22 are original items while 23 were retrieved from the SF-8 and Gastrointestinal Symptoms Rating Scale questionnaires with permission. A nationwide surveillance study to validate PGSAS was conducted and 2368 gastric cancer patients who underwent various types of gastrectomy at 52 medical institutions were enrolled. Of these, 1777 patients who underwent total gastrectomy(TG) reconstructed with Roux-Y(n = 393), distal gastrectomy(DG) reconstructed with Billroth-I(n = 909), or DG reconstructed with Roux-Y(n = 475) were evaluated in the current study. The influence of the type of gastrectomy and other clinical factors such as age, sex, duration after surgery, the symptom severity, the degree of weight loss, dietary intake, and the ability for working on the postoperative QOL(i.e., dissatisfaction for daily life subscale, physical component summary and mental component summary of the SF-8) were examined by multiple regression analysis(MRA). In addition, importance of various symptoms such as esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation and dumping on the postoperative living status and QOL were also appraised by MRA.RESULTS The postoperative QOL were significantly deteriorated in patients who underwent TG compared to those after DG. However, the extent of gastrectomy was not an influential factor on patients' QOL when adjusted by the MRA. Among various clinical factors, the symptom severity, ability for working, and necessity for additional meals were the most influential factorsto the postoperative QOL. As for the individual symptoms, meal-related distress, dumping, abdominal pain, and esophageal reflux significantly affected the postoperative QOL in that order, while the influence of indigestion, diarrhea and constipation was insignificant. CONCLUSION Several clinical factors such as the symptom severity(especially in meal-related distress and dumping), ability for working and necessity for additional meals were the main factors which affected the patients' wellbeing after gastrectomy.

Quality of life after total vs distal gastrectomy with Rouxen-Y reconstruction: Use of the Postgastrectomy Syndrome Assessment Scale-45

AIM To investigate the detrimental impact of loss of reservoir capacity by comparing total gastrectomy(TGRY) and distal gastrectomy with the same Rouxen-Y(DGRY) reconstruction. The study was conducted using an integrated questionnaire, the Postgastrectomy Syndrome Assessment Scale(PGSAS)-45, recently developed by the Japan Postgastrectomy Syndrome Working Party.METHODS The PGSAS-45 comprises 8 items from the Short Form-8, 15 from the Gastrointestinal Symptom Rating Scale, and 22 newly selected items. Uni-and multivariate analysis was performed on 868 questionnaires completed by patients who underwent either TGRY(n = 393) or DGRY(n = 475) for stage I gastric cancer(52 institutions). Multivariate analysis weighed of six explanatory variables, including the type of gastrectomy(TGRY/DGRY), interval after surgery, age, gender, surgical approach(laparoscopic/open), and whether the celiac branch of the vagus nerve was preserved/divided on the quality of life(QOL).RESULTS The patients who underwent TGRY experienced the poorer QOL compared to DGRY in the 15 of 19 main outcome measures of PGSAS-45. Moreover, multiple regression analysis indicated that the type of gastrectomy, TGRY, most strongly and broadly impaired the postoperative QOL among six explanatory variables. CONCLUSION The results of the present study suggested that TGRY had a certain detrimental impact on the postoperative QOL, and the loss of reservoir capacity could be a major cause.

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer

Gastric cancer(GC) is one of the most frequentlydiagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogenous metastasis from GC, such as vascular invasion, advanced age, differentiation, Borrmann type 1 or 2 and expansive growth. Recently, molecular mechanisms that contribute to metastatic site determination have been elucidated by advanced molecular biological techniques. Investigating the molecules that specifically participate in metastasis establishment in distinct secondary organs will lead to the development of novel biomarkers for patient stratification according to their metastatic risk and strategies for preventing and treating distinct metastases. We reviewed articles related to the molecular landscape of hematogenous metastasis from GC.

Splenectomy in living donor liver transplantation and risk factors of portal vein thrombosis

Background:Graft inflow modulation(GIM)during adult-to-adult living donor liver transplantation(LDLT)is a common strategy to avoid small-for-size syndrome,and some transplant surgeons attempt small size graft strategy with frequent GIM procedures,which are mostly performed by splenectomy,in LDLT.However,splenectomy can cause serious complications such as portal vein thrombosis and overwhelming postsplenectomy infection.Methods:Forty-eight adult-to-adult LDLT recipients were enrolled in this study and retrospectively reviewed.We applied the graft selection criteria,which routinely fulfill graft-to-recipient weight ratio≥0.8%,and consider GIM as a backup strategy for high portal venous pressure(PVP).Results:In our current strategy of LDLT,splenectomy was performed mostly due to hepatitis C and splenic arterial aneurysms,but splenectomy for GIM was intended to only one patient(2.1%).The final PVP values≤20 mmHg were achieved in all recipients,and no significant difference was observed in patient survival or postoperative clinical course based on whether splenectomy was performed or not.However,6 of 18 patients with splenectomy(33.3%)developed postsplenectomy portal vein thrombosis(PVT),while none of the 30 patients without splenectomy developed PVT after LDLT.Splenectomy was identified as a risk factor of PVT in this study(P<0.001).Our study revealed that a lower final PVP could be risk factor of postsplenectomy PVT.Conclusions:Using sufficient size grafts was one of the direct solutions to control PVP,and allowed GIM to be reserved as a backup procedure.Splenectomy should be avoided as much as possible during LDLT because splenectomy was found to be a definite risk factor of PVT.In splenectomy cases with a lower final PVP,a close follow-up is required for early detection and treatment of PVT.

Oncological problems in pancreatic cancer surgery

Despite the development of more sophisticated diagnostic techniques, pancreatic carcinoma has not yet been detected in the early stage. Surgical resection provides the only chance for cure or long-term survival. The resection rate has increased due to recent advances in surgical techniques and the application of extensive surgery. However, the postoperative prognosis has been poor due to commonly occurring liver metastasis, local recurrence and peritoneal dissemination. Recent molecular-biological studies have clarified occult metastasis, micrometastasis and systemic disease in pancreatic cancer. Several oncological problems in pancreatic cancer surgery are discussed in the present review.

Modified docetaxel, cisplatin and capecitabine for stage Ⅳ gastric cancer in Japanese patients: A feasibility study

AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage Ⅳ gastric cancer. In particular, 30 or 40 mg/m^2 of docetaxel on day 1, 60 mg/m^2 of cisplatin on day 1, and 2000 mg/m^2 of capecitabine for 2 wk were administered every three weeks.RESULTS Three patients were treated with modified DCX(m DCX) with 30 mg/m^2 docetaxel, and five patients were treated with this regimen with 40 mg/m^2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes.CONCLUSION m DCX was well tolerated by Japanese patients with stage Ⅳ gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.

Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation

Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation(LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow(PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green(ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant(kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT.

Is the measurement of drain amylase content useful for predicting pancreas-related complications after gastrectomy with systematic lymphadenectomy?

Many studies investigating postoperative pancreatic fistula(POPF)after gastrectomy,including studies measuring drain amylase content(D-AMY)as a predictive factor have been reported.This article reviews previous studies and looks to the future of measuring D-AMY in patients after gastrectomy.The causes of pancreatic fluid leakage are;the parenchymal and/or thermal injury to the pancreas,and blunt injury to the pancreas by compression and retraction.Measurement of D-AMY to predict POPF has become common in clinical practice after pancreatic surgery and was later extended to the gastric surgery.Several studies have reported associations between D-AMY and POPF after gastrectomy,and the high value of D-AMY on postoperative day(POD)1 was an independent risk factor.To improve both sensitivity and specificity,attempts have been made to enhance the predictive accuracy of factors on POD 1 as well as on POD 3 as combined markers.Although several studies have shown a high predictive ability of POPF,it has not necessarily been exploited in clinical practice.Many problems remain unresolved;ideal timing for measurement,optimal cut-off value,and means of intervention after prediction.Prospective clinical trial could be imperative in order to develop D-AMY measurement in common clinical practice for gastric surgery.

Comparison of effects of six main gastrectomy procedures on patients’ quality of life assessed by Postgastrectomy Syndrome Assessment Scale-45

BACKGROUND The effects of various gastrectomy procedures on the patient’s quality of life(QOL)are not well understood.Thus,this nationwide multi-institutional crosssectional study using the Postgastrectomy Syndrome Assessment Scale-45(PGSAS-45),a well-established questionnaire designed to clarify the severity and characteristics of the postgastrectomy syndrome,was conducted.AIM To compare the effects of six main gastrectomy procedures on the postoperative QOL.METHODS Eligible questionnaires retrieved from 2368 patients who underwent either of six gastrectomy procedures[total gastrectomy with Roux-en-Y reconstruction(TGRY;n=393),proximal gastrectomy(PG;n=193),distal gastrectomy with Roux-en-Y reconstruction(DGRY;n=475),distal gastrectomy with Billroth-I reconstruction(DGBI;n=909),pylorus-preserving gastrectomy(PPG;n=313),and local resection of the stomach(LR;n=85)]were analyzed.Among the 19 main outcome measures of PGSAS-45,the severity and characteristics of postgastrectomy syndrome were compared for the aforementioned six gastrectomy procedures using analysis of means.RESULTS TGRY and PG significantly impaired the QOL of postoperative patients.Postoperative QOL was excellent in LR(cardia and pylorus were preserved with minimal resection).In procedures removing the distal stomach,diarrhea subscale(SS)and dumping SS were less frequent in PPG than in DGBI and DGRY.However,there was no difference in the postoperative QOL between DGBI and DGRY.The most noticeable adverse effects caused by gastrectomy were mealrelated distress SS,dissatisfaction at the meal,and weight loss,with significant differences among the surgical procedures.CONCLUSION Postoperative QOL greatly differed among six gastrectomy procedures.The severity and characteristics of postgastrectomy syndrome should be considered to select gastrectomy procedures,overcome surgical shortcomings,and enhance postoperative care.

Novel diagnostics for aggravating pancreatic fistulas at the acute phase after pancreatectomy

AIM: To identify sensitive predictors of clinically relevant postoperative pancreatic fistula (POPF) at the acute phase after pancreatectomy.

Background factors influencing postgastrectomy syndromes after various types of gastrectomy

BACKGROUND Postgastrectomy syndromes(PGS) after curative gastrectomy for gastric cancer are influenced by not only gastrectomy type but also by background factors. Recently, a nationwide PGS study was performed using the Postgastrectomy Syndrome Assessment Scale-45(PGSAS-45) questionnaire.AIM To determine the influence of each background factor on PGS for each gastrectomy type using PGS assessment study(PGSAS) data as an additional analysis. METHODS The data of 2368 patients were obtained from the PGSAS. This included patients undergoing distal gastrectomy(DG) with Billroth I reconstruction, DG with Roux-en-Y reconstruction, total gastrectomy with Roux-en-Y, proximal gastrectomy, pylorus-preserving gastrectomy(PPG), and local resection. Multiple regression analysis was performed to explore the independent effects of each background factor on the main outcome measures(MOMs) of PGSAS-45 for each gastrectomy type. The background factors included postoperative period, age, sex, surgical approach(laparoscopic or open), and the status of the celiac branch of the vagal nerve.RESULTS The MOMs of DG and PPG were highly affected by background factors, whereas those of total gastrectomy with Roux-en-Y, proximal gastrectomy, and local resection were not. Worse PGS were found in females, whereas a longer postoperative period alleviated some of the MOMs. For DG and PPG, a laparoscopic approach and preservation of the celiac branch improved several MOMs.CONCLUSION Various background factors affected PGS, and their influence varied with the type of gastrectomy performed. Laparoscopic surgery and celiac branch preservation can improve PGS in patients undergoing DG and PPG.

Defecation disorders are crucial sequelae that impairs the quality of life of patients after conventional gastrectomy

BACKGROUND Defecation disorders are obscure sequelae that occurs after gastrectomy,and its implication on daily lives of patients have not been sufficiently investigated.AIM To examine the features of defecation disorders after gastrectomy and to explore its implication on daily lives of patients in a large cohort using the Postgast rectomy Syndrome Assessment Scale(PGSAS)-45.METHODS We conducted a nationwide multi-institutional study using PGSAS-45 to examine the prevalence of postgastrectomy syndrome and its impact on daily lives of patients after various types of gastrectomy.Data were obtained from 2368 eligible patients at 52 institutions in Japan.Of these,1777 patients who underwent total gastrectomy(TG;n=393)or distal gastrectomy(DG;n=1384)were examined.The severity of defecation disorder symptoms,such as diarrhea and constipation,and their correlation with other postgastrectomy symptoms were examined.The importance of defecation disorder symptoms on the living states and quality of life(QOL)of postgastrectomy patients,and those clinical factors that affect the severity of defecation disorder symptoms were evaluated using multiple regression analysis.RESULTS Among seven symptom subscales of PGSAS-45,the ranking of diarrhea was 4th in TG and 2nd in DG.The ranking of constipation was 5th in TG and 1st in DG.The symptoms that correlated well with diarrhea were dumping and indigestion in both TG and DG;while those with constipation were abdominal pain and mealrelated distress in TG,and were meal-related distress and indigestion in DG.Among five main outcome measures(MOMs)of living status domain,constipation significantly impaired four MOMs,while diarrhea had no effect in TG.Both diarrhea and constipation impaired most of five MOMs in DG.Among six MOMs of QOL domain,diarrhea impaired one MOM,whereas constipation impaired all six MOMs in TG.Both diarrhea and constipation equally impaired all MOMs in DG.Male sex,younger age,division of the celiac branch of vagus nerve,and TG,independently worsened diarrhea,while female sex worsened constipation.CONCLUSION Defecation disorder symptoms,particularly constipation,impair the living status and QOL of patients after gastrectomy;therefore,we should pay attention and adequately treat these relatively modest symptoms to improve postoperative QOL.