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Metagenomic studies using next-generation sequencing technologies have revealed rich human intestinal microbiome, which likely influence host immunity and health conditions including cancer. Evidence indicates a biological link between altered microbiome and cancers in the digestive system. Escherichia coli and Bacteroides fragilis have been found to be enriched in colorectal mucosal tissues from patients with familial adenomatous polyposis that is caused by germline APC mutations. In addition, recent studies have found enrichment of certain oral bacteria, viruses, and fungi in tumor tissue and fecal specimens from patients with gastrointestinal cancer. An integrative approach is required to elucidate the role of microorganisms in the pathogenic process of gastrointestinal cancers, which develop through the accumulation of somatic genetic and epigenetic alterations in neoplastic cells, influenced by host genetic variations, immunity, microbiome, and environmental exposures. The transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to link germline genetics and environmental factors (including diet, lifestyle, and pharmacological factors) to pathologic phenotypes. The integration of microbiology into the MPE model (microbiology–MPE) can contribute to better understanding of the interactive role of environment, tumor cells, immune cells, and microbiome in various diseases. We review major clinical and experimental studies on the microbiome, and describe emerging evidence from the microbiology–MPE research in gastrointestinal cancers. Together with basic experimental research, this new research paradigm can help us to develop new prevention and treatment strategies for gastrointestinal cancers through targeting of the microbiome.

Background With aging of the population, the number of colorectal cancer patients with impairment of activities of daily living (ADLs) has increased. The Barthel index is a validated tool for assessing functional levels of ADLs. In this retrospective study, we aimed to examine associations of Barthel index scores with recurrence and mortality after curative resection of colorectal cancer. Methods We retrospectively analyzed data of 815 consecutive patients who had undergone curative resection of stage I–III colorectal adenocarcinoma between January 2009 and December 2017. Preoperative functional levels of ADLs were assessed prospectively using the Barthel index (range, 0 to 100; higher scores indicate greater independence). Recurrence-free survival (RFS) and overall survival (OS) were compared according to Barthel index scores. The Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. Results Of the 815 patients, Barthel index scores were 40 or lower in 129 (16%), 41–85 in 110 (13%), and 86 or more in 576 (71%). In multivariable analyses adjusting for potential confounders including age and disease stage, scores of 85 or lower on the Barthel index were independently associated with shorter RFS (multivariable HR: 1.74, 95% confidence interval: 1.28–2.37, P <0.001) and OS (multivariable HR: 2.10, 95% confidence interval: 1.45–3.04, P <0.001). Conclusions Lower scores on the Barthel index are associated with shorter RFS and OS following resection of nonmetastatic colorectal cancer. Further studies are needed to establish treatment strategies for colorectal cancer patients with poor functional capacity.

BackgroundSeroma/hematoma formation is the most common postoperative complication after laparoscopic inguinal hernia repair. The occurrence of seroma/hematoma remains unclear. The aim of this study was to determine the risk factors for seroma/hematoma formation after transabdominal preperitoneal patch plasty (TAPP).MethodsThe study enrolled 359 groin hernia patients treated by TAPP at Kumamoto Medical Center between 2014 and 2019. The primary outcome was risk factors for postoperative seroma/hematoma formation after TAPP. The secondary outcomes included recurrence of hernia, postoperative complications, and hospital stay.ResultsAmong the 359 patients, the incidence rate of seroma/hematoma was 16% (n = 69 patients), and the recurrence rate was 0.3% (n = 1 patient, both sides). In total, there were 452 lesions. Japan Hernia Society (JHS) type II was present in 23% (n = 106) of the total cases but was significantly more common in the postoperative seroma/hematoma group (40%; P = 0.0082). Meanwhile, JHS type I-3 comprised 27% of the total JHS type I group but was significantly higher in the postoperative seroma/hematoma JHS type I group (40%; P = 0.016). Compared with JHS type I, the multivariable odds ratio for postoperative seroma/hematoma formation in JHS type II was 2.77 (95% CI 1.54–4.95). Compared with JHS grade 1/2, the multivariable odds ratio for postoperative seroma/hematoma formation in JHS grade 3 was 2.27 (95% CI 1.28–4.03).ConclusionsInternal inguinal hernia and hernia size ≥ 3 cm were considered risk factors for postoperative seroma/hematoma formation after TAPP.

Background A nutritional indicator suitable for predicting complications after esophagectomy has not been confirmed. The nutritional screening tool CONUT is a potential candidate. Methods We retrospectively analyzed 352 patients who underwent elective esophagectomy with lymphadenectomy for esophageal cancer between April 2005 and December 2014. Patients were divided into three groups according to the malnutrition degree in controlling nutritional status (CONUT): normal, light malnutrition, moderate or severe malnutrition. Results The numbers of patients assigned to the normal, light malnutrition, and moderate or severe malnutrition groups were 205, 126, and 21, respectively. One hundred forty-seven (41.8 %) patients were considered malnourished. Patients with moderate or severe malnutrition had a significantly high incidence of any morbidity, severe morbidities, and surgical site infection. Hospital stay in patients with moderate or severe malnutrition was significantly longer. Logistic regression analysis suggested that moderate or severe malnutrition was an independent risk factor for any morbidity [hazard ratio (HR) 2.75, 95 % confidence interval (CI) 1.081–7.020; p  = 0.034] and severe morbidities (HR 3.07, 95 % CI 1.002–9.432; p  = 0.049). Conclusions CONUT was a convenient and useful tool to assess nutritional status before esophagectomy. Patients with moderate or severe malnutrition according to CONUT are at high risk for postoperative complications.

Background Controlling nutritional status (CONUT) score, calculated from serum albumin and total cholesterol concentrations and total lymphocyte count, is reportedly valuable for nutritional assessment. This study investigated whether CONUT score was predictive of outcomes in colorectal cancer (CRC) patients undergoing surgical resection. Methods Preoperative CONUT scores were retrospectively evaluated in 417 CRC patients who underwent potentially curative resection at Kumamoto University Hospital from March 2005 to August 2014. Patients were divided into four groups based on preoperative CONUT scores: normal, light, moderate, and severe. The associations of CONUT score with clinicopathological factors, patient survival, and postoperative complications were examined. Results CONUT score correlated significantly with age ( P  < 0.001), body mass index ( P  = 0.005), carcinoembryonic antigen ( P  = 0.002), and carbohydrate antigen 19-9 ( P  = 0.005) concentrations. Overall survival (OS) rate was significantly lower in patients with moderate/severe than light or normal CONUT scores. CONUT score was independently prognostic of OS [moderate/severe vs. normal, hazard ratio = 5.92, 95 % confidence interval (CI) 2.30–14.92; P  < 0.001)]. Patients with moderate/severe CONUT scores were at greater risk for complications, especially for severe complications. Multivariate analysis showed that CONUT score was independently predictive of severe complications (moderate/severe vs. normal, odds ratio = 4.51, 95 % CI 1.89–10.74; P  < 0.001). Conclusions CONUT score may predict survival and postoperative severe complications in CRC patients undergoing potentially curative resection. Management of CRC patients may need consideration of host nutritional status.

BackgroundExperimental evidence suggests a role of intratumour Fusobacterium nucleatum in the aggressive behaviour of gastrointestinal cancer through downregulating anti-tumour immunity. We investigated the relationship between intratumour F. nucleatum and immune response to oesophageal cancer.MethodsUtilising an unbiased database of 300 resected oesophageal cancers, we measured F. nucleatum DNA in tumour tissue using a quantitative polymerase chain reaction assay, and evaluated the relationship between the abundance of F. nucleatum and the densities of T cells (CD8 + , FOXP3 + and PDCD1 + ), as well as lymphocytic reaction patterns (follicle lymphocytic reaction, peritumoural lymphocytic reaction, stromal lymphocytic reaction and tumour-infiltrating lymphocytes) in oesophageal carcinoma tissue.ResultsF. nucleatum was significantly and inversely associated only with the peritumoural lymphocytic reaction (P = 0.0002). Compared with the F. nucleatum-absent group, the F. nucleatum-high group showed a much lower level of the peritumoural lymphocytic reaction (univariable odds ratio, 0.33; 95% confidence interval, 0.16–0.65; P = 0.0004). A multivariable model yielded a similar finding (multivariable odds ratio, 0.34; 95% confidence interval 0.16–0.69; P = 0.002).ConclusionsIntratumour F. nucleatum is associated with a diminished peritumoural lymphocytic reaction, providing a platform for further investigations on the potential interactive roles between intratumour F. nucleatum and host immunity.

Background Various systemic inflammatory and nutritional scores have been reported to predict postoperative outcomes. This study aimed to investigate the best systemic inflammatory and nutritional scores in colorectal cancer (CRC) patients who underwent potentially curative resection. Method We evaluated 468 consecutive CRC patients in this study. Comparisons of systemic inflammatory and nutritional scores, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS), were performed using univariate/multivariate analyses for patient survival. Results The PNI and mGPS, but not the NLR, PLR, and PI, were significantly associated with overall and relapse-free survival. The mGPS, but not the PNI, was strongly correlated with TNM stage (P < 0.001). Cox multivariate analysis showed that both the PNI and mGPS were exclusive independent prognostic factors for both overall and relapse-free survival (P < 0.001). Furthermore, the PNI status predicted patient survival more clearly than the mGPS in combination with TNM stage. Conclusions This study suggests that the PNI and mGPS are useful predictive scores in CRC patients who undergo potentially curative resection, especially the PNI in combination with TNM stage. Routine evaluation of the host status using the scores may be useful in CRC treatment.

Background Several studies have examined controlling nutritional status (CONUT), which is one of the useful biomarkers for predicting patients’ prognosis following cancer treatment. The aim of this study was to evaluate the value of CONUT as a postoperative prognostic marker in patients with intrahepatic cholangiocarcinoma (ICC) following curative hepatectomy. Methods We retrospectively analyzed 71 patients who underwent curative hepatectomy for ICC between May 2002 and November 2016. Patients were divided into two groups according to their preoperative CONUT score (i.e., CONUT ≧ 2 or CONUT < 2). Results The number of patients assigned to the normal, mild, moderate, or severe malnutrition groups was 40, 28, two, and one, respectively. The high CONUT group (CONUT ≧ 2) consisted of 31 patients (43.7%) and had a poor prognosis with regard to overall survival (OS) ( p  = 0.0149). A high CONUT score is also identified as one of the independent predictors of poor prognosis in OS (hazard ratio 3.02; 95% confidence interval 1.4–6.8; p  = 0.007). However, in the current study, a high CONUT score was not associated with postoperative complications (Clavien–Dindo classification ≧ III or more). Conclusions CONUT may be useful for the preoperative assessment of prognosis in patients with ICC who have undergone curative hepatectomy.

BackgroundWe previously demonstrated the relationship of human microbiome Fusobacterium nucleatum with unfavorable clinical outcomes and inferior chemotherapeutic responses in esophageal cancer. Global DNA methylation is associated with the occurrence and development of various cancers. In our previous study, LINE-1 hypomethylation (i.e., global DNA hypomethylation) was associated with a poor prognosis in esophageal cancer. As the gut microbiota may play crucial roles in the DNA methylation of host cells, we hypothesized that F. nucleatum might influence LINE-1 methylation levels in esophageal cancer.MethodsWe qualified the F. nucleatum DNA using a quantitative PCR assay and LINE-1 methylation via a pyrosequencing assay using formalin-fixed paraffin-embedded specimens from 306 esophageal cancer patients.ResultsIntratumoral F. nucleatum DNA was detected in 65 cases (21.2%). The LINE-1 methylation scores ranged from 26.9 to 91.8 (median = 64.8) in tumors. F. nucleatum DNA was related to the LINE-1 hypomethylation of tumor lesions in esophageal cancer (P < 0.0001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.71 for F. nucleatum positivity. Finally, we found that the impact of F. nucleatum on clinical outcomes was not modified by LINE-1 hypomethylation (P for interaction = 0.34).ConclusionsF. nucleatum alters genome-wide methylation levels in cancer cells, which may be one of the mechanisms by which F. nucleatum affects the malignant behavior of esophageal cancer.

Aim With population aging, the number of frail patients with colorectal cancer has increased. The Clinical Frailty Scale (CFS) is a validated tool for assessing frailty, and higher scores indicate worse clinical outcomes following cardiovascular procedures. This retrospective study aimed to examine preoperative frailty in relation to recurrence and mortality following curative resection of colorectal cancer. Methods We retrospectively analyzed data for 729 consecutive patients undergoing curative resection of stage I–stage III colon and rectal adenocarcinoma between January 2009 and December 2016. Frailty was assessed using the CFS: 1 (very fit) to 9 (terminally ill), and frailty was defined as CFS ≥ 4. Recurrence‐free survival (RFS) and overall survival (OS) were compared between frail and nonfrail patients. Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. Results CFS score was negatively correlated with the Barthel index of activities of daily living (Spearman's ρ = −0.83). Of the 729 patients, 253 (35%) were frail. In multivariable analyses adjusting for potential confounders including age and disease stage, frailty was independently associated with shorter RFS (multivariable HR: 1.70, 95% confidence interval: 1.25‐2.31, P < .001) and OS (multivariable HR: 2.04, 95% confidence interval: 1.40‐2.99, P < .001). There were no significant interactions of frailty with age and disease stage regarding RFS and OS (Pinteraction > .72). Conclusion Preoperative frailty was independently associated with shorter RFS and OS following resection of nonmetastatic colorectal cancer, regardless of age and disease stage. Further trials are needed to establish treatment strategies for frail patients with colorectal cancer.