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Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into Apc Δ14/+ mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between Porphyromonas species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence. Several bacteria in the gut microbiota have been associated with colorectal cancer (CRC) but it is not completely clear whether they have a role in tumourigenesis. Here, the authors show enrichment of 12 bacterial taxa in two cohorts of CRC patients and that two Porphyromonas species accelerate CRC onset through butyrate secretion.

Risk evaluation of lymph node metastasis (LNM) for endoscopically resected submucosal invasive (T1) colorectal cancers (CRC) is critical for determining therapeutic strategies, but interobserver variability for histologic evaluation remains a major problem. To address this issue, we developed a machine-learning model for predicting LNM of T1 CRC without histologic assessment. A total of 783 consecutive T1 CRC cases were randomly split into 548 training and 235 validation cases. First, we trained convolutional neural networks (CNN) to extract cancer tile images from whole-slide images, then re-labeled these cancer tiles with LNM status for re-training. Statistical parameters of the tile images based on the probability of primary endpoints were assembled to predict LNM in cases with a random forest algorithm, and defined its predictive value as random forest score. We evaluated the performance of case-based prediction models for both training and validation datasets with area under the receiver operating characteristic curves (AUC). The accuracy for classifying cancer tiles was 0.980. Among cancer tiles, the accuracy for classifying tiles that were LNM-positive or LNM-negative was 0.740. The AUCs of the prediction models in the training and validation sets were 0.971 and 0.760, respectively. CNN judged the LNM probability by considering histologic tumor grade.

BackgroundDetermining the depth of invasion of early stage colorectal cancer has been emphasized as a means of improving endoscopic diagnostic accuracy. Recent studies have focused on other pathological risk factors for lymph node metastasis (LNM). We investigated the significance of depth of invasion and predictive properties of other endoscopic findings.MethodsWe retrospectively investigated 846 patients with submucosal invasive (T1) colorectal cancer who received an accurate pathological diagnosis and were treated between January 2005 and December 2016. Pathological risk factors associated with LNM were reviewed. We divided patients into groups: low-risk T1 colorectal cancer (LRC; no risk factors) and high-risk T1 colorectal cancer (HRC; exhibiting lymphovascular invasion, tumor budding grade of 2/3, and/or poor differentiation) and studied predictive endoscopic factors for HRC.ResultsSignificant risk factors for LNM in multivariate analysis were lymphovascular invasion [odds ratio (OR) 8.09; 95% confidence interval (CI) 3.84–17.1], tumor budding (OR 1.89; 95% CI 1.09–3.29), and histological differentiation (OR 2.09; 95% CI 1.12–3.89). The LNM-positive rate with only deep submucosal invasion was 1.6%. Significant predictive factors for HRC in multivariate analysis identified rectal tumor location (OR 1.92; 95% CI 1.35 –2.72, depression (OR 2.73; 95% CI 1.96 –3.80), protuberance within the depression (OR 2.58; 95% CI 1.39– 4.78), expansiveness (OR 2.39; 95% CI 1.27– 4.50), and loss of mucosal patterns (OR 1.90; 95% CI 1.20 –3.01) as significant factors.ConclusionsRectal tumor location, depression, protuberance within the depression, expansiveness, and loss of mucosal patterns could be predictive factors for HRC.

INTRODUCTION:To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009.METHODS:We enrolled 4,667 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,257 patients with local resection alone [group A], 1,512 patients with additional surgery after local resection [group B], and 1,898 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively.RESULTS:Any of the risk factors were present in 3,751 patients. The LNM incidence was 10.4% (95% confidence interval 9.4-11.5) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.3) in those without risk factors (P < 0.01). In group A, the incidence of recurrence was 3.6% in patients with risk factors, but it was only 0.4% in patients without risk factors (P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.6%.DISCUSSION:Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.

INTRODUCTION:There is considerable concern about whether endoscopic resection (ER) before additional surgery (AS) for T1 colorectal cancer (CRC) has oncologically potential adverse effects. Therefore, the aim of this study was to compare the long-term outcomes, including overall survival (OS), of patients treated with AS after ER vs primary surgery (PS) for T1 CRC using a propensity score-matched analysis from a large observational study.METHODS:This study investigated 6,105 patients with T1 CRC treated with either ER or surgical resection between 2009 and 2016 at 27 high-volume Japanese institutions, with those undergoing surgery alone included in the PS group and those undergoing AS after ER included in the AS group. Propensity score matching was used for long-term outcomes of mortality and recurrence analysis.RESULTS:After propensity score matching, 1,219 of 2,438 patients were identified in each group. The 5-year OS rates in the AS and PS groups were 97.1% and 96.0%, respectively (hazard ratio: 0.72, 95% confidence interval: 0.49-1.08), indicating the noninferiority of the AS group. Moreover, 32 patients (2.6%) in the AS group and 24 (2.0%) in the PS group had recurrences, with no significant difference between the 2 groups (odds ratio: 1.34, 95% confidence interval: 0.76-2.40, P = 0.344).DISCUSSION:ER before AS for T1 CRC had no adverse effect on patients' long-term outcomes, including the 5-year OS rate. ER is a viable first-line treatment option for endoscopically resectable T1 CRC.

Purpose We investigated the surgical outcomes of para-aortic lymph node (PALN) dissection in patients with colorectal cancer and assessed the prognostic factors related to the survival. Methods This single-center retrospective study included 31 patients with synchronous or metachronous PALN metastasis from colorectal cancer who underwent PALN dissection between January 2006 and December 2018. Results Twenty-one patients had synchronous PALN metastasis, and 10 had metachronous PALN metastasis. Seven patients had either simultaneous distant metastasis or a history of distant metastasis other than PALN metastasis at the time of PALN dissection. Eighteen patients underwent adjuvant chemotherapy. The 5-year overall and recurrence-free survival rates were 54.2 and 17.2%, respectively. A multivariable analysis revealed that rectal cancer, metachronous PALN metastasis, and three or more pathological PALN metastases were significantly poor prognostic factors for the recurrence-free survival. Among patients with rectal cancer, lower rectal cancer and lateral pelvic lymph node metastasis were poor prognostic factors for the overall survival. Conclusion Curative PALN dissection for PALN metastasis from colorectal cancer is feasible with favorable long-term outcomes. A multidisciplinary approach, including surgery and chemotherapy, is needed for colorectal cancer with PALN metastasis to improve the long-term outcomes.

Objectives Endoscopic ultrasonography (EUS) is sometimes used to assess the depth of invasion in esophagogastric junction adenocarcinoma (EGJA); however, its diagnostic performance in EGJA remains unclear. This study aimed to evaluate the additional value of EUS to conventional endoscopy (CE) in assessing invasion depth. Methods In this single‐institution retrospective study, we compared the diagnostic performance of CE alone with that of CE + EUS for preoperative depth assessment of early‐stage EGJA. In addition, we examined the clinicopathologic features associated with incorrect depth assessment. Results The study included 93 cases of early‐stage EGJA. Comparing the diagnostic performance for diagnosing submucosal cancer (CE vs. CE + EUS), CE + EUS had a significantly lower specificity than CE alone (78.4% vs. 62.2%). However, no significant differences were observed in sensitivity (73.2% vs. 71.4%) and accuracy (75.3% vs. 67.7%) between the two modalities. The addition of EUS was associated with significantly higher misdiagnosis rates in the following types of lesions: lesions located on the esophageal side (42.6% vs. 25.5%), elevated lesions (29.2% vs. 15.4%), complex lesions (32.7% vs. 16.3%), and lesions with hiatal hernia (31.1% vs. 19.7%). No clinicopathological factors were significantly associated with overdiagnosis or underdiagnosis. Conclusions The addition of EUS to CE reduced the ability to accurately identify mucosal cancers in early‐stage EGJA, suggesting a risk of overdiagnosis and unnecessary therapeutic escalation.

Aim Pancreatic reconstruction after pancreaticoduodenectomy (PD) that leaves a small remnant pancreas is often difficult. Pancreatic fistula is a major complication after PD, and fistulas are rare in patients with hard pancreas. However, the clinical impact of non‐reconstructed small remnant after PD with hard pancreas is unknown. Methods We included all patients who underwent PD for pancreatic tumor without pancreatic reconstruction in two institutions supervised by one surgeon between January 2004 and March 2021. Their short‐ or long‐term outcome after surgery was retrospectively analyzed. Results PD was performed in 774 patients, of whom 16 patients were without reconstruction (2.1%) with negative margins at the pancreatic stump. Pancreatic transection was performed above or to the left of the superior mesenteric artery, with a median remnant pancreas length of 3.7 cm (range, 1.3–10.0). A major complication (≥ Clavien–Dindo Grade IIIa) occurred in one patient (6%). Fistula of grade B occurred in one patient (6%). After a median follow‐up of 44 months (95%CI, 10.6–77.3), insulin administration was unnecessary in 11 patients. Conclusion The preservation of a small pancreatic remnant without reconstruction after PD can be performed safely and may enable the keeping of pancreatic endocrine function for some selected patients with hard pancreas. The present study investigates the clinical impact of non‐reconstructed small remnant pancreas with hard texture after pancreaticoduodenectomy (PD). When tumor infiltration extends widely from pancreatic head to body/tail, the pancreas is divided on the left side of superior mesenteric artery (SMA) leaving a small pancreatic remnant. Of the 16 patients, only one case had a pancreatic fistula, and 11 patients (69%) did not require insulin therapy.

INTRODUCTION: Colorectal cancer (CRC) can metastasize to various sites, including the liver, lungs, ovaries, adrenal glands, and lymph nodes. Approximately 1%–2% of patients with CRC develop para-aortic lymph node metastases. Herein, we report a case of surgical resection of an isolated, metachronous, retrocaval lymph node recurrence of rectal cancer above the renal vein.CASE PRESENTATION: A 77-year-old woman was diagnosed with a solitary metachronous retrocaval lymph node metastasis from rectal cancer. The patient underwent robot-assisted laparoscopic abdominoperineal resection. The pathological status was T3, N0, M0, or Stage IIA. No recurrence was observed for 13 months after the initial surgery. CT revealed a 24-mm tumor on the dorsal side of the inferior vena cava (IVC). Tumor resection was performed, including right adrenalectomy, Spiegel lobectomy, and partial resection of the IVC. Pathological findings revealed adenocarcinoma metastasis to a solitary lymph node, which invaded the IVC and Spiegel lobe.CONCLUSIONS: This is the first report of a surgical resection of a retrocaval lymph node metastasis from CRC that invaded both the IVC wall and the liver.