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Esophagectomy for esophageal cancer is associated with frequent respiratory morbidities, which may deteriorate postoperative survival outcomes. Thoracoscopic esophagectomy (TE) is less invasive and is associated with fewer respiratory morbidities than open esophagectomy. However, the relationship between post-TE respiratory morbidity and prognosis has not been well established.This study included 378 patients who underwent TE for esophageal cancer between May 2011 and November 2020. Patients were divided into two groups based on the presence of respiratory morbidity. Short-term and long-term outcomes of the groups were retrospectively compared.Respiratory morbidity was significantly associated with heavy past smoking habits (Brinkman index, p = 0.0039), short duration of smoking cessation (p = 0.0012), worse American Society of Anesthesiologists physical status (p = 0.016), frequent cardiovascular comorbidities (p = 0.0085), and long hospital stay (p 0.001). Respiratory morbidity significantly deteriorated overall survival (OS) (p = 0.011) and relapse-free survival (p = 0.062) and could be an independent prognostic factor for OS (hazard ratio = 1.90, 95% confidence interval = 1.093-3.311, p = 0.023) along with clinical stage.Respiratory morbidity can adversely affect prognosis after TE. Various prophylaxes for respiratory morbidity are required to improve the short-term and long-term outcomes of TE for esophageal cancer.

The number of cancer patients with impairment of activities of daily living (ADLs) has increased. This study aimed to examine associations of perioperative Barthel index score, a validated measure of ADLs, with survival outcomes following hepatectomy for hepatocellular carcinoma (HCC).We analyzed data of 492 consecutive patients who underwent hepatectomy for HCC between 2010 and 2018. Pre- and postoperative ADLs were assessed using the Barthel index (range, 0-100; higher scores indicate greater independence). Preoperative Barthel index score ≤85 or postoperative Barthel index score ≤85 was defined as impairment of perioperative ADLs. Cox proportional hazards regression was used to calculate hazard ratios (HRs) after adjusting for potential confounders.Among the 492 patients, 26 (5.2%) had a preoperative Barthel index score ≤85 and 95 (19%) had a postoperative Barthel index score ≤85. Impairment of perioperative ADLs was independently associated with shorter overall survival (multivariable HR: 1.75, 95% confidence interval [CI]: 1.06-2.81, p = 0.028). The association of impairment of perioperative ADLs with recurrence-free survival was not statistically significant.Impairment of perioperative ADLs is associated with poor prognosis following hepatectomy for HCC. Maintenance and improvement of perioperative ADLs would be important to provide favorable long-term outcomes in patients with HCC.

Previously reported Fusobacterium in cancer tissues and patient prognosis

Differentially expressed chemokine genes (fold change >2) in esophageal cancer tissues

Purpose: Fusobacterium nucleatum (F. nucleatum) is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. Although there are several reports of the relationship between F. nucleatum and the clinical outcome in human cancers, its prognostic significance in esophageal cancer remains unclear.Experimental Design: We quantified F. nucleatum DNA in 325 resected esophageal cancer specimens by qPCR. Significant pathways in F. nucleatum–positive esophageal cancer tissues were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using microarray data.Results: Esophageal cancer tissues contained significantly more F. nucleatum DNA than matched normal esophageal mucosa (P = 0.021; n = 60). F. nucleatum DNA was detected in 74 of 325 cases (23%). F. nucleatum DNA positivity was significantly associated with tumor stage, but not with sex, age, performance status, tobacco use, alcohol use, histology, tumor location, or preoperative treatment. F. nucleatum DNA positivity was also significantly associated with cancer-specific survival [log-rank P = 0.0039; univariate HR = 2.01; 95% confidence interval (CI), 1.22–3.23; P = 0.0068; multivariate HR = 1.78; 95% CI, 1.06–2.94; P = 0.031]. The top-ranked KEGG pathway in F. nucleatum–positive tissues was “cytokine–cytokine receptor interaction.” A significant relationship between F. nucleatum and the chemokine CCL20 was validated by IHC.Conclusions: F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574–81. ©2016 AACR.

PDF file - 120K, Clinical or pathological feature according to PPARγ expression.

The transcription factor PPAR-γ plays various roles in lipid metabolism, inflammation, cellular differentiation, and apoptosis. PPAR-γ agonists used to treat diabetes may have utility in cancer treatment. Efatutazone is a novel later generation PPAR-γ agonist that selectively activates PPAR-γ target genes and has antiproliferative effects in a range of malignancies. In this study, we investigated PPAR-γ status in esophageal squamous cell carcinoma (ESCC) and investigated the antiproliferative effects of efatutazone. PPAR-γ was expressed heterogeneously in ESCC, in which it exhibited an inverse relationship with Ki-67 expression. PPAR-γ expression was associated independently with good prognosis in ESCC. Efatutazone, but not the conventional PPAR-γ agonist troglitazone, inhibited ESCC cell proliferation in vitro and in vivo. Mechanistic investigations suggested that efatutazone acted by upregulating p21Cip1 protein in the nucleus through inactivation of the Akt pathway and dephosphorylation of p21Cip1 at Thr145 without affecting the transcriptional activity of p21Cip1. We also found that treatment with efatutazone led to phosphorylation of the EGF receptor and activation of the mitogen-activated protein kinase (MAPK) pathway. Accordingly, the combination of efatutazone with the antiepithelial growth factor receptor antibody cetuximab synergized to negatively regulate the phosphoinositide 3-kinase–Akt and MAPK pathways. Together, our results suggest that efatutazone, alone or in combination with cetuximab, may offer therapeutic effects in ESCC. Cancer Res; 74(2); 575–85. ©2013 AACR.

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PDF file - 818K, The study design for selecting the ESCC patients (S1); TE-4 cells were transfected with PPARG siRNA (S2); In vitro anti-proliferative effects of efatutazone (S3); Anti-proliferative effects of efatutazone in ESCC cells occur via pAkt-p21Cip1 (S4); In vivo anti-proliferative effects of efatutazone (S5); Investigation using condition medium (S6); EGFR/MAPK signaling activation (S7); Anti-proliferative effects of molecule targeted therapy (S8); The primers and probes used for real time RT-PCR (S9).

PDF file - 112K, PPARγ status in ESCC and patient mortality.

Sarcopenia is associated with poor prognosis in patients with colorectal cancer (CRC), but the mechanisms contributing to this association remain unclear. We hypothesized that skeletal muscle status is associated with tumor-infiltrating lymphocytes (TILs) in patients with CRC. Therefore, this study investigated the clinical effect of sarcopenia and its relationship with the local immune system in CRC patients.A total of 256 consecutive patients with CRC who underwent curative resection between 2008 and 2014 were enrolled. Sarcopenia was determined according to the skeletal muscle index (SMI), which was assessed using L3 skeletal muscle mass on axial computed tomography images, and its relationship with patient clinicopathological characteristics and survival was evaluated. Additionally, TILs (CD3Patients with a lower SMI showed significantly shorter recurrence-free and overall survival compared with those with a higher SMI. Low expression of TILs was associated with significantly shorter recurrence-free survival. SMI was significantly correlated with the number of CD3Our data showed an association between skeletal muscle status and local immune cells, and this association may play a pivotal role in the clinical outcome of patients with CRC.

Immune checkpoint inhibitors have shown efficacy in various cancers. Although programmed death ligand 1/2 (PD-L1/L2) expressions have been demonstrated as predictive biomarkers of response to immune checkpoint inhibitors and prognostic markers, whether PD-L1/L2 expression is altered in esophageal squamous cell carcinoma during the therapeutic course is unclear. Whether PD-L1/L2 expression in metastatic or recurrent lesions is consistent with that in primary tumors is also unknown. This study included 561 surgically resected esophageal squamous cell carcinomas and PD-L1/L2 expression was evaluated by immunohistochemistry. We investigated the influence of chemotherapeutic drugs (cisplatin and fluorouracil) on PD-L1/L2 expression and PD-L1/L2-related pathways in vitro. We also examined PD-L1/L2 expression in 18 surgically resected lymph node metastases and 10 recurrent lesions compared with primary lesions. The positive rate of PD-L1 was significantly higher in patients with preoperative chemotherapy than in those without preoperative therapy. The positive rate of PD-L2 expression showed no significant difference between patient groups. Cisplatin increased PD-L1 expression in cancer cell lines in vitro, but decreased PD-L2 in some cell lines. The effects of cisplatin on phosphorylated signal transducer and activator of transcription 1/3 (pSTAT1/3) also differed depending on cell lines. Fluorouracil increased PD-L1 and PD-L2 expression. PD-L1/L2 expression in lymph node metastases and recurrent lesions did not always match expression in primary lesions. PD-L1/L2 expression may be altered by preoperative chemotherapy, and PD-L1 /L2 expression in primary lesions does not always match that of metastatic/recurrent lesions. Thus, one-time evaluation is not sufficient to evaluate PD-L1/L2 expression as a biomarker in esophageal cancer.

Gastrectomy may induce significant postoperative disabilities and worsen the quality of life in elderly patients. Without a functioning esophagogastric junction (EGJ), swallowing is impaired because of the anatomical and physiological changes after surgery, which increases the risk of postoperative pneumonia. The aim of this study was to identify the impact of the type of surgical procedure on death from pneumonia in elderly patients with gastric cancer (GC) over the long term. We analyzed the data of 343 patients with GC who underwent curative gastrectomy in our hospital. We divided the patients into elderly and non-elderly groups. Among them, 109 patients aged ≥ 75 years who underwent curative resection were analyzed, their clinicopathological factors and clinical outcomes were compared, and the impact of the type of surgical procedure on death from pneumonia over the long term was evaluated. The institutional scientific review board of Kumamoto University Hospital was approved for data collection and analysis (No. 1037). There were significantly higher levels of American Society of Anesthesiologists (ASA) and poor nutrition in the elderly group; however, gender, BMI and factors related to pneumonia did not differ significantly between groups. The median duration of follow-up time 1588 days. On the multivariate analysis, age and surgical procedure were selected as independent predictive factors for pneumonia-related survival. Preservation of the EGJ as much as possible while maintaining curability is useful for reducing postoperative death from pneumonia over the long term in elderly patients with gastric cancer.

Background Preoperative treatment is performed for locally advanced colon cancer with extensive tumor proximity or suspected invasion of skeletal muscles, major organs, and blood vessels. Oxaliplatin-based regimens are often used in preoperative chemotherapy. However, microsatellite instability (MSI)-high colorectal cancer is often resistant to cytotoxic anticancer agents. Herein, we describe a case of treatment of anticancer drug-resistant MSI-high locally advanced colon cancer and review cases of complete response to immune checkpoint inhibitor therapy for colorectal cancer. Case presentation A 57-year-old woman was referred to our hospital with a large tumor in the descending colon and extensive thoracic and abdominal wall involvement, including the ribs and diaphragm. No distant metastasis was observed. The tumor had perforated the abdominal wall and formed an abscess. Upon visiting our hospital, emergency surgery was performed. An abdominal wall incision was made to drain the abscess and laparoscopic colostomy was performed. Histopathological examination of biopsy specimens revealed an adenocarcinoma with positive immunohistochemical expressions of both CDX2 and CK20. The patient was diagnosed with a descending colon cancer. Genetic examination found MSI-high, Kras mutation (F12G), and wild-type BRAF. After the inflammation improved, chemotherapy with the FOLFIRI regimen was initiated, but the tumor grew rapidly. As a second-line treatment, nivolumab and ipilimumab combination therapy was initiated. After four cycles of these therapies, the patient was administered nivolumab alone for five cycles. Tumor shrinkage was observed and radical surgery was performed. The patient underwent laparoscopic descending colon and partial thoracic and abdominal wall resection. The abdominal wall muscle was dissected from the abdominal cavity, and subcutaneous tissues, diaphragm, ribs were dissected from the body surface. Pathological examination revealed mucus components, fibrous tissues, and no malignant cells, indicating a complete pathological response (pCR). The patient had a good postoperative course and returned to work after being discharged. No recurrence was observed six months postoperatively. Conclusions Herein, we report a case of anticancer drug-resistant MSI-high colon cancer that was resected after treatment with immune checkpoint inhibitors, and a pCR was achieved. This new treatment strategy can be used for the treatment of cases that are not responsive to conventional therapies.

Accumulating evidence suggests that high levels of Fusobacterium nucleatum in colorectal tumor tissues can be associated with poor prognosis in patients with colorectal cancer (CRC); however, data regarding distinct prognostic subgroups in F. nucleatum-positive CRC remain limited. Herein, we demonstrate that high-iron status was associated with a worse prognosis in patients with CRC with F. nucleatum. Patients with CRC presenting elevated serum transferrin saturation exhibited preferential iron deposition in macrophages in the tumor microenvironment. In addition, F. nucleatum induced CCL8 expression in macrophages via the TLR4/NF-κB signaling pathway, which was inhibited by iron deficiency. Mechanistically, iron attenuated the inhibitory phosphorylation of NF-κB p65 by activating serine/threonine phosphatases, augmenting tumor-promoting chemokine production in macrophages. Our observations indicate a key role for iron in modulating the NF-κB signaling pathway and suggest its prognostic potential as a determining factor for interpatient heterogeneity in F. nucleatum-positive CRC.

This study aimed to examine whether preoperative serum transferrin, a rapid-turnover protein, correlates with short- and long-term outcomes after esophagectomy. Preoperative transferrin levels, calculated by summing serum iron and unsaturated iron-binding capacity, were evaluated in 224 patients who underwent esophagectomy for stage I–III esophageal cancer without preoperative treatment. Transferrin levels are directly proportional to total iron-binding capacity (TIBC), and we defined TIBC

High preoperative hemoglobin A1c (HbA1c) levels have been suggested to increase complications after esophagectomy. Minimally invasive esophagectomy (MIE) is less invasive than open esophagectomy (OE) and may reduce postoperative complications. However, it has not been established whether MIE contributes to low morbidity in patients with high preoperative HbA1c levels. Thus, the current study aimed to elucidate the effect of preoperative HbA1c levels on the incidence of complications each after OE and MIE. A total of 280 patients who underwent OE and 304 patients who underwent MIE for esophageal cancer between April 2005 and April 2020 were retrospectively analyzed. The OE and MIE groups were further divided into two groups according to their preoperative HbA1c levels (

Background/Aim: Chemoradiation is the recommended initial treatment for locally advanced squamous anal cancer. However, there is still no consensus on the course of treatment for anal canal cancer with distant metastasis, and the significance of surgical resection of distant metastases is also unclear. Case Report: A 48-year-old woman presented to the referral hospital complaining of prolonged bleeding for the past 6 months. On examination, a mass was identified in the anal canal and the upper part of the rectum that was diagnosed as squamous cell carcinoma. Liver, ovarian, and right internal iliac lymph node metastases were found on further examination, and the patient was referred to our department for treatment. Systemic chemotherapy was planned, and six courses of modified FOLFOX6 were administered. After chemotherapy, the liver and right internal iliac lymph node metastases tended to shrink, and no new lesions appeared. Therefore, a total posterior pelvic resection and a bilateral lymph node dissection were performed for the primary tumour and ovarian metastases, and a simultaneous laparoscopic right partial hepatectomy was undertaken for the liver metastases. R0 resection was achieved, and the final diagnosis was T3N3M1a(H) stage IV. The patient remains alive 2 years after the surgery without recurrence. Conclusion: We report a rare case of anal canal cancer with distant metastases who achieved R0 resection after modified FOLFOX6 chemotherapy.

C-reactive protein (CRP) levels are reported to predict complications and survival after surgery in various cancers. However, the relationship between postoperative CRP levels and short- and long-term outcomes of esophageal squamous cell carcinoma (ESCC) patients after esophagectomy is unclear.We reviewed the records of 543 ESCC patients who underwent subtotal esophagectomy with gastric conduit reconstruction at Kumamoto University Hospital between August 2010 and July 2021. Blood tests for CRP were done on postoperative days (PODs) 1, 3, 5 or 6, and 7 or 8.The mean CRP levels on day 1, day 3, day 5/6, and day 7/8 were 6.68 ± 0.13 mg/dL, 11.49 ± 0.27 mg/dL, 7.48 ± 0.26 mg/dL, and 5.38 ± 0.22 mg/dL, respectively. Mean CRP levels were highest on day 3, and CRP levels after day 3 correlated with grade2 complications based on the Clavien-Dindo classification. Receiver operating characteristic curve analysis established the optimal cut-off value for CRP day 3 levels to be 12.19 mg/dL. Multivariate logistic regression analyses found that high CRP day 3 levels significantly correlated with grade2 complications (odds ratio [OR] 3.77, 95% confidence interval [CI] 2.56-5.35; p 0.001). Moreover, high day 7/8 CRP levels (3.52) correlated with postoperative survival, and based on multivariate logistic regression analyses, were significantly associated with poor prognosis (hazard ratio 1.67, 95% CI 1.14-2.43; p = 0.008).Our findings suggest CRP day 3 levels as a potential biomarker for predicting postoperative complications and that CRP day 7/8 levels have potential prognostic value for ESCC patients after esophagectomy.

Background: Curative resection for colorectal cancer and their synchronous liver metastases are increasingly performed. However, it is still unclear whether the operative order affects the surgical outcome in laparoscopic simultaneous resection of primary and liver metastatic lesions. Patients and Methods: A total of 27 patients underwent laparoscopic simultaneous resection of primary colorectal cancer and liver metastases at Kumamoto University Hospital. They were divided into two groups based on the order of resection: Colon-first (n=11) and liver-first (n=16) groups. The surgical outcomes between the two groups were retrospectively compared. Results: There was no significant difference in the perioperative surgical outcomes between the two groups except for operative blood loss, which was significantly less in the liver-first group [164 (range=5-820) versus 560 (range=95-2,016) ml, respectively] (p=0.0299). Conclusion: In the simultaneous resection of primary and liver metastatic lesions, the operative order does not affect the short-term surgical outcomes except for operative blood loss.

Background Gastric cancer is relatively prone to metastasis, although distant metastasis is rare during the early stage of disease. Here we report a rare case of schwannoma-associated Virchow metastasis of a patient with early-stage gastric cancer. Case presentation A 73-year-old man, diagnosed with early-stage gastric cancer, underwent preoperative scrutiny, and was only suspected to have Virchow metastasis. Owing to atypical metastatic findings, a lymph node biopsy was performed to confirm the diagnosis and to determine the treatment strategy. The pathology results of the biopsy showed a diagnosis of schwannoma, the patient was judged to be surgically resectable, and a laparoscopic gastrectomy was performed to achieve a radical resection. The patient is currently under outpatient observation with no apparent recurrence. Conclusion Systemic chemotherapy is generally administered according to the physician’s clinical judgment, although the results of a lymph node biopsy contribute to a more curative treatment. When nonspecific metastases are found, it is important to make a reliable diagnosis and to select a treatment that achieves a cure.

Several cohort studies have reported that post-esophagectomy morbidities may worsen prognosis. Smoking cessation is an effective prophylactic measure for reducing post-esophagectomy morbidity; however, whether smoking cessation can contribute to the improvement of prognosis is unknown due to the absence of reliable databases covering the cessation period. This study aimed to elucidate whether sufficient preoperative smoking cessation can improve prognosis after esophageal cancer surgery by reducing post-esophagectomy morbidity.This study included 544 consecutive patients who underwent curative McKeown and Ivor-Lewis esophagectomies for esophageal cancer between May 2011 and June 2021. Data on smoking status and cessation period were prospectively accumulated. Survival data were finally updated on 30 January 2022. Receiver operating characteristic curve analysis for the cut-off value of appropriate cessation period in reducing post-esophagectomy respiratory morbidity as well as analyses for the association of cessation period with short- and long-term outcomes were performed.Post-esophagectomy morbidity significantly diminished overall survival (OS) after esophagectomy (p = 0.0003). A short preoperative smoking cessation period of ≤ 2 months was associated with frequent post-esophagectomy morbidity of Clavien-Dindo classification ≥IIIb (p = 0.0059), pneumonia (p = 0.016), respiratory morbidity (p = 0.0057), and poor OS in clinical stages II and III (p = 0.0015). Moreover, it was an independent factor for poor OS (hazard ratio 1.85, 95% confidence interval 1.068-3.197; p = 0.028), along with body mass index18.5 and R1 resection.Sufficient preoperative smoking cessation 2 months may be effective in improving not only short-term outcomes but also prognosis after esophagectomy for locally advanced esophageal cancer.

Colorectal cancer (CRC) is the most common cancer and the second leading cause of cancer death in Japan. Surgical resection is the only curative option for localized disease. However, undetectable micrometastases remaining after curative surgery may cause disease recurrence. Adjuvant chemotherapy aims to eradicate these micrometastases to improve the cure rate. Unfortunately, few reliable prognostic and predictive markers are available that identify patients at high risk for CRC during early‐stage disease. However, promising biomarkers may become available in the near future. Such biomarkers provide information for stratifying a patient's risk and for selecting the optimal treatment. Here, we provide an overview of current relevant prognostic and predictive biomarkers applicable to adjuvant treatment of early‐stage CRC and focus on the future of this field., During the last decade, numerous efforts have been made to develop precision medicine for patients with early colorectal cancer. We summarize prognostic and predictive biomarkers for adjuvant treatment of early colorectal cancer.

PurposePreoperative malnutrition is a significant risk factor for post-esophagectomy morbidity. The Controlling Nutritional Status (CONUT) is an index used to assess the nutritional status, and it has been suggested to predict post-esophagectomy morbidity. However, the difference in the predictive value of CONUT in estimating morbidities between open esophagectomy (OE) and minimally invasive esophagectomy (MIE) has not yet been elucidated.MethodsThis study included 674 patients(OE, 295; MIE, 378) who underwent three-incision esophagectomy for esophageal cancer between April 2005 and August 2021. The patients were further divided into two groups according to their preoperative CONUT: normal and light malnutrition and moderate and severe malnutrition. Short-term outcomes between these groups were retrospectively compared in the OE and MIE groups.ResultsModerate and severe malnutrition was significantly associated with a low body mass index, a poor performance status and American Society of Anesthesiologists physical status, advanced cancer stage, and frequent preoperative treatment. These patients also experienced significantly more frequent severe (p=0.016), respiratory (p=0.0013) and cardiovascular morbidities (p=0.013) after OE. Moreover, malnutrition in CONUT was an independent risk factor for severe (hazard ratio [HR]=3.38; 95%confidence interval [CI], 1.225-9.332; p=0.019), respiratory (HR=3.00; 95%CI, 1.161-7.736; p=0.023), and cardiovascular morbidities (HR=3.66; 95%CI, 1.068-12.55; p=0.039) after OE. However, it was not associated with the incidence of morbidities after MIE.ConclusionPreoperative malnutrition in CONUT reflects various disadvantageous clinical factors and could be a predictor of worse short-term outcomes after OE. Meanwhile, the low invasiveness of MIE might reduce the effect of preoperative malnutrition on worse short-term outcomes.

Activin A is a member of the transforming growth factor‑β superfamily of cytokines and displays various pathophysiological activities, including regulation of muscle catabolism and atrophy. Activin A expression is upregulated in several human cancer types and in certain pathologies, its expression is associated with poor prognosis. In the present study, activin A expression was assessed in colorectal cancer (CRC) tissue specimens from 157 patients with primary CRC and the relationship between activin A levels and clinicopathological characteristics, including skeletal muscle mass, and prognosis, was determined. Furthermore, the effects of knockdown of endogenous or exposure to exogenous activin A on the malignant behavior of human CRC cell lines were investigated

Preoperative malnutrition is a significant risk factor for post-esophagectomy morbidity. The Controlling Nutritional Status (CONUT) is an index used to assess nutritional status, and it has been suggested to predict post-esophagectomy morbidity. However, the difference in the predictive value of CONUT in estimating morbidities between open esophagectomy (OE) and minimally invasive esophagectomy (MIE) has not yet been elucidated.This study included patients who underwent a three-incision esophagectomy for esophageal cancer between April 2005 and August 2021. The patients were further divided into two groups according to their preoperative CONUT scores: normal and light malnutrition and moderate and severe malnutrition. Short-term outcomes between these groups were retrospectively compared in the OE and MIE groups.A total of 674 patients who underwent OE (296) and MIE (378) were analyzed. Moreover, 32 patients of the OE group and 16 of the MIE group were classified as having moderate and severe malnutrition, respectively. Moderate and severe malnutrition was significantly associated with a low body mass index, poor performance status, poor American Society of Anesthesiologists physical status, advanced cancer stage, and frequent preoperative treatment. These patients also experienced significantly more frequent morbidities of grade ≥ IIIb according to the Clavien-Dindo classification (CDc), respiratory, and cardiovascular morbidities after OE. Moreover, moderate and severe malnutrition in CONUT was an independent risk factor for morbidity of CDc ≥ IIIb (odds ratio [OR] vs. normal and light malnutrition = 3.38; 95% confidence interval [CI], 1.225-9.332; p = 0.019), respiratory (OR = 3.00; 95% CI, 1.161-7.736; p = 0.023), and cardiovascular morbidities (OR = 3.66; 95% CI, 1.068-12.55; p = 0.039) after OE. Meanwhile, moderate and severe malnutrition in CONUT did not increase the incidence of postoperative morbidities after MIE.Preoperative malnutrition in CONUT reflects various disadvantageous clinical factors and could be a predictor of worse short-term outcomes after OE, but it has no value in MIE. The low invasiveness of MIE might reduce the effect of preoperative malnutrition on worse short-term outcomes.

Background Brain metastasis of colorectal cancer is infrequent, and isolated brain metastases are more infrequent. Thus, when neurological symptoms, such as paralysis or disturbance of consciousness appear, there is a high probability that the cancer has spread to other organs. Case presentation Here, we present a 64-year-old man with a progressive headache, decreased motivation, and aphasia who was diagnosed with a brain tumor in the left frontal region. He underwent a craniotomy, and the brain tumor was diagnosed as adenocarcinoma. We performed a colonoscopy and diagnosed rectal cancer without other distant metastases. After whole-brain radiotherapy (WBRT), low anterior resection for primary rectal tumor was performed using a robotic system. The patient was discharged in good condition and received postoperative adjuvant therapy for rectal cancer. He showed no signs of recurrence after 1 year of follow-up. Conclusions We described a rare case of rectal cancer that was diagnosed after resection of isolated brain metastasis. A good prognosis was achieved with surgery and WBRT.

Systemic inflammation markers are useful prognostic indicators for metastatic colorectal cancer. However, the influence of KRAS genotypes on these markers in metastatic colorectal cancer patients is unclear.We evaluated the associations between systems of evaluating pretreatment systemic inflammation and outcomes according to KRAS genotypes in patients with metastatic colorectal cancer.This study was conducted at a university hospital.This was a retrospective study.A total of 272 patients (KRAS wildtype [KRASwt]:mutant [KRASMut] = 169:103) who received first-line systemic chemotherapy for metastatic colorectal cancer.We retrospectively calculated 8 systemic inflammation indices: neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, prognostic nutritional index, Glasgow prognostic score, Naples prognostic score, systemic inflammation score, and systemic immune-inflammation index. Patients were categorized into high or low groups for each index. The prognostic relevance of these indices for overall survival was evaluated according to KRAS genotype.Kaplan-Meier survival analyses showed that median overall survival significantly differed between the high and low groups for all indices in the KRASwt group but not in the KRASMut group, except for Glasgow prognostic score and lymphocyte/monocyte ratio. Multivariate Cox regression analyses identified all indices as independent prognostic factors. In the KRASwt group, all indices except platelet/lymphocyte ratio had strong prognostic effects, but not in the KRASMut group. Interaction tests indicated that KRAS genotype significantly influenced the prognostic impacts of neutrophil/lymphocyte ratio (p = 0.042), prognostic nutritional index (p = 0.048), Naples prognostic score (p0.001), and systemic immune-inflammation index (p = 0.004).A major limitation of this study is the lack of external validation.The prognostic significance of systemic inflammation indices is more useful in patients with KRASwt metastatic colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B921.

Experimental 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.Utilising 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.F. 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).Intratumour 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.

Gastric neuroendocrine carcinoma (NEC) is an aggressive disease with high metastatic ability. Gastric cancer has intra-tumoral and intra-patient heterogeneity and may contain NEC. We discuss the case of a 75-year-old man who underwent distal gastrectomy for early gastric cancer. Tumor pathology revealed that nearly all of the tumor (> 95%) was well-differentiated adenocarcinoma, with NEC detected in a small area (

Background Systemic inflammation may influence the response to systemic chemotherapy or the prognosis in patients with various cancers. The Naples prognostic score, based on inflammatory and nutritional statuses, is a useful prognostic marker in patients undergoing surgery for colorectal cancer; however, its significance in patients with metastatic colorectal cancer remains unclear. Objective We aimed to evaluate the prognostic significance of the Naples prognostic factor in patients with metastatic colorectal cancer receiving first-line chemotherapy and to compare its prognostic accuracy with the neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and the systemic immune-inflammatory index. Design This was a retrospective study of prospectively collected data. Settings This study was conducted at a university hospital. Patients A total of 259 patients received first-line systemic chemotherapy for metastatic colorectal cancer. Main outcome measures The Naples prognostic score was calculated by a composite score of albumin and cholesterol concentrations, lymphocyte:monocyte ratio, and neutrophil:lymphocyte ratio. The patients were divided into 3 groups based on increasing Naples scores (groups 0-2), and the associations of the Naples prognostic score with clinicopathologic features and overall survival were evaluated. Results Higher Naples prognostic score was positively associated with right-sided primary tumors and synchronous metastases and negatively with primary tumor resection. Patients in group 2 (high Naples prognostic score) had significantly shorter overall survival than those in groups 0 and 1 (p = 0.012 and 0.022). Multivariate Cox regression analysis identified the Naples prognostic score as an independent prognostic factor for overall survival (HR = 1.574; p = 0.004). Time-dependent receiver operating characteristic curve analysis showed that Naples prognostic score was more sensitive than other prognostic factors for predicting overall survival. Limitations The main limitations are the sample size, single institutional feature, and treatment heterogeneity. Conclusions The Naples prognostic score may be a useful prognostic marker in patients with metastatic colorectal cancer receiving systemic chemotherapy. See Video Abstract at http://links.lww.com/DCR/B72. LA PUNTUACION PRONOSTICA DE NAPOLES ES UN MARCADOR PRONOSTICO UTIL EN PACIENTES CON CANCER COLORRECTAL METASTASICO: La inflamacion sistemica puede influir en la respuesta a la quimioterapia sistemica o el pronostico en pacientes con varios tipos de cancer. La puntuacion pronostica de Napoles, basada en estados inflamatorios y nutricionales, es un marcador pronostico util en pacientes sometidos a cirugia por cancer colorrectal; sin embargo, su importancia en pacientes con cancer colorrectal metastasico sigue siendo incierta.El objetivo fue evaluar la importancia pronostica del factor pronostico de Napoles en pacientes con cancer colorrectal metastasico que reciben quimioterapia de primera linea y comparar su precision pronostica con la relacion neutrofilos: linfocitos, plaquetas: linfocitos y el indice sistemico inmune-inflamatorio.Este estudio se realizo en un hospital universitario.Este fue un estudio retrospectivo de datos recolectados prospectivamente.Un total de 259 pacientes recibieron quimioterapia sistemica de primera linea para el cancer colorrectal metastasico.La puntuacion pronostica de Napoles se calculo mediante una puntuacion compuesta de concentraciones de albumina y colesterol, proporcion de linfocitos: monocitos y proporcion de neutrofilos: linfocitos. Los pacientes se dividieron en tres grupos basados en el aumento de las puntuaciones de Napoles (grupos 0-2, respectivamente) y se evaluaron las asociaciones de la puntuacion pronostica de Napoles con las caracteristicas clinico-patologicas y la supervivencia general.La puntuacion pronostica de Napoles es mas alta se asocio positivamente con los tumores primarios del lado derecho y metastasis sincronicas, y negativamente con la reseccion del tumor primario. Los pacientes del grupo 2 (alto puntaje pronostico de Napoles) tuvieron una supervivencia general significativamente menor que los de los grupos 0 y 1 (p = 0.012 y 0.022, respectivamente). El analisis de regresion de Cox multivariado identifico la puntuacion pronostica de Napoles como un factor pronostico independiente para la supervivencia global (indice de riesgo = 1.574; p = 0.004). El analisis de la curva caracteristica de funcionamiento del receptor dependiente del tiempo mostro que la puntuacion pronostica de Napoles era mas sensible que otros factores pronosticos para predecir la supervivencia global.Las principales limitaciones son el tamano de la muestra, la caracteristica institucional unica y la heterogeneidad del tratamiento.La puntuacion pronostica de Napoles puede ser un marcador pronostico util en pacientes con cancer colorrectal metastasico que reciben quimioterapia sistemica. Vea el Abstract del video en http://links.lww.com/DCR/B72.

Oncologic emergencies such as perforation and obstruction associated with colorectal cancer are serious diseases that can lead to sepsis. Peritoneal dissemination and other factors may cause cancer progression and worsen the patients' long-term prognosis. In this study, we investigated the effect of colorectal cancer presenting as oncologic emergencies on the patients' clinical course.We performed a retrospective study that included 448 patients with colorectal cancer who underwent primary resection at our institution between January 2014 and December 2018. The primary outcome was overall survival, while secondary outcomes were 30-day mortality and postoperative complications. Cox regression was used to estimate the hazard ratio (HR) for overall survival.We identified 56 patients who presented with oncologic emergencies (OE group) and 392 patients who presented with no emergencies (NE group). Propensity-score matching yielded 56 patients in the OE group and 55 in the NE group with balanced baseline covariates. We found a strong association between overall survival (OS) and oncologic emergencies (HR = 2.4; 95% confidence interval [CI], 1.1-5.5). The 30-day mortality was not significantly different between the OE and NE groups (4% vs 0%,Colorectal cancer presenting as an oncologic emergency could be safely operated on without increasing the 30-day mortality rate and the incidence of severe postoperative complications. However, the long-term prognosis was poor.

The development of new drugs for inflammatory bowel disease (IBD) is remarkable, and treatment strategies using multiple agents and various techniques are required; however, the treatment strategy is likely to be complex. Therefore, appropriate evaluation of traditional surgical treatment strategies and accurate knowledge of the efficacy and limitations of novel treatments are required. Total infectious complications were found to be associated with the use of corticosteroids and anti-tumor necrosis factor-α agents, but not with immunomodulators, anti-integrin agents, and 5-aminosalicylic acid. Regarding surgical procedures for IBD, conceived anastomosis methods, including Kono-S for Crohn's disease stenosis, are associated with better outcomes than conventional techniques. Autologous cell transplantation for Crohn's fistulae has been shown to have a favorable outcome. Diverticulitis is increasing and will be treated more frequently in the future. Risk factors for the incidence of diverticulitis and differences in pathogenesis according to right or left side diverticulitis have been reported. Antibiotic therapy may be omitted for uncomplicated diverticulitis. Moreover, regarding surgical procedures, both bowel resection and anastomosis are associated with favorable short-term outcomes, higher stoma closure rate, and superior medical economy compared to Hartmann's procedure. Risk factors for recurrence after diverticulitis surgery may provide better postoperative follow-up. In this review, we explore the current topics of colorectal benign diseases, focusing on IBD and diverticulitis, based on clinical trials and meta-analyses from 2020-2021. This review consolidates the available knowledge and improves the quality of surgical procedures and perioperative management for IBD and diverticulitis.

Glucose transporter 1 (GLUT1) expression is a prognostic marker for esophageal squamous cell carcinoma (ESCC). Recent work on GLUT1 and development of specific inhibitors supports the feasibility of GLUT1 inhibition as a treatment for various cancers. The anti–proliferative effects of GLUT1‐specific small interfering RNA (siRNA) and a GLUT1 inhibitor were evaluated in ESCC cell lines. Expression of pro–proliferative and anti–proliferative signaling and effector molecules was examined by western blotting and quantitative RT‐PCR. GLUT1 expression in pretreatment clinical biopsy samples was measured by immunohistochemistry and correlated with various clinicopathological parameters and response to chemotherapy. The reduction in standardized uptake value (SUV) of 18F‐fluoro‐deoxyglucose was calculated using the formula: ([pretreatment SUV max – posttreatment SUV max]/pretreatment SUV max) × 100. GLUT1‐specific siRNA expression in ESCC cells inhibited their proliferation, increased expression of p27kip, and decreased expression of cyclin‐dependent kinase 6, pyruvate kinase muscle isozyme M2, lactate dehydrogenase A and phospho‐ERK1/2. Suppression of GLUT1 by siRNA increased low‐dose cisplatin‐induced inhibition of proliferation of TE‐11 ESCC cells, which express high GLUT1 levels. Similarly, BAY‐876, a GLUT1 inhibitor, enhanced cisplatin‐mediated inhibition of ESCC cell proliferation. GLUT1 expression in pretreatment biopsy samples was associated with the response to chemotherapy as well as the pathological tumor stage and histological response grade after esophagectomy. Finally, GLUT1‐negative tumors showed a significantly larger reduction in SUV max (61.2% ± 4.5%) compared with GLUT1‐positive tumors (46.2% ± 4.4%). GLUT1 expression may be a surrogate marker of response to chemotherapy, and inhibition of GLUT1 may be a potential novel therapy for ESCC patients.

Clinical significance of red blood cell distribution (RDW) as a predictive marker for the incidence of postoperative morbidity after esophagectomy for esophageal cancer has not been established. This study included 634 consecutive patients who underwent three-incisional esophagectomy with lymphadenectomy for esophageal cancer between April 2005 and November 2020. Correlation between pretreatment RDW and patient background, cancer background, and short-term outcome after esophagectomy were retrospectively investigated. Eighty patients (12.6%) had a high pretreatment RDW (> 14.2), which correlated with malnutrition estimated by body mass index, hemoglobin, total lymphocyte count, albumin, and total cholesterol. High pretreatment RDW was an independent risk factor for postoperative severe morbidity of grade IIIb or higher based on the Clavien–Dindo classification (hazard ratio [HR] 3.90, 95% confidence interval [CI] 1.707–8.887; p = 0.0012) and reoperation (HR 4.39, 95% CI 1.552–12.390; p = 0.0053) after open esophagectomy (OE). However, RDW was not associated with postoperative morbidity incidence after minimally invasive esophagectomy (MIE). Pretreatment RDW may be a surrogate marker for nutritional status and could be a predictive marker for postoperative severe morbidity, reoperation, and possibly pneumonia after OE. On the contrary, the lower invasiveness of MIE may have reduced the effect of pretreatment malnutrition on morbidity incidence, which could explain the insignificant relationship between RDW and poor short-term outcomes in MIE.

Background: Colorectal cancer is the second most common cause of cancer-related death worldwide. It is well-known that metasta sis to the liver and lung and local recurrences can occur. Additionally, colorectal cancer occasionally metastasizes to other sites. Only a few reports of such metastases have been published and no definitive therapeutic strategies have been proposed for them. Case Report: The case of a 77-year-old man who was diagnosed with rectal cancer is presented. Eighteen months after curative laparoscopic low anterior resection and D3 lymph node resection, an anal fistula metastasis was diagnosed by computed tomography and biopsy. After administering radiotherapy, percutaneous excision of the lesion. was performed. At 21 months from the surgery, the patient is healthy and no recurrence has been found. Conclusion: Metachronous metastasis of a colorectal cancer to an anal fistula is rare. Careful investigation and optimal treatment can result in a disease-free status.

The new World Health Organization (WHO) classification of gastric cancer includes a histological subtype of poorly cohesive carcinoma (PCC), which includes signet-ring cell (SRC) phenotype. We aimed to examine the concordance between preoperative clinical and postoperative histological diagnoses according to the 2010 WHO histological subtypes and to compare the prognoses of these subtypes.The study cohort comprised 665 patients who underwent gastrectomy from 2005 to 2019. Histological subtypes were classified into PCC-NOS (non-signet ring cell subtype), SRC, and non-PCC, which were defined by the predominant component in accordance with the 2010 WHO classification of gastric cancer. The concordance of clinical and pathological diagnosis was examined and clinicopathological characteristics and survival outcome of the three subtypes compared.The cancers of 443 patients (66.7%) were classified as non-PCC, of 112 patients (16.8%) as PCC-NOS, and of 110 patients (16.5%) as SRC predominant subtypes. Significant differences in sex, age, tumor location, size, macroscopic type, and pathological TNM category (all P0.05) were found. The concordance rate of preoperative and postoperative histological subtypes was significantly lower for poorly cohesive than other subtypes (P0.0001). Preoperative stage tended to be underestimated for PCC-NOS subtype and these patients had poorer overall survival than those with the other two subtypes (P=0.005). Multivariate logistic regression analysis of overall survival showed that WHO histological subtype (PCC-NOS vs. non-PCC/SRC, HR: 1.64, 95% CI: 1.18-2.29, P=0.0034) was a significant independent prognostic factor.Our results suggest that poorly cohesive carcinoma subtypes have different biological characteristics and prognoses.

Aim This study aimed to investigate the prognosis after recurrence in patients with stage I–III colon cancer (CC) and rectal cancer (RC). Methods Cancer recurred in 116 (15.2%) out of 763 patients with stage I–III colorectal cancer. The overall survival (OS) after recurrence was evaluated based on the recurrence organs and patterns. Results The first recurrence occurred in the lungs, livers, lymph nodes, and other sites in 32, 22, 12, and 2 patients, respectively. It was localized, disseminated, and involved two or more organs in 14, 9, and 25 patients, respectively. Patients with CC had a shorter OS after recurrence as compared to those with RC (P = .0103). Compared to other organ metastasis, liver metastasis was associated with an earlier recurrence (P = .0026) and shorter OS after recurrence (hazard ratio [HR]: 2.216; 95% confidence interval [CI]: 1.052–4.459; P = .0370). Lung metastasis was associated with a more favorable prognosis as compared to other organ recurrences (HR: 0.338; 95% CI: 0.135–0.741; P = .0057). One‐organ recurrence and oligometastasis were observed in 78.4% and 49.1% of the patients, respectively. The 5‐y OS rates of patients with one‐organ recurrence and oligometastasis were 47.5% and 71.7%, respectively. Invasive treatment was associated with a favorable prognosis (P, One organ recurrence was observed in 78.4% of patients and oligometastasis in 49.1%. The 5‐y OS rates of patients with one organ recurrence and oligometastasis were 47.5% and 71.7%, respectively. Invasive treatment was associated with a favorable prognosis (P

Iron deficiency anemia is represented in colorectal cancer (CRC) patients. Iron surplus load to increase non-transferrin bound iron (NTBI), and NTBI promotes cancer progression and influences microbiota. This study investigated whether preoperative serum iron status was associated with prognosis after CRC resection.We evaluated preoperative iron and transferrin saturation (TSAT), which was calculated as iron divided by total iron-binding capacity, in 327 patients who underwent surgery for Stage II-III CRC. Fe 60 μg/dl and TSAT 40% were defined as low and high iron, respectively. The associations between iron status and overall survival (OS) were evaluated in univariate and multivariate Cox proportional hazards analysis.Of the 327 patients, 179 (54.7%), 124 (37.9%) and 24 (7.3%) had low, normal and high iron, respectively. In univariate analysis, low iron was associated with shorter OS (hazard ratio [HR] 2.821, 95% confidence interval [CI] 1.451-5.485, P = 0.002). High iron was also associated with shorter OS (HR 3.396, 95% CI 1.359-8.489, P = 0.009). In multivariate analysis, high age (P = 0.002), depth of invasion pT4 (P = 0.012), lymph-node metastasis presence (P = 0.035), low albumin (P = 0.011), low iron (HR 2.282, 95% CI 1.163-4.478, P = 0.016) and high iron (HR 3.757, 95% CI 1.486-9.494 P = 0.005) were independently associated with shorter OS. High iron was associated with the amount of intratumoral Fusobacterium nucleatum compared with normal iron.Both low and high preoperative iron in Stage II-III CRC patients were associated with unfavorable OS in univariate and multivariate analyses.

OBJECTIVE To elucidate the latest epidemiology and risk factors for multiple primary cancers (MPCs), and the association between neoadjuvant chemotherapy (NAC) and postoperative metachronous cancer (PMC) in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy. SUMMARY OF BACKGROUND DATA Background data to derive appropriate screening strategies are insufficient. METHODS This study consisted of three retrospective investigations. A total of 766 consecutive patients with ESCC who underwent esophagectomy between April 2005 and December 2019 were eligible for epidemiological analysis. Of these, 688 patients without missing data were analyzed for the risk of MPCs. In total, 364 patients who underwent NAC (115) and no preoperative treatments (249) were investigated for the association between NAC and PMC. RESULTS Of 766 patients, 288 (38%) patients experienced 357 MPCs in their life. PMCs identified after the completion of 5-year postoperative follow-up were significantly more advanced (P = 0.019). Male sex [hazard ratio (HR) = 3.04, P = 0.038], older age (HR = 2.39, P < 0.001), and diabetes mellitus (HR = 1.76, P = 0.034) were risk factors for preoperative metachronous cancers. Heavy smoking (HR = 1.70, P = 0.014) and drinking (HR = 1.61, P = 0.029) were risk factors for synchronous cancers. NAC significantly reduced PMC incidence (P = 0.043). NAC showed a trend to contribute to improved survival via reduced deaths from PMCs, although this did not reach significance (P = 0.082). CONCLUSIONS ESCC is associated with a high risk of MPCs. Continuing follow-up for PMCs after the completion of 5-year postoperative follow-up is important. NAC may reduce PMCs, representing a novel mechanism for improving survival in patients with locally advanced ESCC.

Aim This study investigated whether preoperative serum transferrin, a rapid‐turnover protein, was associated with prognosis after colorectal cancer (CRC) resection. Methods We evaluated preoperative transferrin, which was calculated as iron and unsaturated iron‐binding capacity, in 501 patients who underwent surgery for Stage I–III CRC. Transferrin level was directly proportional to total iron‐binding capacity (TIBC), and TIBC, Fifty‐eight of 501 patients CRC patients (11.5%) had low transferrin, which is a rapid turnover protein. Preoperarive low transferrin was associated with shorter relapse‐free survival (P

The classification of colorectal cancer (CRC) plays a pivotal role in predicting a patient's prognosis and determining treatment strategies. The consensus molecular subtype (CMS) classification system was constructed by analyzing genetic information from 18 CRC data sets, containing 4151 CRC samples. CRC was classified into four subtypes with distinct molecular and biological characteristics: CMS1 (microsatellite instability immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal). Since their designation in 2015, these classifications have been applied to basic and translational research of CRC, with the hope that understanding these subsets will influence a clinician's approach to therapeutic treatment and improve clinical outcomes. We reviewed CRC investigations in accordance with CMSs published in the last 5 years to further explore the clinical significance of these subtypes and identify underlying trends that may direct relevant future research. We determined that CMSs linked common features of CRC cell lines and PDX models in various studies. Furthermore, associations between prognosis and clinicopathological findings, including pathological grade and the stage of carcinogenesis, tumor budding, and tumor location, were correlated with CMS classification. Novel prognostic factors were identified, and the relationship between chemotherapeutic drug resistance and CMS has been fortified by our compilation of research; thus, indicating that this review provides advanced insight into clinical questions and treatment strategies for CRC., CRC was classified into four subtypes with distinct molecular and biological characteristics: CMS1 (microsatellite instability immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal). Novel prognostic factors were identified, and the relationship between chemotherapeutic drug resistance and CMS has been fortified by our compilation of research.

Radiofrequency ablation (RFA) can be a minimally invasive therapeutic option in patients with lung metastasis from colorectal caner. We aimed to elucidate the safety and survival benefit of computed tomography (CT)-guided percutaneous RFA for lung metastasis from colorectal cancer. A total 188 lesions were ablated in 43 patients from 2005 to 2017. The clinicopathological and survival data of patients were collected retrospectively. The short- and long-term outcomes and prognostic factors were analyzed. Eight patients (18.6%) had viable extrapulmonary metastasis at RFA treatment. The median number of treated lung tumors was 2, and the median maximum diameter was 12 mm. Complications, such as pneumothorax, pleural effusion and subcutaneous emphysema, occurred in 24 (55.8%) patients. Although chest tube drainage for pneumothorax was needed in 6 patients (14.0%), there were no mortalities. Repeated RFA for lung recurrence after primary RFA was performed in 14 patients (32.6%). In a median follow-up of 24.3 months, the median progression-free and overall survival (OS) were 6.8 months and 52.7 months, respectively. The presence of extrapulmonary metastasis and a maximum tumors size of > 15 mm were independently associated with a worse disease-free survival and OS. The OS of patients who underwent repeated RFA was significantly better than that of patients who underwent RFA only once. CT-guided percutaneous RFA for lung metastasis from colorectal cancer is a safe and effective procedure in patients not eligible for surgery, particularly for lesions smaller than 1.5 cm without extrapulmonary metastasis.

This study investigated the predictors associated with early recurrence (i.e. within 12 months) after curative gastrectomy for gastric cancer (GC). We evaluated the clinicopathological factors in 429 patients who underwent curative gastrectomy for GC without preoperative chemotherapy and analyzed these factors’ associations with early recurrence. Of 429 patients, 57 experienced recurrences, which were associated with gender, diameter, depth of invasion, lymph node (LN) metastasis, the LN ratio (LNr; LNs with metastasis/dissected LNs), lymphatic invasion, vascular invasion, carbohydrate antigen 19-9 (CA19-9) levels, C-reactive protein levels and the neutrophil/lymphocyte ratio. Twenty-one patients (36.8%) recurred within 12 months. Early recurrence was associated with a high LNr (P = 0.0020) and high CA19-9 levels (P = 0.0415). The other factors were not significantly associated with early recurrence. The 12-month recurrence rate was 33.9% in patients with a high LNr and 1.9% in those with a low LNr and 20.3% in patients with high CA19-9 levels and 3.5% in those with low CA19-9 levels. The 12-month recurrence rate was 62.5% in patients with a high LNr and high CA19-9 levels, 18.4% in those with a high LNr or high-CA19-9 levels, and 1.4% in those with a low LNr and low CA19-9 levels. LNr ≥ 0.15 and CA19-9 ≥ 37 U/ml were effective surrogate markers for predicting early recurrence.

RNF43 mutations are frequently detected in colorectal cancer cells and lead to a loss of function of the ubiquitin E3 ligase. Here, we investigated the clinical significance of RNF43 mutations in a large Japanese cohort and the role of RNF43 at various stages of colorectal cancer development and progression. Mutation analysis of the RNF43 gene locus with pyrosequencing technology detected RNF43 hotspot mutations in one (0.88%) of 113 colorectal polyp cases and in 30 (6.45%) of 465 colorectal cancer cases. Moreover, patients with colorectal cancer harbouring mutated RNF43 experienced a higher recurrence rate than those harbouring non-mutated RNF43. In addition, the growth of RNF43 wild-type colorectal cancer cell lines was significantly increased by RNF43 silencing. We generated Rnf43 knockout mice in a C57BL/6 N background by using the CRISPR-Cas9 system. Although intestinal organoids from Rnf43 knockout mice did not show continuous growth in the absence of R-spondin, an azoxymethane/dextran sodium sulphate mouse model demonstrated that tumours were markedly larger in Rnf43 knockout mice than in wild-type mice. These findings provide evidence that Wnt signalling activation by RNF43 mutations during the tumourigenic stage enhances tumour growth and promotes a high recurrence rate in colorectal cancer patients. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.