Effect of the Japanese herbal medicine Hochuekkito for systemic inflammation, prognostic nutrition index, and body composition status in patients with gastrointestinal cancer.

BACKGROUND & AIMS: A systemic inflammatory response via host-tumor interactions is a cancer hallmark that plays a pivotal role in the pathogenesis of malnutrition and sarcopenia in patients with malignancies. Hochuekkito (TJ-41) is a traditional Japanese herbal medicine that modulates inflammation in patients with various chronic inflammatory diseases. However, the clinical efficacy of TJ-41 in patients with malignancies remains unclear. METHODS: We systemically analyzed chronological changes in levels of systemic inflammatory parameters, nutrition-related parameters, and body composition status in 99 patients who received TJ-41 treatment for more than 3 months. The cohort comprised 56 patients with gastrointestinal cancer (Cancer Cohort) and 43 with other diseases (Other Disease Cohort). We also performed in vivo experiments in mice to validate the clinical findings. RESULTS: Despite no significant changes in serum albumin concentration and prognostic nutrition index, the serum C-reactive protein (CRP) concentration significantly decreased in a time-dependent manner in all patients. However, the serum CRP concentration significantly decreased during TJ-41 treatment in the Cancer Cohort but not the Other Disease Cohort. Furthermore, downregulation of CRP during TJ-41 treatment occurred only in patients with metastases. The psoas muscle index, as a muscle quantity marker, was significantly lower in the CRP-increased group compared with the CRP-decreased group during TJ-41 treatment. In vivo experiments using a Colon-26 syngeneic model showed that the plasma CRP, amyloid A, and interleukin-6 concentrations were significantly lower in the TJ-41 group than the control group. CONCLUSION: TJ-41 might be useful as part of multimodality therapy for gastrointestinal cancer, especially in patients with metastases.

Possible poor prognosis in younger-onset Crohn's disease-associated anorectal cancer: A subanalysis of the Nationwide Japanese study.

Background and aims: Crohn's disease (CD)-associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating evidence revealed that younger-onset sporadic colorectal cancer may exhibit unique biological features. To the best of our knowledge, few previous articles reported clinicopathological features in patients with CD-associated anorectal cancer (CDAAC). Therefore, we aimed to clarify the relationship between the younger onset of cancer and clinicopathological characteristics and prognosis, and the efficacy of cancer surveillance in patients with CDAAC. Methods: CD patients who had been diagnosed with intestinal cancers from 1983 to 2020 were collected from 39 Japanese institutions in this study. Of 316 patients with CD-associated intestinal cancers, we analyzed 211 patients with CDAAC. We divided the patients into two groups according to the median age at cancer diagnosis (45 years old). Results: Younger-onset CDAAC (YO-CDAAC) patients were significantly more likely to have a poor outcome than those with older-onset CDAAC (OO-CDAAC) in terms of both disease-free survival (DFS) (p = 0.0014) and overall survival (OS) (p = 0.023). Multivariate analysis showed that age under 45 years old at diagnosis of cancer was one of the independent factors for poor DFS and OS (hazard ratios: 2.15, 95% confidence interval: 1.09-4.26, p = 0.028, hazard ratios: 1.95, 95% confidence interval: 1.05-3.60, p = 0.033, respectively). Patients detected via surveillance showed significantly better DFS and OS rates than symptomatic patients in YO-CDAAC (p = 0.012 and 0.0031, respectively). Conclusions: YO-CDAAC may have a poorer prognosis compared with OO-CDAAC. Surveillance could be important to improve cancer prognosis, especially in young CD patients with anorectal disease.

Short- and long-term outcomes of surgical treatment for inguinal lymph node metastasis in rectal and anal canal adenocarcinoma.

AIM: The significance of lymphadenectomy and its indications in patients with inguinal lymph node metastasis (ILNM) of anorectal adenocarcinoma is unclear. This study aimed to clarify the surgical outcomes and prognostic factors of inguinal lymphadenectomy for ILNM. METHOD: This study included patients who underwent surgical resection for ILNM of rectal or anal canal adenocarcinoma with pathologically positive metastases between 1997 and 2011 at 20 participating centres in the Study Group for Inguinal Lymph Node Metastasis from Colorectal Cancer organized by the Japanese Society for Cancer of the Colon and Rectum. Clinicopathological characteristics and short- and long-term postoperative outcomes were retrospectively analysed. RESULTS: In total, 107 patients were included. The primary tumour was in the rectum in 57 patients (53.3%) and in the anal canal in 50 (46.7%). The median number of ILNMs was 2.34. Postoperative complications of Clavien-Dindo Grade III or higher were observed in five patients. The 5-year overall survival rate was 38.8%. Multivariate analysis identified undifferentiated histological type (P < 0.001), pathological venous invasion (P = 0.01) and pathological primary tumour depth T0-2 (P = 0.01) as independent prognostic factors for poor overall survival. CONCLUSION: The 5-year overall survival after inguinal lymph node dissection was acceptable, and it warrants consideration in more patients. Further larger-scale studies are needed in order to clarify the surgical indications.

Clinical feasibility of the preoperative C-reactive protein-albumin-lymphocyte index to predict short- and long-term outcomes of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is a major leading cause of cancer-related death worldwide. Systemic inflammation and the nutrition-based score are feasible prognostic markers for malignancies. Emerging evidence has also revealed the C-reactive protein-albumin-lymphocyte (CALLY) index to be a prognostic marker for several cancer types. However, its clinical significance to predict surgical and oncologic outcomes of patients with GC remains unclear. METHODS: We assessed the preoperative CALLY index in 426 patients with GC who received gastrectomy. RESULTS: A low preoperative CALLY index was significantly correlated to all well-established clinicopathologic factors for disease development, including an advanced T stage, the presence of venous invasion, lymphatic vessel invasion, lymph node metastasis, distant metastasis, and an advanced TNM stage. A low preoperative CALLY index was also an independent prognostic factor for overall survival (hazard ratio [HR], 2.64; 95 % CI, 1.66-4.2; P < .0001) and disease-free survival (HR, 1.76; 95 % CI, 1.01-3.05; P = .045). In addition, a low preoperative CALLY index was an independent predictive factor for postoperative surgical site infection (odds ratio, 2.64; 95 % CI, 1.42-4.89; P = .002). CONCLUSION: The preoperative CALLY index is valuable for perioperative and oncologic management of patients with GC.

Prediction of Post-Gastrectomy Pancreatic Complications: A Preoperative Imaging Study Based on Computed Tomography.

BACKGROUND: Postoperative pancreas-related complications (PPRCs) are common after laparoscopic gastrectomy (LG) in patients with gastric cancer. We estimated the anatomical location of the pancreas on a computed tomography (CT) image and investigated its impact on the incidence of PPRCs after LG. METHODS: We retrospectively reviewed the preoperative CT images of 203 patients who underwent LG for gastric cancer between January 2010 and December 2017. From these images, we measured the gap between the upper edge of the pancreatic body and the root of the common hepatic artery. We evaluated the potential relationship between PPRCs and the gap between pancreas and common hepatic artery (GPC) status using an analysis based on the median cutoff value and assessed the impact of GPC status on PPRC incidence. We performed univariate and multivariate analyses to identify predictive factors for PPRC. RESULT: Postoperative pancreas-related complications occurred in 11 patients (5.4%). The median of the optimal cutoff GPC value for predicting PPRC was 0 mm; therefore, we classified the GPC status into two groups: GPC plus group and GPC minus group. Univariate analysis revealed that sex (male), C-reactive protein (CRP) > .07 mg/dl, GPC plus, and visceral fat area (VFA) > 99 cm2 were associated with the development of PPRC. Multivariate analysis identified only GPC plus as independent predictor of PPRC (hazard ratio: 4.60 [95% confidence interval 1.11-31.15], P = .034). CONCLUSION: The GPC is a simple and reliable predictor of PPRC after LG. Surgeons should evaluate GPC status on preoperative CT images before proceeding with laparoscopic gastric cancer surgery.

Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

Impact of resection for ovarian metastases from colorectal cancer and clinicopathologic analysis: A multicenter retrospective study in Japan.

Aim: The aim of this study was to clarify the significance of resection of ovarian metastases from colorectal cancer and to identify the clinicopathologic characteristics. Methods: In this multicenter retrospective study, we evaluated data on ovarian metastases from colorectal cancer obtained from patients at 20 centers in Japan between 2000 and 2014. We examined the impact of resection on the prognosis of patients with ovarian metastases and examined prognostic factors. Results: The study included 296 patients with ovarian metastasis. The 3-y overall survival rate was 68.6% for solitary ovarian metastases. In all cases of this cohort, the 3-y overall survival rates after curative resection, noncurative resection, and nonresection were 65.9%, 31.8%, and 6.1%, respectively (curative resection vs noncurative resection [P < 0.01] and noncurative resection vs nonresection [P < 0.01]). In the multivariate analysis of prognostic factors, tumor size of ovarian metastasis (P < 0.01), bilateral ovarian metastasis (P = 0.01), peritoneal metastasis (P < 0.01), pulmonary metastasis (P = 0.04), liver metastasis (P < 0.01), and remnant of ovarian metastasis (P < 0.01) were statistically significantly different. Conclusion: The prognosis after curative resection for solitary ovarian metastases was shown to be relatively favorable as Stage IV colorectal cancer. Resection of ovarian metastases, not only curative resection but also noncurative resection, confers a survival benefit. Prognostic factors were large ovarian metastases, bilateral ovarian metastases, the presence of extraovarian metastases, and remnant ovarian metastases.

Clinical implications of C-reactive protein-albumin-lymphocyte (CALLY) index in patients with esophageal cancer.

PURPOSE: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory nutritional biomarker. This study aimed to investigate the potential clinical significance and oncological prognostic role of the preoperative CALLY index in patients with esophageal cancer. METHODS: We analyzed the preoperative CALLY index in 146 patients with esophageal cancer. The CALLY index and clinicopathological variables were analyzed by the Mann-Whitney U test, and associations between the CALLY index and survival outcomes were analyzed by Kaplan-Meier analysis and log-rank tests. Univariate and multivariate analyses of prognostic variables were conducted using Cox proportional hazards regression. RESULTS: A lower preoperative CALLY index was significantly correlated with patient age, advanced T stage, presence of lymph node metastasis, neoadjuvant therapy, lymphatic invasion, and advanced stage classification. The preoperative CALLY index decreased significantly in a stage-dependent manner. Patients with esophageal cancer with a low CALLY index had poorer overall survival, disease-free survival than those with a high CALLY index. Multivariate analysis showed that a low CALLY index was an independent prognostic factor for overall survival, disease-free survival and an independent predictor of postoperative surgical site infection. CONCLUSIONS: Preoperative CALLY index is a useful marker to guide the perioperative and postoperative management of patients with esophageal cancer.

Successful management following combined thoracic endovascular aortic repair and minimally invasive esophagectomy for primary aortoesophageal fistula: A case report.

Aortoesophageal fistula (AEF) is a rare but life-threatening pathology. We report a case of a primary AEF that was successfully managed with temporary thoracic endovascular aortic repair (TEVAR) and esophagectomy with video-assisted thoracoscopic surgery. A 73-year-old man was transferred to the emergency department with a complaint of hematemesis. A computed tomography scan identified an AEF due to aortic aneurysm. We placed a stent using TEVAR for the purpose of hemodynamic stasis, and the operation was performed 23 h after admission. Right video-assisted thoracoscopic esophagectomy (VATS-E) was chosen, and a cervical esophagostomy and a feeding gastrostomy tube was constructed. Infection had been effectively controlled postoperatively. Four months after the first operation, we performed esophageal reconstruction. At the 70-month follow-up examination, the patient had no signs of mediastinitis. VATS-E immediately after hemostabilization by TEVAR is useful management for primary AEF.

A Circulating Panel of circRNA Biomarkers for the Noninvasive and Early Detection of Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Delayed manifestation of symptoms and lack of specific diagnostic markers lead patients being diagnosed with PDAC at advanced stages. This study aimed to develop a circular RNA (circRNA)-based biomarker panel to facilitate noninvasive and early detection of PDAC. METHODS: A systematic genome-wide discovery of circRNAs overexpressed in patients with PDAC was conducted. Subsequently, validation of the candidate markers in the primary tumors from patients with PDAC was performed, followed by their translation into a plasma-based liquid biopsy assay by analyzing 2 independent clinical cohorts of patients with PDAC and nondisease controls. The performance of the circRNA panel was assessed in conjunction with the plasma levels of cancer antigen 19-9 for the early detection of PDAC. RESULTS: Initially, a panel of 10 circRNA candidates was identified during the discovery phase. Subsequently, the panel was reduced to 5 circRNAs in the liquid biopsy-based assay, which robustly identified patients with PDAC and distinguished between early-stage (stage I/II) and late-stage (stage III/IV) disease. The areas under the curve of this diagnostic panel for the detection of early-stage PDAC were 0.83 and 0.81 in the training and validation cohorts, respectively. Moreover, when this panel was combined with cancer antigen 19-9 levels, the diagnostic performance for identifying patients with PDAC improved remarkably (area under the curve, 0.94) for patients in the validation cohort. Furthermore, the circRNA panel could also efficiently identify patients with PDAC (area under the curve, 0.85) who were otherwise deemed clinically cancer antigen 19-9-negative (<37 U/mL). CONCLUSIONS: A circRNA-based biomarker panel with a robust noninvasive diagnostic potential for identifying patients with early-stage PDAC was developed.

Promoter methylation levels of microRNA-124 in non-neoplastic rectal mucosa as a potential biomarker for ulcerative colitis-associated colorectal cancer in pediatric-onset patients.

PURPOSE: To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC). METHODS: Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients. RESULTS: Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone (P = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC. CONCLUSION: miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC.

Clinical Significance of the Preoperative Inflammatory Burden Index in Esophageal Cancer.

INTRODUCTION: The inflammatory burden index (IBI) serves as a prognostic marker for several cancers. Here, we evaluated the predictive value of preoperative IBI associated with the surgical and oncological outcomes of patients with esophageal cancer (EC). METHODS: The IBI was formulated as C-reactive protein × neutrophil/lymphocyte. We retrospectively analyzed preoperative IBI of 147 EC patients receiving esophagectomy between 2008 and 2018. Cox proportional hazards models and multivariable logistic regression were employed to identify independent risk factors of surgical site infection and prognosis. RESULTS: Increased preoperative IBI significantly correlated with higher tumor stage. Patients with high IBI experienced shorter overall survival (p = 0.0002) and disease-free survival (p = 0.002) compared with those with low IBI. In the adjusted Cox proportional hazards regression models, increased IBI served as an independent prognostic factor for overall survival (hazard ratio, 3.56; 95% confidence interval, 1.79-7.34; p = 0.0003) and disease-free survival (hazard ratio, 3.03; 95% confidence interval, 1.60-5.92; p = 0.007). Multivariable analysis identified preoperative high IBI which served as an independent risk factor for overall surgical site infection (odds ratio, 2.53; 95% confidence interval, 1.00-6.38; p = 0.049). CONCLUSION: Preoperative IBI may serve as a useful predictor of prognosis and surgical site infection of patients with EC after esophagectomy.

Extraction of a metallic susceptor after accidental ingestion of the heated tobaccostick TEREA™: a case report.

BACKGROUND: Tobacco ingestion is widely known to cause nicotine toxicity, which may result in severe symptoms. Two heated tobacco sticks, called TEREA™ and SENTIA™, were launched in 2021 by Philip Morris International (New York, NY, USA), and their ingestion is associated with a risk of bowel injury because they contain a partially pointed metallic susceptor. However, this risk is not well known to the general public or healthcare providers. To increase awareness of this risk, we herein report a case involving extraction of a metallic susceptor after ingestion of the heated tobacco stick TEREA™. CASE PRESENTATION: A 7-month-old girl presented to the emergency department of a nearby hospital because she was suspected to have accidentally swallowed heated tobacco. Although she presented with no symptoms related to nicotine poisoning, abdominal X-ray examination revealed a metal object in her stomach. According to a statement released by the Japan Poison Information Center, the TEREA™ heated tobacco stick contains a metallic susceptor with a rectangular shape and sharp corners. The patient was transferred to our department because of the risk of bowel injury, and upper gastrointestinal endoscopy was performed. No cigarettes were found by endoscopic observation; however, a metallic susceptor was located in the second part of the duodenum. We grasped it with biopsy forceps and carefully removed it using an endoscope with a cap attached to the tip. The post-endoscopic course was uneventful. CONCLUSIONS: Some patients who ingest heated tobacco sticks might be exposed not only to the effects of nicotine but also to physical damage caused by a metallic susceptor. Infants and toddlers especially could swallow these sticks, therefore tobacco companies need to make the problem more public. Clinicians also should alert the problem, and pay attention to this risk in the clinical setting.

Double inferior vena cava, an uncommon but relevant anatomical anomaly in surgery for lower rectal cancer: a report of two cases.

BACKGROUND: Double inferior vena cava (DIVC) is rare and usually detected incidentally. DIVC may be associated with several anatomical variants of the retroperitoneal and pelvic veins. These variants can pose a clinical problem during colorectal surgery. We present two patients with lower rectal cancer who also had a DIVC. CASE PRESENTATION: Case 1 was a 72-year-old man with advanced lower rectal cancer (T3N0M0) who underwent robot-assisted low anterior resection after neoadjuvant therapy. A DIVC was detected on preoperative computed tomography (CT). During the operation, a presacral vein was injured while mobilizing the rectum and hemostasis could not be achieved. We converted to open surgery and packed the pelvic cavity for hemostasis. Retrospective analysis suggested the injured vein arose from an interiliac vein of the presacral pelvic venous plexus. Case 2 was a 50-year-old woman with lower rectal cancer (T3N0M0), immune thrombocytopenic purpura, and a DIVC. Although preoperative three-dimensional CT angiography showed no obvious pelvic vein abnormalities, a short course of preoperative radiotherapy was delivered to avoid lateral pelvic lymph node dissection. Chemotherapy was deferred owing to her thrombocytopenic disease. Laparoscopic abdominoperineal resection was performed meticulously to minimize bleeding and achieve rapid hemostasis. No intraoperative complications occurred. CONCLUSION: DIVC is often accompanied by venous malformations that may pose a problem when mobilizing the mesorectum from the retroperitoneum. Preoperative assessment of pelvic vessel anatomy using three-dimensional CT is essential in patients with a DIVC who undergo rectal surgery.

A proposed new Japanese classification of synchronous peritoneal metastases from colorectal cancer: A multi-institutional, prospective, observational study conducted by the Japanese Society for Cancer of the Colon and Rectum.

Aim: To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods: This multi-institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results: Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion: This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

Oncological outcomes of Crohn's disease-associated cancers focusing on disease behavior.

Background: The overall risk of colorectal cancer in Crohn's disease (CD) is higher than in the general population, and CD-associated cancer (CDAC) has poorer prognosis than sporadic cancer. Developing treatment strategies for improving the prognosis of CDAC, we evaluated the characteristics of CDAC according to the underlying disease behavior, namely stricturing and penetrating. Methods: This multicenter retrospective study comprises 316 CDAC patients who underwent surgery between 1985 and 2019. Clinicopathological findings including disease behavior and oncological outcomes were investigated. Results: There was no association between the preoperative course of CDAC patients and disease behavior; however, postoperative information revealed distinctly different characteristics between CDAC patients with stricturing behavior and those with penetrating behavior (stricturing with lymphatic invasion and peritoneal dissemination recurrence, and penetrating with histologically poorly differentiated and local recurrence). Oncological outcome of patients with CDAC was distinctly different according to disease behavior, as penetrating provided a poor outcome (overall survival [OS]: p = 0.02; relapse-free survival [RFS]: p = 0.002) whereas stricturing had no effect. Furthermore, penetrating behavior was identified as one of the independent risk factors for poor OS and RFS (OS: hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.16-3.09, p = 0.01; RFS: HR 2.15, 95% CI 1.28-3.63, p = 0.004). Conclusions: Our study highlights the different characteristics of CDAC according to the underlying disease behavior and substantiates the poor prognosis of CDAC patients with penetrating behavior. Treatment planning including screening, surgical procedures, and postoperative treatment, with awareness of these findings, may contribute to improved prognosis for CDAC patients.

Survival impact of surgical site infection in esophageal cancer surgery: A multicenter retrospective cohort study.

Aim: This study was performed to evaluate the oncological impact of surgical site infection (SSI) and pneumonia on long-term outcomes after esophagectomy. Methods: The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 407 patients with curative stage I/II/III esophageal cancer at 11 centers from April 2013 to March 2015. We investigated the association of SSI and postoperative pneumonia with oncological outcomes in terms of relapse-free survival (RFS) and overall survival (OS). Results: Ninety (22.1%), 65 (16.0%), and 22 (5.4%) patients had SSI, pneumonia, and both SSI and pneumonia, respectively. The univariate analysis demonstrated that SSI and pneumonia were associated with worse RFS and OS. In the multivariate analysis, however, only SSI had a significant negative impact on RFS (HR, 1.63; 95% confidence interval, 1.12-2.36; P = 0.010) and OS (HR, 2.06; 95% confidence interval, 1.41-3.01; P < 0.001). The presence of both SSI and pneumonia and the presence of severe SSI had profound negative oncological impacts. Diabetes mellitus and an American Society of Anesthesiologists score of III were independent predictive factors for both SSI and pneumonia. The subgroup analysis showed that three-field lymph node dissection and neoadjuvant therapy canceled out the negative oncological impact of SSI on RFS. Conclusion: Our study demonstrated that SSI, rather than pneumonia, after esophagectomy was associated with impaired oncological outcomes. Further progress in the development of strategies for SSI prevention may improve the quality of care and oncological outcomes in patients undergoing curative esophagectomy.

The role of miR-21 as a predictive biomarker and a potential target to improve the effects of chemoradiotherapy against head and neck squamous cell carcinoma.

This study aimed to clarify whether circulating miR-21 represents a predictive biomarker in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy, and to investigate the effect of miR-21 inhibitor for chemoradiation in human SCC cells. Plasma samples were obtained from 22 patients with HNSCC and 25 non-cancer volunteers. Plasma miR-21 expression was measured using real-time quantitative reverse transcription polymerase chain reaction. The effects of miR-21 inhibitor in human SCC cells were investigated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and western blot analysis. As a result, plasma miR-21 expression was higher in HNSCC patients than in control patients (P < 0.001). Seven patients with recurrence showed significantly higher plasma miR-21 than the 15 patients without recurrence. And high miR-21 expression group showed poor overall survival. Moreover, miR-21 inhibition significantly enhanced cisplatin- or radiation-induced apoptosis. Western blot analysis suggested the programmed cell death 4 protein as a potential target of miR-21 in relation to apoptosis. In conclusion, this study provides new insights into the role of miR-21 as a predictive biomarker for HNSCC treated with chemoradiotherapy and suggests a potential target to improve the effects of chemoradiotherapy against HNSCC.

Robot-assisted laparoscopic abdominoperineal resection for anal canal cancer associated with Crohn's disease: A case report.

A 37-year-old man with Crohn's disease (CD) and a history of abdominal surgery was diagnosed with anal canal cancer. Robot-assisted laparoscopic abdominoperineal resection was performed and the patient was discharged without any postoperative complications. Recently, minimally invasive surgery for CD patients has grown in popularity. However, there have been few studies of robotic surgery for CD patients with anal canal cancer. To the best of our knowledge, we present the first report of a patient with CD-associated anal canal cancer who underwent robot-assisted laparoscopic abdominoperineal resection.