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The safety of early stoma closure after lower anterior resection (LAR) for rectal cancer remains controversial. In this study, patients scheduled to undergo LAR and stoma creation for rectal cancer were recruited. In absence of anastomotic leakage on radiological examination, closure of the diverting ileostomy was performed within 2 weeks. The primary endpoint was incidence of the colorectal anastomosis leakage after early stoma closure. Because of the slow accrual rate, the study was closed before recruitment reached the planned number of patients (n = 20). Among the 13 patients enrolled between April 2019 and March 2021, early stoma closure was performed in seven patients (53.8%). Non-clinical anastomotic leakage, leakage identified only on radiological examination, occurred in five cases, resulting in rescheduling of stoma closure. One patient did not undergo early stoma closure due to ileus. After stoma closure, colorectal anastomotic leakage manifested in one case; its incidence rate was 14.2%. Surgical site infection occurred in 42.8% of patients. This study revealed that asymptomatic anastomotic leakage occurred frequently. Considering the low rate of successful cases and the high rate of complications, early stoma closure within 2 weeks after LAR should not be performed routinely. Trial registration: (UMIN000036382 registered on 03/04/2019)., (© 2023. The Author(s).)

We report a case of solitary port-site recurrence after laparoscopy-assisted distal gastrectomy for advanced gastric cancer. A 66-year-old man had previously undergone laparoscopy-assisted gastrectomy with regional lymph-node dissection for advanced gastric cancer, which was a poorly differentiated adenocarcinoma invading the subserosal layer with lymphatic infiltration and no lymph-node metastases. He experienced dull pain in the left upper quadrant of the abdomen 42 months after the surgery. On physical examination, erythematous induration of the skin around the scar of the port insertion was observed in the left upper quadrant of the abdomen. Abdominal ultrasonography and contrast-enhanced computed tomography revealed a subcutaneous lesion with a well-defined mass measuring 3.0 cm in diameter located in the left upper quadrant of the abdomen. A skin biopsy revealed a metastatic adenocarcinoma from gastric cancer. Since there was no evidence of further metastatic lesions in other organs, the patient underwent surgical resection of the metastatic tumor arising at the port site. The abdominal wall tumor was resected with a leaf-skin incision and an adequate safety margin, and the inferior border of the tumor reached the muscular layer, which was resected with the tumor. Pathological examination confirmed the diagnosis of a poorly differentiated adenocarcinoma in the subcutaneous tissue with invasion of the muscle layer at the port site. The postoperative course was uneventful; chemotherapy using oxaliplatin plus S-1 was administered, and the patient was in good health with no evidence of the disease for 3 months postoperatively. Although port-site metastasis after laparoscopic gastrectomy for gastric cancer is a rare recurrence form, we should be aware of this issue, and further studies and assessments of additional cases are needed to establish a treatment strategy., (© 2021. Japanese Society of Gastroenterology.)

Isolated adrenocorticotropic hormone (ACTH) deficiency is a rare immune-related adverse event associated with immunotherapy using immune checkpoint inhibitors for malignant tumors. A 68-year-old man had previously undergone a complete gastrectomy with regional lymph-node dissection for remnant gastric cancer, with a final diagnosis of T4aN2M1, Stage IV. Because he developed lymph-node metastases during postoperative chemotherapy using S-1 plus oxaliplatin, he was treated with ramucirumab plus nab-paclitaxel. Eight months after the operation, the patient developed multiple liver metastases and was treated with nivolumab (3 mg/kg, every 2 weeks). After four cycles of nivolumab treatment, the cortisol level decreased, and the patient reported general fatigue and appetite loss. Pituitary stimulation testing using a combination of corticotropin-releasing hormone, luteinizing hormone-releasing hormone, and thyrotropin-releasing hormone revealed markedly low ACTH and cortisol responses. Magnetic resonance imaging revealed no enlargement of the pituitary gland or thickening of the stalk. After steroid replacement therapy using hydrocortisone, the patient's symptoms of general fatigue improved. After discharge, nivolumab and steroid replacement were continued. During the subsequent 6 months, the clinical course of the patient was mostly uneventful. Abdominal computed tomography revealed a marked shrinkage of liver and lymph-node metastases, which indicated a partial response with a 95.0% decrease in target lesions compared with baseline. To the best of our knowledge, this is the first case reported in the English literature of a patient who developed isolated ACTH deficiency during nivolumab treatment for a metastatic advanced gastric cancer., (© 2021. Japanese Society of Gastroenterology.)

Grade 3, well-differentiated, gastric neuroendocrine tumors (NET G3) are extremely rare. Herein, we report the case of a 64-year-old man with a grade 3 neuroendocrine tumor of the stomach who experienced intra-abdominal bleeding during the course of drug treatment. The patient was referred to our hospital for examination of a gastric tumor that was initially diagnosed by a local medical doctor. Esophagogastroduodenoscopy revealed an elevated lesion with a central ulcer in the upper body of the stomach, and biopsy specimens confirmed the pathological diagnosis of NET G3. Abdominal contrast-enhanced computed tomography (CT) showed a 25-cm, well-defined mass lesion showing heterogeneous enhancement in the liver. A clinical diagnosis of NET G3 with multiple liver metastases was given, after which everolimus was administered in combination with a somatostatin analogue. However, the patient developed sudden-onset epigastric abdominal pain and general fatigue 2 months later, and emergency abdominal contrast-enhanced CT confirmed the presence of intra-abdominal hemorrhage. Following blood transfusion, the patient's symptoms and general condition improved. Although the patient was treated with streptozocin, abdominal CT indicated progression of the liver metastases. Unfortunately, despite receiving best supportive care, the patient died 8 months after the initial of the treatment. To the best of our knowledge, this is the first case of a patient who developed spontaneous hemoperitoneum during drug treatment for a NET G3 to be reported in the English literature. It is essential that additional data be obtained to determine the optimal treatment for this disease., (© 2021. Japanese Society of Gastroenterology.)

Background: This study aimed to clarify the safety of early closure in diverting ileostomy with lower anterior rectal-cancer resection., Methods: We retrospectively reviewed consecutive 47 patients who underwent diverting ileostomy with lower rectal-cancer resection between May 2009 and October 2017. The results of the stoma closure were compared between patients who underwent stoma closure within 90 days (early closure [EC] group) and those who underwent late closure (LC group; closure after 90 days). Because of the small sample size, the frequency of severe complications post closure was analyzed., Results: Among 47 patients, 29 were in the EC group. Postoperative complications occurred in 48.3% (14/29) and 27.8% (5/18) of patients in the EC and LC groups, respectively. This difference was due to minor complications (Clavien-Dindo Classification I/II), such as superficial incisional surgical site infections (n=5) in the EC group. The rate of severe complications (Clavien-Dindo Classification ≥ III) was similar between the groups (20.7% vs. 16.7%, p=1, Fisher's exact test)., Conclusions: No association was observed between the time of closure and development of major complications; however, there was an increased likelihood of minor complications after EC. This study provides a basis on which future treatment guidelines for early stoma closure may be developed without affecting patient quality of life.

Objective: The aim of this study was to clarify the correlation between oropharyngeal microflora and postoperative complications as well as long-term survival after esophagectomy., Background: Although the oral cavity is known to be a potential reservoir for pathogens, the influence of abnormal oropharyngeal microflora on the outcomes of patients undergoing esophagectomy remains unknown., Methods: This study included 675 patients who underwent esophagectomy between 2007 and 2014. Saliva samples from the oropharynx were collected 2 days before the operation. There were 442 patients with indigenous flora (Ind group) and 233 with allopatric flora. Among the patients with allopatric flora, 140 had antibiotic-sensitive microbes only (Allo-S group) while 93 had different types of antibiotic-resistant microbes (Allo-R group). We investigated the correlation between the types of oropharyngeal microflora and the incidence of postoperative complications as well as long-term outcomes., Results: Sixteen microbes could be cultivated from the saliva samples. The incidence of postoperative pneumonia in the Allo-S and Allo-R groups was significantly higher than in the Ind group (P < 0.001). In addition, acute respiratory distress syndrome was more often observed in the Allo-R group than in the other groups (P = 0.002). A significantly higher rate of antibiotic use and longer hospital stays were observed in the Allo-R group compared with the Ind group. Multivariate logistic regression analysis revealed that the presence of allopatric antibiotic-resistant microbes in the oropharynx was an independent risk factor for postoperative pneumonia (odds ratio, 3.93; 95% confidence interval, 2.41-6.42). The overall survival was significantly poorer in the Allo-R group than in the other groups., Conclusions: Preoperative oropharyngeal culture is a simple and low-cost method that can predict both the occurrence of postoperative pneumonia and poor prognosis after esophagectomy.

Purpose: To investigate the usefulness of clinicopathological systemic inflammatory response and nutritional biomarkers for predicting the efficacy of nivolumab in patients with advanced gastric cancer., Methods: The subjects of this study were 29 patients who received nivolumab treatment for advanced gastric cancer at the Kochi Medical School between 2017 and 2019. Clinicopathological information, including systemic inflammatory response data, were obtained to investigate the associations between baseline cancer-related prognostic variables and survival outcomes., Results: Immune-related adverse events (irAEs) of any grade were identified in 34.5% (10/29) of the patients. The median progression-free survival of patients with irAEs was significantly greater than that of patients without irAEs (5.8 months vs. 1.2 months, respectively; P = 0.028). The neutrophil to lymphocyte ratio (NLR) after 4 weeks of treatment in the complete response (CR) or partial response (PR) group was significantly lower than that in the stable disease (SD) or progression disease (PD) group (2.2 vs. 2.9, respectively; P = 0.044). The prognostic nutrition index (PNI) before treatment in the CR or PR group was significantly higher than that in the SD or PD group (37.1 vs. 32.1, respectively; P = 0.011). The PNI 8 weeks after treatment and the Glasgow prognostic score (GPS) before treatment were significantly associated with a poor outcome., Conclusion: The irAE, NLR, PNI, and GPS may be useful predictive markers for nivolumab efficacy in patients with advanced gastric cancer.

Aim: To determine whether markers of systemic inflammatory response and nutrition are a predictor of treatment response in patients with trastuzumab-treated unresectable advanced gastric cancer., Patients and Methods: Twenty-one patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2013 to 2020 were enrolled. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes., Results: The median overall survival (OS) and progression-free survival (PFS) for the whole cohort were 24.5 (range=1.9-88.4) months and 7.0 (range=2.0-23.4) months, respectively. The objective response rate and disease control rate were 52.4% and 81.0%, respectively. The median PFS for patients with a neutrophil to lymphocyte ratio (NLR) <2.8 was significantly longer than that for those with NLR ≥2.8 (8.9 vs. 6.0 months; p=0.048). Although the median OS also tended to be longer for patients with NLR <2.8, the difference was not statistically significant. No significant differences in median OS and PFS were observed between patients with a prognostic nutrition index (PNI) <41.6 and those with PNI ≥41.6., Conclusion: An NLR ≥2.8 is a predictor of poorer prognosis in patients receiving systemic treatment with trastuzumab and chemotherapy for unresectable advanced or recurrent gastric cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: This study compared the efficacy of two different methods for lymph node (LN) searching after colorectal cancer surgery: the fat dissolution and the conventional manual method., Methods: For the fat dissolution method, we used a commercially available solution of collagenase and lipase (FD group). The primary endpoint was the number of identified LNs in the FD group compared to an historical control (control group) after adjusting by propensity score matching., Results: Using 37 matched patients from each group, we identified 20.6 ± 7.2 LNs using the fat dissolution method compared to 13.5 ± 5.9 using the conventional method (t test, P < 0.01). Three patients in the FD group received an inappropriate LN examination in terms of number, while the number of the retrieved LNs was < 12 in 12 patients in the control group. The mean diameter of LNs without metastasis was 3.2 ± 1.9 mm in the FD group, and 40% of metastasis cases were found in LNs < 5 mm in diameter. A pathological examination confirmed that using the fat resolution method did not change the morphological or immunochemical staining findings., Conclusion: We demonstrated that fat dissolution had a positive impact on the number of retrieved LNs after colorectal cancer surgery without disturbing the microscopic observation.

Background: The three-dimensional video-assisted (3D-VA) system is known to provide depth perception and the precise measurement of anatomical spaces, unlike the two-dimensional video-assisted (2D-VA) system. However, the advantages of the 3D-VA system in thoracoscopic esophagectomy remains unclear., Methods: We retrospectively analyzed data from 104 patients who underwent thoracoscopic esophagectomy for esophageal cancer from 2016 to 2017. We performed thoracic esophagectomy using either the 2D-VA or 3D-VA system during this period. Whenever the 3D-VA system was available in our surgical center, we performed 3D-VA thoracoscopic esophagectomy. Perioperative parameters, including operation times, blood loss, the number of dissected lymph nodes, postoperative complications, and the duration of postoperative hospital stays, were compared between the 2D-VA and 3D-VA system groups., Results: There were 51 and 53 patients in the 2D-VA and 3D-VA system groups, respectively. Preoperative parameters, including age, sex, tumor location, clinical stage and the distribution of preoperative treatment, were not significantly different between the groups. Although intraoperative blood loss did not differ between the two groups, operation times were significantly shorter in the 3D-VA system group than the 2D-VA system group (P = 0.023). The number of dissected mediastinal lymph nodes was similar in both groups. The incidences of postoperative complications, including pneumonia, recurrent nerve palsy, anastomotic leakages and chylothorax, were similar between the groups. The duration of postoperative hospital stays was also comparable between the groups., Conclusions: An introduction of 3D-VA endoscopy into minimally invasive esophagectomies may contribute to the shortening of the duration of thoracoscopic procedures.

Background: Esophagectomy for esophageal cancer is one of the most invasive surgeries. However, the factors influencing postoperative systemic inflammatory response following esophagectomy have not been elucidated. Recently, visceral fat has been shown to play an important role in both chronic and acute inflammation. In this study, we assessed the relationship between visceral obesity and postoperative inflammatory response following minimally invasive esophagectomy (MIE)., Methods: Visceral fat area (VFA) was measured using computed tomography in 152 patients undergoing MIE for esophageal cancer. We assessed perioperative serum C-reactive protein (CRP) levels preoperatively and on postoperative days (PODs) 1-5 and analyzed the relationship between VFA and perioperative serum CRP levels., Results: VFA was positively associated with preoperative serum CRP level (P < 0.001). Univariate analysis revealed that VFA was significantly associated with increased serum CRP levels on PODs 1-5 (P < 0.001 for each day), whereas multivariate analysis revealed that it was independently associated with increased serum CRP levels on PODs 1-4 (P = 0.033, 0.035, 0.001, and 0.006, respectively). Similar results were observed in patients who did not have postoperative infectious complications, such as pneumonia, anastomotic leak, and surgical site infection. VFA was not an independent risk factor for the occurrence of these postoperative infectious complications., Conclusions: Visceral obesity might be associated with chronic inflammation in patients with esophageal cancer and promote postoperative inflammatory response following MIE.

Background: Minimally invasive esophagectomy (MIE) for patients with esophageal cancer has recently spread worldwide. However, whether MIE is less invasive has not yet been fully evaluated., Methods: We retrospectively analyzed data from 551 patients who underwent curative esophagectomy for esophageal cancer from 2005 to 2014: 145 patients underwent minimally invasive esophagectomy (MIE) and 406 patients underwent open transthoracic esophagectomy (OE). We compared postoperative CRP levels with propensity score matching. In addition, long-term outcomes were also compared between the groups., Results: Operative time was significantly longer, and intraoperative blood loss was significantly less in the MIE group compared with the OE group. Although the incidence of postoperative complications was similar between the 2 groups, postoperative serum CRP levels during the first 3 and 5 postoperative days and peak postoperative CRP levels were significantly lower after MIE versus OE (MIE vs. OE, median, 15.21 vs. 19.50 mg/dl; P < 0.001). The MIE group had significantly more favorable disease-free survival (DFS) and overall survival (OS) rates than the OE group (3-year DFS rate, 81.7 vs. 69.3%, log-rank P = 0.021; 3-year OS rate, 89.9 vs. 79.2%, log-rank P = 0.007). MIE was an independent prognostic factor for patients with esophageal cancer. The incidence of regional lymph node recurrence was lower in the MIE group., Conclusions: MIE significantly attenuated postoperative serum CRP levels compared with OE. MIE could contribute to improved survival.

Esophagectomy remains the mainstay of curative intent treatment for esophageal cancer. Oncologic esophagectomy is a highly invasive surgery and both morbidity and mortality rates still remain high. Recently, it has been revealed that multidisciplinary perioperative management can decrease the postoperative complications after esophagectomy. In this review, we summarized the recent progress in each component of multidisciplinary perioperative care bundle, including oral hygiene, cessation of smoking and alcohol, respiratory training, measurement of physical fitness, swallowing evaluation and rehabilitation, nutritional support, pain control and management of delirium. The accumulation of evidence and the popularization of knowledge will increase safety of esophagectomy and thus improve the outcome of patients with esophageal cancer.

Purpose: The aim of this study was to clarify the influence of Charlson comorbidity index (CCI) on treatment options, and on short- and mid-term outcomes in esophageal cancer patients who underwent esophagectomy., Methods: Patients who underwent curative-intent esophagectomy from 2009 to 2014 were classified by CCI. A CCI of ≥ 2 was defined as high, while a CCI of 0 or 1 was classified as low. Clinicopathological parameters, including overall survival (OS) and disease-specific survival (DSS), were compared between the groups., Results: Among 548 patients, the most frequent comorbidity was chronic obstructive pulmonary disease (n = 142, 25.9%), followed by solid tumor (n = 79, 14.4%). A high CCI was significantly correlated with older age (P < 0.001), surgery alone (P = 0.020), a lower number of dissected lymph nodes (P < 0.001), lower rate of R0 resection (P = 0.048), and prolonged hospital stay (P < 0.001). In the low group, OS after surgery was favorable in comparison to the the high group. Although DSS was comparable between the groups, the CCI was significantly associated with a poor prognosis in patients with stage ≥ II disease., Conclusions: The CCI was significantly correlated with the prognosis of esophageal cancer patients who underwent curative-intent esophagectomy.

Background: Minimally invasive esophagectomy (MIE) is being increasingly performed; however, it is still associated with high morbidity and mortality. The correlation between surgical team proficiency and patient load lacks clarity. This study evaluates surgical outcomes during the first 3-year period after establishment of a new surgical team., Methods: A new surgical team was established in September 2013 by two expert surgeons having experience of performing more than 100 MIEs. We assessed 237 consecutive patients who underwent MIE for esophageal cancer and evaluated the impact of surgical team proficiency on postoperative outcomes, as well as the team learning curve., Results: In the cumulative sum analysis, a point of downward inflection for operative time and blood loss was observed in case 175. After 175 cases, both operative time and blood loss significantly decreased (P < 0.001 and P < 0.001, respectively), and postoperative incidence of pneumonia significantly decreased from 18.9 to 6.5% (P = 0.024). Median postoperative hospital stay also decreased from 20 to 18 days (P = 0.022). Additionally, serum CRP levels on postoperative day 1 showed a significant, but weak inverse association with the number of cases (P = 0.024)., Conclusions: After 175 cases, both operative time and blood loss significantly decreased. In addition, the incidence of pneumonia decreased significantly. Additionally, surgical team proficiency may decrease serum CRP levels immediately after MIE. Surgical team proficiency based on team experience had beneficial effects on patients undergoing MIE.

Backgrounds: In the setting of routine use of preoperative chemoradiotherapy(CRT)for cStage II / III rectal cancer, shortcourse radiotherapy(short-RT)is selectively used for reducing local recurrence.The purpose of this study is to clarify the safety of laparoscopic surgery after preoperative short-RT for lower rectal cancer., Methods: Twenty-eight patients who un- derwent short-RT followed by laparoscopic total mesorectal excision for cStage II / III lower rectal cancer were retrospectively analyzed., Results: The reasons for selecting short-RT included comorbidity(n=10), refusal of CRT(n=8), multiple cancers (n=6)and others(n=4).All patients completed planned dose of radiation without severe acute toxicity.Median interval from completion of short-RT to surgery was 17 days(range 7-58).All patients underwent laparoscopic surgery without conversion to open surgery.Median operation time, blood loss and the number of dissected lymph nodes were 379 minutes (range 175-890), 90mL(range 0-1,185)and 27(range 12-71), respectively.Grade 3-4 complications occurred in 3 cases (10.7%).There were 2 cases with pathological complete response., Conclusions: Laparoscopic surgery for lower rectal cancer after short-RT is safe and feasible.

Herein we report on a case of two adenocarcinomas arising from an upside-down stomach in an elderly patient. An 83-year-old man was referred to our hospital with gastric cancer. Esophagogastroduodenoscopy showed two superficial depressed lesions in the stomach that were confirmed on biopsy as constituting a moderately differentiated tubular adenocarcinoma. CT and an upper gastrointestinal barium study revealed that the entire stomach and parts of the duodenum were located in the mediastinum. The patient underwent laparoscopy-assisted distal gastrectomy and regional lymph node dissection with Billroth I reconstruction, followed by reduction of the migrated stomach. The hiatal defect was closed by primary suturing of the right and left crura at the anterior space of the esophagus. The patient's postoperative course was good, and follow-up after discharge was uneventful. To the best of our knowledge, this is the first case report of multiple adenocarcinomas in an upside-down stomach treated by laparoscopy-assisted distal gastrectomy., (© 2016 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Context: Yokukansan (YKS) is a traditional Japanese herbal medicine called kampo medicine in Japan. Its extract comprises seven crude drugs: Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix. YKS is used to treat neurosis, insomnia, as well as behavioral and psychological symptoms of dementia., Objective: To confirm the exposure and pharmacokinetics of the active components of YKS in healthy volunteers., Design, Setting, and Participants: A randomized, open-label, 3-arm, 3-period, crossover trial was conducted on 21 healthy Japanese volunteers at the Kochi Medical University between May 2012 and November 2012., Interventions: Single oral administration of YKS (2.5 g, 5.0 g, or 7.5 g/day) during each period., Main Outcome Measure: Plasma concentrations of three active compounds in YKS, namely 18β-glycyrrhetinic acid (GA), geissoschizine methyl ether (GM), and hirsuteine (HTE)., Results: The mean maximum plasma concentrations (Cmax) of GM and HTE increased dose-dependently (ranges: 0.650-1.98 ng/mL and 0.138-0.450 ng/mL, respectively). The times to maximum plasma concentration after drug administration (tmax) were 0.500 h for GM and 0.975-1.00 h for HTE. The apparent elimination half-lives (t1/2) were 1.72-1.95 h for GM and 2.47-3.03 h for HTE. These data indicate the rapid absorption and elimination of GM and HTE. On the other hand, the Cmax, tmax, and t1/2 of GA were 57.7-108 ng/mL, 8.00-8.01 h, and 9.39-12.3 h, respectively., Conclusion: We demonstrated that pharmacologically active components of YKS are detected in humans. Further, we determined the pharmacokinetics of GM, HTE, and GA. This information will be useful to elucidate the pharmacological effects of YKS., Trial Registration: Japan Pharmaceutical Information Center JAPIC CTI-121811.