Search

Yoichiro Yoshida,1 Keiji Hirata,2 Hiroshi Matsuoka,3 Shigeyoshi Iwamoto,4 Masahito Kotaka,5 Hideto Fujita,6 Naoya Aisu,1 Seiichiro Hoshino,1 Takeo Kosaka,6 Kotaro Maeda,3 Fumiaki Kiyomi,7 Yuichi Yamashita1 1Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan; 2Department of Surgery, Fukuoka Sanno Hospital, Fukuoka, Japan; 3Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan; 4Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan; 5Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan; 6Department of Surgical Oncology, Kanazawa Medical University, Uchinada, Japan; 7Academia, Industry and Government Collaborative Research Institute of Translational Medicine for Life Innovation, Fukuoka University, Fukuoka, Japan Background: Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%–20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions.Patients and methods: The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of hypersensitivity reactions.Results: Hypersensitivity reactions occurred in three patients (4.1%); all three experienced a cutaneous reaction (grade 1 erythema). None of the 73 patients developed respiratory symptoms, ocular symptoms, or anaphylaxis. Grade 3 or higher hemotoxicity occurred in 13.7% of the patients and grade 3 or higher nonhematological toxicity occurred in 13.7%. The response rate to treatment was 64.4%.Conclusion: The coinfusion of dexamethasone and oxaliplatin effectively reduced oxaliplatin-induced hypersensitivity reactions in patients with colorectal cancer. This approach should be considered for all patients treated with oxaliplatin, allowing treatment to be completed as planned. Keywords: oxaliplatin, dexamethasone, hypersensitivity, allergy

Aim: The aim of the present study was to clarify differences in node metastasis mode and clinical outcomes based on tumor location in patients with esophageal squamous cell carcinoma (ESCC). Patients and Methods: Participants comprised 228 patients with ESCC who underwent radical esophagectomy without preoperative supplement therapies. Lymph nodes were harvested from three fields: the neck, thorax, and abdomen. Patients were divided into three groups depending on tumor location [upper esophagus (UE), middle esophagus, or lower esophagus (LE)] and analyzed clinicopathologically. Results: The LE group showed significantly more progressive ESCC in terms of tumor invasion (p = 0.025), node metastasis (p = 0.0071), and TNM stage (p = 0.0043). The LE group revealed a tendency to metastasize to extrathoracic (especially abdominal) nodes (p = 0.0008). Recurrent laryngeal node metastasis was increased in the UE group (p = 0.016). However, no prognostic differences were detected between groups according to tumor location. Likewise, subgroup analyses by surgical approach (open thoracotomy vs. thoracoscopy) and cancer stage (stage I/II, III, and IV) did not reveal any significant prognostic impact of tumor location. Conclusion: Lymphatic spread varied by tumor location, but no prognostic impact of tumor location could be detected in patients with ESCC in spite of surgical approach or cancer stage. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Brain metastasis (BM) is infrequent in colorectal cancer (CRC) patients. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. The prognosis of patients with BM from CRC is associated with the curability of the therapy for BM and number of metastatic organs. The start of chemotherapy treatment usually requires a delay of about 4 weeks after surgical resection in patients with primary CRC having synchronous distant metastasis. However, there is no evidence to indicate the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. Here, we present a case where combination chemotherapy with capecitabine and oxaliplatin (XELOX) was started within 1 week after resection of BM from colon cancer for synchronous multiple liver metastases. To our knowledge, this is the first report of the start of chemotherapy, involving treatments such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and XELOX within 1 week after resection of BM from colon cancer with synchronous multiple liver metastases. These findings suggest possible changes in the start time of chemotherapy after surgery in the future.

Abstract Background The start of chemotherapy usually requires a delay of about 4 weeks after surgical resection of colorectal cancer. However, there is no evidence for the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. We therefore conducted a pilot study to determine the safety and feasibility of an early start of chemotherapy after the resection of colorectal cancer with distant metastases. Methods Five patients were enrolled. They received XELOX therapy (130 mg/m2 of oxaliplatin on day 1 plus 1,000 mg/m2 of capecitabine twice daily on days 1 to 14) on the 7th postoperative day and XELOX + bevacizumab (7.5 mg/kg of bevacizumab on day 1) after the 2nd cycle of chemotherapy. Results Five patients underwent open surgery. The procedures included right hemicolectomy in 1 patient, sigmoidectomy in 2 patients, high anterior resection in 1 patient, and Hartmann procedure in 1 patient. All patients started chemotherapy on postoperative day 7. The median number of cycles of chemotherapy was 11 (8 to 22). No postoperative complications were observed. The tumor reduction rate was 44.3% (32.0 to 66.6%). Progression-free survival was 10.3 months. Conclusions An early start of chemotherapy after surgery is feasible and safe. These findings suggest possible changes in the start time of chemotherapy after surgery in the future. We have already started a new phase II trial to confirm the effects of the early start of chemotherapy after surgery. Trial registration UMIN000004361.

Background: Loop ileostomy is a common surgical procedure but is associated with complications such as outlet obstruction (OO), parastomal hernia (PH), and high-output stoma (HOS). This study aimed to identify risk factors for these complications, as well as their causal relationships., Methods: The study included 188 consecutive patients who underwent loop ileostomy between April 2016 and September 2021. Clinical factors and postoperative stoma-related complications (OO, HOS, and PH) were analyzed retrospectively. Stoma-related factors were evaluated using specific measurements from computed tomography (CT) scans. The incidence, clinical course, and risk factors for the stoma-related complications were investigated., Results: OO was diagnosed in 28 cases (15.7%), PH in 60 (32%), and HOS in 57 (31.8%). A small longitudinal stoma diameter at the rectus abdominis level on CT and a right-sided stoma were significantly associated with OO. Creation of an ileostomy for anastomotic leakage was independently associated with HOS. Higher body weight and a large longitudinal stoma diameter at the rectus abdominis level on CT were significantly associated with PH. There was a significant relationship between the occurrence of OO and HOS. However, the association between OO and PH was marginal., Conclusion: This study identified key risk factors for OO, HOS, and PH as complications of loop ileostomy and their causal relationships. Our findings provide insights that may guide the prevention and management of complications related to loop ileostomy., (© 2024. Springer Nature Switzerland AG.)

Background: Colonic varices are a rare gastrointestinal anomaly often associated with portal hypertension. Arteriovenous fistula (AVF) in the inferior mesenteric artery (IMA) region is even rarer. Diagnosis and treatment of these entities present unique challenges, especially when the IMA is involved., Case Presentation: A 48-year-old man with a history of cholecystectomy presented with after a positive fecal occult blood test. Investigations revealed varices from the splenic flexure to the transverse colon and suspected AVF in the IMA region. Given the high risk and low efficacy of endoscopic and radiological interventions, laparoscopic sigmoidectomy was performed. This surgical approach successfully addressed both the AVF and the associated varices., Conclusion: This case underscores the importance of surgical intervention for AVF and colonic varices in the IMA region, particularly when other treatment options pose high risks and have limited efficacy. The favorable postoperative outcome in this case highlights the effectiveness of carefully chosen surgical methods when managing such complex and rare conditions., (© 2024. The Author(s).)

Background Accurate lymph node evaluation is essential for staging colon cancer and guiding postoperative treatment decisions. In this study, we compared the efficacy of a simple enzymatic fat dissolution method with the conventional method for lymph node sampling from specimens after colon cancer surgery. Methods We enrolled 58 patients who underwent elective laparoscopic surgery for colon adenocarcinoma between May 2018 and May 2021 at Fukuoka University Hospital in Fukuoka, Japan. The specimens from these patients were treated using fat dissolution and were compared with specimens from 58 patients for which conventional manual palpation was used. Results A significantly greater number of lymph nodes were detected by the fat dissolution method compared with the conventional method (average per patient, 27.5 vs. 22.6, P = 0.02). In particular, the between-group difference was significant for lymph nodes measuring <5 mm (average per patient, 26.1 vs. 20.9; P = 0.01). Multivariate analysis showed that, compared with the conventional method, the fat dissolution method was significantly associated with the identification of lymph node metastasis. The positive rate of lymph nodes ≥10 mm in diameter was markedly higher along the inferior mesenteric artery than the ileocolic artery (100% vs. 52.6%). Conclusions The use of the fat dissolution method led to an increase in the number of small lymph nodes detected. Rates of metastasis according to lymph node size may depend on the lymph node station., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kajitani et al.)

The AirSeal system (CONMED, NY, USA) can outstandingly keep pneumoperitoneum stable. However, water droplets form on the access port, impairing the performance of comfortable surgical procedures because of the resultant wet surgical field. This study was performed to clarify the mechanism of water droplet formation and to prevent it. Condensation was observed on the AirSeal system. A heater was wrapped around the tri-lumen tube, and the heating effect was assessed. The simulator experiments revealed that condensation formed in the tri-lumen tube and on the wall of the access port. The accumulated weight of the condensation on the wall of the access port was 41.6 g in the Heated group, 138.2 g in the Control group, and 479.4 g in the Cooled group. In the clinical assessment, the accumulated volume of the condensation attached to the inside wall was significantly smaller in the Heated group than in the Unheated group (111.7 g vs. 332.9 g, respectively). We clarified that the volume of condensation attached to the wall of the access port depended on the temperature of the tri-lumen tube. The clinical study revealed that the condensation on the access port was reduced by heating the tri-lumen tube. The development of a novel heating device for the insufflation tube would be effective and useful., (© 2024. The Author(s).)

Purpose: Elderly people are thought to be more likely than their non-elderly counterparts to experience a decline in activities of daily living (ADL) and quality of life (QOL) due to the onset and treatment of disease. In this study, we investigated whether there was an age-related difference in changes in health-related QOL indices after surgical resection of colorectal cancer (CRC)., Methods: Patients who underwent elective surgery for primary CRC at our hospital between September 2017 and November 2021 were enrolled. Changes in QOL after surgery were evaluated after dividing the study population into a non-elderly (NE) group (younger than 75 years) and an elderly (E) group. A Short-Form 36-Item Health Survey was used as an index of QOL. The subscale and component summary scores before and 6 months after surgery were compared., Results: Forty-seven patients were included in the E group and 166 patients were the NE group. The E group had significantly worse preoperative performance and physical status than the NE group. However, indices of physical function were not worsened after surgery in either group. In the NE group, there were significant decreases in role physical and role component summary scores and significant increases in general health, mental health, and mental component summary scores. In the E group, there were no significant changes in the subscale or component summary scores after surgery., Conclusion: Our study demonstrated elderly patient did not necessarily show a decline in QOL more than non-elderly patients after CRC surgery. Surgical resection for CRC should be considered even for elderly patients, while considering possible risk factors for worsening ADL and QOL., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: It remains controversial whether the abdominoperineal resection (APR) procedure itself has a negative impact on prognosis compared with sphincter-saving surgery (SSS). The purpose of this study was to investigate whether the operation type affects the prognostic outcome in rectal cancer using a multicenter database in Japan., Methods: The study involved 2533 patients who underwent APR or SSS and were registered in the Japanese Society for Cancer of the Colon and Rectum database, which includes data from 74 centers, between 2003 and 2007. The primary endpoints were overall survival (OS) and relapse-free survival (RFS). The secondary endpoints were local recurrence rate (LRR) and pathological radial margin (pRM) status., Results: Multivariate analysis identified pathological tumor depth, lymph node status, and pRM status to be associated with oncological outcomes (OS, RFS, LRR). Although the oncological outcomes were worse after APR than after SSS in univariate analysis, there was no significant difference in OS (hazard ratio 1.08; 95% confidence interval [CI] 0.85-1.37) or RFS (hazard ratio 1.06; 95% CI 0.87-1.30) between APR and SSS. There was also no significant difference in LRR (odds ratio 1.11, 95% CI 0.70-1.77). Multivariate analysis showed that operation type was associated with positive pRM (odds ratio 3.13, 95% CI 0.18-0.56)., Conclusions: There was no significant difference in oncological outcomes between APR and SSS for rectal cancer. The risk of positive pRM was higher for APR and performing radial margin-negative surgery is an important factor in improving the oncological outcomes of APR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The transanal/perineal (ta/tp) endoscopic approach has been widely used for anorectal surgery in recent years, but carbon dioxide embolism is a possible lethal complication. The frequency of this complication in this approach is not known. In this study, we investigated the frequency of intraoperative (including occult) carbon dioxide embolism using transesophageal echocardiography. Patients who underwent surgery via the ta/tp approach and consented to participate were included. Intraoperative transesophageal echocardiography was used to observe the right ventricular system in a four-chamber view. Changes in end-tidal carbon dioxide (EtCO 2 ), oxygen saturation (SpO 2 ), and blood pressure were taken from anesthesia records. Median maximum insufflation pressure during the ta/tp approach was 13.5 (12-18) mmHg. One patient (4.8%) was observed to have a bubble in the right atrium on intraoperative transesophageal echocardiography, with a decrease in EtCO 2 from 39 to 35 mmHg but no obvious change in SpO 2 or blood pressure. By lowering the insufflation pressure from 15 to 10 mmHg and controlling bleeding from the veins around the prostate, the gas rapidly disappeared and the operation could be continued. Among all patients, the range of variation in intraoperative EtCO 2 was 5-22 mmHg, and an intraoperative decrease in EtCO 2 of > 3 mmHg within 5 min was observed in 19 patients (median 5 mmHg in 1-10 times).Clinicians should be aware of carbon dioxide embolism as a rare but potentially lethal complication of anorectal surgery, especially when using the ta/tp approach., (© 2022. The Author(s).)

Background: Several serious complications are associated with the lithotomy position, including well-leg compartment syndrome and peroneal nerve paralysis. The aims of this study were to identify risk factors for the intraoperative elevation of lower leg pressure and to evaluate the effectiveness of monitoring external pressure during surgery for preventing these complications., Methods: The study included 106 patients with a diagnosis of sigmoid colon or rectal cancer who underwent elective laparoscopic surgery between June 2019 and December 2020. We divided the posterior side of the lower leg into four parts (upper outside, upper inside, lower outside, lower inside) and recorded the peak pressure applied to each area at hourly intervals during surgery (called "regular points") and when the operating position was changed (e.g., by head-tilt or leg elevation; called "points after change in position"). When the pressure was observed to be higher than 50 mmHg, we adjusted the position of the leg and re-recorded the data. Data on postoperative leg-associated complications were also collected., Results: The pressure was measured at a total of 1125 points (regular, n = 620; after change of position, n = 505). The external pressure on the upper outer side of the right leg (median, 36 mmHg) was higher than that on any other area of the lower leg. The pressure increase to more than 50 mmHg was observed not only during the change of position (27.5%) but also during regular points (22.4%). Bodyweight, strong leg elevation, and low head position were identified as factors associated with increased external pressure. There have been no compression-related complications in 534 cases at our institution since the introduction of intraoperative pressure monitoring., Conclusions: Several risk factors associated with increased external pressure on the lower leg were identified. Intraoperative pressure monitoring might help reduction of pressure-related complications, needing further and larger prospective data collections., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The detection of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) by liquid biopsy may have prognostic information. In this perioperative study, we evaluate if there is a relationship between mutant allele frequency (MAF) of Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumor recurrence and how that could be useful in the early detection of recurrence., Methods: Among 304 cases of colorectal cancer surgery, ctDNA was sampled from the perioperative blood of 84 patients with CRC with KRAS mutation (exon 4 p.A146T, exon 4 p.A146V, exon 2 p.G12A, exon 2 p.G12C, exon 2 p.G12D, exon 2 p.G12S, exon 2 p.G12V, exon 2 p.G13D, exon 3 p.Q61H) and analyzed using the digital polymerase chain reaction system. The median observation period was 26 months., Results: Although the relationship between the perioperative MAF of KRAS and recurrence was not proved, tumor diameter, tumor depth, and stage were correlated with the preoperative MAF of KRAS (p = 0.034, p = 0.002, p = 0.008). However, tumor diameter, tumor depth, and stage did not correlate with MAF of KRAS at postoperative day 30., Conclusions: In this study, pathological tumor size, tumor depth, and stage were correlated with preoperative MAF of KRAS, but it was unreliable to predict recurrence by detection of ctDNA with KRAS mutation in the perioperative period of colorectal surgery., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Surgery for anal fistula cancer (AFC) associated with Crohn's disease usually entails extensive perineal wounds and dead space in the pelvis, which is often filled with a myocutaneous flap. However, use of a myocutaneous flap is invasive. We report a case of total pelvic exenteration (TPE) for AFC in which a myocutaneous flap was avoided by using an omental flap and negative pressure wound therapy (NPWT)., Case Presentation: The patient was a 47-year-old woman who had been treated for Crohn's disease involving the small and large intestine for 30 years and had repeatedly developed anal fistulas. She was referred with a diagnosis of AFC that had spread extensively in the pelvis. We performed laparoscopic TPE via a transperineal endoscopic approach. To prevent infection in the large skin defect and extensive pelvic dead space postoperatively, the perineal wound was reconstructed using an omental flap and NPWT. During 20 days of NPWT, the wound steadily decreased in size and closed on postoperative day (POD) 20. She was discharged without complications on POD 30., Discussion: NPWT is useful for preventing perineal wound infection and promoting granulation tissue formation. However, direct contact with the intestine may lead to intestinal perforation. In this case, the combination of an omental flap with NPWT effectively prevented surgical site infection. The flap filled the large pelvic dead space and physically separated the intestine from the polyurethane foam used for NPWT., Conclusion: NPWT and an omental flap may become an option when performing TPE., (© 2022. The Author(s).)

Purpose: To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC)., Design: Retrospective cohort study., Participants: A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded., Methods: All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed., Main Outcome Measures: The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate)., Results: A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients' backgrounds were well balanced after IPTW with standardized differences of < 0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%, P <  0.001, 12 months; 85.7% vs. 69.8%, P = 0.019, 24 months). The rf-PDT group tended to show better VA improvement, but was not statistically significant (-0.06 vs. -0.008, P = 0.07, 12 months; -0.06 vs. -0.03, P =  0.32, 24 months). An IPTW Cox regression showed a significantly higher rate of complete SRD remission in the rf-PDT group (hazard ratio, 5.05; 95% confidence interval, 3.24-7.89; P < 0.001)., Conclusions: The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting., (© 2022 by the American Academy of Ophthalmology.)

Machine learning (ML) and deep learning (DL) are changing the world and reshaping the medical field. Thus, we conducted a systematic review to determine the status of regulatory-approved ML/DL-based medical devices in Japan, a leading stakeholder in international regulatory harmonization. Information about the medical devices were obtained from the Japan Association for the Advancement of Medical Equipment search service. The usage of ML/DL methodology in the medical devices was confirmed using public announcements or by contacting the marketing authorization holders via e-mail when the public announcements were insufficient for confirmation. Among the 114,150 medical devices found, 11 were regulatory-approved ML/DL-based Software as a Medical Device, with 6 products (54.5%) related to radiology and 5 products (45.5%) related to gastroenterology. The domestic ML/DL-based Software as a Medical Device were mostly related to health check-ups, which are common in Japan. Our review can help understanding the global overview that can foster international competitiveness and further tailored advancements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Aisu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Accurate preoperative T staging is important when determining the treatment strategy for advanced colorectal cancer. We have previously reported the usefulness of preoperative T staging based on the spatial relationship of tumors and "bordering vessels" by computed tomography colonography (CTC) with multiplanar reconstruction (MPR). The aims of this study were to evaluate the external validity of this method and to determine whether there is a difference in the accuracy of T staging between the mesenteric and antimesenteric sides., Methods: The study subjects were 110 patients with colorectal cancer who underwent preoperative CTC and surgical resection from June 2016 to March 2018. Preoperative T stage was determined by CTC based on the relationship between the tumor and the bordering vessels and compared with the pathological T stage. The influence of tumor location, namely, whether the tumor was on the antimesenteric or mesenteric side, on preoperative T staging was assessed in 78 patients with colorectal cancer., Results: Sensitivity, specificity, accuracy, positive, and negative predictive values were respectively, 65%, 91%, 83%, 76%, and 85% for T2 (n = 34); 76%, 82%, 81%, 50%, and 94% for T3 (n = 23); and 77%, 93%, 87%, 86%, and 88% for T4a disease (n = 39). Overall right answer rate was 83.3% (15/18) for the mesenteric side and 65% (39/60) for the antimesenteric side (n = 0.14)., Conclusion: Diagnostic criteria based on the bordering vessels seen on CTC images with MPR are useful for T staging of colorectal cancer. However, the accuracy differs between the antimesenteric and mesenteric sides., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The detection of circulating cell-free DNA (cfDNA) by liquid biopsy is reported to provide prognostic information in colorectal cancer (CRC). Although the frequency of BRAF V600E mutation in CRC is less than 10%, it is associated with poor responses to conventional chemotherapy. We conducted a prospective study to investigate the relationship between the perioperative mutant allele frequency (MAF) of BRAF V600E and tumor recurrence, and to evaluate the possibility of early detection of recurrence. Among 362 patients who underwent radical resection, cfDNA was extracted from the perioperative blood of 11 CRC patients with BRAF V600E mutation and analyzed using the digital polymerase chain reaction (dPCR) system. The median follow-up time was 22 months, and there were four cases of recurrence. Although there was no correlation between recurrence and the perioperative MAF of BRAF V600E, tumor diameter was correlated with the MAF (p = 0.024), and the MAF increased with time in two patients from whom additional samples were obtained prior to recurrence. In this study, we identified a correlation between the pathological tumor diameter and the MAF, but it was difficult to predict recurrence by measuring cfDNA with BRAF V600E mutation in the perioperative period of radical resection of CRC.

Background: Complete mesocolic excision with central vascular ligation is a standard advanced technique for achieving favorable long-term oncological outcomes in colon cancer surgery. Clinical evidence abounds demonstrating the safety of high ligation of the inferior mesenteric artery (IMA) for sigmoid colon cancer but is scarce for descending colon cancer. A major concern is the blood supply to the remnant distal sigmoid colon, especially for cases with a long sigmoid colon. We sought to clarify the safety and feasibility of high ligation of the IMA in surgery for descending colon cancer using indocyanine green (ICG) fluorescence imaging., Methods: In this prospective single-center pilot study, we examined 20 patients with descending colon cancer who underwent laparoscopic colectomy between April 2018 and September 2019. Following full mobilization and division of the proximal colonic mesentery, we temporarily clamped the root of the IMA and performed ICG fluorescence imaging of the blood flow to the sigmoid colon. The postoperative anastomosis-related complications (primary endpoint) and length of viable remnant colon, and the number of lymph nodes retrieved (secondary endpoints) were evaluated and compared with historical controls who underwent conventional IMA-preserving surgery (n = 20)., Results: Blood flow reached 40 (17-66) cm retrograde from the peritoneal reflection, even after IMA clamping. Accordingly, IMA high ligation was performed in all cases. No anastomotic anastomosis-related complications occurred in each group. Retrieved total lymph nodes were higher in number in the ICG-guided group than in the conventional group (p = 0.035). Specifically, more principal nodes were retrieved in the ICG-guided group, compared with the conventional group (p = 0.023). However, the distal margin was not as long compared with the conventional group., Conclusion: We demonstrated the safety and feasibility of high ligation of the IMA for descending colon cancer without sacrificing additional distal colon using fluorescence evaluation of blood flow in the remnant colon.

The patient was a 66-year-old woman. She underwent central venous port insertion as part of postoperative adjuvant chemotherapy for sigmoid colon cancer. At the beginning of the 2 cycle, she experienced discomfort in the neck, and computed tomography was performed. As a result, catheter deviation and a thrombus in the internal jugular vein were observed. It was considered that breast displacement due to gravity caused the catheter deviation and that the position of the tip of the catheter deviating to immediately above the venous valve caused thrombus formation. We examined the factors that may cause catheter deviation.

Purpose: The incidence and time of onset of acute chemotherapy-induced peripheral neuropathy (ACIPN) caused by oxaliplatin remain unclarified. Hence, we investigated the prevalence, onset time, and location of ACIPN symptoms in patients with colorectal cancer (CRC) receiving oxaliplatin without cold stimulation., Methods: The study cohort comprised patients receiving oxaliplatin for CRC at our hospital between April 2017 and August 2018. Patients were instructed not to touch and/or drink cold things and were monitored for ACIPN symptoms in the hospital for 24 h after chemotherapy. ACIPN symptoms that appeared > 24 h after chemotherapy were recorded at the next visit. Symptom appearance time was defined as the duration from the administration of chemotherapy until the appearance of paresthesia classified as grade 1 using the Common Terminology Criteria for Adverse Events., Results: Forty-five patients received chemotherapy, comprising 23 men and 22 women, aged 67 years (29-88 years). The location of ACIPN was the fingers in 55.6% of cases, pharynx in 26.7%, perioral region in 24.4%, and feet in 6.7%. The average duration from oxaliplatin administration to symptom development was 182 min (range 62-443 min) for the fingers, 291 min (176-432 min) for the pharynx, 311 min (127-494 min) for the perioral region, and 297 min (234-355 min) for the feet. Pharyngeal symptoms were more common in patients older than 65 years than in those younger than 65 years., Conclusions: The incidence and time of the onset of ACIPN caused by oxaliplatin varies between the body and regions.

Background: In abdominoperineal resection (APR) in male patients with rectal cancer, high margin involvement and urethral injury have been reported to result from difficulty in dissecting the anterior anorectum. Recently, the efficacy of an endoscopic down-to-up rectal dissection was reported. Here, we present a safe and simple technique for anterior dissection using a simultaneous laparoscopic and transperineal endoscopic approach., Methods: We perform transperineal APR (TpAPR) using both the laparoscopic and transperineal approach (a 2-team approach). Anterior dissection commences just behind the superficial transverse perineal muscle. Next, the striated muscle complex surrounding the rectum (levator ani and puborectalis muscle) is divided. At this point, it is difficult to identify the dissection plane between the membranous urethra and anterior rectum; thus, dissection along the lateral aspect of neurovascular bundle from the lateral to anterior side with the assistance of the laparoscopic team is helpful in identifying the posterior surface of the prostate. Once the prostate is identified, it is relatively easy to divide the rectourethralis muscles. The key steps of our procedure are shown in the video., Results: Between April 2016 and July 2019, we performed 14 TpAPR procedures in male patients with rectal cancer without distant metastasis. Extended surgery was performed in 8 patients, including pelvic sidewall dissection and combined resection of adjacent organs. Median operative time was 453 min and median blood loss was 46 g. There was 1 (7.1%) circumferential-positive case, but no cases of urethral injury or rectal perforation., Conclusions: The 2-team TpAPR procedure is beneficial for appropriate dissection of the anterior side during APR surgery.

In recent years, therapeutic drug monitoring (TDM) of intravenous administration of 5-fluorouracil (5-FU) has resulted in reduced toxicity and improved efficacy. Prodrugs of 5-FU were developed to reduce toxicity, extend the duration of action, and increase tumour selectivity of 5-FU. These drugs are important in daily practice because of their ease of administration. Dose adjustment of 5-FU prodrugs by TDM is expected to reduce its toxicity and improve its efficacy. This review focuses on data from a recent study of personalized treatment using TDM of 5-FU and its prodrugs., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Chemoimmunotherapy is a promising treatment for various malignant diseases. In this study, we examined whether first-line chemoimmunotherapy using adoptive immune-cell therapy was effective for metastatic colorectal cancer (mCRC)., Patients and Methods: The therapeutic efficacy and safety of the standard first-line chemoimmunotherapy with adoptive αβ T cell therapy and bevacizumab were assessed using thirty-two patients with mCRC in our hospital. Immunological status after this chemoimmunotherapy was also evaluated., Results: The response and disease control rates were 68.8% and 87.5%, respectively. Further, median progression-free and overall survival were 14.2 and 35.3 months. Immunotherapy-associated toxicity was minimal. Significant decrease in the change of monocyte number (p=0.006) and increase in the change of rate of lymphocyte-to-monocyte ratio (p=0.039) were seen in the complete response group., Conclusion: First-line chemoimmunotherapy with adoptive αβ T cell therapy may be useful for mCRC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Capecitabine is selectively converted from 5'-DFUR to 5-fluorouracil (5-FU) in tumours by thymidine phosphorylase (TP). We investigated the addition of 5-nitrouracil (5-NU), a TP inhibitor, into blood samples for precise measurements of plasma 5-FU concentrations. The plasma concentration of 5-FU was measured after capecitabine administration. Two samples were obtained at 1 or 2 h after capecitabine administration and 5-NU was added to one of each pair. Samples were stored at room temperature or 4 °C and 5-FU concentrations were measured immediately or 1.5 or 3 h later. The mean plasma 5-FU concentration was significantly higher at room temperature than at 4 °C (p < 0.001). The 5-FU concentration was significantly increased in the absence of 5-NU than in the presence of 5-NU (p < 0.001). The 5-FU change in concentration was greater in the absence of 5-NU, and reached 190% of the maximum compared with baseline. A significant interaction was found between temperature and 5-NU conditions (p < 0.001). Differences between the presence or absence of 5-NU were greater at room temperature than under refrigerated conditions. 5-FU plasma concentrations after capecitabine administration varied with time, temperature, and the presence or absence of 5-NU. This indicates that plasma concentrations of 5-FU change dependent on storage conditions after blood collection.

Numbness and pain are currently evaluated using subjective methods such as the visual analogue scale (VAS). PainVision (PV) is an analytical instrument that was designed to quantitatively assess sense perception and nociception in patients. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most important adverse events that renders prolonged chemotherapy difficult. To assess the features of CIPN, we aimed to compare PV methods with existing methods. A total of 73 patients received oxaliplatin for metastatic colorectal cancer. Registered patients included 37 men and 36 women in the range of 37 to 89 years (median 70). CIPN was evaluated a total of 483 times (median per patient six times). Our study examined the correlation between evaluation methods of CIPN using VAS and PV, respectively. The average VAS (hand), VAS (foot) and PV scores of CIPN were 18.4 (range: 0-100), 23.8 (range: 0-100), and 24.7 (range: 0-496), respectively. VAS (hand), VAS (foot), and FACT/GOG-NTX (NTX2, NTX4 and NTX8) were significantly correlated with PV. PV showed no correlation with a Disk-Criminator or the monofilament test used as a quantitative evaluation. The evaluation of CIPN is complex, and further improvement is required for evaluation with PV.

This phase 2 study evaluated the safety and efficacy of perioperative chemotherapy with S-1 plus oxaliplatin (SOX) for stage III colorectal cancer (CRC). Patients with stage III CRC received surgery after neoadjuvant chemotherapy (NAC; SOX 4 cycles) and adjuvant chemotherapy (AC; SOX 4 cycles). The primary endpoints were response rate and safety. We enrolled 30 patients. Their median age was 62 years (range: 43-87 years); 53% were women. They received a median of 4 cycles (range: 1-4) of NAC and a median 4 cycles (range: 0-4) of AC. Five patients interrupted NAC treatment because of toxicity (grade 3 diarrhoea [n = 1], grade 3 ileus [n = 1], and grade 3-4 thrombocytopenia [n = 3]). Patients' responses were complete responses: n = 2 (6.6%), partial responses: n = 21 (70%), stable disease: n = 6 (20.0%), and progressive disease: n = 1 (3.3%; response rate: 73.3%). Curative resection was performed in 29 patients. No patients showed anastomotic leakage. Five-year overall survival and disease-free survival were 83.3% and 76.7%, respectively (median follow-up time: 48 months). NAC using SOX regimen is safe and effective, and may lead to reduced local recurrence and distant metastasis. Long-term outcomes are awaited to evaluate further the efficacy of this strategy (UMIN000006790).

Oxaliplatin is a key chemotherapy drug in patients with colorectal cancer. Administration of oxaliplatin via a peripheral vein often causes vascular pain. However, no studies have evaluated vascular pain in patients with colorectal cancer in relation to peripheral venous administration of chemotherapy with or without oxaliplatin. We evaluated oxaliplatin-induced vascular pain using subjective and objective methods. We determined if oxaliplatin induced vascular pain in patients with colorectal cancer using a Visual Analog Scale (VAS) and a PainVision PS-2100 device. We compared VAS score between chemotherapy regimens with or without oxaliplatin, and between genders. We also examined the correlations of VAS score with pain intensity examined by the PainVision PS-2100, and with age and vessel diameter. A total of 98 patients with colorectal cancer were enrolled in this study, including 78 patients who received oxaliplatin via peripheral venous administration and 20 who received chemotherapy without oxaliplatin. The median VAS scores in patients with and without oxaliplatin were 36.5 (interquartile range 9.0-60.0) and 0 (0-4.0), respectively (P < 0.001), and the median pain intensities according to PainVision were 43.5 (14.3-98) and 36.5 (9.3-58.5), respectively (P < 0.001). There was a positive correlation between VAS and pain intensity (r = 0.584), but no correlation between VAS score and age (r = -0.174) or vessel diameter (r = -0.107). Peripheral venous administration of oxaliplatin induced vascular pain, measured both subjectively and objectively, in patients with colorectal cancer, regardless of vessel diameter.

Transanal total mesorectal excision (taTME) has been developed to overcome the difficulty of laparoscopic dissection and transection in the deep pelvis. TaTME has several clinical benefits over laparoscopic surgery, such as better exposure of the distal rectum and direct determination of distal resection margin. Although evidence demonstrating the true benefits of taTME over laparoscopic TME (LapTME) is still insufficient, accumulating data have revealed that, as compared with LapTME, taTME is associated with shorter operative time and a lower conversion rate without jeopardizing other short-term outcomes. However, taTME is a technically demanding procedure with specific complications such as urethral injury, and so sufficient experience of LapTME and step-by-step acquisition of the skills needed for this procedure are requisite. The role of transanal endoscopic surgery is expected to change, along with the recent progress in the treatment of rectal cancer, such as robotic surgery and the watch-and-wait strategy. Optimization of treatment will be needed in the future in terms not only of oncological but also of functional outcomes., Competing Interests: Conflicts of Interest There are no conflicts of interest.

Background/aim: TAS-102 has led to a significant improvement in overall survival (OS) and progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC). Neutropenia is the most common adverse event and an important factor impacting chemotherapy continuation. In this retrospective study, factors associated with grade ≥3 neutropenia, that is frequently observed in TAS-102-treated patients, were examined., Patients and Methods: The medical records of 41 patients with CRC who received TAS-102 between October 2014 and June 2017 at the Fukuoka University Hospital were retrospectively reviewed. Response rate, PFS, OS, and adverse events were analyzed using KRAS mutation, administration method, concomitant drug administration, neutrophil-to-lymphocyte ratio (NLR), and Onodera's prognostic nutritional index (Onodera's index) as a stratification factors., Results: Both PFS and OS were significantly higher with TAS-102 plus bevacizumab combination therapy. Biweekly administration (7.1%) was associated with significantly less neutropenia compared to normal administration (44.4%). DCR with biweekly administration was better than that with normal administration, although without statistical significance. No significant difference was observed in OS rates between the biweekly and normal administration regimens; however, the biweekly regimen was associated with significantly prolonged PFS. By multivariate analysis, a significant difference was noted in the Onodera's index for OS and in the administration method and NLR for PFS., Conclusion: Biweekly administration without a change in the drug dose intensity was associated with reduced neutropenia in patients with mCRC. The effects and adverse events of TAS-102 were associated with concomitant drug administration, administration method, and nutritional status., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Initiating chemotherapy usually requires a delay of more than 4 weeks after surgically resecting colorectal cancer. However, there is little evidence regarding the required delay interval. We have previously reported a pilot study to determine the safety and feasibility of early initiation of chemotherapy after resecting primary colorectal cancer with distant metastases. We aimed to determine the safety and efficacy of early initiation of chemotherapy after resecting colorectal cancer with distant metastases., This phase II study (trial number UMIN000006310) was a prospective, single-arm trial. A total of 20 patients (men, 15 and women, 5) were enrolled. They underwent XELOX therapy (130 mg/m 2 oxaliplatin on day 1+1000 mg/m 2 capecitabine twice daily on days 1-4) on postoperative day 7 and XELOX+bevacizumab (7.5 mg/kg bevacizumab on day 1) after the second chemotherapy cycle., Baseline characteristics included a median age of 64 (range, 43-72) years. Surgical procedures included right hemicolectomy in six patients, sigmoidectomy in three, anterior resection in five, and Hartmann procedure in six. All patients started chemotherapy on postoperative day 7. Median progression-free survival was 14.9 months; overall response rate was 80%. Disease control rate was 100%. Grade 3 or higher hemotoxicity and grade 3 or higher non-hematological toxicity was noted in 5.0% and 25.0% of patients, respectively. Postoperative complications were observed in two patients (superficial incisional surgical site infection and ileus)., Early initiation of chemotherapy after surgery is feasible. These findings suggest future changes of the start time of chemotherapy after surgery.

Background: Adoptive immunotherapy for cancer has evolved through development of novel technologies for generating a large number of activated killer cells, such as αβ T-cells, γδ T-cells, and natural killer cells. There has been no prospective trial of combination therapy involving adoptive immunotherapy and first-line chemotherapy for stage IV colorectal cancer. The present pilot study aimed to evaluate the safety and feasibility of combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer (COMVI study)., Patients and Methods: The COMVI study was a prospective, single-arm pilot trial. Therapy in each 21-day treatment cycle involved XELOX (130 mg/m 2 of oxaliplatin on day 1 plus 1,000 mg/m 2 of capecitabine twice daily on days 1-14), bevacizumab (7.5 mg/kg on day 1), and αβ T-lymphocytes (over 5×10 9 on day 18) cultured ex vivo with an immobilized antibody to CD3 and interleukin-2., Results: The study included six patients (two men and four women) between June 2013 and September 2014. The median patient age was 68 years (range=55-75 years). The overall response rate was 83.3% [complete response in two (33.3%); partial response in three (50.0%); stable disease in one (16.7%); no cases of progressive disease]. The tumor volume reduction rate was 53% (range=38.0-100%). The median progression-free and overall survival durations were 567 and 966 days, respectively. Most adverse events were mild-to-moderate in intensity, and no grade 4 adverse events occurred in the six patients. Only one patient experienced grade 3 hypertension and ileus. Immunotherapy-associated toxicity was minimal in this study., Conclusion: Combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer is feasible and safe. Phase II prospective studies are needed to confirm the safety and efficacy of such chemoimmunotherapy., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Various types of chemoimmunotherapies for malignant tumors have been reported. However, there are few reports on hepatectomy after chemoimmunotherapy. We evaluated the safety and efficacy of hepatectomy for patients with stage IV colorectal liver metastases (CLM) after chemoimmunotherapy using activated αβ T-cells., Patients and Methods: From June 2012 to December 2016, five patients who underwent hepatectomy after receiving capecitabine and oxaliplatin (XELOX) plus bevacizumab and ex vivo-expanded αβ T-lymphocytes as first-line chemoimmunotherapy were included., Results: The median age of the five patients (two men, three women) was 61.4 (range=56-75) years. The surgical procedure was partial hepatectomy in two, laparoscopic partial hepatectomy in two, and one case of partial hepatectomy with subsegmentectomy. There was no postoperative complication of Clavien-Dindo grade 3A or higher. One patient had multiple lung metastases., Conclusion: Hepatectomy after chemoimmunotherapy using activated αβ T-cells for CLM can be performed safely., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Among all procedures, surgical site infections (SSIs) in colorectal surgery continue to have the highest rate, accounting for 5%-45%. To prevent the bacterial colonization of suture material, which disables local mechanisms of wound decontamination, triclosan-coated sutures were developed. We assessed the effectiveness of triclosan-coated sutures used for skin closure on the rate of SSIs in colorectal cancer surgery., Methods: Until August 2012, we used conventional methods for skin closure in colorectal cancer surgery at the Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine. Therefore, for the control group, we retrospectively collected surveillance data over a 1.5-y period. From September 2012, we began using triclosan-coated polydioxanone antimicrobial sutures (PDS plus) for skin and fascia closure. Hence, we collected data for the study group from September 2012 to October 2013. Differences in baseline characteristics and selection bias were adjusted using the propensity score-matching method., Results: A total of 399 patients who underwent colorectal surgery were included in this study. There were 214 patients in the control group and 185 patients in the study group. Baseline patient characteristics were similar between the propensity score-matched groups. The incidence of SSIs was less in the study group. Multivariate logistic regression analysis showed that the site of the procedure, laparoscopic surgery, and using triclosan-coated sutures remained the independent predictors of SSIs., Conclusions: The use of triclosan-coated sutures was advantageous for decreasing the risk of SSIs after colorectal surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: During oxaliplatin chemotherapy administration via a peripheral vein, vascular pain requires changing of the intravenous infusion route on occasion. Vascular pain induced by anticancer drugs reduces the rate of patient continuation and completion of chemotherapy. Pain is presently appraised using subjective methods, such as the visual analog scale (VAS). However, because pain evaluation can vary depending on the physical state and mood of the patient at the time of assessment, it is desirable to evaluate pain objectively. PainVision PS-2100 (PV) is a medical device that was designed to objectively and quantitatively assess patient nociception and perception., Methods: The present study examined the correlation of subjective and objective assessment of oxaliplatin-induced vascular pain using VAS and PV, respectively., Results: Vascular pain was assessed using both PV and VAS a total of 173 times for 58 colorectal cancer patients. Partial correlation analysis was performed to evaluate the relationship between PV and VAS. The mean PV and VAS scores were 44.5 (range: 0-596) and 24.8 (range: 0-100), respectively. The partial correlation coefficient was 0.408 (p < 0.0001)., Conclusions: A strong correlation was not observed between the results, and a weak correlation was observed between VAS and PV scores. Objective evaluation of oxaliplatin-induced vascular pain will be required to help patients overcome vascular pain.