Change in antimicrobial susceptibility of pathogens isolated from surgical site infections over the past decade in Japanese nation-wide surveillance study.

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014-2015 surveillance studies. Although the rate of detection of extended-spectrum ß-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014-2015, the incidence decreased to 8.7% in 2018-2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 µg/mL). By contrast, relatively low geometric mean MICs (0.397 µg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018-2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014-2015, and 38.9% in 2018-2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group.

[A Surgical Case of Desmoid Tumor in the Transverse Mesocolon with Pancreatic Invasion].

A 40-year-old man with no previous history of abdominal surgery or noteworthy family history presented to our hospital because of a palpable abdominal mass. Abdominal CT revealed a 9 cm diameter mass in the mesocolon. The differential diagnosis included desmoid tumor, and right hemicolectomy with partial resection of the pancreas head and duodenum was performed. Pathologically, the tumor cells were negative for S-100, c-kit, CD34, and desmin but partially positive for a-SMA and slightly for b-catenin. From these findings, desmoid tumor of the mesocolon was diagnosed. Invasion of the pancreas was also found. Desmoid tumor is pathologically benign, but because of its malignant-like characteristics, such as direct invasion and local recurrence, it is treated as a malignant tumor. Desmoid tumors are associated with familial adenomatous polyposis coli and Gardner syndrome, or they arise in patients who have a history of laparotomy or antecedent trauma. In this paper, we report a rare case of resected sporadic desmoid tumor in the mesocolon with pancreatic invasion, together with a review of the literature.

Intramucosal colorectal carcinoma with lymphovascular invasion: clinicopathological characteristics of nine cases.

AIMS: Recent studies have provided the concept of invasive intramucosal colorectal carcinoma (CRC), and a case of intramucosal CRC with lymphatic invasion has been reported; however, the characteristics of such cases and the risk of lymph node metastasis have never been investigated. Therefore, we aimed to assess the pathological characteristics of intramucosal CRCs with lymphovascular invasion as well as the possibility of lymph node metastasis as an indication for additional surgery. METHODS AND RESULTS: To delineate the histological features of intramucosal CRCs with lymphovascular invasion, we analysed several histological features and compared their incidence among nine such cases, as well as 20 other cases of intramucosal CRCs without lymphovascular invasion. High-grade tumour budding and a pattern of 'eosinophilic cytoplasm and round nuclei with inflammatory reaction (ERI)' were morphological characteristics of intramucosal CRCs with lymphovascular invasion, compared with those without lymphovascular invasion (both P < 0.05). Among the seven lymph node-dissected cases of intramucosal CRCs with lymphovascular invasion, none showed lymph node metastasis. CONCLUSIONS: In intramucosal CRCs with lymphovascular invasion, high-grade tumour budding and the 'ERI' pattern are morphological characteristics that are distinct from those of non-invasive CRC, which is synonymous with high-grade dysplasia. Further studies using a larger number of cases by focusing on the above-mentioned histological pattern are expected to clarify the potential of lymph node metastasis of such cases.

Portal encasement: Significant CT findings to diagnose local recurrence after pancreaticoduodenectomy for pancreatic cancer.

BACKGROUND/OBJECTIVES: To demonstrate the utility of portal encasement as a criterion for early diagnosis of local recurrence (LR) after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 61 patients who underwent PD for PDAC were included in this retrospective study. Portal stenosis was evaluated by sequential postoperative computed tomography (CT) scans and correlated with disease recurrence. In addition to the conventional LR diagnostic criterion of a growing soft tissue mass, LR was evaluated using portal encasement as an additional diagnostic criterion. Portal encasement was defined as progressive stenosis of the portal system accompanied by a soft tissue mass, notwithstanding the enlargement of the mass. RESULTS: Benign portal stenosis was found on the first postoperative CT imaging in 16 patients. However, stenosis resolved a median of 81 days later in all but one patient whose stenosis was due to portal reconstruction during PD. Portal encasement could be distinguished from benign portal stenosis based on the timing of emergence of the portal stenosis. Portal encasement developed in 13 of the 19 patients with LR, including 6 patients in whom the finding of portal encasement led to the diagnosis of LR a median of 147 days earlier with our diagnostic criterion compared with the conventional diagnostic criteria. CONCLUSIONS: Portal encasement should be considered as a promising diagnostic criterion for earlier diagnosis of LR after PD for PDAC.

Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan.

The principle of empirical therapy for patients with intra-abdominal infections (IAI) should include antibiotics with activity against Enterobacteriaceae and Bacteroides fragilis group species. Coverage of Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis is also recommended for hospital-associated IAI. A nationwide survey was conducted to investigate the antimicrobial susceptibility of pathogens isolated from postoperative IAI. All 504 isolates were collected at 26 institutions and referred to a central laboratory for susceptibility testing. Lower susceptibility rates to ciprofloxacin and cefepime were demonstrated in Escherichia coli. Among E. coli, 24.1% of strains produced extended-spectrum ß-lactamase (ESBL). Carbapenems, piperacillin/tazobactam, cephamycins/oxacephem, aminoglycosides, and tigecycline had high activity against E. coli, including ESBL-producing isolates. Among E. cloacae, low susceptibility rates to ceftazidime were demonstrated, whereas cefepime retained its activity. P. aeruginosa revealed high susceptibility rates to all antimicrobials tested except for imipenem. Among B. fragilis group species, low levels of susceptibility were observed for cefoxitin, moxifloxacin, and clindamycin, and high susceptibility rates were observed for piperacillin/tazobactam, meropenem, and metronidazole. Ampicillin, piperacillin, and glycopeptides had good activity against E. faecalis. Imipenem had the highest activity against E. faecalis among carbapenems. In conclusion, we suggested the empirical use of antimicrobials with the specific intent of covering the main organisms isolated from postoperative IAI. Piperacillin/tazobactam, meropenem, or doripenem, are appropriate in critically ill patients. Combination therapy of cefepime (aztreonam in patients with ß-lactam allergy) plus metronidazole plus glycopeptides, imipenem/cilastatin or cephamycins/oxacephem plus ciprofloxacin plus metronidazole are potential therapeutic options.

Clinical evaluation of the aberrant left hepatic artery arising from the left gastric artery in esophagectomy.

PURPOSE: The left gastric artery (LGA) is commonly severed when the gastric tube is made for esophageal reconstruction. Sacrifice of the LGA can cause liver ischemic necrosis in patients with an aberrant left hepatic artery (ALHA) arising from the LGA. We experienced a case of life-threatening hepatic abscess after severing the ALHA. Therefore, the purpose of this study is to evaluate clinical outcomes of severing the ALHA. METHODS: We retrospectively enrolled 176 consecutive patients who underwent esophagectomy with gastric tube reconstruction. They were classified into the ALHA (N = 16, 9.1%) and non-ALHA (N = 160, 90.9%) groups. Univariate analysis was performed to compare the clinicopathological variables. Long-term survival was analyzed using the Kaplan-Meier method in matched pair case-control analysis. RESULTS: The postoperative morbidities were not statistically different between the two groups, although serum alanine aminotransferase levels on postoperative days 1 and 3 were significantly higher in the ALHA group (36 IU/L, 14-515; 32 IU/L, 13-295) than in the non-ALHA group (24 IU/L, 8-163; 19 IU/L, 6-180), respectively (p = 0.0055; p = 0.0073). Overall survival was not statistically different between the two groups (p = 0.26). CONCLUSIONS: Severe hepatic abscess occurred in 6.3% of the patients with the ALHA after esophagectomy, even though the results presented here found no statistical differences in morbidity or mortality with or without the ALHA. Surgeons should probably attempt to preserve the ALHA especially in patients with altered liver function while making a gastric tube for esophageal reconstruction.

Real-time confocal laser endomicroscopic evaluation of primary liver cancer based on human liver autofluorescence.

BACKGROUND: Confocal laser endomicroscopy (CLE) is available for real-time microscopic examination. This study aims to evaluate the usefulness of intraoperative CLE examination as a modality to evaluate surgical margins in surgery for primary liver cancer. METHODS: A probe-based CLE system (Cellvizio 100, Mauna Kea Technologies, Paris, France) was used. The subjects comprised seven specimens obtained from six patients with primary liver cancer in November 2015. The probe was manually attached to the surfaces of specimens, and images were collected without external fluorophores. CLE images were compared with hematoxylin and eosin-stained slides. Fluorescence intensity (FI) values of the CLE images were assessed using luminance-analyzing software. RESULTS: CLE examination visualized non-cancerous regions in the background liver as regular structures with high fluorescence because of human liver autofluorescence. Conversely, hepatocellular carcinoma and intrahepatic cholangiocarcinoma were depicted as irregular structures with low fluorescence. The median FI values of the non-cancerous regions and the cancerous regions were 104 (79.8-156) and 74.9 (60.6-106), respectively, and were significantly different (P = 0.031). CONCLUSIONS: The probe-based CLE enables real-time differentiation of cancerous regions from non-cancerous tissues in surgical specimens because of human liver autofluorescence. CLE can be used to confirm negative surgical margins in the operating room. J. Surg. Oncol. 2017;115:151-157. © 2016 Wiley Periodicals, Inc.

Antimicrobial susceptibility of pathogens isolated from surgical site infections in Japan: Comparison of data from nationwide surveillance studies conducted in 2010 and 2014-2015.

A nationwide survey was conducted in Japan from 2014 to 2015 to investigate the antimicrobial susceptibility of pathogens isolated from surgical site infections (SSI). The resulting data were compared with that obtained in an earlier survey, conducted in 2010. Seven main organisms were collected, and 883 isolates were studied. A significant reduction in methicillin resistance was observed among Staphylococcus aureus isolates, dropping from 72.5% in 2010 to 53.8% in 2014-2015 (p < 0.001). MRSA isolates with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL accounted for 1.2% of all MRSA isolates, which was significantly lower than in 2010 (9.7%, p = 0.029). Of the Escherichia coli isolates, 23.0% produced an extended spectrum ß-lactamase (ESBL) in the 2014-2015 survey, which was a significant increase from 9.5% in 2010 (p = 0.011). The geometric mean MICs for ESBL-producing isolates were 0.07 µg/mL for meropenem, 9.51 µg/mL for tazobactam/piperacillin, 0.15 µg/mL for flomoxef, and 1.56 µg/mL for gentamycin. There was a significant increase in the isolation rate of non-fragilis Bacteroides among Bacteroides fragilis group species between the two study periods (35.2% vs. 53.1%, p = 0.007). More than 90% of isolates belonging to the B. fragilis group remained susceptible to tazobactam/piperacillin, meropenem, and metronidazole. In contrast, lower levels of susceptibility were observed for cefmetazole (49.6%), moxifloxacin (61.9%), and clindamycin (46.9%). Non-fragilis Bacteroides isolates had lower rates of antibiotic susceptibility compared with B. fragilis. Overall, the surveillance data clarified trends in antimicrobial susceptibility for organisms commonly associated with SSI.

[Coproductive teamwork in surgical cancer treatment].

With regard to surgical treatment of cancer, there is a strong demand for safe treatment with few errors: treatment must be based on transparency, understandability, and rationality. There is also demand for treatment which is quick, efficient and not wasteful. Rather than maintaining our current pyramidal system which has doctors standing as authorities at the top, there is a need for a flat, non-authoritarian system at every level and section of the hospital. As we change methodology, electronic medical records and clinical pathways will be important tools. Among the surgical department's treatment team in our hospital, there are many branches at work on peri-operative management aside from operations; There are teams for infection control (ICT), nutrition support (NST), decubitus and stoma management, rehabilitaion, and chemotherapy, and team cooperation after discharge from hospital. In addition, the collaborative and coproductive team focusing on pain releif and palliative care in terminal phase (PCT) is important. Having introduced each of the parts of team treatment within the setting of the surgical department, the need now for strong leadership from young and brightful surgeons is also emphasized.

Utility of preoperative small-bowel endoscopy for hemorrhagic lesions in the small intestine.

PURPOSE: We evaluated a small group of patients with hemorrhagic lesions in the small intestine diagnosed preoperatively by video capsule endoscopy (VCE) and/or double-balloon endoscopy (DBE), who underwent surgery in our hospital. METHODS: The subjects were 20 patients with hemorrhagic lesions in the small intestine diagnosed preoperatively by VCE and/or DBE, who underwent surgery between April 2004 and December 2008. RESULTS: VCE, DBE, and computed tomography were performed in 12, 17, and 20 patients, respectively. Eleven patients also had a biopsy taken during DBE, resulting in a definitive diagnosis in eight. Because of the risk of hemorrhage during DBE in five patients, a biopsy was not taken and the sites of the lesion were marked in these patients. Twenty patients underwent surgery, and the diagnoses were small-intestinal cancer in eight, gastrointestinal stromal tumor in seven, arteriovenous malformation in two, and Crohn's disease, angioectasia, and leiomyoma in one each. The interval between the onset of symptoms and surgery was less than 50 days for six patients, 50-100 days for two, 100-200 days for five, and more than 200 days for seven. CONCLUSION: Preoperative small-bowel endoscopy proved useful for diagnosing the cause of hemorrhagic lesions in the small intestine.

Long-term survival after pancreatic metastasis resection from breast cancer: a systematic literature review.

BACKGROUND: Patients with advanced-stage breast cancer often demonstrate pancreatic metastases. However, pancreatic metastases resection from breast cancer has been rarely performed, with only 20 cases having been reported to date. CASE PRESENTATION: A 49-year-old woman presented to our hospital in September 2003 with complaints of uncontrollable oozing from her left breast tumor. Computed tomography revealed a left breast tumor approximately 9.3 cm in diameter as well as heterogeneously enhanced solid mass lesions with necrotic foci in the pancreatic tail and body, up to 6.2 cm, which were radiologically diagnosed as pancreatic metastases from breast cancer. An emergent left simple mastectomy was performed to control bleeding. After epirubicin and cyclophosphamide hydrate treatment failed to improve her condition, the pancreatic metastases responded to weekly paclitaxel treatment, but eventually regrew. The patient underwent distal pancreatectomy with splenectomy, left adrenalectomy, partial stomach resection, and paraaortic lymph nodes excision in December 2004 after no other metastasis was confirmed. Furthermore, she received radiation therapy for left parasternal lymph node metastasis 6 months later. The patient recovered well. Consequently, she has no evidence of disease > 15 years after pancreatectomy. CONCLUSIONS: This is the first reported case of pancreatectomy for pancreatic metastases from breast cancer, which was simultaneously diagnosed. Patients with no metastasis other than resectable pancreatic metastases and breast cancer and who possess some sensitivity for chemotherapy may benefit from pancreatectomy.

Maximal sterile barrier precautions do not reduce catheter-related bloodstream infections in general surgery units: a multi-institutional randomized controlled trial.

OBJECTIVE: To investigate whether maximal sterile barrier precautions (MSBPs) during central venous catheter (CVC) insertion are truly effective in preventing catheter-related bloodstream infections (CRBSIs) in patients in general surgical units. SUMMARY BACKGROUND DATA: The reported effectiveness of MSBPs was based on the results of a single-center randomized controlled trial by Raad et al and the majority of the patients (99%) in the study were chemotherapy outpatients. METHODS: Between March 14, 2004 and December 28, 2006, the patients scheduled for CVC insertion in surgical units at 9 medical centers in Japan were randomly assigned to either an MSBP group (n = 211) or a standard sterile barrier precaution (SSBP) group (n = 213). This study was registered in the UMIN Clinical Trials Registry (registration ID number: UMIN000001400). RESULTS: The median (range) duration of catheterization was 14 days (0-92 days) in the MSBP group and 14 days (0-112 days) in the SSBP group. There were 5 cases (2.4%) of CRBSI in the MSBP group and 6 cases (2.8%) in the SSBP group (relative risk, 0.84; 95% confidence interval, 0.26-2.7; P = 0.77). The rate of CRBSIs per 1000 catheter days was 1.5 in the MSBP group and 1.6 in the SSBP group. There were 8 cases (3.8%) of catheter-related infections in the MSBP group and 7 cases (3.3%) in the SSBP group (relative risk, 1.2; 95% confidence interval, 0.43-3.1; P = 0.78). The rate of catheter-related infection per 1000 catheter days was 2.4 in the MSBP group and 1.9 in the SSBP group. CONCLUSIONS: This study is larger in sample size than the one performed by Raad et al and could not demonstrate better prevention of CRBSIs by MSBP compared with SSBP. A large randomized controlled trial or at least a meta-analysis of any other studies in the literature is necessary to reach to a conclusion on this issue.

Fat replacement of the distal pancreas in a case of advanced gastric cancer.

Preoperative computed tomography in a 67-year-old man admitted with type 2 advanced gastric cancer involving the upper body of the stomach revealed marked atrophy of the left lobe of the liver and atrophy of the distal pancreas. Total gastrectomy with D2 lymph node dissection was planned; however, additional distal pancreatectomy with splenectomy was also performed during the operation because of direct invasion of the pancreas by the gastric cancer. Histopathologic examination of the resected pancreas revealed the absence of lobules, acini, conduits, and pancreatic ducts, with only islets of Langerhans found scattered in the adipose tissue. The findings revealed that the gastric cancer had directly invaded the fat, replacing the distal pancreas. In patients with fat-replaced pancreas, preoperative evaluation of direct invasion of adjacent organs/tissues by gastric cancer is difficult.

[Effectiveness of antimicrobial prophylaxis in prevention of surgical site infections].

Preventing surgical site infection (SSI) is important in providing safe and high-quality surgical care. Antimicrobial prophylaxis is given to prevent SSI. Many reports revealed that antimicrobial prophylaxis is effective to reduce SSI rates, when its initial dose is given at proper timing and additional dose is properly given in longer operations. Initial dose of antimicrobial prophylaxis is recommended to be administered within one hour before starting operation. Additional dose is recommended to be administered each two to three hours in longer operations. Antimicrobial prophylaxis should be given according to pharmacokinetics/pharmacodynamics (PK/PD). Beta-lactam drugs are recommended to be administered three or four times a day to obtain longer time above MIC and effective antimicrobial activity. In United States, Surgical Care Improvement Project (SCIP) is ongoing to reduce complications after surgery. Proper usage of antimicrobial prophylaxis is strongly recommended to reduce SSI in this project. Surgical team hopes to reduce SSI by proper administration of antimicrobial prophylaxis with the cooperatiing of anesthesiologists and operating room staffs.

[Risk management and postoperative infection control].

Review of nine cases of judicial precedent on the issue of the postoperative infection in Japan indicates the following issues: indication of surgery; violation of informed consent; preventive measures against nosocomial infection during the preoperative period; cleanliness control during surgery; and treatment of postoperative infection. The most important yardstick for judgment is whether the provided treatment is conformed to the level of standard medical treatment available at the time. Therefore, we should be well versed in the standard postoperative infection treatment, particularly infection surveillance data and CDC standard precautions and related guidelines. Moreover, in each hospital, an infection control team should play an important role in infection control and prevention through preparing manuals and clinical paths incorporating precautions to ensure that the whole staff comply with the prescribed procedures.

Colonic Neurogenic Lesion: An Admixture of Mucosal Neurofibromatous Lesion and Submucosal Ganglioneuromatous Lesion With Transition.

Benign neural tumors or tumor-like lesions are rarely detected in the gastrointestinal tract. In this article, we present the case of a neural lesion of the sigmoid colon, which was incidentally detected in a 68-year-old man treated with laparoscopic low anterior resection for an advanced carcinoma of the rectosigmoid junction. Within the resected specimen, a submucosal tumor-like protruding lesion was found in the sigmoid colon. Histologically, the growth was composed of mucosal neurofibromatous and submucosal ganglioneuromatous lesions, between which there was transition. Immunohistochemical analysis revealed a rupture of the perineurium in the area of transition, along with a proliferation of Schwann cells and supporting cells extending into the deep mucosa. This transition indicated that the mucosal and submucosal lesions comprised a single lesion, and that a diagnosis of neurofibroma or ganglioneuroma would be inadequate in this case. Because we could not classify it as an established single entity, we diagnosed the mass as an unclassifiable colonic neurogenic lesion. In summary, we report the case of an extremely rare occurrence of an unclassifiable colonic neurogenic lesion comprising an admixture of transitioning mucosal neurofibromatous and submucosal ganglioneuromatous lesions.

A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma.

Perineural invasion (PNI) is one of the major pathological characteristics of pancreatic ductal adeno-carcinoma (PDAC), which is mediated by invading cancer cells into nerve cells. Herein, we identify the overexpression of Interleukin-13 Receptor alpha2 (IL-13Rα2) in the PNI from 236 PDAC samples by studying its expression at the protein levels by immunohistochemistry (IHC) and the RNA level by in situ hybridization (ISH). We observe that ≥75% samples overexpressed IL-13Rα2 by IHC and ISH in grade 2 and 3 tumors, while ≥64% stage II and III tumors overexpressed IL-13Rα2 (≥2+). Interestingly, ≥36 % peripancreatic neural plexus (PL) and ≥70% nerve endings (Ne) among PNI in PDAC samples showed higher levels of IL-13Rα2 (≥2+). IL-13Rα2 +ve PL and Ne subjects survived significantly less than IL-13Rα2 -ve subjects, suggesting that IL-13Rα2 may have a unique role as a biomarker of PNI-aggressiveness. Importantly, IL-13Rα2 may be a therapeutic target for intervention, which might not only prolong patient survival but also help alleviate pain attributed to perineural invasion. Our study uncovers a novel role of IL-13Rα2 in PNI as a key factor of the disease severity, thus revealing a therapeutically targetable option for PDAC and to facilitate PNI-associated pain management.

A placebo-controlled, double-blind, randomized study of recombinant thrombomodulin (ART-123) to prevent oxaliplatin-induced peripheral neuropathy.

PURPOSE: The purpose of this clinical study was to be the first to explore whether ART-123, a recombinant human soluble thrombomodulin, prevents oxaliplatin-induced peripheral neuropathy (OIPN). METHODS: This randomized, phase IIa trial enrolled stage II/III colon cancer patients who received adjuvant mFOLFOX6 chemotherapy. Participants were randomly allocated to 3 arms in a double-blind manner: placebo (placebo: days 1-3); 1-day ART (ART-123: day 1, placebo: days 2-3); and 3-day ART (ART-123: days 1-3). ART-123 (380 U/kg/day) or placebo was infused intravenously before each 2-week cycle of mFOLFOX6. OIPN was assessed with the Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity-12 (FACT/GOG-Ntx-12) score by participants and the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) by investigators. RESULTS: Seventy-nine participants (placebo n = 28, 1-day ART n = 27, 3-day ART n = 24) received study drugs. The least-squares mean FACT/GOG-Ntx-12 scores at cycle 12 from the mixed effect model for repeated measures were 28.9 with placebo, 36.3 with 1-day ART (vs. placebo: 7.3 [95% CI 1.9 to12.8, p = 0.009]), and 32.3 with 3-day ART (vs. placebo: 3.4 [95% CI -.1 to 9.0, p = 0.222]). The cumulative incidence of NCI-CTCAE grade ≥ 2 sensory neuropathy at cycle 12 was 64.3% with placebo, 40.7% with 1-day ART (vs. placebo: -23.5 [95% CI -48.4 to 4.0], p = 0.108), and 45.8% with 3-day ART (vs. placebo: -18.5 [95% CI -44.2 to 9.4], p = 0.264). Common adverse events were consistent with those reported with mFOLFOX6; no severe bleeding adverse events occurred. CONCLUSION: ART-123 showed a potential preventive effect against OIPN with good tolerability. A larger study with 1-day ART is warranted. NCT02792842, registration date: June 8, 2016.