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Background/Objectives: In addition to oncological applications, poly(ADP-ribose) polymerase (PARP) inhibitors have potential as anti-inflammatory agents. Colon-targeted delivery of PARP inhibitors has been evaluated as a pharmaceutical strategy to enhance their safety and therapeutic efficacy against gut inflammation. Methods: Colon-targeted PARP inhibitors 5-aminoisoquinoline (5-AIQ) and 3-aminobenzamide (3-AB) were designed and synthesized by azo coupling with salicylic acid (SA), yielding 5-AIQ azo-linked with SA (AQSA) and 3-AB azo-linked with SA (ABSA). Additional conjugation of AQSA with acidic amino acids yielded glutamic acid-conjugated AQSA (AQSA-Glu) and aspartic acid-conjugated AQSA, which further increased the hydrophilicity of AQSA. Results: The distribution coefficients of PARP inhibitors were lowered by chemical modifications, which correlated well with drug permeability via the Caco-2 cell monolayer. All derivatives were effectively converted to their corresponding PARP inhibitors in the cecal contents. Compared with observations in the oral administration of PARP inhibitors, AQSA-Glu and ABSA resulted in the accumulation of much greater amounts of each PARP inhibitor in the cecum. ABSA accumulated mesalazine (5-ASA) in the cecum to a similar extent as sulfasalazine (SSZ), a colon-targeted 5-ASA prodrug. In the DNBS-induced rat colitis model, AQSA-Glu enhanced the anticolitic potency of 5-AIQ. Furthermore, ABSA was more effective against rat colitis than SSZ or AQSA-Glu, and the anticolitic effects of AQSA-Glu were augmented by combined treatment with a colon-targeted 5-ASA prodrug. In addition, the colon-targeted delivery of PARP inhibitors substantially reduced their systemic absorption. Conclusions: Colon-targeted PARP inhibitors may improve the therapeutic and toxicological properties of inhibitors and synergize the anticolitic effects of 5-ASA.

Introduction and Importance: Oesophageal fistula is a severe complication that may occasionally develop after chemoradiotherapy (CRT) for oesophageal cancer and is difficult to treat., Case Presentation: A 51-year-old man who had undergone CRT for oesophageal cancer presented with haematemesis and was diagnosed with a descending aortic aneurysm and an oesophageal fistula. Thoracic endovascular aneurysm repair was performed to achieve haemostasis. After 3 days, the patient underwent subtotal oesophagectomy and cervical oesophagostomy with delivery of a pedicled omental flap to the exposed aortic stent. Six months later, ileocecal reconstruction was performed. The second patient was a 49-year-old woman who had undergone CRT 1 year previously. She complained of leg weakness and gait disorder. After a workup, she was diagnosed with perforation of the posterior wall of the cervical oesophagus with abscess formation and purulent spondylitis. After two spinal fusion surgeries, we performed tracheotomy and drained the cervical region to reduce local infection. After 7 days, she underwent pharyngolaryngoesophagectomy and reconstruction using a gastric conduit, to which a large section of the omental flap was attached. After the multi-stage surgery, oral intake became possible, and both patients were discharged., Clinical Discussion: The optimal treatment strategy for post-CRT oesophageal fistula remains controversial. Radical surgery, including oesophagectomy, is the treatment of choice, although it is associated with high mortality rates. Multi-stage surgery may be useful for reducing surgical stress in moribund patients., Conclusion: We reported two cases involving radiation-induced oesophageal fistula successfully treated by multi-stage surgery without major complications., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Surgical-site infections (SSIs) are the most common complication after stoma closure. We propose a new method for wound closure using the subcutaneous large-bite buried suture (SLBS) technique and a closed suction drain (CSD). In this study, we aimed to investigate the efficacy of a combination of the SLBS technique and a CSD to prevent superficial SSIs following stoma closure., Methods: We retrospectively analyzed patients who underwent stoma closure between January 2019 and July 2022. Primary closure of the stomal site was performed using the SLBS technique and a CSD for wound closure. The CSD was placed until postoperative day 7. The occurrence of superficial postoperative SSIs was also evaluated., Results: In total, 67 patients were included in the study. Within 30 days postoperatively, nine patients (13%) developed superficial SSIs. Considering the type of stoma, only 1 (2%) of 45 patients with ileostomy showed superficial SSIs, whereas 8 (36%) of 22 patients with colostomy showed superficial SSIs. Univariate analysis of the risk factors associated with the occurrence of superficial SSIs revealed that colostomy (p < 0.001) and hand-sewn anastomosis were significant risk factors (p = 0.019). Multivariate analysis of the risk factors associated with the occurrence of superficial SSIs revealed that colostomy was significant risk factor (p = 0.003)., Conclusions: This new method of stoma closure is feasible for preventing superficial SSIs, especially in ileostomy closure., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Pancreatic ductal adenocarcinoma (PDAC) is especially hypoxic and composed of heterogeneous cell populations containing hypoxia-adapted cells. Hypoxia as a microenvironment of PDAC is known to cause epithelial-mesenchymal transition (EMT) and resistance to therapy. Therefore, cells adapted to hypoxia possess malignant traits that should be targeted for therapy. However, current 3D organoid culture systems are usually cultured under normoxia, losing hypoxia-adapted cells due to selectivity bias at the time of organoid establishment. To overcome any potential selection bias, we focused on oxygen concentration during the establishment of 3D organoids. We subjected identical PDAC surgical samples to normoxia (O2 20%) or hypoxia (O2 1%), yielding glandular and solid organoid morphology, respectively. Pancreatic cancer organoids established under hypoxia displayed higher expression of EMT-related proteins, a Moffitt basal-like subtype transcriptome, and higher 5-FU resistance in contrast to organoids established under normoxia. We suggest that hypoxia during organoid establishment efficiently selects for hypoxia-adapted cells possibly responsible for PDAC malignant traits, facilitating a fundamental source for elucidating and developing new treatment strategies against PDAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kumano, Nakahashi, Louphrasitthiphol, Kuroda, Miyazaki, Shimomura, Hashimoto, Akashi, Mathis, Kim, Owada, Goding and Oda.)

In our previous study, riluzole azo-linked to salicylic acid (RAS) was prepared as a colon-targeted prodrug of riluzole (RLZ) to facilitate the repositioning of RLZ as an anticolitic drug. RAS is more effective against rat colitis than RLZ and sulfasalazine, currently used as an anti-inflammatory bowel disease drug. The aim of this study is to further improve colon specificity, anticolitic potency, and safety of RAS. N-succinylaspart-1-ylRLZ (SAR) and N-succinylglutam-1-ylRLZ (SGR) were synthesized and evaluated as a "me-better" colon-targeted prodrug of RLZ against rat colitis. SAR but not SGR was converted to RLZ in the cecal contents, whereas both conjugates remained intact in the small intestine. When comparing the colon specificity of SAR with that of RAS, the distribution coefficient and cell permeability of SAR were lower than those of RAS. In parallel, oral SAR delivered a greater amount of RLZ to the cecum of rats than oral RAS. In a DNBS-induced rat model of colitis, oral SAR mitigated colonic damage and inflammation and was more potent than oral RAS. Moreover, upon oral administration, SAR had a greater ability to limit the systemic absorption of RLZ than RAS, indicating a reduced risk of systemic side effects of SAR. Taken together, SAR may be a "me-better" colon-targeted prodrug of RLZ to improve the safety and anticolitic potency of RAS, an azo-type colon-targeted prodrug of RLZ.

Background: Although the transmediastinal approach as a radical esophagectomy for esophageal carcinoma patients has attracted attention, its advantages over the transthoracic approach remain unclear. This study aimed to evaluate the efficacy of transmediastinal esophagectomy (TME) in terms of postoperative respiratory complications compared to that of open transthoracic esophagectomy (TTE)., Methods: We reviewed patients with thoracic and abdominal esophageal carcinoma who underwent TME or TTE between February 2014 and November 2021. We compared postoperative respiratory complications as the primary outcome. The secondary outcomes included perioperative operation time, blood loss, postoperative complications, and the number of harvested mediastinal lymph nodes., Results: Overall, 60 and 54 patients underwent TME and TTE, respectively. The baseline characteristics were similar between the two groups, except for age and histological type. There were no intraoperative lethal complications in either group. The incidence of respiratory complications was significantly lower in the TME group than in the TTE group (6.7 vs. 22.2%, p = 0.03). The TME group had a shorter operation time (403 vs. 451 min, p < 0.01), less blood loss (107 vs. 253 mL, p < 0.01), and slightly higher anastomotic leakage (11.7 vs. 5.6%, p = 0.33). The number of harvested lymph nodes was similar in both groups (24 vs. 26, p = 0.10). Multivariate analysis revealed that TME is an independent factor in reducing respiratory complications (odds ratio = 0.27, p = 0.04)., Conclusions: TME for esophageal carcinoma was performed safely. TME was superior to TTE in terms of postoperative respiratory complications; however, the relatively higher frequency of anastomotic leakage should be considered and requires further evaluation., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

As our previous study revealed that N -benzyl- N -methyldecan-1-amine (BMDA), a new molecule originated from Allium sativum , exhibits anti-neoplastic activities, we herein explored other functions of the compound and its derivative [decyl-(4-methoxy-benzyl)-methyl-amine; DMMA] including anti-inflammatory and anti-oxidative activities. Pretreatment of THP-1 cells with BMDA or DMMA inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-1β production, and blocked c-jun terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), MAPKAP kinase (MK)2 and NF-κΒ inflammatory signaling during LPS stimulation. Rectal treatment with BMDA or DMMA reduced the severity of colitis in 2,4-dinitrobenzenesulfonic acid (DNBS)-treated rat. Consistently, administration of the compounds decreased myeloperoxidase ( MPO) activity (representing neutrophil infiltration in colonic mucosa), production of inflammatory mediators such as cytokine-induced neutrophil chemoattractant (CINC)-3 and TNF-α, and activation of JNK and p38 MAPK in the colon tissues. In addition, oral administration of these compounds ameliorated collagen-induced rheumatoid arthritis (RA) in mice. The treatment diminished the levels of inflammatory cytokine transcripts, and protected connective tissues through the expression of anti-oxidation proteins such as nuclear factor erythroid-related factor (Nrf)2 and heme oxygenase (HO)1. Additionally, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels did not differ between the BMDA- or DMMA-treated and control animals, indicating that the compounds do not possess liver toxicity. Taken together, these findings propose that BMDA and DMMA could be used as new drugs for curing inflammatory bowel disease (IBD) and RA., Competing Interests: Author I-RC was employed by Hayoung Meditech Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Kang, Budluang, Yawut, Cho, Choi, Kim, Ju, Lee, Sohn, Yim, Lee, Han, Jung, Kang, Park, Jung, Hwang and Chung.)

Background: Chloroquine (CQ) is an effective and safe antimalarial drug that is also used as a disease-modifying antirheumatic drug. Recent studies have shown that CQ can sensitize cancer cells to anti-cancer therapies., Methods: In this study, we investigated the molecular mechanisms underlying CQ-mediated chemosensitization in human colon carcinoma cells., Results: CQ prevented hypoxia-inducible factor (HIF)-1α protein induction in human colon carcinoma cells. CQ also suppressed HIF-1 activity, as represented by CQ inhibition of HIF-1-dependent luciferase activity and reduced induction of vascular endothelial growth factor. Under hypoxia, CQ restricted HIF-1α synthesis but did not affect HIF-1α transcription and protein stability. The hypoxic state activated ataxia telangiectasia and Rad3-related (ATR) kinase and increased the level of phosphorylated checkpoint kinase 1, a substrate of ATR kinase; however, this was prevented by CQ. An ATR kinase inhibitor suppressed the hypoxic induction of HIF-1α protein and was as effective as CQ. The cytotoxicity of 5-fluorouracil (5-FU), the first choice for the treatment of colorectal cancer, was attenuated under hypoxia. CQ enhanced the cytotoxicity of 5-FU treatment, which was mimicked by the transient transfection with HIF-1α siRNA., Conclusions: Under hypoxia, CQ-mediated sensitization of colon carcinoma HCT116 cells to 5-FU involves HIF-1 inhibition via ATR kinase suppression., (© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

N-Acetylserotonin (NAS) is an intermediate in the melatonin biosynthetic pathway. We investigated the anti-inflammatory activity of NAS by focusing on its chemical feature oxidizable to an electrophile. NAS was readily oxidized by reaction with HOCl, an oxidant produced in the inflammatory state. HOCl-reacted NAS (Oxi-NAS), but not NAS, activated the anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway in cells. Chromatographic and mass analyses demonstrated that Oxi-NAS was the iminoquinone form of NAS and could react with N-acetylcysteine possessing a nucleophilic thiol to form a covalent adduct. Oxi-NAS bound to Kelch-like ECH-associated protein 1, resulting in Nrf2 dissociation. Moreover, rectally administered NAS increased the levels of nuclear Nrf2 and HO-1 proteins in the inflamed colon of rats. Simultaneously, NAS was converted to Oxi-NAS in the inflamed colon. Rectal NAS mitigated colonic damage and inflammation. The anticolitic effects were significantly compromised by the coadministration of an HO-1 inhibitor., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We designed colon-targeted trans-cinnamic acid (tCA) and synthesized its conjugates with glutamic acid (tCA-GA) and aspartic acid (tCA-AA). We evaluated the anti-colitic activity of colon-targeted tCA using a dinitrobenzenesulfonic acid-induced rat colitis model. The conjugates lowered the distribution coefficient and Caco-2 cell permeability of tCA and converted to tCA in the cecum, with higher rates and percentages with tCA-GA than with tCA-AA. Following oral gavage, tCA-GA delivered a higher amount of tCA to the cecum and exhibited better anti-colitic effects than tCA and sulfasalazine (SSZ), which is the current treatment for inflammatory bowel disease. In the cellular assay, tCA acted as a full agonist of GPR109A (EC50: 530 µM). The anti-colitic effects of tCA-GA were significantly compromised by the co-administration of the GPR109A antagonist, mepenzolate. Collectively, colon-targeted tCA potentiated the anti-colitic activity of tCA by effectively activating GPR109A in the inflamed colon, enabling tCA to elicit therapeutic superiority over SSZ.

Background: The treatment of duplicated thoracic ducts (TDs) injury after esophagectomy generally requires a bilateral transthoracic approach. We present the cases of two patients with postoperative chylothorax who underwent transhiatal bilateral TD ligation for duplicated TDs., Case Presentation: Two patients diagnosed with chylothorax after esophagectomy performed for thoracic esophageal cancer underwent transhiatal TD ligation. Although supradiaphragmatic mass ligation was performed on the fat tissue of the right side of the aorta containing the TD, chyle leakage persisted. To tackle this, the fat tissue of the left side of the aorta was ligated, after which the chyle leakage stopped., Conclusion: Compared to the conventional transthoracic approach, the transhiatal approach enables the ligation of both left- and right-sided TD in a single surgical operation, without the need to change the patient's posture. This approach may be appropriate for the treatment of chylothorax after esophagectomy, considering the possibility of duplicated TDs., (© 2022. The Author(s).)

Riluzole (RLZ) is a neuroprotective drug indicated for amyotrophic lateral sclerosis. To examine the feasibility of RLZ for repositioning as an anti-inflammatory bowel disease (IBD) drug, RLZ (2, 5, and 10 mg/kg) was administered orally to rats with colitis induced by 2,4-dinitrobenzenesulfonic acid. Oral RLZ was effective against rat colitis in a dose-dependent manner, which was statistically significant at doses over 5 mg/kg. To address safety issues upon repositioning and further improve anti-colitic effectiveness, RLZ was coupled with salicylic acid (SA) via an azo-bond to yield RLZ-azo-SA (RAS) for the targeted colonic delivery of RLZ. Upon oral gavage, RAS (oral RAS) was efficiently delivered to and activated to RLZ in the large intestine, and systemic absorption of RLZ was substantially reduced. Oral RAS ameliorated colonic damage and inflammation in rat colitis and was more effective than oral RLZ and sulfasalazine, a current anti-IBD drug. Moreover, oral RAS potently inhibited glycogen synthase kinase 3β (GSK3β) in the inflamed distal colon, leading to the suppression of NFκB activity and an increase in the level of the anti-inflammatory cytokine interleukin-10. Taken together, RAS, which enables RLZ to be delivered to and inhibit GSK3β in the inflamed colon, may facilitate repositioning of RLZ as an anti-IBD drug.

Purpose: General surgeons are at high risk for work-related musculoskeletal disorders (WRMSDs), especially in their neck and back. The prevalence and risk factors for surgeons' WRMSDs in Japan have not been well surveyed., Methods: A cross-sectional questionnaire survey on WRMSDs was conducted among general surgeons in Japan. Surgeons were asked about the presence and degree of neck, shoulder, and back disability in relation to open and laparoscopic surgery., Results: The questionnaire was sent to 174 general surgeons in 21 hospitals and 106 (60.9%) responded. The prevalence of WRMSDs in the last month was 65.1%, and the prevalence at least once in a lifetime was 79.2%. The rate of WRMSDs of the neck and back was higher after open surgery (44.3%, 42.5%) than after laparoscopic surgery (28.2%, 31.1%), but there was no marked difference in shoulder pain. Age was the strongest risk factor for WRMSDs, and the pain scores, prevalence of chronic pain, and rate of WRMSD-related absence from work tended to increase with age., Conclusion: A questionnaire survey of surgeons in Japan showed that about 80% of surgeons suffer from WRMSDs. Countermeasures for WRMSDs among surgeons are urgently desired to ensure that limited numbers of surgeons work in the operating theatre throughout their career., Clinical Trial Registration: Registry name: a survey of surgeons' musculoskeletal pain associated with performing surgery. University of Tsukuba Institutional Review Board registration number: 1519., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Mediastinoscope and laparoscope-assisted esophagectomy for esophageal cancer occasionally causes postoperative accumulation of pleural effusion despite the preservation of the mediastinal pleura. Transhiatal chest drainage has been reported to be useful for thoracic esophagectomy; however, its use in mediastinoscope and laparoscope-assisted esophagectomy remains unelucidated. This study aimed to evaluate the effectiveness and safety of transhiatal chest drainage in mediastinoscope and laparoscope-assisted esophagectomy., Methods: This retrospective study included patients who underwent mediastinoscope and laparoscope-assisted esophagectomy for esophageal cancer from 2018 to 2021. Transhiatal chest drainage involved the insertion of a 19-Fr Blake® drain from the abdomen to the left thoracic cavity through the hiatus. We assessed its effectiveness and safety by the daily drainage output, accumulation of postoperative pleural effusion, frequency of postoperative thoracentesis, and other complications. The drainage group comprising 24 patients was compared with the non-drainage group comprising 13 patients, in whom a transhiatal chest drainage tube was not placed during mediastinoscope and laparoscope-assisted esophagectomy., Results: The median daily output of the transhiatal chest drainage was 230 mL on day 1, 385 mL on day 2, and 313 mL on day 3. The number of patients with postoperative pleural effusion was significantly reduced from 10/13 (76.9%) in the non-drainage group to 4/24 (16.7%) in the drainage group (p = 0.001). The frequency of thoracentesis in the drainage group was significantly lower than that in the non-drainage group (p = 0.002). There were no significant differences in the occurrence of other postoperative complications., Conclusions: Transhiatal chest drainage could evacuate pleural effusion effectively and safely after mediastinoscope and laparoscope-assisted esophagectomy., (© 2022. The Author(s).)

Background: Pancreatic fistula remains the biggest problem in pancreatic surgery. We have previously reported a new pancreatojejunostomy method using an inter-anastomosis drainage (IAD) suction tube with Blumgart anastomosis for drainage of the pancreatic juice leaking from the branched pancreatic ducts. This study aimed to evaluate the postoperative outcomes of our novel method, in pancreatojejunostomy and investigate the nature of the inter-anastomosis space between jejunal wall and pancreas parenchyma., Methods: This retrospectively study consist of 282 pancreatoduodenectomy cases, including 86 reconstructions via the Blumgart method plus IAD (B + IAD group) and 196 cases reconstructed using the Blumgart method alone (B group). Postoperative outcomes and the amylase value and the volume of the drainage fluids were compared between the two groups. The IAD tube was placed to collect amylase-rich fluid from the inter-anastomosis space during operative procedure between the jejunal wall and pancreatic stump., Results: The daily IAD drainage volume and the amylase level was significantly higher in patients with a soft pancreas (vs hard pancreas; 16.5 vs. 10.0 mL/day, p = 0.012; 90,900 vs. 1634 IU/L, p < 0.001, respectively). The mean amylase value of IAD collection in 86 cases of B + IAD group was 63,100 IU/L. The incidence of clinically relevant pancreatic fistula grade B and C (23.2% vs. 23.0%, p = 0.55) and the hospital stay was similar between the groups (median 17 vs. 18 days, p = 0.55). In 176 patients with soft pancreas, the incidence of pancreatic fistula grade B and C (33.3% vs. 35.3%, p = 0.67) and the hospital stay was also similar between the groups (median 22.5 vs. 21 days, p = 0.81)., Conclusions: Positive effect of the IAD method observed in the pilot cases was not reproduced in the current study. IAD tube objectively demonstrated the existence of amylase-rich discharge at the anastomosis site, and countermeasures to eliminate this liquid are highly desired for preventing pancreatic fistula, especially in patients with soft pancreatic texture. Trial registration Retrospectively registered., (© 2022. The Author(s).)

This paper reports the 5-year operational status of the third phase of the"All Japan E-Learning Cloud of the Training Program for Oncology Professionals"by tabulating the viewing trends of available lecture contents. In this phase, the goal was to train cancer genome medical professionals in this new, advanced medical technology field as well as train personnel to treat rarely encountered pediatric, adolescent/young adult, and other life stage cancers. Additionally, new lecture items have been added to the e-learning cloud in collaboration with 7 oncology specialist centers, contributing to the development of human capital in cancer care(including graduate student education)and faculty development for local medical professionals.

Dapsone (DpS) is an antimicrobial and antiprotozoal agent, especially used to treat leprosy. The drug shares a similar mode of action with sulfonamides. Additionally, it possesses anti-inflammatory activity, useful for treating autoimmune diseases. Here, we developed a "me-better" alternative to sulfasalazine (SSZ), a colon-specific prodrug of mesalazine (5-ASA) used as an anti-inflammatory bowel diseases drug; DpS azo-linked with two molecules of 5-ASA (AS-DpS-AS) was designed and synthesized, and its colon specificity and anti-colitic activity were evaluated. AS-DpS-AS was converted to DpS and the two molecules of 5-ASA (up to approximately 87% conversion) within 24 h after incubation in the cecal contents. Compared to SSZ, AS-DpS-AS showed greater efficiency in colonic drug delivery following oral gavage. Simultaneously, AS-DpS-AS substantially limited the systemic absorption of DpS. In a dinitrobenzene sulfonic acid-induced rat colitis model, oral AS-DpS-AS elicited better efficacy against rat colitis than oral SSZ. Moreover, intracolonic treatment with DpS and/or 5-ASA clearly showed that combined treatment with DpS and 5-ASA was more effective against rat colitis than the single treatment with either DpS or 5-ASA. These results suggest that AS-DpS-AS may be a "me-better" drug of SSZ with higher therapeutic efficacy, owing to the combined anti-colitic effects of 5-ASA and DpS.

Background: Posthepatectomy liver failure (PHLF) is a main cause of death after partial hepatectomy. The aim of this study was to develop a practical stratification system using the albumin-bilirubin (ALBI) score and liver resection percentage to predict severe PHLF and conduct safe hepatectomy., Methods: Between January 2002 and March 2021, 361 hepatocellular carcinoma (HCC) patients who underwent partial hepatectomy were enrolled. Medical image analysis software was applied postoperatively to accurately simulate hepatectomy. The liver resection percentage was calculated as follows: (postoperatively reconstructed resected specimen volume [ml] - tumor volume [ml])/total functional liver volume (ml) × 100. Multivariate analysis was performed to identify risk factors for PHLF grade B/C. A heatmap for predicting grade B/C PHLF was generated by combining the ALBI score and liver resection percentage., Results: Thirty-nine patients developed grade B/C PHLF; 2 of these patients (5.1%) died. Multivariate analysis demonstrated that a high ALBI score and high liver resection percentage were independent predictors of severe PHLF (odds ratio [OR], 8.68, p < 0.001; OR, 1.10, p < 0.001). With a threshold PHLF probability of 50% for the heatmap, hepatectomy was performed for 346 patients meeting our criteria (95.8%) and 325 patients meeting the Makuuchi criteria (90.0%). The positive predictive value and negative predictive value for severe PHLF were 91.6% and 66.7% for our system and 91.7% and 33.3% for the Makuuchi criteria., Conclusion: Our stratification system could increase the number of hepatectomy candidates and is practical for deciding the surgical indications and determining the upper limit of the liver resection percentage corresponding to each patient's liver function reserve, which could prevent PHLF and yield better postoperative outcomes., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Early allograft dysfunction (EAD) is a criterion to evaluate initial graft dysfunction associated with inferior graft survival and postoperative complications after liver transplantation (LT). This study defined the lactate-to-platelet ratio (LPR) as lactate level immediately post-LT/platelet count on postoperative day 1 and evaluated its association with EAD and short-term graft failure., Materials and Methods: This study reviewed 434 deceased-donor LTs from individuals with confirmed brain death between January 2008 and December 2014. The area under the curve (AUC) was used to compare the predictive capacity for 3-month graft survival between EAD and the LPR. Along with LPR, the risk factors for 3-month graft failure were analyzed by multivariate analysis., Results: EAD was reported in 127 patients (31%). The LPR in patients with EAD was significantly higher than that in patients without EAD (9.8 vs 5.9, P < .001). In the multivariate analysis, both the LPR (per 1.0 increase) and EAD were independent risk factors for 3-month graft failure (hazard ratio [HR] =1.03, P = .03; and HR = 9.14, P = .001). The comparison of the AUCs between the LPR and EAD showed no significant difference (0.79 vs 0.78, P = .84), whereas the combination of EAD and LPR had a better predictive capacity than EAD alone (0.86 vs 0.78, P < .001). The LPR showed an inverse relationship for predicting 3-month graft survival., Conclusions: The LPR is a continuous parameter that enables prediction of initial graft function and estimation of the 3-month graft failure rate with the advantages of early availability and simple calculations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: An open abdomen with frozen adherent bowels is classified as grade 4 in Björck's open abdomen classification, and skin grafting after wound granulation is a typical closure option. We achieved delayed primary fascia closure for a patient who developed open abdomen with enteroatmospheric fistulas due to severe adherent small bowel obstruction. We present here the details of his management., Case Presentation: A 52-year-old man suffered acute abdominal pain during a flight and received an emergency laparotomy due to adhesive small bowel obstruction. Repeated laparotomies were required, and later open abdomen and proximal site jejunostomy were selected. After negative pressure wound therapy, he was transferred to our institution. Two enteroatmospheric fistulas emerged on the exposed intestine, and we diagnosed the condition as a Björck grade 4 open abdomen. After 8 months of wound care and parenteral nutrition, we decided to attempt primary wound closure because the patient required permanent oral restriction and total parenteral nutrition due to short bowel syndrome. A circular incision along the circumference of the exposed bowel allowed us to take a safe approach into the abdominal cavity. We removed the intestinal adhesions completely and resected the bowels, including the fistulas and anastomosed parts. Finally, the abdominal wall defect was reconstructed using the component separation technique, and the patient was discharged without an ostomy., Conclusions: Primary fascia closure for grade 4 open abdomen is hard, but leaving a long interval before radical surgery and applying pertinent wound management may help solve this adverse situation., (© 2021. The Author(s).)

Introduction: Obstetric severe perineal laceration can frequently occur as a surgical site infection (SSI), which sometimes leads to rectovaginal fistula after repair. We encountered a rare case of a rectoperineal fistula 5 months after repair of a severe perineal laceration. Case presentation: The patient was a 39-year-old woman who underwent repair of a fourth-degree perineal laceration after vaginal delivery. Five months after primary repair, she presented with perineal swelling and pain followed by uncontrollable flatulence or passage of feces at the perineum, which was finally diagnosed as a rectoperineal fistula. Transperineal repair with fistulous tract excision was performed for the rectoperineal fistula. Closure of the rectum, perineal body, and vagina was performed layer-by-layer constructing a thick perineum to prevent anal dysfunction. The fistula was successfully closed, and the patient did not show any symptoms of fecal incontinence 6 months after surgery. Discussion: As the rectoperineal fistula might have resulted in SSI at the primary repair of the obstetric injury, the delayed occurrence of the rectoperineal fistula was unusual. A perineal approach should be performed for complete fistulous tract excision, reconstruction of a robust perineal structure, and preservation of anal sphincter function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ohara, Enomoto, Owada, Hisakura, Akashi, Ogawa, Doi, Takahashi, Shimomura, Furuya, Kim, Hashimoto, Ohara, Obata-Yasuoka, Hamada and Oda.)

Background: Persistent pancreatic leakage (PL) due to disconnected pancreatic duct syndrome (DPDS) is associated with severe morbidity and mortality and it usually treated with internal drainage. However, in cases without localized fistula formation, internal drainage is challenging to perform. We report an original one-stage surgical approach for nonlocalized persistent PL, namely, the "intentional internal drainage tube method"., Case Presentation: A 49-year-old woman whose main pancreatic duct was penetrated during endoscopic retrograde cholangiopancreatography experienced severe PL. Peritoneal lavage and a second operation involving central pancreatectomy failed to relieve the symptoms, and nonlocalized PL persisted due to DPDS. Although we attempted a radical resection of the pancreatic remnants as a third strategy, the highly inflamed tissue and massive bleeding prevented the completion of the procedure. We sutured the pancreatic head margin and performed a pancreaticojejunostomy to the distal margin. Because these two cut margins could possibly be the source of the persistent PL, we created a hole at the Roux-en-Y jejunal limb, and a silicone drainage tube was inserted into the peritoneal space via this hole. Postoperatively, we continuously suctioned the intentional internal drainage tube, and the residual PL cavity gradually diminished. Even after removal of the tube, the residual PL drained internally into the jejunum through this hole., Conclusions: We present this intentional internal drainage tube method as a novel alternative approach for the management of nonlocalized PL consequential of DPDS. Due to the simplicity and minimally invasive nature of this method, we propose this technique may also be used to treat various types of nonlocalized persistent PL or be used prophylactically for central pancreatectomy.

Background: Hepatocellular carcinoma (HCC) accompanied by portal vein tumour thrombus (PVTT) presents an aggressive disease course, worsening liver function reserve, and a high recurrence rate. Clinical practice guidelines recommend systemic therapy as the first-line option for HCC with portal invasion. However, to achieve longer survival in these patients, the treatment strategy should be concluded with removal of the tumour by locoregional therapy. We experienced a case of initially unresectable HCC with main PVTT converted to radical hepatectomy after lenvatinib treatment., Case Summary: A 59-year-old male with chronic hepatitis C infection visited our clinic as a regular post-surgery follow-up. Contrast-enhanced abdominal computed tomography revealed a liver mass diffusely located at the lateral segment with a massive PVTT extending from the umbilical portion to the main and contralateral third-order portal branches. With the diagnosis of unresectable HCC with Vp4 (main trunk/contralateral branch) PVTT, lenvatinib was started at 12 mg/d. The computed tomography taken 3 mo after starting lenvatinib showed regression of the PVTT, which had retreated to the contralateral first-order portal branch. He tolerated the full dose without major adverse effects. With cessation of lenvatinib for 7 d, radical left lobectomy and PVTT thrombectomy were conducted. The patient's postoperative course was uneventful. Microscopically, the primary lesion showed fibrotic changes, with moderately to poorly differentiated tumour cells surrounded by granulation tissues in some areas. The majority of the PVTT showed necrosis. He was alive without recurrence for 8 mo., Conclusion: This is the first case of HCC with Vp4 PVTT in which radical conversion hepatectomy was succeeded after lenvatinib treatment., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: To develop a novel 3-dimensional (3D) virtual hepatectomy simulation software, Liversim, to visualize the real-time deformation of the liver., Methods: We developed a novel real-time virtual hepatectomy simulation software program called Liversim. The software provides 4 basic functions: viewing 3D models from arbitrary directions, changing the colors and opacities of the models, deforming the models based on user interaction, and incising the liver parenchyma and intrahepatic vessels based on user operations. From April 2010 through 2013, 99 patients underwent virtual hepatectomies that used the conventional software program SYNAPSE VINCENT preoperatively. Between April 2012 and October 2013, 11 patients received virtual hepatectomies using the novel software program Liversim; these hepatectomies were performed both preoperatively and at the same that the actual hepatectomy was performed in an operating room. The perioperative outcomes were analyzed between the patients for whom SYNAPSE VINCENT was used and those for whom Liversim was used. Furthermore, medical students and surgical residents were asked to complete questionnaires regarding the new software., Results: There were no obvious discrepancies (i.e., the emergence of branches in the portal vein or hepatic vein or the depth and direction of the resection line) between our simulation and the actual surgery during the resection process. The median operating time was 304 min (range, 110 to 846) in the VINCENT group and 397 min (range, 232 to 497) in the Liversim group (P = 0.30). The median amount of intraoperative bleeding was 510 mL (range, 18 to 5120) in the VINCENT group and 470 mL (range, 130 to 1600) in the Liversim group (P = 0.44). The median postoperative stay was 12 d (range, 6 to 100) in the VINCENT group and 13 d (range, 9 to 21) in the Liversim group (P = 0.36). There were no significant differences in the preoperative outcomes between the two groups. Liversim was not found to be clinically inferior to SYNAPSE VINCENT. Both students and surgical residents reported that the Liversim image was almost the same as the actual hepatectomy., Conclusion: Virtual hepatectomy with real-time deformation of the liver using Liversim is useful for the safe performance of hepatectomies and for surgical education.