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Objective: This study evaluated the clinical implications of sarcopenia for patients with rectal cancer according to cancer progression., Summary Background Data: The negative impact of body composition on long-term outcome has been demonstrated for various malignancies., Methods: We retrospectively reviewed 708 patients with rectal cancer who underwent curative resection at our institution between 2003 and 2020. Factors contributing to long-term outcomes and the incidence of secondary cancer (ISC) were analyzed. Psoas muscle mass index (PMI) was assessed using preoperative computed tomography. Sarcopenia was defined using the PMI cut-off values for Asian adults (6.36 cm 2 /m 2 for males and 3.92 cm2/m2 for females)., Results: Sarcopenia was identified in 306 patients (43.2%). Sarcopenia was associated with advanced age, low body mass index, smoking history, and advanced T-stage. Multivariate analysis showed sarcopenia was an independent poor prognostic factor for OS (HR 1.71; P = .0102) and cancer-specific survival (HR 1.64; P = .0490). Patients with sarcopenia had significantly higher mortality due to cancer-related death in stages III and IV, whereas non-rectal cancer-related death, including secondary cancer, was markedly increased in stage 0-II sarcopenic rectal patients. Five-year cumulative ISC in patients with and without sarcopenia was 11.8% and 5.9%, respectively. Multivariate analysis revealed that sarcopenia was an independent predictive factor for ISC (HR 2.05; P = .0063)., Conclusions: Sarcopenia helps predict survival outcomes and cause of death according to cancer stage for patients with middle/lower rectal cancer who underwent radical surgery. Furthermore, sarcopenia increased the development of secondary cancer in those patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Obstructive colitis (OC) is a risk factor of anastomotic leakage in colorectal cancer resection. We aimed to clarify the relationship between the severity of OC and clinicopathological findings and to detect predictive factors of OC., Methods: We retrospectively reviewed 43 cases of colectomy after self-expandable metallic stent placement for left-sided colorectal cancer. Preoperative diagnosis of OC was made by multiple modalities (initial computed tomography (CT), presurgical CT, and colonoscopy). We classified OC macroscopically in resected specimens into five groups (Grade 0: none, 1: mild [mild edema], 2: moderate [severe edema, redness, erosion], 3: severe [ulceration, bleeding], 4: very severe [necrosis, perforation]), and investigated the relationship between the preoperative assessment, surgical findings and the severity of OC., Results: OC of Grade 2 or more (53.5%) was significantly correlated with severe edema in initial CT. There was no significant correlation between OC and anastomosis rate. The creation of covering stoma was significantly higher in the Grade 2 or more OC group. No leakage was observed in either group., Conclusions: Initial CT may be most useful for prediction of OC. It is important to make a preoperative diagnosis of OC by combining multiple modalities, which enables to determine the appropriate location for resection, anastomosis, and construction of a covering stoma., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Analysis of long-term clinical outcomes of patients with familial adenomatous polyposis is critical in reducing or preventing the incidence of extracolonic malignancies after initial surgery. The aim of the present study was to clarify the long-term outcomes, and establish a surveillance strategy for surgically treated familial adenomatous polyposis patients., Methods: Between January 1967 and March 2020, retrospective data were collected from 37 patients with familial adenomatous polyposis treated or monitored in our department. Occurrence of metachronous cancers, including rectal cancers and extracolonic malignancies, and other diseases was analyzed., Results: The median follow-up duration after the first surgery was 13.8 years. Initially, 16 patients underwent total proctocolectomy with ileal pouch-anal anastomosis, 18 underwent total colectomy with ileorectal anastomosis, and three underwent other procedures. A secondary proctectomy was performed for 9 of the 18 patients who underwent ileorectal anastomosis. Rectal cancer was diagnosed in 6 patients who underwent ileorectal anastomosis. In addition, 5 gastric cancer, 2 duodenal cancer, 1 gallbladder cancer, and 1 thyroid cancer cases were diagnosed. The age at which the extracolonic malignancies were diagnosed was >50 years. 4 patients died due to metachronous rectal cancer, gastric cancer, or gallbladder cancer., Conclusion: Careful consideration should be paid before choosing ileorectal anastomosis as the treatment procedure for familial adenomatous polyposis patients because completion proctectomy was eventually necessary for half of the patients. Long-term surveillance, with more frequent gastric surveillance for patients over 50 years, is important for the prevention and treatment of extracolonic malignancies in familial adenomatous polyposis patients., Competing Interests: Declaration of competing interest The authors have no conflicts to disclose., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

We have previously demonstrated the unique properties of a new triazolopyrimidine derivative, NK026680, which exerts immunosuppressive effects in rat heart transplant model and confers tolerogeneic properties on ex vivo-conditioned dendritic cells in mice. We herein demonstrate that NK026680 promotes the expansion of regulatory T cells (Tregs) with potent immunoregulatory effects when used in combination with donor-specific transfusion (DST). BALB/c (H-2 d ) heart graft were transplanted into C57BL/6 (H-2 b ) mice following intravenous injection of donor splenocytes (DST) and oral administration of NK026680. The NK026680 plus DST treatment markedly prolonged the survival time of the donor-graft, but not that of the 3rd party-graft (C3H; H-2 k ). Treg cells in the recipient spleen on day 0 expanded when stimulated with donor-antigens in vivo and in vitro. After heart transplantation, Treg cells accumulated into the graft and increased in the spleen. NK026680 plus DST also decreased activated CD8 + T cells in the spleen and inhibited infiltration of CD8 + T cells into the graft. Depletion of CD25 + cells inhibited the graft prolonging effect of the NK026680 plus DST treatment. NK026680 administration together with DST induces potent immunoregulatory effects in an antigen-specific manner, likely due to the in vivo generation of donor-specific Tregs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In Uganda, artemether-lumefantrine was introduced as an artemisinin-based combination therapy (ACT) for malaria in 2006. We have previously reported a moderate decrease in ex vivo efficacy of lumefantrine in Northern Uganda, where we also detected ex vivo artemisinin-resistant Plasmodium falciparum. Therefore, it is necessary to search for candidate partner alternatives for ACT. Here, we investigated ex vivo susceptibility to four ACT partner drugs as well as quinine and chloroquine, in 321 cases between 2013 and 2018. Drug-resistant mutations in pfcrt and pfmdr1 were also determined. Ex vivo susceptibility to amodiaquine, quinine, and chloroquine was well preserved, whereas resistance to mefloquine was found in 45.8%. There were few cases of multi-drug resistance. Reduced sensitivity to mefloquine and lumefantrine was significantly associated with the pfcrt K76 wild-type allele, in contrast to the association between chloroquine resistance and the K76T allele. Pfmdr1 duplication was not detected in any of the cases. Amodiaquine, a widely used partner drug for ACT in African countries, may be the first promising alternative in case lumefantrine resistance emerges. Therapeutic use of mefloquine may not be recommended in this area. This study also emphasizes the need for sustained monitoring of antimalarial susceptibility in Northern Uganda to develop proper treatment strategies., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Desmoid tumors, which are often estrogen-dependent, frequently develop in surgical wounds. Here we report the case of 33-year-old woman with a 4-cm solid mass detected in her left adnexal area. She had previously undergone a laparoscopic surgery for endometriosis at age 29 years and had been using a combined oral contraceptive (COC) to prevent recurrence. The mass was diagnosed as a uterine myoma on the basis of ultrasonography and magnetic resonance imaging. Gonadotropin-releasing hormone agonist therapy for 3 months resulted in shrinkage of the tumor. Using a second laparoscopy, we identified a tumor originating from the sigmoid colon. The pathological diagnosis was desmoid tumor. Gynecologists should consider the possibility of desmoid tumor in patients who have been using COCs and undergone previous surgeries., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Colorectal surgery is associated with a high risk of perioperative venous thromboembolism (VTE), and this risk is especially high following colorectal cancer resection and surgery for inflammatory bowel disease. Previous analyses of large databases have reported the incidence of postoperative VTE in this population to be approximately 1.1%-2.5%. Therefore, to minimize this risk, patients should be offered appropriate prophylaxis, which may involve a combination of mechanical and pharmacologic prophylaxis with low-dose unfractionated heparin or low molecular weight heparin as recommended by several guidelines. Prior to initiation of treatment, appropriate risk stratification should be performed according to the patients' basic and disease-related as well as procedure-related risk factors, and post-operative factors. Furthermore, a risk-benefit calculation that takes into account patients' VTE and bleeding risk should be performed prior to starting pharmacologic prophylaxis and to help determine the duration of treatment., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Background: It is unclear whether neoadjuvant chemoradiation for lower rectal cancer causes a deterioration in urinary function. This study aimed to prospectively compare the postoperative urinary function of patients with lower rectal cancer treated by surgery after neoadjuvant chemoradiation with that of patients treated with surgery alone., Method: Urinary function was assessed before treatment and 1, 3, and 6 months after surgery by calculating the changes in the scores of the seven items of the International Prostatic Symptom Score (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) and Quality of life index., Results: Among 123 patients with lower rectal cancer treated with chemoradiotherapy plus surgery and surgery alone between 2014 and 2016, 29 eligible patients in the surgery after neoadjuvant chemoradiation group and 34 eligible patients in the surgery alone group were analyzed. The changes in each item score at 1, 3, and 6 months after surgery were similar between the two treatment groups. The scores of all items were already recovered at 6 months after surgery, except for weak stream and straining in the Surgery + chemoradiotherapy group and nocturia in the Surgery-alone group., Conclusion: Neoadjuvant chemoradiotherapy for lower rectal cancer did not affect postoperative urinary function., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Objective: This study aimed to assess the learning curve of robotic rectal surgery, a procedure that has gained increasing focus in recent years because it is expected that the advanced devices used in this approach provide advantages resulting in a shorter learning curve than that of laparoscopic surgery. However, no studies have assessed the learning curve of robotic rectal surgery, especially when lateral lymph node dissection is required., Design: This was a nonrandomized, retrospective study from a single institution., Setting: All consecutive patients who underwent robotic rectal or sigmoid colon surgery by a single surgeon between February 2012 and July 2016 in the University of Tokyo Hospital were enrolled. The learning curve for console time was assessed using a cumulative sum analysis and multiple linear regression analysis., Participants: A total of 131 consecutive patients underwent robotic rectal or sigmoid colon surgery performed by a single experienced surgeon. Of these, 41 patients received lateral lymph node dissection., Results: A cumulative sum plot for console time demonstrated that the learning period could be divided into 3 phases: Phase I, Cases 1 to 19; Phase II, Cases 20 to 78; and Phase III, Cases 79 to 131. Multiple linear regression analysis indicated that console time decreased significantly from one phase to another (Phase I-II, Δconsole time 83.0 minutes; Phase II-III, Δconsole time 40.1 minutes). Other factors affecting console time included body mass index, operative procedure, and lateral lymph node dissection, but not neoadjuvant therapy (such as chemoradiotherapy) or depth of invasion. Lateral lymph node dissection required an additional 138.4 minutes., Conclusions: Our findings suggest that the first phase of the learning curve consists of the first 19 cases, which seems sufficient to master the manipulation of robotic arms and to understand spatial relationships unique to the robotic procedure., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Lysophosphatidic acid (LysoPA) has been proposed to be involved in the pathogenesis of various cancers. Moreover, glycero-lysophospholipids (glycero-LysoPLs) other than LysoPA are now emerging as novel lipid mediators. Therefore, we aimed to elucidate the possible involvement of glycero-LysoPLs in the pathogenesis of gastric cancer by measuring glycero-LysoPLs, autotaxin (ATX), and phosphatidylserine-specific phospholipase A1 (PS-PLA 1 ) in ascites obtained from patients with gastric cancer and those with cirrhosis (as a control). We observed that after adjustments according to the albumin levels, the lysophosphatidylserine (LysoPS) and lysophosphatidylglycerol (LysoPG) levels were significantly higher, while the LysoPA and ATX levels were lower, in the ascites from patients with gastric cancer. We also found that multiple regression analyses revealed that ATX was selected as a significant explanatory factor for all the detectable LysoPA species only in the cirrhosis group and that a significant positive correlation was observed between LysoPS and PS-PLA 1 only in the gastric cancer group. In conclusion, the LysoPA levels might be determined largely by LysoPC and LysoPI (possible precursors) and the PS-PLA 1 -mediated pathway might be involved in the production of LysoPS in gastric cancer. Glycero-LysoPLs other than LysoPA might also be involved in the pathogenesis of cancer directly or through being converted into LysoPA., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Unpreventable allograft rejection is one of the main problems in pancreatic islet transplantation (PIT). Therefore, it is imperative to develop a more effective immunosuppressive strategy. The blockade of transcription factors has been a central part of T cell-depleting immunosuppressive therapies, as typified by the use of calcineurin inhibitors. The inhibition of activator protein-1 (AP-1) offers a novel strategy for immunosuppression in PIT, although to date, no reports on the effects of AP-1 inhibition are available. In this study, we investigated the immunosuppressive effects of T-5224, a c-Fos/AP-1-selective inhibitor, on murine T cells activated by αCD3+αCD28 mAbs. T-5224 inhibited proliferation, CD25 up-regulation, and the production of IL-2 and interferon-γ. In addition, T-5224 blocked the nuclear translocation of c-Fos/AP-1 in activated murine T cells. In BALB/c (H-2(d) )-to-C57BL/6J (H-2(b) ) mouse PIT, the 2-week administration of T-5224 prolonged survival of 600 islet allografts in a dose-dependent manner. When combined with a 2-week low-dose tacrolimus, the T-5224 treatment markedly prolonged allograft survival to over 300 days, while the efficacy was indeterminate when transplanted islet allograft mass was reduced to 300. We conclude that the c-Fos/AP-1 inhibition by T-5224 is a potentially attractive strategy for allogeneic PIT., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Massive malignant ascites originating from peritoneal metastasis of gastric cancer is difficult to control and resistant to chemotherapy. Cell-free and Concentrated Ascites Reinfusion Therapy (CART) is one of the types of apheresis therapy, by which filtered and concentrated ascites containing albumin and globulin is reinfused intravenously to patients. We retrospectively studied the feasibility of intraperitoneal (IP) chemotherapy combined with CART in gastric cancer patients with massive malignant ascites., Methods: Paclitaxel (PTX) was administered via an IP access port implanted in the subcutaneous space. If patient had massive ascites at the start of treatment, paracentesis was performed through a percutaneous IP catheter and then CART was performed. PTX was administered through the catheter until the ascites diminished., Results: A total of 127 CART procedures in 30 patients were analyzed. The average volume of processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g protein on average. Significant increases in urine volume, serum total protein and albumin level were found after the CART. Increase in body temperature (0.3°C), decrease in platelet count (3.8 × 10(4)/μl), and changes in blood pressure (2 mm Hg) were found after the CART procedure, but no clinically significant adverse event was experienced. The median survival time and 1-year survival of 30 patients who received IP chemotherapy combined with the CART procedure was 10.2 months and 43.3% respectively., Conclusions: IP chemotherapy combined with CART might be a promising strategy for patients with massive malignant ascites originating from peritoneal metastasis of gastric cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this study, we analyzed intraperitoneal cells recovered from human samples and found that CD90(+)CD45(-) cells exist as a minor population but vigorously grow in culture, showing the morphological features of mesothelial cells (MC). Interestingly, the MC highly expressed arginase I and markedly suppressed T cell proliferation with the reduction of CD3 ζ chain expression in T cells stimulated by coated anti-CD3 mAb. The addition of nor-NOHA (500 μM), or L-arginine (1 mM) mostly restored the inhibitory effect of MC on T cell proliferation as well as the reduced expression of CD3 ζ chain. The expression level of CD3 ζ chain in T cells in the peritoneal cavity was significantly down-regulated from circulating T cells. These results suggest that intraperitoneal free MC have immunomodulatory functions through the control of L-arginine level, and thus may play significant roles in the pathogenesis of various diseases in the peritoneal cavity., (Copyright © 2014 Elsevier Inc. All rights reserved.)