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Purpose We delineated the learning phases of robot-assisted laparoscopic surgery for rectal cancer and compared the surgical and clinical outcomes between robot-assisted laparoscopic surgery and conventional laparoscopic surgery. Methods In total, 210 patients underwent rectal cancer surgery at Sendai Medical Center from 2015 to 2020. Conventional laparoscopic surgery was performed in 110 patients, while robot-assisted laparoscopic surgery was performed in 100 patients. The learning curve was evaluated using the cumulative summation method, risk-adjusted cumulative summation method, and logistic regression analysis. Results The risk-adjusted cumulative summation learning curve was divided into three phases: phase 1 (cases 1–48), phase 2 (cases 49–80), and phase 3 (cases 81–100). The length of hospital stay (13.1 days vs. 18.0 days, respectively; p = 0.016) and the surgical duration (209.1 minutes vs. 249.5 minutes, respectively; p = 0.045) were significantly shorter in the robot-assisted laparoscopic surgery group (phase 3) than in the conventional laparoscopic surgery group. The volume of blood loss was significantly lower in the robot-assisted laparoscopic surgery group (phase 1) than in the conventional laparoscopic surgery group (17.7 ml vs. 79.7 ml, respectively; p = 0.036). The International Prostate Symptom Score was significantly lower (indicating less severe symptoms) in the robot-assisted laparoscopic surgery group (p = 0.0131). Conclusions Robot-assisted laparoscopic surgery for rectal cancer was safe and demonstrated better surgical and clinical outcomes, including a shorter hospital stay, less blood loss, and a shorter surgical duration, than conventional laparoscopic surgery. Tactile familiarity can be acquired from visual information beyond 80 cases.

Background Bariatric surgery is effective for the treatment of patients with morbid obesity and type 2 diabetes mellitus (T2DM), for body weight loss and glycemic control. However, in Japan, there has been no previous report of the effectiveness bariatric surgery in a case of morbid obesity associated with acute onset type 1 diabetes mellitus (T1DM), in which pancreatic β-cells were destroyed and endogenous insulin was depleted. Case presentation A 36-year-old woman with morbid obesity and T1DM, diagnosed when she was 6 years, was admitted for bariatric surgery. At her first consultation, she had a body weight of 106.7 kg and a body mass index of 42.2 kg/m2. Her HbA1c level was 9.0%, with a required daily insulin dose of 75 units. She underwent laparoscopic sleeve gastrectomy. At 1 year after surgery, her body weight had decreased to 81.0 kg and her body mass index to 32.2 kg/m2. In addition, her daily required dose of insulin had decreased to 24 units, with an improvement in her HbA1c level to 7.7%. Conclusions Although further evidence needs to be accumulated, including long-term outcomes, laparoscopic sleeve gastrectomy may provide an effective treatment for patients with morbid obesity and T1DM for body weight loss, improvement in HbA1c level, and insulin dose reduction.

Background Transabdominal robotic surgery and transanal total mesorectal excision (TaTME) are newly introduced strategies for rectal cancer. These procedures might have many advantages in rectal cancer treatment in terms of improving oncological and functional outcomes, especially in cases involving advanced cancer or technical difficulty. In the present study, we aimed to clarify the advantages and disadvantages of transabdominal robotic surgery and laparoscopic TaTME as a hybrid surgery for rectal cancer. Materials and methods We retrospectively evaluated six patients who underwent hybrid surgery for rectal cancer from August 2018 to April 2020. Both clinical and pathological outcomes were assessed. Results Two patients showed circumferential margin involvement both before and after neoadjuvant therapy. Three patients were planned to undergo hybrid surgery with intersphincteric resection because of a narrow pelvis. One patient was planned to undergo hybrid surgery for a giant tumor of >10 cm. The median length of hospitalization was 17 days. No patients required conversion to an open procedure. All patients underwent formation of defunctioning ileostomies. Two patients had a stapled anastomosis and four had a hand-sewn coloanal anastomosis. Complications included one case of anastomotic leakage, which was managed conservatively with ultrasound- and computed tomography-guided drainage and antibiotics. Histological analysis revealed that all specimens had a negative radial margin and distal margin. The median number of lymph nodes harvested was 17.5. Two patients showed extensive lymph node metastases, including lateral node metastasis. Conclusion Hybrid surgery was performed safely and may improve oncological outcomes for rectal cancer. This technique has many potential benefits and would be alternative option in multimodal strategies for rectal cancer., Highlights • No studies to date have focused on treatment of locally advanced rectal cancer in men using intersphincteric resection hybrid technology involving transabdominal robotic surgery with conventional transanal total mesorectal excision. • We found that hybrid surgery is feasible and may improve the quality of total mesorectal excision and the rate of radical resection for advanced rectal cancer. • Hybrid surgery may improve urinary and sexual function. • This technique has many potential benefits and would be an alternative approach for rectal cancer.

Urinary incontinence is one of the common complications after radical prostatectomy along with inguinal hernia. Artificial urethral sphincter implantation is widely accepted as a treatment option. We report two surgical cases of inguinal hernia after artificial urethral sphincter implantation for urinary incontinence following radical prostatectomy. In Case 1, since the device went through the inguinal canal, adhesion around the pubis was extremely hard. In Case 2, the device was placed on the ventral side of the rectus abdominis muscle, so it was operable almost as normal. In each case, the surgical procedure was considered carefully after confirming the location of the device by preoperative computed tomography and ultrasonography. Hernia repair was successfully performed using the Lichtenstein method. There are few reports regarding surgical repair of inguinal hernia following artificial urinary sphincter implantation. Preoperative image and appropriate choice of approach could facilitate safe and secure surgery.

A 66-year-old man was admitted to our hospital because of multiple refractory skin ulcers. Based on his severe systemic arterial calcification and severe calcium-phosphate imbalance due to severe kidney dysfunction, we initially considered calciphylaxis. However, a skin biopsy provided a diagnosis of cholesterol crystal embolization. Although we initiated hemodialysis, steroid treatment, and low-density lipoprotein-cholesterol apheresis, he died of multiple intestinal perforation. An autopsy showed cholesterol crystals occluding multiple organ arterioles. This case suggests that skin ulcers in patients with chronic kidney disease may be an important diagnostic hallmark and may be associated with several serious diseases.

腹腔鏡下鼠径ヘルニア修復術の経腹腔的アプローチ（TAPP）は，前方アプローチのメッシュ手術より利点が多い．しかし，新たな手技習得が必要でラーニングカーブが長いため本邦では必ずしも普及していない．筆者らは，TAPPの手技的難点を軽減する目的に，経皮的に鼠径部腹膜前腔にロピバカインとエピネフリンの膨潤麻酔剤希釈液約150ml注入することを先行する膨潤TAPPを考案し22例を経験した．対象は，男21例，女性1例で平均年齢は58.2歳，24病変，間接ヘルニア19病変，直接ヘルニア5病変であった．手技的に，従来TAPPと比べて，腹膜前腔の膨化によって層確認が容易となり剥離しやすく，出血も少なく，比較的確実な手術が可能となった．合併症は，血腫，水腫各1例でいずれも軽微で，術後疼痛も少ないと考えられた．今後，さらなる症例集積と従来TAPPとの比較試験による検証が必要であるが，膨潤TAPPは従来TAPPを手技的，臨床的に改善すると推察された．

[Introduction] 5-fluorouracil (5-FU), a core anticancer agent used for various malignancies, induces gastrointestinal (GI) toxicities. The tegafur-based oral 5-FU prodrug S-1 is recognized to be a key drug for GI and other malignancies in Japan and some Asian countries. S-1 was developed to potentiate antitumor activity of 5-FU and to reduce gastrointestinal toxicities. However, S-1 also causes GI toxicities by the standard daily regimen. On the other hand, the alternate-day administration of S-1 has been proposed to minimize toxicities without reducing the anticancer efficacy of 5-FU. Recently, tumor immunology has greatly advanced, and the role of T cells in antitumor immunity has been well investigated. However, it remains unknown how GI toxicities of 5-FU affect T cell subsets related to antitumor immunity. [Purpose] The purpose of this study is to clarify the influence of 5-FU mediated GI toxicities on T cell subsets related to antitumor immunity. [Methods] Two regimens of S-1 were compared to evaluate the impact of GI toxicities of 5-FU on T cells using Balb/c mice. The first regimen consisted of the daily administration of S-1 (daily group) as a 5-FU GI toxicity model, and the second regimen consisted of the alternate-day administration of S-1 (alternate-day group) as a 5-FU non-GI toxicity model. S-1 was orally administered at a dose of 12 mg/kg as tegafur. We then investigated the degree of GI toxicities and T cell subsets in intra-abdominal lymphoid tissues (spleen, mesenteric lymph node and gut-associated lymphoid tissue). [Results] Only the daily group exhibited body weight loss and GI toxicities. Flow cytometric analyses demonstrated that the proportion of regulatory T cells in the intestinal tissue was 6-fold higher in the daily group than that in the control group, and the proportions of Th1 cells in the daily group showed a decreasing trend. However, the alternate-day group exhibited almost no changes in the proportions of T cell subsets. [Conclusions] GI toxicities of 5-FU increase the proportion of regulatory T cells in intestinal tissue and decrease the proportions of Th1 cells systemically, which suggests that GI toxicities of 5-FU have a negative influence on T cell-dependent antitumor immunity, and the alternate-day administration of S-1 has neither GI toxicities nor the influence on T cell subsets, which suggests that 5-FU regimens without GI toxicities are more useful than those with GI toxicities from the viewpoint of antitumor immunity. Citation Format: Taiki Kajiwara, Koh Miura, Shinobu Ohnuma, Tetsuhiko Shirasaka, Toshihiro Komura, Masahide Toshima, Atsushi Kohyama, Katsuyoshi Kudoh, Sho Haneda, Hiroaki Musha, Fuyuhiko Motoi, Yu Katayose, Takeshi Naitoh, Michiaki Unno. Gastrointestinal toxicities of 5-FU increase the proportion of regulatory T cells in murine intestinal tract: Advantages of alternate-day S-1 administration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 631. doi:10.1158/1538-7445.AM2014-631

[Background] A clinical trial of S-1 with leucovorin (S-1/LV) in metastatic colorectal cancer (CRC) patients demonstrated promising efficacy; however, the gastrointestinal toxicities were so severe that it has not been applied in the clinical setting. On the other hand, alternate-day administration of S-1 has been proposed to attenuate the adverse events without reducing its anticancer activity. The aim of this study was to confirm the feasibility of alternate-day administration of S-1/LV in in vivo xenograft tumor models. [Methods] Mice were treated with S-1/LV either in a daily group (two weeks of administration followed by two weeks of withdrawal) or an alternate-day group (administration on alternate days for four weeks), then the mice of both groups were sacrificed and the xenograft tumors were resected. To assess the adverse reactions, the body weight changes, the condition of feces, mucosal injury of small intestine and myelosuppression were compared between both groups. Furthermore, tumor volume, tumor growth inhibition (TGI) and the expression of Ki67, TUNEL, cIAP2 and XIAP were analyzed to evaluate the antitumor activity and tumor apoptosis. [Results] Severe weight loss, diarrhea, mucosal injury and myelosuppression were observed only in the daily group; however, no adverse reactions were observed in the alternate-day group, except slight myelosuppression. The TGI in the alternate-day group was better than that in the daily group, possibly resulting from apoptosis of tumor cells due to the suppression of cIAP2. [Conclusion] Our findings suggest that alternate-day administration of S-1/LV for CRC treatment can achieve higher antitumor activity without severe adverse reactions. Therefore, we propose that clinical trials with this regimen should be conducted in CRC patients. Citation Format: Toshihiro Komura, Shinobu Ohnuma, Koh Miura, Tetsuhiko Shirasaka, Taiki Kajiwara, Katsuyoshi Kudoh, Sho Haneda, Masahide Toshima, Atsushi Kohyama, Hiroaki Musha, Takeshi Naitoh, Yu Katayose, Michiaki Unno. Usefulness of alternate-day administration of S-1 and leucovorin in a xenograft mouse model of colorectal cancer: A shorter drug-free interval leads to more efficient antitumor effects. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 792. doi:10.1158/1538-7445.AM2014-792

Purpose The aim of this study was to investigate the association between 5-fluorouracil (5-FU)-related adverse events (AEs) in Japanese patients with gastrointestinal cancer treated with 5-FU and the patient genotypes DPYD, MTHFR, OPRT, and TYMS. Methods Sequence analyses of 33 gene polymorphisms in four genes were performed using genomic DNA extracted from peripheral blood mononuclear cells of 103 patients with gastric (n = 34) or colorectal (n = 69) cancer. The 5-FU-related AEs of 157 regimens in these 103 patients were evaluated based on the medical records of patients in each of three groups: the intravenous administration group (i.v. group, n = 51), oral administration group (p.o. group, n = 106), and all-regimens group (both i.v. and p.o. group, n = 157). The associations between the incidence of AEs and each genotype were statistically analyzed. Results Six single-nucleotide polymorphisms (SNPs) were identified (three SNPs in DPYD: c.496A>G, c.1905+1G>A, and c.2303C>A; two SNPs in MTHFR: c.677C>T and c.1298A>C; and one SNP in OPRT: c.638G>C). Among them, the patients in the all-regimens group carrying any one of three DPYD SNPs showed statistically significant associations with the incidence of AEs of any type and fatigue. Furthermore, the MTHFR SNP c.1298A>C was significantly associated with the incidence of neutropenia. A similar trend was observed in the p.o. group, but not in the i.v. group. Conclusion These findings suggest that the DPYD SNPs c.496A>G, c.1905+1G>A, and c.2303C>A and the MTHFR SNP c.1298A>C may be predictive factors for the occurrence of severe 5-FU-related AEs. Citation Format: Masahide Toshima, Shinobu Ohnuma, Michiiro Tanaka, Koh Miura, Wataru Fujibuchi, Taiki Kajiwara, Toshihiro Komura, Hiroaki Musha, Sho Haneda, Katsuyoshi Kudoh, Atsushi Kohyama, Takeshi Naitoh, Michiaki Unno. Single nucleotide polymorphisms of DPYD and MTHFR predict adverse events associated with 5-fluorouracil in patients with gastrointestinal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2832. doi:10.1158/1538-7445.AM2014-2832