Learning curve of robotic rectal surgery using risk-adjusted cumulative summation: a 5-year institutional experience.

PURPOSE: Outline learning phases of robot-assisted laparoscopic surgery for rectal cancer and compare surgical and clinical outcomes between each phase of robot-assisted laparoscopic surgery and the mastery phase of conventional laparoscopic surgery. METHODS: From 2015 to 2020, 210 patients underwent rectal cancer surgery at Sendai Medical Center. We performed conventional laparoscopic surgery in 110 patients and, laparoscopic surgery 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). Duration of hospital stay (13.1 days vs. 18.0 days, respectively; p = 0.016) and surgery (209.1 min vs. 249.5 min, respectively; p = 0.045) were significantly shorter in phase 3 of the robot-assisted laparoscopic surgery group than in the conventional laparoscopic surgery group. Blood loss volume was significantly lower in phase 1 of the robot-assisted laparoscopic surgery group 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 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. After experience with at least 80 cases, tactile familiarity can be acquired from visual information only (visual haptic feedback). CLINICAL TRIAL REGISTRATION: UMIN reference no. UMIN000019857.

Potential urinary function benefits of initial robotic surgery for rectal cancer in the introductory phase.

We aimed to evaluate the advantages and disadvantages of initial robotic surgery for rectal cancer in the introduction phase. This study retrospectively evaluated patients who underwent initial robotic surgery (n = 36) vs. patients who underwent conventional laparoscopic surgery (n = 95) for rectal cancer. We compared the clinical and pathological characteristics of patients using a propensity score analysis and clarified short-term outcomes, urinary function, and sexual function at the time of robotic surgery introduction. The mean surgical duration was longer in the robot-assisted laparoscopy group compared with the conventional laparoscopy group (288.4 vs. 245.2 min, respectively; p = 0.051). With lateral pelvic lymph node dissection, no significant difference was observed in surgical duration (508.0 min for robot-assisted laparoscopy vs. 480.4 min for conventional laparoscopy; p = 0.595). The length of postoperative hospital stay was significantly shorter in the robot-assisted laparoscopy group compared with the conventional laparoscopy group (15 days vs. 13.0 days, respectively; p = 0.026). Conversion to open surgery was not necessary in either group. The International Prostate Symptom Score was significantly lower in the robot-assisted laparoscopy group compared with the conventional laparoscopy group. Moderate-to-severe symptoms were more frequently observed in the conventional laparoscopy group compared with the robot-assisted laparoscopy group (p = 0.051). Robotic surgery is safe and could improve functional disorder after rectal cancer surgery in the introduction phase. This may depend on the surgeon's experience in performing robotic surgery and strictly confined criteria in Japan.

Laparoscopic Proctocolectomy With Transanal Total Mesorectal Excision for Ulcerative Colitis.

Transanal total mesorectal excision (TaTME) refers to endoscopic retrograde total mesorectal excision and is becoming increasingly popular worldwide. TaTME improves surgical manipulation and minimizes the risk of local recurrence of rectal cancer by ensuring circumferential resection margins. TaTME is mainly indicated for patients in whom transabdominal approaches are expected to be technically challenging. We extended the indications for TaTME to include surgery for ulcerative colitis lesions that might be cancerous in the rectum. Here, we report a case of proctocolectomy with TaTME for ulcerative colitis. A 38-year-old woman who was receiving treatment for ulcerative colitis underwent a biopsy for random samples from the transverse colon to the rectum. Histopathological findings revealed noninvasive dysplasia with p53 overexpression, suggestive of cancer. We extended the indication of TaTME to surgery for ulcerative colitis. We formed two surgical teams and performed laparoscopic proctocolectomy with TaTME simultaneously. This simultaneous operation reduced the duration of the procedures in the present case. The patient was discharged without any complications and underwent loop ileostomy closure four months postoperatively. The patient recovered without significant loss of the anal sphincter function and is doing well four months after the second surgery. We propose laparoscopic proctocolectomy with TaTME to be conducted simultaneously by two teams as a safe and effective technique that is associated with a shorter operation time than that reported previously. Additionally, TaTME was useful in confirming the appropriate dissection layer as well as in surgical manipulation. Hence, TaTME could serve as a useful therapeutic option for ulcerative colitis surgery.

Transanal total mesorectal excision and transabdominal robotic surgery for rectal cancer: A retrospective study.

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.

Efficacy of oral administration of cystine and theanine in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery: a multi-institutional, randomized, double-blinded, placebo-controlled, phase II trial (JORTC-CAM03).

PURPOSE: Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery. METHODS: A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (n = 52) or the placebo group (n = 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale. RESULTS: There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%, p = 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%, p = 0.185, 67.3% vs. 80.0%, p = 0.124, respectively). CONCLUSION: This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS. TRIAL REGISTRATION: UMIN000024784.

Transanal total mesorectal excision of giant villous tumor of the lower rectum with McKittrick-Wheelock syndrome: a case report of a novel surgical approach.

BACKGROUND: McKittrick-Wheelock syndrome (MKWS) is caused by a villous tumor of the rectosigmoid colon with hypersecretion of mucus containing electrolytes. Complete resection of the tumor is needed to cure this disease. Transanal total mesorectal excision (TaTME) is currently a promising treatment for lower rectal tumor because of the reliability of its resection margin especially in bulky tumor. We present this first case report of a TaTME for MKWS with a lower rectal tumor. CASE PRESENTATION: An 81-year-old woman was admitted to our hospital with diarrhea and acute renal failure. Computed tomography and magnetic resonance imaging examinations revealed an 80-mm-sized enhanced tumor located in her lower rectum without lymph node swelling and distant metastasis. A giant villous tumor secreting mucus was seen in the lower rectum to the anal canal during colonoscopy. The result of tumor biopsy was adenocarcinoma. To preserve the anal function and ensure distal margin, we chose TaTME for curative resection. After improving the electrolyte imbalance, TaTME was performed successfully and R0 resection was achieved. There was no sign of recurrence or electrolyte depletion for 1 year after the surgery. CONCLUSION: TaTME could be a promising surgical approach for giant villous tumor with MKWS in the lower rectum.

Bile acids repress E-cadherin through the induction of Snail and increase cancer invasiveness in human hepatobiliary carcinoma.

Although some kinds of bile acids have been implicated in colorectal cancer development, the mechanism of cancer progression remains unexplored in hepatobiliary cancer. From our personal results using complementary DNA microarray, we found that chenodeoxycholic acid (CDCA) induced Snail expression in human carcinoma cell lines derived from hepatocellular carcinoma and cholangiocarcinoma. Snail expression plays an important role in the regulation of E-cadherin and in the acquisition of invasive potential in many types of human cancers including hepatocellular carcinoma. We found that CDCA and lithocholic acid (LCA) induced Snail expression in a concentration-dependent manner and down-regulated E-cadherin expression in hepatocellular carcinoma and cholangiocarcinoma cell lines. Moreover, Snail short interference RNA (siRNA) treatment reduced the down-regulation of E-cadherin by CDCA or LCA. Luciferase analysis demonstrated that the promoter region from -111 to -24 relative to the transcriptional start site was necessary for this induction and, at least in part, nuclear factor Y (NF-Y) and stimulating protein 1 (Sp1) might be an inducer of Snail expression in response to bile acids. In addition, using an in vitro wound healing assay and invasion assay, we observed that CDCA and LCA induced cell migration and invasion. These results suggest that bile acids repress E-cadherin through the induction of transcription factor Snail and increase cancer invasiveness in human hepatocellular carcinoma and cholangiocarcinoma. Inhibition of this bile acid-stimulated pathway may prove useful as an adjuvant in the therapy of hepatocellular carcinoma.

Peroxisome proliferator-activated receptor alpha activates cyclooxygenase-2 gene transcription through bile acid transport in human colorectal cancer cell lines.

BACKGROUND: Evidence is accumulating that bile acids are involved in colon cancer development, but their molecular mechanisms remain unexplored. Bile acid has been reported to be associated with induction of the cyclooxygenase-2 (COX-2) gene. Because the human liver-specific organic anion transporter-2 (LST-2/OATP8/OATP1B3) is expressed in gastrointestinal cancers and might transport bile acids to the intracellular space, we studied the molecular mechanisms by which bile acids induce the transcription of COX-2, and the role of LST-2 in colonic cell lines. METHODS: Transcriptional activity of COX-2 was measured using a human COX-2 promoter-luciferase assay under various concentrations of bile acids. Electrophoresis mobility shift assays (EMSAs) for peroxisome proliferators-activated receptor (PPAR) alpha and cyclic AMP responsive element (CRE) were performed. RESULTS: The COX-2 promoter was induced by lithocholic acid (LCA), deoxycholic acid (DCA), and chenodeoxycholic acid (CDCA). Deletion and site-directed mutation analyses showed that CRE is the responsive element for LCA. An adenovirus expression system revealed that LST-2 is responsible for induction of COX-2. By EMSA using oligonucleotides of CRE, we observed formation of a specific protein-DNA complex, which was inhibited by a specific antibody against PPARalpha and CRE. A PPARalpha-specific agonist induced transcription of COX-2. CONCLUSION: These results indicate that COX-2 is transcriptionally activated by the addition of LCA, CDCA, and DCA and that LST-2 plays an important role by transporting bile acid to the intracellular space. Moreover, LCA-dependent COX-2 gene activation consists of a transcriptional complex including PPARalpha and CRE-binding protein. Thus, this induction of COX-2 may participate in carcinogenesis and progression of colorectal cancer cells.

Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.

BACKGROUND: We isolated the human liver-specific organic anion transporter gene, LST-2 (OATP8/SLCO1B3), which is exclusively expressed in the basolateral membrane of the hepatocytes. In this study, we analyzed the transcriptional regulation of the LST-2 gene in hepatocyte-derived cells and the effect of bile acid. METHODS: Transcriptional activity of the LST-2 gene was measured using a human LST-2 promoter-luciferase reporter plasmid under various concentrations of bile acids. Electrophoresis mobility shift assays of farnesoid X receptor (FXR), hepatocyte nuclear factor (HNF) 1alpha, and HNF3beta were performed. RESULTS: Luciferase analysis showed that the 5'-flanking region from -180 to -20 bp is responsible for LST-2 transcriptional activity. By site-directed mutation analysis, it was revealed that the consensus binding sites for FXR, HNF1alpha, and HNF3beta play important roles in the transcriptional activity of the LST-2 gene. By electrophoresis mobility shift assay, we observed specific protein-DNA complexes of FXR, HNF1alpha, and HNF-3beta. Luciferase activity was increased fivefold when chenodeoxycholate or deoxycholate were added. Northern blot analyses revealed that the expression of LST-2 was increased by addition of chenodeoxycholate or deoxycholate in a dose-dependent manner. CONCLUSIONS: This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta. HNF1alpha and HNF3beta might contribute to its liver-specific expression, and FXR might play a role in its transcriptional activation by bile acids.