"Role-sharing surgery": a new surgical education system that gives beginner surgeons more chances to operate while ensuring the surgical quality of robotic surgery.

It has been pointed out that robotic surgery is more time-consuming than laparoscopic surgery, and a major challenge for the future is educating young surgeons while maintaining the surgical quality. To solve these problems, we report a role-sharing surgery (RSS) approach in which the surgery is divided into several areas and timetabled, with roles shared by several operators. We performed RSS for 19 standard colorectal cancer surgeries. The surgery was completed within + 28 min of the scheduled operation time, and a beginner robotic surgeon (BRS) was able to perform approximately 66% of the total surgery. There were no statistically significant differences in the short-term outcomes between the RSS and conventional surgery groups. Based on these findings, RSS has the potential to be the best practice for educating BRSs in robotic surgery, the use of which is expected to increase steadily in the future.

[A Case of Transverse Colon Cancer with Gastrointestinal Amyloidosis Prevented from Anastomotic Leakage by Multidimensional Approach].

The patient was a 68-year-old woman who was on hemodialysis due to systemic amyloidosis and nephrotic syndrome. Biopsy revealed amyloid deposition in the stomach, duodenum, and colon. A transverse colon tumor was found on a follow- up CT after the aortic dissection surgery. We performed lower gastrointestinal endoscopy and contrast-enhanced CT and diagnosed transverse colon cancer with gastric wall infiltration(cStage Ⅲc). We considered that transverse colon resection was oncologically sufficient. However, due to concurrent gastrointestinal amyloidosis, which increased the risk of anastomotic leakage we performed laparoscopic extended right hemicolectomy to avoid colon-colon anastomosis with partial gastrectomy. Additionally intraoperative indocyanine green(ICG)fluorescence imaging showed that the fluorescence signal in the small intestinal wall was satisfactory, while it was weak in the colon wall. As a result, we suspected of impaired blood flow of colon wall due to an amyloidosis, so we additionally created a loop ileostomy. It is said that gastrointestinal amyloidosis raises the risk of anastomotic leakage. A case of transverse colon cancer complicated by gastrointestinal amyloidosis in which we successfully prevented anastomotic leakage through a multidimensional evaluation and approach is reported, along with a literature review.

Exploratory analysis of lateral pelvic sentinel lymph node status for optimal management of laparoscopic lateral lymph node dissection in advanced lower rectal cancer without suspected lateral lymph node metastasis.

BACKGROUND: Total mesorectal excision (TME) and lateral lymph node dissection (LLND) without radiotherapy (RT) are standard treatment for lower cT3/4 rectal cancers in Eastern countries. In comparative studies, both TME + LLND and RT + TME yield good local control. Although Japanese guidelines recommend LLND for locally advanced rectal cancers below the peritoneal reflection, LLND dissection of clinically negative lateral pelvic lymph nodes (LPLN) is controversial, and laparoscopic TME + LLND is technically challenging and time-consuming. New optical instruments for laparoscopy allow easy perioperative sentinel lymph node (SLN) identification using ICG. The SLN concept may facilitate accurate diagnosis of LPLN involvement, and thus reduce LLND in laparoscopic rectal cancer surgery. Here we investigated lateral pelvic SLN navigation surgery for SLN detection during laparoscopic rectal cancer surgery. METHODS: This study included 21 patients with clinical StageII/III lower rectal cancer without LPLN enlargement, who underwent curative laparoscopic surgery. All patients underwent TME, followed by lateral SLN identification and biopsy using ICG, and then laparoscopic LLND. ICG fluorescence imaging was conducted using the laparoscopic near-infrared camera system. RESULTS: Lateral SLNs were successfully identified in 16 (76.2%) of the 21 patients. Among the 15 patients without SLN tumor metastasis, the dissected lateral non-SLNs were all negative. CONCLUSIONS: A lack of metastasis in the lateral pelvic SLN seems to reflect a lack of metastases to all lateral LNs. Our present results suggest that this laparoscopic ICG-guided SLN strategy may be a low-risk and time-saving method to prevent laparoscopic LLND in cases with negative lateral pelvic lymph nodes.

Prognostic Impact of Postoperative Complications following Salvage Esophagectomy for Esophageal Cancer after Definitive Chemoradiotherapy.

BACKGROUND: Recent studies have reported that the occurrence of postoperative complications after esophagectomy for esophageal cancer has a negative impact on long-term survival. Although salvage esophagectomy is associated with higher rates of morbidity and mortality, the impact of postoperative complications on long-term survival following salvage esophagectomy has not been fully investigated. METHODS: We retrospectively analyzed 73 patients with thoracic esophageal cancer who underwent salvage esophagectomy between January 1997 and December 2017 after definitive chemoradiotherapy. We investigated the clinical impact of postoperative complications on long-term survival after salvage esophagectomy. RESULTS: Postoperative complications, pulmonary complications, and anastomotic leakage occurred in 34 (47%), 14 (13%), and 14 (19%) of the patients, respectively. Patients with complications had significantly poorer survival than patients who did not have complications (HR [hazard ratio], 2.06; p = 0.017), but there were no significant differences in overall survival between patients with and those without pulmonary complications or anastomotic leakage (HR, 1.48, p = 0.318, and HR, 1.37, p = 0.377, respectively). Multivariate analysis revealed that pathological T3-4 disease (HR, 4.63; p = 0.001), residual disease (HR, 5.09; p = 0.001), and postoperative complications (HR, 3.85; p = 0.001) were significant independent prognostic factors. In particular, the frequency of death from other diseases among patients with postoperative complications was nonsignificantly higher than among patients without postoperative complications (26 vs. 10%; p = 0.071). CONCLUSION: The occurrence of complications leads to a poor prognosis for patients with esophageal cancer after salvage esophagectomy. Prevention of postoperative complications and long-term postoperative general supportive care might be important for improving patients' prognosis.

Clinical implications of the serum CA19-9 level in "biological borderline resectability" and "biological downstaging" in the setting of preoperative chemoradiation therapy for pancreatic cancer.

BACKGROUND: Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and "biological downstaging" in chemoradiation therapy (CRT) for pancreatic cancer (PC). METHODS: A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. "Biological downstaging" was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor). RESULTS: The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986). CONCLUSIONS: Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated "biological downstaging" in b-BR in the preoperative CRT strategy.

Decreased CT-number in the pancreatic parenchyma is a reliable imaging biomarker of the presence of malignancies in patients with high-risk intraductal papillary mucinous neoplasm.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a premalignant cystic neoplasm of the pancreas and is frequently detected in imaging investigations. A proportion of the patients with IPMN develop malignancies including high-grade dysplasia and invasive carcinoma. To predict the presence of malignancies in IPMN, constant imaging follow-up is usually required. Pancreatic steatosis (PS) has been recently identified as a facilitating factor for pancreatic cancer, and can be predicted through computed tomography (CT). We hypothesized that the CT-number of the pancreatic parenchyma could be a new reliable imaging biomarker for IPMN patients. METHODS: Eighty-six patients undergoing pancreatectomy for IPMN were investigated. Using preoperative CT, the pancreatic index (PI) was calculated by dividing the CT-number of the pancreas by that of the spleen. RESULTS: Malignancies were pathologically detected in 63 cases (73.3%). Patients were divided into two cohorts according to the presence of malignancies and were compared for various factors including the PI scores. The comparison of the two cohorts detected significant differences in two parameters (CA19-9 and PI score), and the PI score was the most sensitive biomarker to predict the presence of malignancies in patients showing high-risk stigmata of IPMN. CONCLUSIONS: Pancreatic CT-number is an additional reliable imaging biomarker in distinguishing patients with IPMN having malignancies when investigating the patients showing high-risk stigmata.

Comparison of the intracorporeal triangular and delta-shaped anastomotic techniques in totally laparoscopic distal gastrectomy for gastric cancer: an analysis with propensity score matching.

BACKGROUND: The delta-shaped anastomotic technique (Delta-SA) has been accepted as a standard reconstruction method in totally laparoscopic distal gastrectomy with Billroth I reconstruction (TLDG B-I). However, some anastomosis-related surgical complications have been reported. We evaluated the safety and feasibility of modified Delta-SA, called intracorporeal triangular anastomotic technique (INTACT), in this study. METHODS: From January 2010 to May 2018, we identified patients who underwent TLDG B-I with INTACT (n = 289) and Delta-SA (n = 221). Using one-to-one propensity score matching, surgical outcomes and gastrointestinal function were compared between the two groups. RESULTS: After one-to-one propensity score matching, 177 pairs of INTACT and Delta-SA patients were selected. Patient background was closely balanced between the two groups. Operative time (186 [159, 213] min vs. 237 [213, 264] min; P < 0.001), estimated blood loss (0 [0, 10] g vs. 20 [0, 50] g; P < 0.001), and postoperative hospital stay (7 [7, 9] days vs. 10 [9, 13] days; P < 0.001) were significantly lower in the INTACT group than in Delta-SA group. There were no patients with postoperative leakage in the INTACT group and three patients in the Delta group (0.0% vs. 1.7%; P = 0.041). Endoscopic food residue grade ≥ 3 based on the Residue, Gastritis, Bile classification system at 1 year after surgery was observed in 14 patients in the INTACT group and 30 patients in the Delta group (9.6% vs. 17.0%; P = 0.052). CONCLUSION: INTACT in TLDG B-I is safe and feasible for gastric cancer. Given its acceptable surgical outcomes, this alternative reconstruction method can be an option with TLDG B-I.

The treatment strategy of R0 resection in colorectal cancer with synchronous para-aortic lymph node metastasis.

BACKGROUND: Synchronous metastatic para-aortic lymph node (mPALN) dissectionin colorectal cancer has relatively good oncological outcomes, though many patients develop recurrence. Universal prognostic factor remain unclear and no definitive perioperative chemotherapy is available, making the treatment of mPALN controversial. In the present study, we aimed to establish a treatment strategy for synchronous mPALN. METHODS: This retrospective study involved 20 patients with pathological mPALN below the renal vein who underwent R0 resection. Long-term outcomes, recurrence type, and prognostic factors for survival were investigated. RESULTS: The 5-year overall survival and recurrence-free survival rates were 39% and 25%, respectively. Seventeen patients (85%) developed recurrence, including 13 (76%) within 1 year after surgery, and ~ 70% of all recurrences were multiple recurrences. Four patients (20%) survived > 5 years. Pathological T stage (p= 0.011), time to recurrence (p = 0.007), and recurrence resection (p = 0.009) were identified as prognostic factors for long-term survival. CONCLUSIONS: R0 resection of synchronous mPALN in colorectal cancer resulted in acceptable oncological outcomes, though we found a high rate of early unresectable recurrence. If the recurrence occurs late or isolated, surgical resection should be considered for longer survival.

Prophylactic Effect of Premedication with Intravenous Magnesium on Renal Dysfunction in Preoperative Cisplatin-Based Chemotherapy for Esophageal Cancer.

BACKGROUND: Magnesium premedication is reported to have a significant effect on reducing cisplatin-induced nephrotoxicity in several types of cancer. However, the effectiveness of magnesium administration in reducing nephrotoxicity remains unknown in esophageal cancer, especially regarding neoadjuvant therapy. METHODS: Between January 2017 and January 2019, 105 patients who underwent neoadjuvant chemotherapy followed by surgery were included in this study. Of these patients, 40 received intravenous magnesium premedication (magnesium group), whereas the remaining 65 did not (control group). We investigated the -association between magnesium premedication and chemotherapy-related nephrotoxicity. RESULTS: Baseline characteristics, such as age, body mass index, clinical stage, comorbidity, and pretreatment renal function, were not significantly different -between the magnesium and control groups. Clinical and -pathological responses were similar between the 2 groups. Regarding chemotherapy-related toxicity, there were no significant differences in hematological side effects, such as anemia, thrombopenia, and neutropenia, between both groups. However, nephrotoxicity of grade 2 and higher was significantly less frequent in the magnesium group than in the control group (2.5 vs. 21.5%, p = 0.0026), although there was no significant difference in the incidence of other nonhematological adverse events, such as nausea and diarrhea. Multivariate analysis indicated magnesium premedication and heart disease as independent factors associated with cisplatin-induced nephrotoxicity (p = 0.0026 and p = 0.0424, respectively). CONCLUSION: We showed that intravenous magnesium premedication exerts a protective effect against renal dysfunction in esophageal cancer patients undergoing neoadjuvant chemotherapy including high-dose cisplatin. Large-scale prospective studies are needed to confirm the effect of magnesium premedication on reducing nephrotoxicity in esophageal cancer patients undergoing neoadjuvant therapy.

Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Docetaxel/Cisplatin/5-Fluorouracil Followed by Surgery.

BACKGROUND: Preoperative therapy followed by surgery has become the clinical standard for resectable advanced esophageal cancer. Several studies showed that neoadjuvant docetaxel/cisplatin/5-fluorouracil (DCF) resulted in a high response rate and prolonged relapse-free survival, but what constitutes appropriate additional therapy is unknown. METHODS: A total of 101 consecutive patients with cStage I B-III esophageal cancer were treated with preoperative DCF between April 2011 and December 2015. After completing 2 cycles of DCF neoadjuvant chemotherapy (NAC), esophagectomy was performed. We investigated prognostic factors and recurrence patterns in patients with resectable esophageal cancer who underwent DCF NAC followed by surgery. RESULTS: Univariate analysis showed that performance status (hazard ratio, HR 2.85; p = 0.033), clinical response (HR 2.16; p = 0.048), pT stage (HR 2.20; p = 0.047), pN stage (HR 5.83; p< 0.001), pathological curability (HR 5.64; p = 0.038), and histological grade (HR 1.92; p = 0.048) were significant factors. Multivariate prognostic analysis revealed that pN stage and pathological curability were significant prognostic factors (HR 11.20; p < 0.001, and HR 27.41; p = 0.007, respectively). In addition, based on the number of metastatic lymph nodes (LNs), the difference in overall survival was the largest between patients with ≤2 and ≥3 metastatic LNs (HR 5.83; p< 0.001). Distant metastatic recurrence increased significantly in patients with 3 or more pathologically confirmed metastatic LNs (p = 0.008). CONCLUSION: Distant recurrence occurred more frequently and prognosis was poorer in patients with 3 or more pathologically confirmed metastatic LNs; they might need additional systemic therapy.

[Safety of Laparoscopic Surgery after Preoperative Short Course Radiotherapy for Lower Rectal Cancer].

BACKGROUNDS: In the setting of routine use of preoperative chemoradiotherapy(CRT)for cStage II / III rectal cancer, shortcourse radiotherapy(short-RT)is selectively used for reducing local recurrence.The purpose of this study is to clarify the safety of laparoscopic surgery after preoperative short-RT for lower rectal cancer. METHODS: Twenty-eight patients who un- derwent short-RT followed by laparoscopic total mesorectal excision for cStage II / III lower rectal cancer were retrospectively analyzed. RESULTS: The reasons for selecting short-RT included comorbidity(n=10), refusal of CRT(n=8), multiple cancers (n=6)and others(n=4).All patients completed planned dose of radiation without severe acute toxicity.Median interval from completion of short-RT to surgery was 17 days(range 7-58).All patients underwent laparoscopic surgery without conversion to open surgery.Median operation time, blood loss and the number of dissected lymph nodes were 379 minutes (range 175-890), 90mL(range 0-1,185)and 27(range 12-71), respectively.Grade 3-4 complications occurred in 3 cases (10.7%).There were 2 cases with pathological complete response. CONCLUSIONS: Laparoscopic surgery for lower rectal cancer after short-RT is safe and feasible.

[A Case with Metastatic Huge Ovarian Tumor from Transverse Colon Cancer, Who Underwent Systemic Chemotherapy after Bilateral Oophorectomy and Right Hemi Colectomy].

Metastatic ovarian tumors from colon cancer would be resistant to chemotherapy, and compromising quality of life(QOL) of these patients was caused by acute enlargement of the tumors. A 37-year-old woman with abdominal distension was diagnosed with transverse colon cancer, bilateral ovarian metastases, liver metastases, and peritoneal dissemination at prior hospital. Two courses of chemotherapy(FOLFOX)were administered, but metastaticovarian tumors enlarged. Chemotherapy was discontinued and she was referred to our institution. To achieve symptom relief, improving QOL, and to resume chemotherapy, we planned bilateral oophorectomy and primary tumor resection if other stenotic lesion was not present. As a result, we safely performed open bilateral oophorectomy and right hemi colectomy, and the patient discharged on postoperative day 11 without complications. Chemotherapy was resumed and continued for 7 months up to this time. Even though, curative resection could not be achieved, oophorectomy should be performed in patients with enlarged metastatic ovarian tumor from colon cancer, in spite of administration of chemotherapy.

[A Case of Lymph Node Metastasis of Rectal Laterally Spreading Tumor with Mucosal Cancer after Endoscopic Submucosal Dissection].

A screening fecal occult blood test was positive in a 76-year-old female. Colonoscopy showed laterally spreading tumor (LST)over 15 cm at lower rectum. endoscopic submucosal dissection(ESD)was performed. Pathological findings showed LST-G, 150×100 mm, adenocarcinoma(tub1-tub2), tubular adenoma, moderate-severe atypia, Tis(M), ly(-), v(-), HMX, VMX. Two years later CT detected one swollen lymph node at mesorectum and PET-CT showed FDG up take at the lymph node. We diagnosed lymph node metastasis, performed laparoscopic very low anterior resection. Pathological findings showed one lymph node metastasis, but there were no residual cancer at rectum. We cut the surgical specimen at 5mm intervals because of it's big size. It might be impossible with this procedure to detect SM invasion at this specimen.

Evaluation of the delta-shaped anastomosis in laparoscopic distal gastrectomy: midterm results of a comparison with Roux-en-Y anastomosis.

BACKGROUND: Various methods of reconstruction after laparoscopic distal gastrectomy (LDG) have been developed and published, whereas only a limited number of reports are available on the utility of the delta-shaped anastomosis (Delta). This study compared Delta and Roux-en-Y anastomoses (RY), with the aim to clarify the utility of Delta. METHODS: Stage 1 gastric cancer patients who had undergone LDG with Delta (group D, n = 68) and those who had undergone LDG with RY (group RY, n = 60) were compared in terms of operative outcomes, postoperative clinical symptoms, gastrointestinal fiberscopic findings, and changes in body weight. RESULTS: Both the operative and anastomotic times were significantly shorter in group D (230 and 13 min, respectively) than in group RY (258 and 38 min, respectively) (p < 0.001). Among the complications observed at the anastomotic site, obstruction was seen in one group D patient and two group RY patients but was relieved with conservative management. Postoperative clinical symptoms were reported for 26.4% of the group D patients but had decreased to 5.9% 1 year later. Group RY yielded similar results. Upper gastrointestinal fiberscopy performed 1 year postoperatively showed no intergroup differences in the incidence of gastritis or residual retention and a significantly more frequent occurrence of bile reflux in group D. Postoperative weight changes did not differ between the two groups. CONCLUSIONS: Delta reconstruction after LDG is a safe and effective procedure that is totally laparoscopic, less time consuming, and associated with a favorable postoperative course and a better quality of life.

Suctionable Gauze Ball Operated by the Console Surgeon Overcomes Wet Scenes during Robotic Rectal Surgery.

Although robotic rectal resections are now widely performed, there are few robotic suction tools that can be easily used by console surgeons. It can therefore be difficult to maintain a clear visual field in the pelvis when there is effusion and bleeding from either a highly advanced cancer or from preoperative cancer treatment. In this report, we introduce our unique surgical technique that uses a soft catheter with a small gauze ball attached, inserted through the assistant port. This simple and inexpensive "instrument" can be used by the console surgeon as a retractor as well as a reliable suction device to secure their view of the operative field in the pelvis. This technique can be used in a narrow surgical field and does not rely on an assistant surgeon, making it potentially applicable to all types of surgery.

Visualization of cecal tumor by near-infrared laparoscopy and intraoperative colonoscopy.

BACKGROUND: In laparoscopic colorectal surgery, accurate localization of a tumor is essential for ensuring an adequate ablative margin. Therefore, a new method, near-infrared laparoscopy combined with intraoperative colonoscopy, was developed for visualizing the contour of a cecal tumor from outside of the bowel. The method was used after it was verified on a model that employed a silicone tube. CASE PRESENTATION: The patient was a 77-year-old man with a cecal tumor near the appendiceal orifice. Laparoscopy was used to clamp of the terminal ileum, and a colonoscope was then inserted through the anus to the cecum. The laparoscope in the normal light mode could not be used to identify the cecal tumor. However, a laparoscope in the near-infrared ray mode could clearly visualize the contour of the cecal tumor from outside of the bowel, and the tumor could be safely resected by a stapler. The histopathological diagnosis of the resected specimen was adenocarcinoma with an invasion depth of M and a clear negative margin. CONCLUSIONS: This is the first report of the laparoscopic detection of the contour of a cecal tumor from outside the bowel. This technique is useful and safe for contouring tumors in laparoscopic colorectal surgery and can be used in various surgeries that combine endoscopy and laparoscopy.

Unanticipated pathological clearance in two cases of clinical T4b dMMR/MSI-h advanced colorectal cancer: the potential of immune checkpoint inhibitors despite positive positron-emission tomography results.

BACKGROUND: The standard treatment for colorectal cancer consists of surgery and chemotherapy, which can be combined to improve outcomes. Immune checkpoint inhibitors (ICI) are a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair (dMMR). However, limited data are available about the use of ICI in the neoadjuvant and conversion settings. Here, we present two cases treated with ICI. CASE PRESENTATION: Case 1: A 75-year-old male with a large, borderline resectable rectal cancer diagnosed as cT4bN1bM0 who underwent neoadjuvant chemotherapy, followed by combination ICI consisting of ipilimumab and nivolumab. After four courses of ICI, the tumor significantly shrank, but positron emission tomography still showed a positive result and R0 resection was performed. Pathological analysis revealed no residual cancer cells. The patient has been monitored without adjuvant chemotherapy, and no recurrences have occurred after one year. Case 2: A 60-year-old male with locally advanced sigmoid colon cancer who received neoadjuvant treatment with pembrolizumab. The tumor partially shrank after three courses, and continued pembrolizumab monotherapy resulted in further tumor shrinkage which still showed positive positron emission tomography. Curative sigmoidectomy with partial resection of the ileum and bladder was performed, and the pathological outcome was pCR. There was no viable tumor in the specimen. The patient has been monitored without adjuvant chemotherapy for six months, and no recurrence has been observed. CONCLUSIONS: The present study reports two cases, including a large, borderline resectable rectal cancer after failure of chemotherapy followed by combination treatment with nivolumab and ipilimumab and one case of sigmoid colon cancer after pembrolizumab treatment, which resulted in pathological complete response. However, it remains unknown whether ICI therapy can replace surgery or diminish the optimal extent of resection, or whether adjuvant chemotherapy is needed after surgery in the case of achieving pCR after ICI therapy. Overall, this case report suggests that ICI before colorectal surgery can be effective and potentially a 'watch-and-wait" strategy could be used for cases in which ICI is effective.

AZD6738 promotes the tumor suppressive effects of trifluridine in colorectal cancer cells.

Ataxia telangiectasia and Rad3­related (ATR) is a kinase that repairs DNA damage. Although inhibitors that selectively target ATR have been developed, their effectiveness in colorectal cancer has not been widely reported. The present study hypothesized that anticancer agents that effectively act in the S phase before the G2/M checkpoint may be ideal agents for concomitant use with ATR inhibitors, which act at the G2/M checkpoint. Therefore, the present study examined the combined effects of AZD6738, an ATR inhibitor, and trifluridine (FTD), which acts in the S phase and has a high DNA uptake rate. In vitro cell viability assays, flow cytometry and western blotting were performed to evaluate cell viability, and changes in cell cycle localization and protein expression. The results revealed that in colorectal cancer cells, the combination of AZD6738 and FTD inhibited cell viability, cell cycle arrest at the G2/M checkpoint and Chk1 phosphorylation, and increased apoptotic protein expression levels more than that when treated with FTD alone. HT29, a BRAF­mutant cell line known to be resistant to anticancer drugs, was used to induce tumors in vivo. Since FTD does not have sufficient efficacy when administered orally, it was mixed with tipiracil to prevent degradation; this mixture is known as TAS­102. TAS­102 alone exerted minimal tumor suppressive effects; however, when used in combination with AZD6738, tumor suppression was observed, suggesting that AZD6738 may increase the effectiveness of a weakly effective drug. Although ATR inhibitors are effective against p53 mutants, the present study demonstrated that these inhibitors were also effective against the p53 wild­type HCT116 colorectal cancer cell line. In conclusion, combination therapy with AZD6738 and FTD enhanced the inhibition of tumor proliferation in vitro and in vivo. In the future, we aim to investigate the potentiating effect of AZD6738 on 5­fluouracil­resistant cell lines that are difficult to treat.

Incomplete lymphatic sealing around the inferior mesenteric artery is a risk factor for chylous ascites in robotic rectal cancer surgery.

INTRODUCTION: Compared with laparoscopic surgery (LS), robotic surgery (RS) is considered to have acceptable outcomes in rectal cancer, but few reports have focused on chylous ascites in RS. The aim of this study was to investigate the incidence and etiology of chylous ascites after RS. METHODS: This retrospective study included 291 patients with rectal cancer who underwent RS (n = 165) or LS (n = 126) with high ligation of the inferior mesenteric artery (IMA). Propensity score matching (PSM) was performed to compare the two groups. RESULTS: \Dissection around the IMA was achieved using ultrasonic coagulating shears in most LS cases, and monopolar scissors in most RS cases, sometimes using bipolar vessel sealing device or bipolar forceps. The incidence of chylous ascites was 12.2% in RS and 4.1% in LS after PSM (P = .037). When limited to the RS group, multivariate analysis identified absence of lymphatic sealing at the left side of the IMA and shorter operative time as independent risk factors for chylous ascites. Except for duration of drain placement, no outcomes differed significantly with or without chylous ascites. One patient with chylous ascites developed later infection and required antibiotic treatment. CONCLUSION: The incidence of chylous ascites is significantly higher in RS than in LS, and RS with incomplete lymphatic sealing around the IMA is a risk factor for chylous ascites in rectal cancer. Although outcomes for patients with chylous ascites were acceptable, adequate lymphatic sealing during dissection around the IMA is crucial to prevent chylous ascites in RS.