Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

Weekday Surgery Associated With Short-Term Outcomes in Patients With Colorectal Cancers.

INTRODUCTION: The "weekday effect" on elective surgery remains controversial. We aimed to examine the association between the day of surgery and short-term outcomes after elective surgery for stage I-III colorectal cancer (CRC). METHODS: We performed a multicenter retrospective analysis of 2574 patients who underwent primary colorectal resection for CRC between January 2017 and December 2019 at 15 institutions belonging to the Hiroshima Surgical Study Group of Clinical Oncology. Patients were divided into two groups according to the day of surgery: Friday and non-Friday (Monday to Thursday). After propensity score matching (PSM), we compared 30-day mortality and postoperative outcomes. RESULTS: Out of the total, 368 patients underwent surgery on Fridays, and the remaining 2206 underwent surgery on non-Fridays. The overall mortality rate was 0.04% (n = 1). In 1685 patients with colon cancer, the proportion of American Society of Anesthesiologists scores was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM of patient, tumor, and operative characteristics, operative time was slightly more prolonged and blood loss was slightly greater in the Friday group; however, these differences were not clinically meaningful. In the 889 patients with rectal cancer, the proportion of patients with abnormal respiratory patterns was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM, the Friday group had a higher incidence of morbidity (≥ Clavien-Dindo 3a), higher incidence of digestive complications, and prolonged postoperative hospital stay. CONCLUSIONS: The results may be useful in determining the day of the week for CRC surgery, which requires more advanced techniques and higher skills.

Survival outcomes of patients with stage III colorectal cancer aged ≥ 80 years who underwent curative resection: the HiSCO-04 prospective cohort study.

BACKGROUND: The efficacy of adjuvant chemotherapy in elderly patients aged ≥ 80 years with stage III colorectal cancer remains unclear. In parallel with a multicenter prospective phase II trial evaluating the efficacy of uracil-tegafur and leucovorin as adjuvant chemotherapy (HiSCO-03), we conducted a prospective observational study of these patients to assess survival outcomes, including those ineligible for chemotherapy. METHODS: This multi-institutional prospective cohort study included 17 institutions in Hiroshima, Japan. Patients aged ≥ 80 years with stage III colorectal cancer who underwent curative resection were enrolled. The primary endpoint was 3-year disease-free survival, and the secondary endpoints were 3-year overall and relapse-free survival. Propensity score matching was used to assess the effects of adjuvant chemotherapy on survival outcomes. RESULTS: A total of 214 patients were analyzed between 2013 and 2018, including 99 males and 115 females with a median age of 84 years (range 80-101 years). Recurrence occurred in 58 patients and secondary cancers were observed in 17. The 3-year disease-free, overall, and relapse-free survival rates were 63.3%, 76.9%, and 62.9%, respectively. Adjuvant chemotherapy was administered to 65 patients with a completion rate of 52%. In a study of 80 patients that adjusted for background factors using propensity score matching, patients who completed the planned treatment showed improved disease-free survival (3-year disease-free survival: completed, 80.0%; not received, 65.5%; and discontinued, 56.3%; p = 0.029). CONCLUSIONS: Completion of adjuvant chemotherapy may improve the prognosis of patients with colorectal cancer aged ≥ 80 years, although the number of patients who would benefit from it is limited.

Association between social background and implementation of postoperative adjuvant chemotherapy for older patients undergoing curative resection of colorectal cancers, sub-analysis of the HiSCO-04 study.

PURPOSE: Adjuvant chemotherapy is recommended following colorectal cancer resection based on risk of recurrence. In older patients, treatment decisions should consider recurrence rates and tolerability, as well as functional prognosis, residual disease, and social factors. This study aims to investigate factors, including social background, influencing implementation of postoperative adjuvant chemotherapy in older patients undergoing curative resection for colorectal cancer. METHODS: This multi-institutional prospective cohort study included 15 institutions belonging to the Hiroshima Surgical study group for Clinical Oncology. We analyzed 159 older patients aged ≥ 80 years, who underwent curative resection for stage III colorectal cancer between December 2013 and June 2018, as sub-analysis of the HiSCO-04 study. RESULTS: In total, 62 (39.0%) patients underwent postoperative adjuvant chemotherapy. Four factors were significantly associated with its implementation: performance status < 2, Charlson Comorbidity Index < 2, prognostic nutritional index ≥ 40, and presence of a spouse or siblings as lifestyle supporters. No significant difference was found in the backgrounds between complete and incomplete postoperative adjuvant chemotherapy patients. CONCLUSION: Performance status, Charlson Comorbidity Index, nutritional status, and presence of a spouse or siblings as lifestyle supporters are possible factors influencing the implementation of postoperative adjuvant chemotherapy in older patients. To select appropriate treatment options, including postoperative adjuvant chemotherapy, it is essential to consider physical condition and comorbidities of older patients, thoroughly explain the situation to their families, and establish a support system to enhance understanding of the available treatment options.

Predictive factors associated with anastomotic leakage after resection of rectal cancer: a multicenter study with the Hiroshima Surgical study group of Clinical Oncology.

PURPOSE: Several factors have been reported as risk factors for anastomotic leakage after resection of rectal cancer. This study aimed to evaluate the risk factors for anastomotic leakage, including nutritional and immunological indices, following rectal cancer resection. METHODS: This study used a multicenter database of 803 patients from the Hiroshima Surgical study group of Clinical Oncology who underwent rectal resection with stapled anastomosis for rectal cancer between October 2016 and April 2020. RESULTS: In total, 64 patients (8.0%) developed postoperative anastomotic leakage. Five factors were significantly associated with the development of anastomotic leakage after rectal cancer resection with stapled anastomosis: male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection. The incidence of anastomotic leakage was correlated with the number of risk factors. The novel predictive formula based on odds ratios in the multivariate analysis was useful for identifying patients at high risk for anastomotic leakage. Diverting ileostomy reduced the ratio of anastomotic leakage ≥ grade III after rectal cancer resection. CONCLUSIONS: Male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection are possible risk factors for developing anastomotic leakage after rectal cancer resection with the stapled anastomosis. Patients at high risk of anastomotic leakage should be assessed for the potential benefits of diverting stoma.

[Clinical Outcome of Robot-Assisted Distal Pancreatectomy in Our Institutional Introduction].

We evaluated the clinical outcome and assessed the safety of robot-assisted distal pancreatectomy(RADP)of early 5 cases in our institutional introduction. We followed the guidelines for introduction of robot-assisted pancreatectomy proposed by Japanese Society of Endoscopic Surgery. Patients' characteristics were 2 men and 3 women, 45-79(median 52) years old, and 3 patients with neuroendocrine neoplasm, 1 with intraductal papillary neoplasm and 1 with mucinous cystic neoplasm. Spleen-preserving RADP was performed in 2 cases. Clinical outcomes of 5 cases underwent RADP were, operation time was 308-437(median 330)minutes, blood loss was 5-270(median 100)mL and none received transfusion. Postoperative pancreatic fistula and postoperative complication more than Grade Ⅲa(Clavien-Dindo classification)were none. Postoperative hospital stay was 7-11(median 8)days. RADP in our institution was safely introduced by following the proposal of guidelines.

Prognostic value of preoperative carcinoembryonic antigen and D-dimer concentrations in patients undergoing curative resection for colorectal cancer.

PURPOSE: Carcinoembryonic antigen (CEA) has limited value as a standalone predictor of the survival in patients with colorectal cancer (CRC). D-dimer (DD) is a predictor of the survival in patients with metastatic CRC. We aimed to predict the prognosis in patients undergoing curative resection for the treatment of CRC by integrating the evaluation of preoperative CEA and DD concentrations with the pathological classification for stage grouping (pStage). METHODS: The study enrolled 304 patients between 2007 and 2012. The Combination of DD and CEA Score (CDCS) awarded 1 point each for a CEA concentration of > 5.0 ng/ml and DD concentration of > 1.0 µg/ml. Patients were classified according to the total points: CDCS 2, increased DD and CEA concentrations; CDCS 1, increased concentration of either DD or CEA; CDCS 0, normal concentrations. RESULTS: The overall survival (OS) and relapse-free survival (RFS) were significantly lower in patients with CDCS 2 than in those with CDCS 1 or 0. The pStage and CDCS were not independent prognostic predictors of the OS but were predictors of the RFS. The C-index value of the combination of the pStage and CDCS was better than that of either alone for the OS and RFS. CONCLUSION: The combination of the pStage and CDCS accurately predicts relapse in patients with CRC.

[Two Cases of Stevens-Johnson Syndrome after Nivolumab Therapy for Gastric Cancer].

Case 1: A 51-year-old man with advanced gastric cancer and peritoneal metastasis was referred to our hospital. He received fourth-line chemotherapy with nivolumab, but it became PD. Next, he received S-1 plus docetaxel therapy as fifth- line therapy. After 2 courses of S-1 plus docetaxel, erythema and blisters appeared on his limbs, with erosions of the oral mucosa and penis. We diagnosed Stevens-Johnson syndrome(SJS)based on the clinical and pathological findings. He received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue the chemotherapy because of the SJS. Case 2: A 75-year-old woman with recurrence of peritoneally disseminated gastric cancer received third-line chemotherapy with nivolumab. After 1 course of nivolumab, erythema appeared on her body and limbs, with erosion of the lips and oral mucosa. We diagnosed SJS based on the clinical findings. She received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue chemotherapy because of the SJS. It should be noted that the onset of serious irAEs, such as SJS, might make continuous chemotherapy difficult.

[Laparoscopic Left Hemicolectomy-It Is Confirmed That the Accessory Middle Colonic Artery Branched from the Splenic Artery Showed by Preoperative 3D-CT].

There is a wide variety of vessel types in the transverse colon region. Among them, it is very rare that the accessory middle colonic artery(A-MCA)is branched from the splenic artery. We found a transverse colon cancer. The dominant vessel of the cancer was the A-MCA branched from the splenic artery. This vessel type was confirmed by preoperative 3D-CT. We performed a laparoscopic left hemicolectomy for the cancer. In this study, we report a case of safe laparoscopic surgery in which we separate the A-MCA branched from the splenic artery using the preoperative 3D-CT image.

[Outcome of Repeated Surgical Resections of Hepatic and Pulmonary Metastases from Colorectal Cancer].

Previous reports have demonstrated that repeated surgical resections of resectable hepatic and pulmonary metastases from colorectal cancer contribute to a better prognosis. We retrospectively assessed the outcomes of 19 patients with colorectal cancer who underwent repeated resections of hepatic and pulmonary metastases between February 2007 and February 2017. The median observation period was 69.9 months, and 26 liver and 27 lung resections were performed. The cumulative 5-year survival rates after resection of the last metastasis was 75.1% and the median disease-free survival after resection of the last metastasis was 34.7 months. Although 7 patients showed recurrence and 4 patients died, 7 patients exhibited long-term survival. Univariate analysis revealed that simultaneous liver and lung metastases were significantly predictor of poor prognosis(p=0.039). Progress of the patients in the present study were comparable to those in previous reports. Therefore, we propose that repeated surgical resection of hepatic and pulmonary metastasis from colorectal cancer could improve patient prognosis. Further studies should examine to identify more accurate prognostic factor with large series.

[Effect on Prognosis of Immune-Related Adverse Events after Nivolumab Treatment in Gastric Cancer].

BACKGROUND: The clinical efficacy of nivolumab has been shown as a third-line treatment for advanced gastric cancer; however, nivolumab sometimes causes immune-related adverse events(irAEs). We retrospectively examined the clinical features and influence on treatment in cases of irAEs after nivolumab treatment. METHOD: We retrospectively examined 43 patients who received nivolumab treatment at our institution between October 2017 and December 2019. RESULT: The incidence of irAEs was 23.2%(10/43), and Grade 3 or higher irAEs included interstitial pneumonia, hypoadrenalism, Stevens- Johnson syndrome(SJS), and type 1 diabetes. Three patients showed long-term disease control after irAE onset. Meanwhile, SJS prevented patients from continuing treatment for gastric cancer. DISCUSSION: Nivolumab is effective in some patients with gastric cancer, while irAEs made subsequent treatment difficult. Trifluridine/tipiracil or irinotecan are also known to be effective as therapeutic drugs after third-line treatment for gastric cancer in addition to nivolumab; therefore, the choice of the third-line drug and management of irAEs owing to individual cases are considered desirable. CONCLUSION: Long-term efficacy is expected with nivolumab, but it may be necessary to recognize that the onset of serious irAEs might make subsequent treatment difficult.

[Total Pelvic Exenteration and Perineal Reconstruction with a Gracilis Myocutaneous Flap for Local Recurrence of Rectal Cancer].

The case involved a female in her 70s. Six years prior, she had undergone an abdominoperineal rectal resection for rectal cancer. Local recurrence was observed during follow-up so preoperative chemoradiotherapy was performed to shrink the tumor, followed by a total pelvic exenteration, bilateral ureterocutaneous fistula, and perineal reconstruction with a gracilis myocutaneous flap. She was discharged from hospital 39 days following surgery with no major complications. We herein report on a case of a good postoperative course due to surgery including a total pelvic exenteration and perineal reconstruction with a gracilis myocutaneous flap for postoperative local recurrence.

[Simultaneous Distal Gastrectomy, Distal Pancreatectomy, and Splenectomy Based on Remnant Gastric Blood-Flow Evaluation with Intraoperative ICG Fluorescence].

The splenic artery and vein are important to the remnant stomach after distal gastrectomy(DG). Hence, total gastrectomy is recommended when performing gastrectomy and distal pancreatectomy(DP)with splenectomy(S). In the present case, a man in his 70s was diagnosed with early gastric cancer. Abdominal CT detected a dilated main pancreatic duct. Chronic pancreatitis was suspected, but malignancy could not be completely ruled out. Thus, DG with Roux-en-Y reconstruction and DP with S were performed simultaneously. The remnant gastric blood flow was evaluated with intraoperative indocyanine green(ICG)fluorography and the blood flow was confirmed. Finally, the remnant stomach was preserved. The postoperative course was uneventful, except for the occurrence of anastomosis edema. This result suggests that ICG fluorescence is useful to evaluate remnant gastric blood flow and that it may be possible to perform DG and DP with S simultaneously depending on the case.

[A Case of Gastric Cancer with Continued Progression-Free Survival Even after Total Gastrectomy and Nivolumab Therapy].

This is a first report of gastrectomy after nivolumab immunotherapy. We describe a case in an elderly woman with gastric cancer diagnosed with cT4bN3M1(LYM), cStage ⅣB disease. Although she was administered 2 courses of SOX chemotherapy as the primary treatment, she could not continue the treatment to due to bone marrowsuppression. The second-line treatment was weekly PTX therapy, but she experienced Grade 3 neutropenia and thrombocytopenia in the first course and could not continue treatment. Nivolumab as the next treatment was effective but was discontinued for suspected druginduced pneumonia. During that time, tumor hemorrhage occurred and we performed total gastrectomy. Postoperatively, nivolumab chemotherapy was resumed. There were no adverse events and the patient has had a continued partial response for 30 courses. Gastrectomy was necessary in this case, allowing observation of the pathological findings of this highly effective case.

[Microsatellite Instability in Gastric Cancer].

INTRODUCTION: Pembrolizumab and nivolumab are anti-programmed death receptor-1(PD-1)antibodies. The use of pembrolizumab for unresectable or metastatic cancer with microsatellite instability-high(MSI-High)has been recently approved. However, there were few clinical reports on MSI in gastric cancer. MATERIALS AND METHODS: We examined the clinicopathological features and MSI for 37 patients who underwent chemotherapy for unresectable gastric cancer in January 2019. RESULTS: MSI-High was observed in 3 patients(8.1%). Among the MSI-High patients, there was a tendency towards older age, female sex, undifferentiated type, distal-located lesions and lymphatic vessel invasions, but the differences were not significant. Eleven patients underwent chemotherapy with nivolumab, 4 of them had partial response(PR). Three out of the 4 patients (75%)were MSI-High. CONCLUSIONS: These results suggested that anti-PD-1 antibody could be effective as a secondary treatment for unresectable or metastatic gastric cancer among MSI-High patients.

Short-term outcomes of laparoscopic surgery in octogenarians with colorectal cancer: a single-institution analysis.

PURPOSE: The number of elderly patients with colorectal cancer (CRC) treated with surgery has gradually increased. The aim of this study was to evaluate the short-term outcomes in patients ≥80 years of age who underwent laparoscopic or open surgery for CRC using a propensity score-matched analysis to make uniform the patient background characteristics affecting the postoperative morbidity and mortality. METHODS: We compared the short-term outcomes of open vs. laparoscopic surgery in patients with CRC ≥80 years of age between 2010 and 2015. Fifty-two patients undergoing laparoscopic colectomy for CRC were matched to 52 patients undergoing open colectomy with respect to gender, age, body mass index, performance status, prognostic nutritional index, Charlson Comorbidity Index score, tumor-node-metastasis stage, and tumor location. The operative time, blood loss, length of hospital stay, and postoperative complications were investigated. RESULTS: Blood loss was less during laparoscopic surgery than during open surgery (40 vs. 140 ml, p < 0.001). In the laparoscopic surgery group, the hospital stay was shorter (11 vs. 14 days, p < 0.001) and the morbidity rate lower (21.2 vs. 40.4%) than in the open surgery group. The mortality for both groups was similar (0 vs. 1.9% for laparoscopic surgery vs. open surgery). CONCLUSION: Laparoscopic surgery in octogenarians with CRC is a safe, low-invasive alternative to open surgery with less blood loss and a shorter hospital stay.

Invasive micropapillary carcinoma component is an independent prognosticator of poorer survival in Stage III colorectal cancer patients.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma found in several organs. Recent studies showed that IMPC in colorectal cancer leads to poorer prognosis than conventional colorectal cancer; however, the influence of IMPC on outcomes remains unclear. The present study aimed to identify the clinicopathological characteristics of colorectal cancers with IMPCs, and to evaluate the prognostic significance of IMPCs per se. METHODS: We retrospectively analyzed data from 837 patients with colorectal cancer who underwent surgical treatment. We compared the clinicopathological characteristics and survival outcomes of colorectal cancer patients with IMPCs to those without. RESULTS: Among 837 patients, 130 (16%) had an IMPC component, including 0 (0%) of 18, 9 (4.2%) of 215, 34 (13%) of 254, 59 (24%) of 249 and 28 (27%) of 101 patients with TNM Stages 0, I, II, III and IV, respectively. The 3-year disease-free survival (DFS) rates were significantly worse for Stage III patients with IMPC than for those without (55.3% vs. 78.7% respectively, P < 0.001), but not in patients with other stages. Multivariate analyses of patients with Stage III colorectal cancer found IMPC to be associated with significantly worse DFS (P = 0.026), as were high CEA levels, tumor budding and TNM staging. IMPC was only significantly associated with tumor invasion (P = 0.045) and venous invasion (P = 0.045) in Stage III tumors. CONCLUSIONS: Identifying IMPC components in Stage III colorectal cancer is crucial, as their presence is significantly associated with poorer survival.

[Abdominoperineal Resection for Anal Metastasis of Rectal Cancer].

Anal metastasis of colorectal cancer is rare, and no standardized effective therapeutic strategy exists. We report a case of abdominoperineal resection for anal metastasis of rectal cancer. A 65-year-old man underwent laparoscopic low anterior resection for rectal cancer in August 2013. Histopathological examination revealed a moderately differentiated adenocarcinoma( tub2, pSS, ly3, v2, pN1, H0, P0, M0, Stage III a, Cur A). In February 2015, he complained of anal discomfort, and tumor markers were elevated. Enhanced CT revealed a 15-mm high-density solid tumor in the anal canal. The results of needle biopsy indicated a moderately differentiated adenocarcinoma. This tumor was suspected to be metastasis from rectal cancer, and we performed abdominoperineal resection. Histopathological examination revealed a moderately differentiated adenocarcinoma, which was the same histological type as the primary rectal cancer and was covered with normal anal epithelium. Collectively, the findings indicated anal metastasis from rectal cancer. The patient is alive without recurrence for 18 months after resection. Anal metastasis should be considered as a differential diagnosis in patients with anal discomfort who have a history of colon/rectal cancer. Abdominoperineal resection may be an effective treatment modality for this condition.