Incidence and risk factors of bowel dysfunction after minimally invasive rectal cancer surgery and discrepancies between the Wexner score and the low anterior resection syndrome (LARS) score.

PURPOSE: Bowel dysfunction after sphincter-preserving-surgery (SPS) impacts quality of life. The Wexner score (WS) and the low anterior resection syndrome (LARS) score (LS) are instruments for assessing postoperative bowel dysfunction. We analyzed the incidence of and risk factors for each symptom and examined the discrepancies between the two scores. METHODS: A total of 142 patients with rectal cancer, who underwent minimally invasive SPS between May, 2018 and July, 2019, were included. A questionnaire survey using the two scores was given to the patients 2 years after SPS. RESULTS: Tumor location and preoperative radiotherapy were independent risk factors for major LARS. Intersphincteric resection with a hand-sewn anastomosis (HSA) was an independent risk factor for high WS. Among the patients who underwent HSA, 82% experienced incontinence for liquid stools, needed to wear pads, and suffered lifestyle alterations. Of the 35 patients with minor LARS, only 1 had a high WS, and 80.0% reported no lifestyle alterations. Among the 75 patients with major LARS, 58.7% had a low WS and 21.3% reported no lifestyle alterations. CONCLUSION: The results of this study provide practical data to help patients understand potential bowel dysfunction after SPS. The discrepancies between the WS and LS were clarified, and further efforts are required to utilize these scores in clinical practice.

The impact of staple transection of the dorsal venous complex and urethra on intraoperative blood loss in cooperative laparoscopic and transperineal endoscopic pelvic exenteration.

PURPOSE: While laparoscopic pelvic exenteration reduces intraoperative blood loss, dorsal venous complex bleeding during this procedure causes issues. We previously introduced a method to transect the dorsal venous complex and urethra using a linear stapler during cooperative laparoscopic and transperineal endoscopic (two-team) pelvic exenteration. The present study assessed its effectiveness in reducing intraoperative blood loss by comparing it with conventional laparoscopic pelvic exenteration. METHODS: This retrospective cohort study was conducted at a Japanese tertiary referral center. Eleven cases of two-team laparoscopic pelvic exenteration with staple transection of the dorsal venous complex (T-PE group) were compared to 25 cases of conventional laparoscopic pelvic exenteration (C-PE group). The primary outcome measure was intraoperative blood loss. RESULTS: There were no significant between-group differences in patient background. The mean intraoperative blood loss was significantly lower in the T-PE group than in the C-PE group (200 vs. 850 mL, p = 0.01). The respective mean operation time, postoperative complication rate, and R0 resection rate were similar between the T-PE and C-PE groups (636 min vs. 688 min, p = 0.36; 36% vs. 44%, p = 0.65; 100% vs. 100%, p = 1.00). CONCLUSIONS: Two-team laparoscopic pelvic exenteration with staple transection of the dorsal venous complex reduced intraoperative blood loss from the dorsal venous complex in a technically safe and oncologically feasible manner.

Prognostic factors of para-aortic lymph node metastasis from colorectal cancer in highly selected patients undergoing para-aortic lymph node dissection.

PURPOSE: We investigated the surgical outcomes of para-aortic lymph node (PALN) dissection in patients with colorectal cancer and assessed the prognostic factors related to the survival. METHODS: This single-center retrospective study included 31 patients with synchronous or metachronous PALN metastasis from colorectal cancer who underwent PALN dissection between January 2006 and December 2018. RESULTS: Twenty-one patients had synchronous PALN metastasis, and 10 had metachronous PALN metastasis. Seven patients had either simultaneous distant metastasis or a history of distant metastasis other than PALN metastasis at the time of PALN dissection. Eighteen patients underwent adjuvant chemotherapy. The 5-year overall and recurrence-free survival rates were 54.2 and 17.2%, respectively. A multivariable analysis revealed that rectal cancer, metachronous PALN metastasis, and three or more pathological PALN metastases were significantly poor prognostic factors for the recurrence-free survival. Among patients with rectal cancer, lower rectal cancer and lateral pelvic lymph node metastasis were poor prognostic factors for the overall survival. CONCLUSION: Curative PALN dissection for PALN metastasis from colorectal cancer is feasible with favorable long-term outcomes. A multidisciplinary approach, including surgery and chemotherapy, is needed for colorectal cancer with PALN metastasis to improve the long-term outcomes.

Clinical utility of the carcinoembryonic antigen level in patients with stage III colon cancer after surgery and adjuvant chemotherapy.

PURPOSE: The association between perioperative and post-adjuvant carcinoembryonic antigen (CEA) levels and recurrence and prognosis remains unclear. We aimed to evaluate whether perioperative CEA levels are an integral component of the assessment of recurrence and prognosis of patients with stage III colon cancer (CC). METHODS: This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 2005 to 2013. We enrolled patients with stage III CC who underwent complete resection of a primary tumor and received adjuvant chemotherapy. We analyzed the association between perioperative and post-adjuvant CEA levels and recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 564 consecutive patients were included in the analysis. The RFS and OS of patients with high postoperative CEA levels were significantly worse than those of patients with normal postoperative CEA levels. In the multivariate analysis, high postoperative CEA levels were associated with shorter RFS and OS. The number of risk factors, postoperative CEA levels, and T/N-stage all had a cumulative effect on RFS and OS. CONCLUSIONS: High postoperative CEA levels and the number of risk factors are associated with recurrence and worse prognosis for patients with stage III CC.

Intratumoral Budding and CD8-Positive T-cell Density in Pretreatment Biopsies as a Predictor of Response to Neoadjuvant Chemoradiotherapy in Advanced Rectal Cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression. MATERIALS AND METHODS: The impact of intratumoral budding (ITB) and intratumoral CD8+ cell density on response to CRT and survival were evaluated in biopsy samples from 266 patients with advanced rectal cancer who were treated with long-course neoadjuvant CRT. The expression of epithelial-mesenchymal transition (EMT) markers was compared between patients with high and low ITB, using data from 174 patients with RNA sequencing. RESULTS: High ITB was observed in 62 patients (23.3%). There was no association between ITB and CD8+ cell density. The multivariable logistic regression analysis showed that high CD8+ cell density (OR, 2.69; 95% CI, 1.45-4.98; P = .002) was associated with good response to CRT, whereas high ITB (OR, 0.33; 95% CI, 0.14-0.80; P = .014) was associated with poor response. Multivariable Cox regression analysis for survival showed that high CD8+ cell density was associated with better recurrence-free survival (HR, 0.41; 95% CI, 0.24-0.72; P = .002) and overall survival (HR, 0.36; 95% CI, 0.17-0.74; P = .005), but significance values for ITB were marginal (P = .104 for recurrence-free survival and P = .163 for overall survival). The expression of EMT-related genes was not significantly different between patients with high and low ITB. CONCLUSION: ITB and CD8+ cell density in biopsy samples may serve as useful biomarkers to predict therapy response in patients with rectal cancer treated with neoadjuvant CRT.

Geriatric nutritional risk index after neoadjuvant chemoradiotherapy and survival in older patients with advanced rectal cancer.

PURPOSE: To investigate the clinical impact of malnutrition on the survival of older patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. METHODS: We investigated the clinical significance of the geriatric nutritional risk index (GNRI) in 237 patients aged over 60 years with clinical stage II/III rectal adenocarcinoma who were treated with neoadjuvant long-course chemoradiotherapy or total neoadjuvant therapy followed by radical resection from 2004 to 2017. Pre-treatment and post-treatment GNRI were evaluated, with patients split into low (< 98) and high (≥ 98) GNRI groups. The prognostic impact of pre-treatment and post-treatment GNRI levels on overall survival (OS), post-recurrence survival (PRS), and disease-free survival (DFS) was evaluated using univariate and multivariate analyses. RESULTS: Fifty-seven patients (24.1%) before neoadjuvant treatment and 94 patients (39.7%) after neoadjuvant treatment were categorized with low GNRI. Pre-treatment GNRI levels were not associated with OS (p = 0.80) or DFS (p = 0.70). Patients in the post-treatment low GNRI group had significantly poorer OS than those in the post-treatment high GNRI group (p = 0.0005). The multivariate analysis showed that post-treatment low GNRI levels were independently associated with poorer OS (hazard ratio, 3.06; 95% confidence interval, 1.55-6.05; p = 0.001). Although post-treatment GNRI levels were not associated with DFS (p = 0.24), among the 50 patients with recurrence, post-treatment low GNRI levels were associated with poorer PRS (p = 0.02). CONCLUSION: Post-treatment GNRI is a promising nutritional score associated with OS and PRS in patients over 60 years with advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

Adding Induction Chemotherapy Before Chemoradiotherapy with Total Mesorectal Excision and Selective Lateral Lymph Node Dissection for Patients with Poor-Risk, Locally Advanced, Mid-to-Low Rectal Cancer May Improve Oncologic Outcomes: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to investigate whether the addition of induction chemotherapy before chemoradiotherapy (CRT) and total mesorectal excision (TME) with selective lateral lymph node dissection improves disease-free survival for patients with poor-risk, mid-to-low rectal cancer. METHODS: The authors' institutional prospective database was queried for consecutive patients with clinical stage II or III, primary, poor-risk, mid-to-low rectal cancer who received neoadjuvant treatment followed by TME from 2004 to 2019. The outcomes for the patients who received induction chemotherapy before neoadjuvant CRT (induction-CRT group) were compared (via log-rank tests) with those for a propensity score-matched cohort of patients who received neoadjuvant CRT without induction chemotherapy (CRT group). RESULTS: From 715 eligible patients, the study selected two matched cohorts with 130 patients each. The median follow-up duration was 5.4 years for the CRT group and 4.1 years for the induction-CRT group. The induction-CRT group had significantly higher rates of 3-year disease-free survival (83.5 % vs 71.4 %; p = 0.015), distant metastasis-free survival (84.3 % vs 75.2 %; p = 0.049), and local recurrence-free survival (98.4 % vs 94.4 %; p = 0.048) than the CRT group. The pathologically complete response rate also was higher in the induction-CRT group than in the CRT group (26.2 % vs 10.0 %; p < 0.001). Postoperative major complications (Clavien-Dindo classification ≥III) did not differ significantly between the two groups (12.3 % vs 10.8 %; p = 0.698). CONCLUSIONS: The addition of induction chemotherapy to neoadjuvant CRT appeared to improve oncologic outcomes significantly, including disease-free survival, for the patients with poor-risk, mid-to-low rectal cancer who underwent TME using selective lateral lymph node dissection.

Risk Factors for Lymph Node Metastasis of Rectal Neuroendocrine Tumor and Its Prognostic Impact: A Single-Center Retrospective Analysis of 195 Cases with Radical Resection.

PURPOSE: The incidence of rectal neuroendocrine tumors (NETs) has been steadily increasing. The risk factors for and prognostic impact of lymph node (LN) metastasis were analyzed in 195 patients with stage I-III rectal NET who underwent radical surgery. METHODS: This retrospective, single-center study analyzed risk factors for LN metastasis focusing on previously identified factors and a novel risk factor: multiple rectal NETs. The association between LN metastasis and the prognosis was also analyzed. RESULTS: Pathologically, the LN metastasis rate (also the rate of stage III disease) was 39%, which was higher than the clinical LN metastasis rate of 14%. Tumor size > 10 mm, presence of central depression, tumor grade G2, depth of invasion, LN swelling on preoperative imaging (cN1), venous invasion and multiple NETs were identified as risk factors for LN metastasis. As the tumor size and risk factors increased, the rate of LN metastasis increased. Among these 7 factors, venous invasion, cN1, and multiple NETs were identified as independent predictors of LN metastasis. LN metastasis of rectal NETs was associated with significantly poor disease-free and disease-specific survival. CONCLUSIONS: As risk factors increase, the potential for rectal NETs to metastasize to the LNs increases and LN metastasis is associated with a poor prognosis. This is the first study to report multiple NETs as a risk factor for LN metastasis. A future study examining the survival benefit of radical surgery accompanying LN dissection compared with local resection is warranted.

Novel mobilization of the medial approach without changing the position for robotic right hemicolectomy.

Conventional laparoscopic or robotic surgery for right-sided colon cancer often requires intraoperative repositioning and removal of the bowel. Changing positions during robotic surgery can be troublesome and robotic removal of the small intestine carries a risk of unexpected injury because robotic devices have a strong grasping force and no sense of touch. Herein, we introduce a novel mobilization of the medial approach without changing the position for robotic right hemicolectomy. Using this technique, mobilization is performed in counterclockwise succession, allowing all mobilizations and bowel removal to be completed sequentially, without positional change.

Transcriptomic Analyses of Pretreatment Tumor Biopsy Samples, Response to Neoadjuvant Chemoradiotherapy, and Survival in Patients With Advanced Rectal Cancer.

Importance: Neoadjuvant chemoradiotherapy (CRT) is the standard of care for advanced rectal cancer. Yet, estimating response to CRT remains an unmet clinical challenge. Objective: To investigate and better understand the transcriptomic factors associated with response to neoadjuvant CRT and survival in patients with advanced rectal cancer. Design, Setting, and Participants: A single-center, retrospective, case series was conducted at a comprehensive cancer center. Pretreatment biopsies from 298 patients with rectal cancer who were later treated with neoadjuvant CRT between April 1, 2004, and September 30, 2020, were analyzed by RNA sequencing. Data analysis was performed from July 1, 2021, to May 31, 2022. Exposures: Chemoradiotherapy followed by total mesorectal excision or watch-and-wait management. Main Outcomes and Measures: Transcriptional subtyping was performed by consensus molecular subtype (CMS) classification. Immune cell infiltration was assessed using microenvironment cell populations-counter (MCP-counter) scores and single-sample gene set enrichment analysis (ssGSEA). Patients with surgical specimens of tumor regression grade 3 to 4 or whose care was managed by the watch-and-wait approach for more than 3 years were defined as good responders. Results: Of the 298 patients in the study, 205 patients (68.8%) were men, and the median age was 61 (IQR, 52-67) years. Patients classified as CMS1 (6.4%) had a significantly higher rate of good response, albeit survival was comparable among the 4 subtypes. Good responders exhibited an enrichment in various immune-related pathways, as determined by ssGSEA. Microenvironment cell populations-counter scores for cytotoxic lymphocytes were significantly higher for good responders than nonresponders (median, 0.76 [IQR, 0.53-1.01] vs 0.58 [IQR, 0.43-0.83]; P < .001). Cytotoxic lymphocyte MCP-counter score was independently associated with response to CRT, as determined in the multivariable analysis (odds ratio, 3.81; 95% CI, 1.82-7.97; P < .001). Multivariable Cox proportional hazards regression analysis, including postoperative pathologic factors, revealed the cytotoxic lymphocyte MCP-counter score to be independently associated with recurrence-free survival (hazard ratio [HR], 0.38; 95% CI, 0.16-0.92; P = .03) and overall survival (HR, 0.16; 95% CI, 0.03-0.83; P = .03). Conclusions and Relevance: In this case series of patients with rectal cancer treated with neoadjuvant CRT, the cytotoxic lymphocyte score in pretreatment biopsy samples, as computed by RNA sequencing, was associated with response to CRT and survival. This finding suggests that the cytotoxic lymphocyte score might serve as a biomarker in personalized multimodal rectal cancer treatment.

Short-term outcomes of intracorporeal versus extracorporeal anastomosis in laparoscopic surgery for right-sided colon cancer: A propensity score-matched study.

INTRODUCTION: Recently, intracorporeal anastomosis (IA) has been attracting attention. We aimed to compare the short-term outcomes of IA and extracorporeal anastomosis (EA) in laparoscopic surgery for right-sided colon cancer, after propensity score matching. METHODS: We retrospectively reviewed 404 consecutive patients with right-sided primary colon cancer between January 2019 and July 2021, 359 of whom underwent laparoscopic surgery. We classified them into IA (n = 72) and EA (n = 287) groups. Propensity score matching analysis was performed, and the matched groups were compared. RESULTS: The IA group had a longer operation time and shorter time to first flatus, passage of stool, and oral intake. There were no differences in blood loss, postoperative complications, and postoperative hospital stay between the groups. The IA group had a higher inflammatory response in the laboratory data on postoperative day 1 compared to the EA group; however, there were no differences in the incidence of abdominal or surgical site infection (SSI). The IA group had a longer distal resection margin, and there were no peritoneal recurrences in either group. CONCLUSION: In the IA group, patients had earlier bowel recovery and a longer distal resection margin; however, other postoperative clinical outcomes were comparable. Although there was a higher postoperative inflammatory response in IA, there was no significant difference in postoperative complications, including SSI and intra-abdominal infection. Although long-term outcomes are not yet available, IA could be a useful procedure.

Advantages of the umbilical minilaparotomy-first approach in robotic rectal cancer surgery.

BACKGROUND: Since 2018, we have performed robotic rectal cancer surgery at our institution via the umbilical mini-laparotomy-first approach. In the present technical note, we introduce the advantages of this approach. METHODS: In this approach, a 3-cm mini-laparotomy and the wound protector attachment are performed prior to port placement for the da Vinci® Xi system. During robotic surgery, the assistant can adjust the location of the camera port within the wound protector. RESULTS: This approach is only different from the standard port placement in terms of the timing of minilaparotomy; therefore, there is no additional cost. This approach has several advantages. 1: Intraabdominal adhesion around the umbilicus can be dissected under direct vision. 2: Robot arm collision can be diminished. 3: The diverting stoma can be located just at the preoperative stoma-site marking. 4: The da Vinci® camera is less likely to be dirty. 5: Assistant ports can be added through the wound protector. However, sometimes interference between the wound protector extends inside the abdomen and other ports can be a problem, especially in small patients. A smaller-size wound protector is thus recommended in such cases. CONCLUSIONS: The umbilical minilaparotomy-first approach in robotic rectal cancer surgery is a simple and feasible technique with great advantages for not only ensuring successful robotic surgery but also reducing the stoma-associated complications.

Clinicopathological features of appendiceal goblet cell adenocarcinoma in Japan: a multicenter retrospective study.

PURPOSE: In the 5th edition of the World Health Organization classification, appendiceal goblet cell adenocarcinoma (GCA) is categorized separately from neuroendocrine tumors and other appendiceal adenocarcinomas. We clarified the clinicopathological characteristics of Japanese appendiceal GCA. METHODS: We designed a retrospective multicenter cohort study and retrieved the data of patients with appendiceal neoplasms and histologically diagnosed appendiceal goblet cell carcinoid (GCC) treated from January 2000 to December 2017 in Japan. The available GCC slides were reviewed and diagnosed with a new grading system of GCA. RESULTS: A total of 922 patients from 43 institutions were enrolled; of these, 32 cases were patients with GCC (3.5%), and 20 cases were ultimately analyzed. The 5-year survival rate was 61.4% (95% confidence interval: 27.4-83.2), and the median survival time was 93.1 months. For peritoneal metastasis, regional lymph node metastasis was a significant factor (p = 0.04), and Grade 3 was a potential factor (p = 0.07). No peritoneal metastasis was observed in either T1/2 patients (n = 2) or Grade 1 patients (n = 4). We were unable to detect any significant factors associated with regional lymph node metastasis. CONCLUSION: For peritoneal metastasis, regional lymph node metastasis was a significant factor, and Grade 3 was a potential factor.

Inferior versus medial approach in laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer: A propensity-score-matched analysis.

AIM: In laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer, either an inferior approach (IA) or a medial approach (MA) is selected in our institution based on the surgeon's preference. The present study compared the treatment outcomes between IA and MA. METHOD: This retrospective, single-centre study using propensity score matching analysed the short- and long-term outcomes of laparoscopic surgery in patients with right-sided colon cancer from 2010 to 2019 at Cancer Institute Hospital. RESULTS: After patient selection, 1011 patients remained for the analysis, of which 67% underwent IA surgery and 33% underwent MA surgery. After propensity score matching (1:1), 325 patients in each group were analysed. Regarding the short-term outcomes, there were no significant differences in the operation time, rate of conversion to open surgery or postoperative complication rate (Clavien-Dindo Grade ≥ III) between the two groups, although the intra-operative median blood loss was significantly less in the IA group than in the MA group (IA, 13 ml vs. MA, 20 ml, P < 0.0001). Regarding the long-term outcomes, the relapse-free survival, liver-relapse-free survival, cancer-specific survival and overall survival were all similar between groups. CONCLUSION: Both the IA and MA in laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer are safe and feasible approaches; the IA may have an advantage over the MA in terms of reduced intra-operative blood loss. Based on their similar oncological outcomes, either the IA or MA can be selected, based on one's preference.

The evaluation of postoperative bowel dysfunction in Japanese patients with rectal cancer.

PURPOSE: The present study assessed postoperative bowel dysfunction in Japanese patients with rectal cancer, including patients who underwent preoperative radiotherapy (RT). METHODS: A total of 277 rectal cancer patients who underwent primary resection were included in the analyses. A questionnaire survey was administered using the low anterior resection syndrome (LARS) score and Wexner score. Scores were determined one year after rectal surgery or diverting ileostomy closure. The LARS score was categorized as minor LARS (21-29) and major LARS (30-42). RESULTS: The proportions of patients with minor and major LARS were significantly larger and Wexner scores significantly higher in patients with distal tumors and a lower anastomosis level than in those with proximal tumors and a higher anastomosis level. Among the patients with lower rectal cancer, the proportions with minor and major LARS were similar between those with and without preoperative RT. The Wexner scores in patients with preoperative RT were significantly higher than in patients without RT. A distal tumor location and lower anastomosis level were independent risk factors of major LARS in multivariate analyses. CONCLUSION: A distal tumor location, low anastomosis level, and preoperative RT might be associated with postoperative bowel dysfunction in rectal cancer patients.