Prognostic Relevance of Primary Tumor Sidedness in Early-stage Colorectal Cancer: An Integrated Analysis of 4 Randomized Controlled Trials (JCOG2003A).

OBJECTIVE: The aim of this study was to determine the genuine prognostic relevance of primary tumor sidedness (PTS) in patients with early-stage colorectal cancer (CRC). BACKGROUND: The prognostic relevance of PTS in early-stage CRC remains a topic of debate. Several large epidemiological studies investigated survival only and did not consider the risk of recurrence so far. METHODS: Patients with stage II/III adenocarcinoma of the colon and upper rectum from 4 randomized controlled trials were analyzed. Survival outcomes were compared according to the tumor location: right-sided (cecum to transverse colon) or left-sided (descending colon to upper rectum). RESULTS: A total of 4113 patients were divided into a right-sided group (N=1349) and a left-sided group (N=2764). Relapse-free survival after primary surgery was not associated with PTS in all patients and each stage [hazard ratio (HR) adjusted =1.024 (95% CI: 0.886-1.183) in all patients; 1.327 (0.852-2.067) in stage II; and 0.990 (0.850-1.154) in stage III]. Also, overall survival after primary surgery was not associated with PTS in all patients and each stage [HR adjusted =0.879 (95% CI: 0.726-1.064) in all patients; 1.517 (0.738-3.115) in stage II; and 0.840 (0.689-1.024) in stage III]. In total, 795 patients (right-sided, N=257; left-sided, N=538) developed recurrence after primary surgery. PTS was significantly associated with overall survival after recurrence (HR adjusted =0.773, 95% CI: 0.627-0.954). CONCLUSIONS: PTS had no impact on the risk of recurrence for stage II/III CRC. Treatment stratification based on PTS is unnecessary for early-stage CRC.

The Effectiveness of Screening Total Colonoscopy for Preoperative Patients with Gastric Cancer.

BACKGROUND: Colorectal cancer (CRC) is the most common cancer that coincides with gastric cancer (GC). Although the usefulness of total colonoscopy (TCS) as a CRC screening tool has been reported in preoperative patients with GC, the long-term outcome of patients with synchronous CRC (SCRC) remains unclear. This study aims to clarify the significance of preoperative screening TCS for GC in terms of survival outcomes. PATIENTS AND METHODS: We included 796 patients who underwent preoperative screening TCS for GC. The risk factors, clinicopathological features, and survival outcome of SCRC were examined. Furthermore, the cost-effectiveness was evaluated from the perspective of improving the rates of mortality caused by CRC. RESULTS: SCRC was observed in 43 patients (5.4%). Endoscopic treatment for SCRC was performed on 30 patients. In total, 15 patients underwent surgical resection, including 2 patients requiring additional surgery after endoscopic treatment. Regarding pathological stages, 25 patients had stage 0, 12 patients had stage I, 5 patients had stage II, and 1 patient had stage IIIB disease. The cumulative mortality rates were as follows: GC-related deaths, 12.6%; deaths from cancers other than CRC, 1%; deaths from other causes, 5.5%. No deaths were attributed to SCRC. Comparing the patients who did not undergo TCS, an incremental cost-effectiveness ratio analysis suggested that a screening cost of 5.86 million yen was required to prevent one CRC death. CONCLUSIONS: Curative treatment was possible in all patients with SCRC. No deaths were attributed to SCRC, suggesting that screening TCS for GC is effective.

Long-term Outcome After Surgical Resection of Paraaortic Lymph Node Metastasis of Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND: The significance of resection of paraaortic lymph node metastasis in colorectal cancer is controversial. OBJECTIVE: To clarify the prognosis of colorectal cancer after paraaortic lymph node metastasis resection. DESIGN: Multicenter retrospective study. SETTINGS: Thirty-six institutions in Japan participated in this study. PATIENTS: Patients with resected and pathologically proven paraaortic lymph node metastasis of CRC between 2010 and 2015. DATA SOURCES: Database and medical records at each institution. MAIN OUTCOME MEASURES: Overall survival after paraaortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of paraaortic lymph node metastasis. RESULTS: A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% confidence interval [CI]) was 41.0% (32.0, 49.8), and the median survival (95% CI) was 4.1 (3.4, 4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs. pT1- 3, adjusted hazard ratio [aHR]: 1.91, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.98, p = 0.005), time to metastases (synchronous vs. metachronous, aHR: 2.02, p = 0.02), and number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5, 29.7), with a median (95% CI) of 1.2 (0.9, 1.4) years. The primary tumor location (left- vs. right-sided colon, aHR: 4.77, p = 0.01; rectum vs. right-sided colon, aHR: 5.27, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.90, p = 0.03), number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.20, p = 0.001), and hospital volume (<10 vs. ≥10, aHR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Paraaortic lymph node recurrence was the most common at 33.3%. LIMITATIONS: Selection bias cannot be ruled out because of the retrospective nature of the study. CONCLUSIONS: Less than three paraaortic lymph node metastasis was a favorable prognostic factor for both overall survival and recurrence-free survival. However, paraaortic lymph node metastases were considered to be a systemic disease and the significance of resection was limited. See Video Abstract.

Risk factors for lateral lymph node metastasis based on the molecular profiling of rectal cancer.

AIM: The association between molecular profiles and lateral lymph node metastasis (LLNM) in patients with rectal cancer remains unclear. Therefore, this study aimed to identify the molecular profiles of rectal cancer associated with LLNM. METHOD: We retrospectively examined patients who underwent rectal cancer surgery with lateral lymph node dissection without preoperative treatment and whose surgically resected specimens were evaluated using multiomics-based analyses from 2014 to 2019. We compared the clinical characteristics and molecular profiles of patients with pathological LLNM (pLLNM+) with those of patients without (pLLNM-) and identified risk factors for LLNM. RESULTS: We evaluated a total of 123 patients: 18 with and 105 without pLLNM. The accumulation of mutations in genes key for the development of colorectal cancer were similar between the groups, as was the tumour mutation burden. The distribution of consensus molecular subtypes (CMS) was significantly different between the groups (p = 0.0497). The pLLNM+ patients had a higher prevalance of CMS4 than the pLLNM- patients (77.8% vs. 51.4%). According to the multivariate analysis, the independent risk factors for LLNM were a short-axis diameter of the lateral lymph node of ≥6.0 mm and CMS4; furthermore, the presence of either or both had a sensitivity of 100% for the diagnosis of LLNM. CONCLUSION: Lateral lymph node size and CMS4 are useful predictors of LLNM. The combination of CMS classification and size criteria was remarkably sensitive for the diagnosis of LLNM.

Risk factors for stoma prolapse after laparoscopic loop colostomy.

BACKGROUND: Stoma prolapse (SP) is a common stoma-related complication, particularly in loop colostomies. This study aimed to investigate potential risk factors for SP development after laparoscopic loop colostomy. METHODS: In total, data from 140 patients who underwent laparoscopic loop colostomy were analyzed between September 2016 and March 2022. Risk factors for SP were investigated retrospectively. RESULTS: The median follow-up duration after colostomy was 12.5 months, and SP occurred in 33 (23.6%) patients. Multivariate analysis showed that being overweight (body mass index ≥ 25; odds ratio [OR], 8.69; 95% confidential interval [CI], 1.61-46.72; p = 0.012) and having a thin rectus abdominis penetration of the stoma (< 8.9 mm; OR, 8.22; 95% CI, 2.50-27.05; p < 0.001) were independent risk factors for SP. Other patient characteristics and surgical factors associated with stoma construction were unrelated to SP development. CONCLUSIONS: Being overweight and the route penetrating the thinner rectus abdominis during stoma construction was associated with a significantly higher incidence of SP after laparoscopic loop colostomy. Selecting a construction site that penetrates the thicker rectus abdominis muscle may be crucial for preventing SP.

Molecular profiling of risk factors for relapse in Japanese patients with stage II colorectal cancer: a retrospective cohort study.

BACKGROUND: The association between the molecular profiles and prognosis of Stage II colorectal cancer remains unclear. This study aimed to examine the risk factors for relapse of Stage II colorectal cancer using molecular profiling. METHODS: We retrospectively enrolled patients with pStage II colorectal cancer who did not receive perioperative adjuvant therapy and whose surgically resected specimens were evaluated using gene expression and whole-exome analyses between January 2014 and December 2018. We evaluated the long-term outcomes and examined the risk factors for relapse-free survival. RESULTS: We evaluated 322 patients with pStage II colorectal cancer, including 126 (39.1%) with right colon cancer. Eighty-seven patients (27.0%) had pT4 tumor, 175 (54.3%) had positive venous invasion, 120 (37.3%) had positive lymphatic invasion, and 68 (21.1%) had perineural invasion. The presence of mutations in key genes for colorectal cancer development based on whole-exome analyses was as follows: APC, 245 (76.1%); TP53, 208 (64.6%); and KRAS, 134 (41.6%). According to the consensus molecular subtype classification based on gene expression, 76 patients (23.6%) had consensus molecular subtype 4 and a significantly lower relapse-free survival than the other patients (5-year relapse-free survival: 83.8% vs. 92.9%, p = 0.017). Perineural invasion (hazard ratio: 5.316, p < 0.001) and consensus molecular subtype 4 (hazard ratio: 2.399, p = 0.020) were identified as independent risk factors for relapse-free survival. CONCLUSIONS: Molecular profiling of Stage II colorectal cancer to assess the risk factors for relapse may contribute to the indication and drug selection for adjuvant chemotherapy.

The KRAS G12D mutation increases the risk of unresectable recurrence of resectable colorectal liver-only metastasis.

PURPOSE: Unresectable recurrence is a critical predictor of outcomes for colorectal cancer patients. We attempted to identify the prognostic factors, especially for unresectable recurrence-free survival (URFS) as a new endpoint, in patients with resectable colorectal liver-only metastasis (CRLOM). METHODS: We investigated patients with resectable CRLOM, who underwent an R0 resection for both CRC and CRLOM between January, 2014 and March, 2019 at a single institution. The exclusion criteria were patients who received neoadjuvant treatment, the absence of data for genetic analyses, and the presence of multiple cancers, synchronous CRC, or familial adenomatous polyposis. The prognostic factors were examined retrospectively using data on pre-hepatectomy factors, including primary tumor molecular profiling results. RESULTS: We analyzed the data of 101 patients who underwent curative-intent surgery for CRLOM. Multivariate analysis revealed that KRAS G12D mutation-positivity (hazard ratio [HR]: 7.69; p < 0.01), RYR2 mutation-positivity (HR: 4.03; p < 0.01), and KRAS G12S mutation-positivity (HR: 3.96; p = 0.03), CA19-9 > 37 U/ml before hepatectomy (HR: 3.62; p < 0.01), and primary tumor pN2 stage (HR: 3.22; p = 0.03) were significant predictors of the URFS. CONCLUSIONS: This is the first study to show that specific KRAS and RYR2 mutations were associated with the URFS.

Short-term and long-term outcomes after robotic radical surgery for rectal gastrointestinal stromal tumor.

BACKGROUND: The optimal approach for ensuring both complete resection and preservation of anal function in rectal gastrointestinal stromal tumor (GIST) remains unknown. The aim of this study was to clarify short-term and long-term outcomes after robotic radical surgery for rectal GIST. METHODS: A total of 13 patients who underwent robotic radical surgery for rectal GIST between December 2011 and April 2022 were included. All robotic procedures were performed using a systematic approach. A supplemental video of robotic radical surgery for rectal GIST is attached. The short-term outcome was the incidence of postoperative complications during the first 30 days after surgery. Surgical outcomes were retrieved from a prospective database. Long-term outcomes, including overall survival and recurrence-free survival, were determined in all patients. RESULTS: Median distance from the tumor to the anal verge was 4.0 cm. Surgical margins were negative in all patients. Two patients underwent neoadjuvant imatinib therapy. All patients underwent sphincter-preserving surgery. None underwent conversion to open or laparoscopic surgery. The incidence of postoperative Clavien-Dindo grade II and grade ≥ III complications was 7.7% and 0%, respectively. The median postoperative hospital stay was 7 days. Twelve patients (92.3%) underwent stoma closure within 5 months of the initial surgery. Median follow-up time was 76 months. The 5-year overall survival and recurrence-free survival rates were both 100%. None of the patients had recurrence. CONCLUSION: Short-term and long-term outcomes after radical robotic surgery for rectal GIST were favorable. Robotic surgery might be a useful surgical approach for rectal GIST.

Proportions and characteristics of interval cancer in annual fecal immunochemical test screening and postcolonoscopy colorectal cancer: Results from a Japanese multicenter prospective study using questionnaires, the C-DETECT study.

OBJECTIVES: There are several types of colorectal cancer (CRC) according to the detection methods and intervals, including interval CRC (iCRC) and postcolonoscopy CRC (PCCRC). We aimed to examine their proportions and characteristics. METHODS: We conducted a multicenter prospective study using questionnaires in Japan ("C-DETECT study"), in which differences in CRC characteristics according to detection methods and intervals were examined from consecutive adult patients. Because the annual fecal immunochemical test (FIT) was used in population-based screening, the annual FIT-iCRC was assessed. RESULTS: In total, 1241 CRC patients (1064 with invasive CRC) were included. Annual FIT-iCRC (a), 3-year PCCRC (b), and CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy (c) accounted for 4.5%, 7.0%, and 3.9% of all CRCs, respectively, and for 3.9%, 5.4%, and 4.3% of invasive CRCs, respectively. The comparison among these (a, b, c) and other CRCs (d) demonstrated differences in the proportions of ≥T2 invasion ([a] 58.9%, [b] 44.8%, [c] 87.5%, [d] 73.0%), metastasis ([a] 33.9%, [b] 21.8%, [c] 54.2%, [d] 43.9%), right-sided CRC ([a] 42.9%, [b] 40.2%, [c] 18.8%, [d] 28.6%), and female sex ([a] 53.6%, [b] 49.4%, [c] 27.1%, [d] 41.6%). In metastatic CRC, (a) and (b) showed a higher proportions of BRAF mutations ([a] [b] 12.0%, [c] [d] 3.1%). CONCLUSIONS: Annual FIT-iCRC and 3-year PCCRC existed in nonnegligible proportions. They were characterized by higher proportions of right-sided tumors, female sex, and BRAF mutations. These findings suggest that annual FIT-iCRC and 3-year PCCRC may have biological features different from those of other CRCs.

Development of a Diagnostic Artificial Intelligence Tool for Lateral Lymph Node Metastasis in Advanced Rectal Cancer.

BACKGROUND: Metastatic lateral lymph node dissection can improve survival in patients with rectal adenocarcinoma, with or without chemoradiotherapy. However, the optimal imaging diagnostic criteria for lateral lymph node metastases remain undetermined. OBJECTIVE: To develop a lateral lymph node metastasis diagnostic artificial intelligence tool using deep learning, for patients with rectal adenocarcinoma who underwent radical surgery and lateral lymph node dissection. DESIGN: Retrospective study. SETTINGS: Multicenter study. PATIENTS: A total of 209 patients with rectal adenocarcinoma, who underwent radical surgery and lateral lymph node dissection at 15 participating hospitals, were enrolled in the study and allocated to training (n = 139), test (n = 17), or validation (n = 53) cohorts. MAIN OUTCOME MEASURES: In the neoadjuvant treatment group, images taken before pretreatment were classified as baseline images and those taken after pretreatment as presurgery images. In the upfront surgery group, presurgery images were classified as both baseline and presurgery images. We constructed 2 types of artificial intelligence, using baseline and presurgery images, by inputting the patches from these images into ResNet-18, and we assessed their diagnostic accuracy. RESULTS: Overall, 124 patients underwent surgery alone, 52 received neoadjuvant chemotherapy, and 33 received chemoradiotherapy. The number of resected lateral lymph nodes in the training, test, and validation cohorts was 2418, 279, and 850, respectively. The metastatic rates were 2.8%, 0.7%, and 3.7%, respectively. In the validation cohort, the precision-recall area under the curve was 0.870 and 0.963 for the baseline and presurgery images, respectively. Although both baseline and presurgery images provided good accuracy for diagnosing lateral lymph node metastases, the accuracy of presurgery images was better than that of baseline images. LIMITATIONS: The number of cases is small. CONCLUSIONS: An artificial intelligence tool is a promising tool for diagnosing lateral lymph node metastasis with high accuracy. DESARROLLO DE UNA HERRAMIENTA DE INTELIGENCIA ARTIFICIAL PARA EL DIAGNSTICO DE METSTASIS EN GANGLIOS LINFTICOS LATERALES EN CNCER DE RECTO AVANZADO: ANTECEDENTES:Disección de nódulos linfáticos laterales metastásicos puede mejorar la supervivencia en pacientes con adenocarcinoma del recto, con o sin quimiorradioterapia. Sin embargo, aún no se han determinado los criterios óptimos de diagnóstico por imágenes de los nódulos linfáticos laterales metastásicos.OBJETIVO:Nuestro objetivo fue desarrollar una herramienta de inteligencia artificial para el diagnóstico de metástasis en nódulos linfáticos laterales mediante el aprendizaje profundo, para pacientes con adenocarcinoma del recto que se sometieron a cirugía radical y disección de nódulos linfáticos laterales.DISEÑO:Estudio retrospectivo.AJUSTES:Estudio multicéntrico.PACIENTES:Un total de 209 pacientes con adenocarcinoma del recto, que se sometieron a cirugía radical y disección de nódulos linfáticos laterales en 15 hospitales participantes, se inscribieron en el estudio y se asignaron a cohortes de entrenamiento (n = 139), prueba (n = 17) o validación (n = 53).PRINCIPALES MEDIDAS DE RESULTADO:En el grupo de tratamiento neoadyuvante, las imágenes tomadas antes del tratamiento se clasificaron como imágenes de referencia y las posteriores al tratamiento, como imágenes previas a la cirugía. En el grupo de cirugía inicial, las imágenes previas a la cirugía se clasificaron como imágenes de referencia y previas a la cirugía. Construimos dos tipos de inteligencia artificial, utilizando imágenes de referencia y previas a la cirugía, ingresando los parches de estas imágenes en ResNet-18. Evaluamos la precisión diagnóstica de los dos tipos de inteligencia artificial.RESULTADOS:En general, 124 pacientes se sometieron a cirugía solamente, 52 recibieron quimioterapia neoadyuvante y 33 recibieron quimiorradioterapia. El número de nódulos linfáticos laterales removidos en los cohortes de entrenamiento, prueba y validación fue de 2,418; 279 y 850, respectivamente. Las tasas metastásicas fueron 2.8%, 0.7%, y 3.7%, respectivamente. En el cohorte de validación, el área de recuperación de precisión bajo la curva fue de 0.870 y 0.963 para las imágenes de referencia y antes de la cirugía, respectivamente. Aunque tanto las imágenes previas a la cirugía como las iniciales proporcionaron una buena precisión para diagnosticar metástasis en los nódulos linfáticos laterales, la precisión de las imágenes previas a la cirugía fue mejor que la de las imágenes iniciales.LIMITACIONES:El número de casos es pequeño.CONCLUSIÓN:La inteligencia artificial es una herramienta prometedora para diagnosticar metástasis en los nódulos linfáticos laterales con alta precisión. (Traducción-Dr. Aurian Garcia Gonzalez ).

Feasibility of two laparoscopic surgeries for colon cancer performed by the same surgeon on a single day.

BACKGROUND: Although the proportion of laparoscopic colectomies (LCs) for colon cancer is increasing, the feasibility of the same surgeon performing two LCs on a single day remains unknown. This study was conducted to clarify the feasibility of this practice by evaluating short-term and long-term outcomes. METHODS: This retrospective analysis enrolled patients with pathological stage I-III colon cancer who underwent LC at the Shizuoka Cancer Center between 2010 and 2020. Patients were divided into two groups based on the timing of the surgery for the surgeon. The first group (n = 1485) comprised patients who underwent LC as the first surgery of the day for the surgeon. The second group (n = 163) comprised patients who underwent LC as the second LC of the day for the surgeon. Propensity score matching was performed to balance the baseline characteristics of the first and second groups. The short-term and long-term outcomes of the two groups were compared. RESULTS: After propensity score matching, there were no significant differences in the incidence of postoperative complications of Clavien-Dindo classification grade II or higher between the first (10.4%, 17/163) and second groups (5.5%, 9/163). There were no significant differences in other perioperative outcomes, including operative time, intraoperative blood loss, and incidence of conversion to open surgery, between the two groups. Regarding long-term outcomes, there were no significant differences in overall survival or relapse-free survival between the two groups both in the full cohort and in the propensity score-matched cohort. In the propensity score-matched cohort, 5-year overall survival was 92.7% in the first group and 94.4% in the second group; 5-year relapse-free survival was 87.1% and 90.3%, respectively. CONCLUSION: Our results suggest that the same surgeon performing two LCs for colon cancer on a single day is feasible in terms of short-term and long-term outcomes.

Risk factors for and longitudinal course of male sexual dysfunction after robotic rectal cancer surgery.

AIM: The aim of this work was to investigate the risk factors associated with the incidence of sexual dysfunction in patients who underwent robot-assisted surgery with several treatment options, such as neoadjuvant chemoradiotherapy and lateral lymph node dissection, and clarify the longitudinal course of erectile function in risk groups. METHOD: A total of 203 male patients who underwent robot-assisted total mesorectal excision for rectal cancer between 2013 and 2019 were included. The risk factors for erectile and ejaculatory dysfunction as well as the longitudinal course of erectile function were retrospectively investigated in all cohorts and several risk groups, including those who underwent neoadjuvant chemoradiotherapy, lateral lymph node dissection and adjuvant chemotherapy. Erectile dysfunction was assessed using the International Index of Erectile Function and ejaculatory dysfunction was assessed using original questions. The survey was performed preoperatively and at 3, 6 and 12 months postoperatively. RESULTS: Erectile and ejaculatory dysfunction occurred in 46.8% and 15.7% of the patients, respectively. Multivariate analysis showed that neoadjuvant chemoradiotherapy was an independent risk factor for erectile dysfunction. Erectile function recovered longitudinally to the preoperative level overall, as well as in lateral lymph node dissection and postoperative adjuvant chemotherapy subgroups; however, recovery was poor in the neoadjuvant chemoradiotherapy group, even at 12 months postoperatively. CONCLUSION: Neoadjuvant chemoradiotherapy was found to be a risk factor for erectile dysfunction after robot-assisted surgery for rectal cancer. Erectile function recovered postoperatively in patients undergoing lateral lymph node dissection; however, those receiving neoadjuvant chemoradiotherapy showed poor recovery, even at 12 months postoperatively.

The impact of mesorectal fat area on recurrence following total mesorectal excision for lower rectal cancer.

BACKGROUND: The mesorectal fat area (MFA) at the tip of the ischial spines on magnetic resonance imaging has been used to characterize mesorectal morphology. Recent studies reported that a larger MFA correlated with difficulties in rectal cancer surgery. However, the relationship between MFA and rectal cancer prognosis remains unclear. This study evaluated the impact of MFA on recurrence following robotic total mesorectal excision (TME) for rectal cancer. METHODS: Patients who underwent robotic TME for lower rectal cancer from December 2011 to December 2016 were enrolled. Cox regression analysis was performed to determine variables associated with relapse-free survival (RFS). Patients were divided into groups based on MFA, and RFS was compared. RESULTS: Of 230 patients, 173 (75.3%) were male. The median age was 63 years, and median MFA was 19.7 cm2. In multivariate analysis, smaller MFA (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.88-0.97; p < 0.01), p/yp stage II (HR, 3.81; 95% CI, 1.40-10.35; p < 0.01), and p/yp stage III (HR, 5.35; 95% CI, 1.88-15.27; p < 0.01) were independently associated with worse RFS. Sex, body mass index, and visceral fat area were not correlated with RFS. In the median follow-up period of 60.8 months, patients with MFA < 19.7 cm2 had a significantly lower 5-year RFS rate (72.7%) than those with MFA ≥ 19.7 cm2 (85.0%). CONCLUSIONS: Smaller MFA was associated with worse RFS in patients undergoing robotic TME for lower rectal cancer. MFA is considered to be a prognostic factor in rectal cancer.

Incidence and clinical significance of 491 known fusion genes in a large cohort of Japanese patients with colorectal cancer.

BACKGROUND: The clinical significance of fusion genes in colorectal cancer remains unclear. The purpose of this study was to determine the incidence of fusion genes in colorectal cancer and explore their clinical significance by screening for common fusion genes in a large Japanese cohort. METHODS: This study involved 1588 patients. The incidence of 491 fusion genes was examined using a designed fusion panel. In addition, the patients were classified into two groups (RSPO fusion-positive or -negative) according to the presence of RSPO fusions, and the clinicopathological and genetic characteristics of both groups were compared. Long-term outcomes were analyzed in patients without distant metastases. RESULTS: Fusion genes were detected in 2% (31/1588) of colorectal cancers. The incidence of RSPO fusions (such as PTPRK-RSPO3 and EIF3E-RSPO2) was 1.5% (24/1588), making them the most common fusions, whereas the incidence of other fusion genes was extremely low. The distribution of consensus molecular subtypes and frequency of APC mutations were significantly different between the RSPO fusion-positive and -negative groups. The 3-year cumulative incidence rate of recurrence was higher in the RSPO fusion-positive group than in the RSPO fusion-negative group (positive, 31.2% vs. negative, 13.5%, hazard ratio = 2.357; p = 0.040). CONCLUSION: Broad screening for fusion genes showed that RSPO fusions were the most common in colorectal cancer, with an incidence of 1.5%. RSPO fusions may be clinically significant in identifying patients at a high risk of recurrence who would be responsive to specific treatments.

Long-term outcomes of upfront robotic rectal cancer surgery: a single-center, retrospective cohort study in Japan.

PURPOSE: The purpose of this study was to evaluate the long-term outcomes of robotic rectal cancer surgery and to examine the risk factors for recurrence. METHODS: In a high-volume center in Japan, we retrospectively enrolled patients with pStage I-III rectal cancer within 15 cm of the anal verge who underwent robotic surgery from 2011 to 2017. Almost all patients underwent upfront surgery, and lateral lymph-node dissection (LLND) was performed for patients with locally advanced lower rectal cancer. We evaluated the 5-year overall survival (OS), relapse-free survival (RFS), and cumulative local recurrence (LR) rates and examined the risk factors for the RFS. RESULTS: We evaluated 488 patients who underwent robotic rectal cancer surgery, including 5.1% who underwent preoperative chemoradiotherapy to obtain clear resection margins and 33.6% who underwent LLND. There were 203, 87, and 198 patients with pStage I, II, and III, respectively, and the positive resection margin rate was 1.0%. The 5-year OS, RFS, and LR rates were 95.5%, 81.7%, and 2.2%, respectively. The independent risk factors for the RFS were the presence of venous invasion, extramural tumor deposits without lymph-node structure, and pT ≥ 3. CONCLUSION: This study demonstrated the favorable long-term outcomes of robotic rectal cancer surgery.

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses.

BACKGROUND: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). AIM: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. METHODS: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. RESULTS: The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. CONCLUSIONS: MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

Lymph node metastasis in T1 colorectal cancer with the only high-risk histology of submucosal invasion depth ≥ 1000 µm.

PURPOSE: The number of patients undergoing additional surgery after endoscopic resection (ER) for T1 colorectal cancer (CRC) is increasing. Regarding high-risk histology of lymph node metastasis (LNM) in T1 CRC, a submucosal invasion depth ≥ 1000 µm (T1b) alone may be related to a low incidence of LNM. This study was conducted to clarify the incidence of LNM and to identify factors associated with LNM in T1 CRC with high-risk histology characterized only by T1b. METHODS: We retrospectively investigated patients with pathological T1b CRC who underwent colorectal resection between 2010 and 2020. Patients were divided into two groups with high-risk histology: those in whom the only high-risk feature was T1b (low-risk T1b group, n = 263), and those with T1b as well as lymphovascular invasion, tumor budding, or poorly differentiated or mucinous adenocarcinoma (high-risk T1b group, n = 289). The incidences of LNM and recurrence were compared. Multivariate analysis was performed to identify factors associated with LNM in the low-risk T1b group. RESULTS: The incidences of LNM were 3.8% and 21.6% in the Low- and High-risk T1b groups, respectively (p < 0.01), while the 5-year recurrence rates in the two groups were 0.6% and 3.4%, respectively (p = 0.10). Multivariate analysis revealed that only a predominant histological type of moderately differentiated adenocarcinoma (p = 0.04) was independently associated with LNM in the low-risk T1b group. CONCLUSION: When considering the omission of additional surgery after ER in cases of T1 CRC whose only high-risk histological feature is T1b, attention should be paid to the predominant histological type.

Preoperative and postoperative prognostic factors of patients with stage II/III lower rectal cancer without neoadjuvant therapy in the clinical trial (JCOG0212).

BACKGROUND: The JCOG0212 trial was a randomized controlled trial comparing mesorectal excision alone to mesorectal excision with lateral lymph node dissection for stage II/III lower rectal cancer patients without clinical lateral lymph node enlargement. This study aimed to identify clinicopathological prognostic factors for relapse-free survival and overall survival of lower rectal cancer in the trial. METHODS: Prospective data were selected from 663 patients with complete data. Uni and multivariable Cox regression model was applied to evaluate the preoperative and the combined preoperative and postoperative factors, respectively. Preoperative factors included age, sex, performance status, clinical T, clinical N and operative procedures. Postoperative factors included histological grade, pathological T, number of metastatic lymph nodes and number of dissected lymph nodes. No patient received neoadjuvant treatment. RESULTS: Regarding preoperative factors, multivariable analysis revealed that performance status 1 (vs. 0: HR 2.079, P = 0.0041) and cT4a (vs. cT2-3: HR 2.721, P = 0.0002) were independent risk factors for relapse-free survival, and those for overall survival were male (vs. female: HR 1.660, P = 0.0228) and cT4a (vs. cT2-3: HR 2.486, P = 0.0473). The only independent preoperative risk factor common for relapse-free survival and overall survival was cT4a. Taking preoperative and postoperative factors together, the number of metastatic lymph nodes was the only independent risk factor common for relapse-free survival and overall survival. CONCLUSIONS: Clinical stage II/III lower rectal cancer patients with cT4a should be a target of therapeutic development of neoadjuvant therapy. Postoperatively, intensive chemotherapy should be investigated for patients with more metastatic lymph nodes.

Success rate of acquiring informed consent and barriers to participation in a randomized controlled trial of laparoscopic versus open surgery for non-curative stage IV colon cancer in Japan (JCOG1107).

BACKGROUND: Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC. METHODS: A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires. RESULTS: In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n = 84) or open surgery group (n = 84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients' preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization. CONCLUSIONS: The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

Robotic surgery for clinical T4 rectal cancer: short- and long-term outcomes.

BACKGROUND: The optimal surgical approach for clinical T4 (cT4) rectal cancer is unknown. This study was conducted to clarify short- and long-term outcomes of robotic surgery for cT4 rectal cancer. METHODS: In our retrospective cohort study, we enrolled patients who underwent robotic surgery for cT4 rectal cancer within 15 cm from the anal verge between 2011 and 2018. The short- and long-term outcomes were evaluated. RESULTS: Of a total of 122 eligible patients, 70 (57%) had cT4a tumors and 52 (43%) had cT4b tumors. Thirty-five patients (29%) had distant metastasis and 21 (17%) underwent preoperative chemoradiotherapy. Thirty-four patients (28%) underwent combined resection of adjacent organs and 43 (35%) underwent lateral lymph node dissection. The median operative time was 288 min and the median blood loss was 11 ml. No patients required conversion to open surgery. The incidences of postoperative complications of grades II, III, and IV or more according to the Clavien-Dindo classification were 17.2%, 3.5%, and 0%, respectively. Seventy-three patients (60%) had pathological T4 tumors, and the incidence of positive resection margins was 4.9%. The median follow-up time was 42.9 months. The 3-year overall survival, disease-free survival, and cumulative local recurrence rates were 87.5%, 70.4%, and 4.0%, respectively. CONCLUSIONS: The short- and long-term outcomes of robotic surgery for cT4 rectal cancer were favorable. Robotic surgery is considered to be a useful approach for cT4 rectal cancer.