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.

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.

Prediction model of the risk for lateral local recurrence in locally advanced rectal cancer without enlarged lateral lymph nodes: Lessons from a Japanese multicenter pooled analysis of 812 patients.

Aim: Although the oncological impact of lateral lymph node dissection on enlarged lateral lymph nodes has been gradually accepted over the last decade, that on lateral lymph nodes without swelling remains doubtful. This study aimed to develop a prediction model for the future risk of lateral local recurrence and to clarify the value of adding lateral lymph node dissection in locally advanced rectal cancer without enlarged lateral lymph nodes. Methods: This retrospective, multi-institutional study recruited 812 patients with cStage II/III low rectal cancer without enlarged lateral lymph nodes <7 mm. Total lateral local recurrence was a hypothetical value of future risk of lateral local recurrence when lateral lymph node dissection was never performed. Results: Overall, total lateral local recurrences were observed in 67 patients (8.3%). In the multivariate analyses, the strongest risk factor for total local recurrences was no preoperative chemoradiotherapy (odds ratio [OR][95%Cl]: 33.2 [4.56-241.7], P < 0.001), followed by tumor distance ≤40 mm (OR [95%Cl]: 2.71 [1.51-4.86], P < 0.001) and lateral lymph node 5-7 mm (OR[95%Cl]: 2.38 [1.26-4.48], P = 0.007). In patients with lateral lymph nodes of 5-7 mm, the total lateral recurrence rate was 4.8% after preoperative chemoradiotherapy. Lateral lymph node dissection could reduce from a total lateral local recurrence of 21.6% to an actual lateral local recurrence of 8.0% in patients without preoperative treatment. Conclusion: We introduce a novel prediction model of future risk of lateral local recurrences, which has the potential to enable us to indicate lateral lymph node dissection selectively according to the patients' risks.

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.

Clinicopathological features and prognosis of primary small bowel adenocarcinoma: a large multicenter analysis of the JSCCR database in Japan.

BACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.

Outcomes of Metastatic and Unresectable Small Bowel Adenocarcinoma in Japan According to the Treatment Strategy: A Nationwide Observational Study.

PURPOSE: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA. METHODS: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests. RESULTS: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively. CONCLUSION: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

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.

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.

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.

Impact of Mutations in Subunit Genes of the Mammalian SWI/SNF Complex on Immunological Tumor Microenvironment.

BACKGROUND/AIM: Recently, inactivating somatic mutations of SWI/SNF chromatin-remodeling genes in cancers have been reported. However, few studies have been performed regarding the immunological analysis of the tumor microenvironment (TME) in chromatin remodeling complex gene-mutated tumors. In the present study, we identified cancer patients harboring various mammalian SWI/SNF complex mutations and investigated the immunological features in those mutated cancers. PATIENTS AND METHODS: Cancer patients harboring any type of chromatin remodeling complex gene mutation were selected and clinicopathological features were compared between chromatin remodeling complex gene expression-low and expression-high groups. Specifically, expression levels of immune response-associated genes and cancer-associated genes were compared between the SMARCA4 expression-low and expression-high groups using volcano plot analysis. RESULTS: Among cancers harboring PBRM1, SAMRACA4 and ARID2 gene mutations, T-cell marker and mature B-cell marker genes were up-regulated in the tumor. Specifically, T-cell effector genes (CD8B, CD40LG), central memory marker genes (CD27, CCR7) and mature B-cell marker genes (CD20, CD38, CD79 and IRF4) were up-regulated, and cancer-associated genes including MYB, MYC and AURKB genes were down-regulated in the SMARCA4 expression-low group. Remarkably, heatmap of gene expression and immunohistochemistry (IHC) data demonstrated that the tertiary lymphoid structure (TLS) gene signature of mature B cells was up-regulated in SMACA4 gene-mutated stomach cancers. CONCLUSION: These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.

Robotic-assisted colectomy for right-sided colon cancer: Short-term surgical outcomes of a multi-institutional prospective cohort study in Japan.

Background: In Japan, there are no substantial reports on robotic-assisted colectomy because few institutions performed the procedure, as it was not covered by national insurance until March 2022. Aim: This study aimed to evaluate the safety and feasibility of robotic-assisted colectomy for patients with curatively resectable colon cancer in Japan. Methods: This multi-institutional, prospective, single-arm, observational study enrolled patients diagnosed with curatively resectable clinical stage I-IIIC colon adenocarcinoma with D2 or D3 lymph node dissection and treated with robotic-assisted colectomy. The primary endpoint was the conversion rate to laparotomy. The non-inferiority of outcomes for robotic-assisted colectomy versus laparoscopic colectomy, which was determined from historical data, was verified. Results: One hundred patients were registered between July 2019 and March 2022 and underwent robotic-assisted colectomy performed by seven expert surgeons at six institutions. Thirteen patients were excluded because their surgeons had insufficient experience performing robotic-assisted colectomy; therefore, 87 patients were eligible for the primary endpoint analysis. There was no conversion in these 87 patients, and robotic-assisted colectomy was non-inferior to laparoscopic colectomy in terms of conversion rate (90% confidence interval 0-3.38, p = 0.0006). No intraoperative adverse events occurred, and no mortality was observed in a total of 100 patients. The rate of patients with Clavien-Dindo complications grade III or higher was 4%. Conclusion: This study showed the non-inferiority of the conversion rates between robotic-assisted colectomy and laparoscopic colectomy. Favorable perioperative outcomes also suggest the safety and feasibility of robotic-assisted colectomy.

Generation of novel complete HLA class I monoallelic cell lines used in an MHC stabilization assay for neoantigen evaluation.

Immunogenic neoantigens derived from somatic mutations in cancer have been identified through clinical studies with the cloning of tumor-infiltrating T cells, and cancer driver gene mutation-derived epitopes have been reported; however, these are rare. At present, the validation of epitopes predicted in silico is difficult as human T-cell clonal diversity cannot be reproduced in vitro or in experimental animal models. To confirm the epitope peptides presented by human leukocyte antigen (HLA) class I molecules predicted in silico, biochemical methods such as major histocompatibility complex (MHC) stabilization assays and mass spectrometry-mediated identification have been developed based on HLA-A*02:01 monoallelic T2 cells and HLA-C*01:02 monoallelic LCL721.221 cells. Therefore, in the present study, to prevent confusion due to peptide cross-presentation among HLA molecules, HLA class I monoallelic B-cell clones were generated from the TISI cell line by knocking out HLA-ABC and TAP2, and knocking in HLA alleles. To explore cancer driver mutations as potential targets for immunotherapy, exome sequencing data from 5,143 patients with cancer enrolled in a comprehensive genome analysis project at the Shizuoka Cancer Center were used to identify somatic amino acid substituted mutations and the 50 most frequent mutations in five genes, TP53, EGFR, PIK3CA, KRAS and BRAF, were identified. Using NetMHC4.1, the present study predicted whether epitopes derived from these mutations are presented on major HLA-ABC alleles in Japanese individuals and synthesized 138 peptides for MHC stabilization assays. The authors also attempted to examine the candidate epitopes at physiological temperatures by using antibody clone G46-2.6, which can detect HLA-ABC, independent of ß2-microglobulin association. In the assays, although the peptide-induced HLA expression levels were associated with the predicted affinities, the respective HLA alleles exhibited varying degrees of responsiveness, and unexpectedly, p53-mutant epitopes with predicted weak affinities exhibited strong responses. These results suggested that MHC stabilization assays using completely monoallelic HLA-expressing B-cell lines are useful for evaluating the presentation of neoantigen epitopes.

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 ).

Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557-558 Deletion Mutations.

Gastrointestinal stromal tumors (GIST) with KIT exon 11 deletions involving in codons 557-558 (KIT Δ557-558) exhibit higher proliferation rates and shorter disease-free survival times compared with GISTs with other KIT exon 11 mutations. We analyzed 30 GIST cases and observed genomic instability and global DNA hypomethylation only in high-risk malignant GISTs with KIT Δ557-558. Whole-genome sequencing revealed that the high-risk malignant GISTs with KIT Δ557-558 (12 cases) had more structural variations (SV), single-nucleotide variants, and insertions and deletions compared with the low-risk, less malignant GISTs with KIT Δ557-558 (six cases) and the high-risk (six cases) or low-risk (6 cases) GISTs with other KIT exon 11 mutations. The malignant GISTs with KIT Δ557-558 showed higher frequency and significance in copy number (CN) reduction on chromosome arms 9p and 22q, and 50% of them had LOH or CN-dependent expression reduction in CDKN2A. In addition, SVs with driver potential were detected in 75% of them, in which AKT3 and MGMT were recurrently identified. Genome-wide DNA methylation and gene expression analyses showed global intergenic DNA hypomethylation, SNAI2 upregulation, and higher expression signatures, including p53 inactivation and chromosomal instability, as characteristics of malignant GISTs with KIT Δ557-558 that distinguished them from other GISTs. These genomic and epigenomic profiling results revealed that KIT Δ557-558 mutations are associated with increased genomic instability in malignant GISTs. Significance: We present genomic and epigenomic insights into the malignant progression of GISTs with KIT exon 11 deletions involving in 557-558, demonstrating their unique chromosomal instability and global intergenic DNA hypomethylation.

Optimal bowel resection margin in colon cancer surgery: prospective multicentre cohort study with lymph node and feeding artery mapping.

Background: There are no standardised criteria for the 'regional' pericolic node in colon cancer, which represents a major cause of the international uncertainty regarding the optimal bowel resection margin. This study aimed to determine 'regional' pericolic nodes based on prospective lymph node (LN) mapping. Methods: According to preplanned in vivo measurements of the bowel, the anatomical distributions of the feeding artery and LNs were determined in 2996 stages I-III colon cancer patients who underwent colectomy with resection margin >10 cm at 25 institutions in Japan. Findings: The mean number of retrieved pericolic nodes was 20.9 (standard deviation, 10.8) per patient. In all patients except seven (0.2%), the primary feeding artery was distributed within 10 cm of the primary tumour. The metastatic pericolic node most distant from the primary tumour was within 3 cm in 837 patients, 3-5 cm in 130 patients, 5-7 cm in 39 patients and 7-10 cm in 34 patients. Only four patients (0.1%) had pericolic lymphatic spread beyond 10 cm; all of whom had T3/4 tumours accompanying extensive mesenteric lymphatic spread. The location of metastatic pericolic node did not differ by the feeding artery's distribution. Postoperatively, none of the 2996 patients developed recurrence in the remaining pericolic nodes. Interpretation: The pericolic nodes designated as 'regional' were those located within 10 cm of the primary tumours, which should be fully considered when determining the bowel resection margin, even in the era of complete mesocolic excision. Funding: Japanese Society for Cancer of the Colon and Rectum.

Use of a Powered Circular Stapler Can Prevent Anastomotic Air Leakage in Robotic Low Anterior Resection for Rectal Cancer.

Objectives: Preventing anastomotic complications during rectal cancer surgery is important. Compared with a manual circular stapler, a powered circular stapler is expected to reduce undesirable tension during anastomosis. However, whether a powered circular stapler can reduce anastomotic complications during robotic low anterior resection (Ro-LAR) remains unclear. We aimed to investigate whether the use of a powered circular stapler contributes to safe anastomosis in Ro-LAR. Methods: A total of 271 patients who underwent Ro-LAR for rectal cancer between April 2019 and April 2022 were included. Depending on the type of device employed, patients were divided into a powered circular stapler group (PCSG) and a manual circular stapler group (MCSG). Clinicopathological features and surgical outcomes were compared between the two groups. Results: There were no differences in clinicopathological characteristics and surgical outcomes, except for anastomotic outcomes, between the two groups. Patients with positive air leak tests were significantly more in the MCSG (p=0.026; PCSG, 1.5%; MCSG, 8.0%). Frequencies of anastomotic leakage (p=0.486; PCSG, 6.1%; MCSG, 8.9%) and anastomotic bleeding (p=1.000; PCSG, 0.7%; MCSG, 0.8%) were similar between the two groups. Multivariate analysis showed that the use of a powered circular stapler significantly increased the negative leak tests (p=0.020, odds ratio 6.74, 95% confidence interval 1.35-33.56). Conclusions: Use of a powered circular stapler in Ro-LAR for rectal cancer was significantly associated with a negative air leak test, suggesting that it contributes to stable and safe anastomosis.

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.