An aggressive gastric CIC-DUX4 sarcoma surgically resected with multivisceral organs: a case report.

BACKGROUND: Capicua transcriptional repressor-double homeobox 4 sarcoma (CDS) is a rare and aggressive malignant soft tissue tumor that typically arises within the soft tissues. We report an exceptionally rare case of a gastric CDS successfully resected despite its extensive invasion into surrounding organs. CASE PRESENTATION: A 48-year-old male presented with a progressively enlarging abdominal mass. Upper gastrointestinal endoscopy revealed a large ulcerative tumor on the posterior gastric wall. Biopsy results initially suggested a neuroendocrine cell carcinoma. Contrast-enhanced computed tomography showed a 20 cm tumor protruding from the posterior stomach wall, directly invading the pancreas and colon. We performed a multivisceral resection (stomach, pancreatic tail, spleen, and transverse colon) achieving an R0 resection. Pathological examination of the permanent specimen revealed small round cells with high nuclear-to-cytoplasmic ratios. Immunohistochemical staining confirmed the diagnosis of CDS. The patient recovered well and was discharged on postoperative day 33. CONCLUSIONS: This case report describes the first detailed account of a surgically resected aggressive CDS originating from the stomach.

Reduced port laparoscopic rectopexy for full-thickness rectal prolapse.

BACKGROUND: Laparoscopic rectopexy is an established treatment option for full-thickness rectal prolapse. Recently, reduced port surgery (RPS) has emerged as a novel concept, offering reduced postoperative pain and improved cosmetic outcomes compared with conventional multiport surgery (MPS). This study aimed to evaluate the feasibility and safety of RPS for full-thickness rectal prolapse. METHODS: From October 2012 to December 2018, 37 patients (MPS: 10 cases, RPS: 27 cases) underwent laparoscopic rectopexy for full-thickness rectal prolapse. Laparoscopic posterior mesh rectopexy (Wells procedure) is the standard technique for full-thickness rectal prolapse at our hospital. RPS was performed using a multi-channel access device, with an additional 12-mm right-hand port. Short-term outcomes were retrospectively compared between MPS and RPS. RESULTS: No significant differences were observed between MPS and RPS in the median operative time, the median blood loss volume, the postoperative complication rates, and median hospital stay duration after surgery. CONCLUSION: Reduced port laparoscopic posterior mesh rectopexy may serve as an effective therapeutic option for full-thickness rectal prolapse. However, to establish the superiority of RPS over MPS, a prospective, randomized, controlled trial is warranted.

Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors.

Although comprehensive genomic profiling has become standard in oncology for advanced solid tumors, the full potential of circulating tumor DNA (ctDNA)-based profiling in capturing tumor heterogeneity and guiding therapy selection remains underexploited, marked by a scarcity of evidence on its clinical impact and the assessment of intratumoral heterogeneity. The GOZILA study, a nationwide, prospective observational ctDNA profiling study, previously demonstrated higher clinical trial enrollment rates using liquid biopsy compared with tissue screening. This updated analysis of 4,037 patients further delineates the clinical utility of ctDNA profiling in advanced solid tumors, showcasing a significant enhancement in patient outcomes with a 24% match rate for targeted therapy. Patients treated with matched targeted therapy based on ctDNA profiling demonstrated significantly improved overall survival compared with those receiving unmatched therapy (hazard ratio, 0.54). Notably, biomarker clonality and adjusted plasma copy number were identified as predictors of therapeutic efficacy, reinforcing the value of ctDNA in reflecting tumor heterogeneity for precise treatment decisions. These new insights into the relationship between ctDNA characteristics and treatment outcomes advance our understanding beyond the initial enrollment benefits. Our findings advocate for the broader adoption of ctDNA-guided treatment, signifying an advancement in precision oncology and improving survival outcomes in advanced solid tumors.

ctDNA-based molecular residual disease and survival in resectable colorectal cancer.

The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.0001) and overall survival (OS; HR: 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.

Laparoscopic transabdominal preperitoneal repair for a patient with Laugier's and inguinal hernia.

BACKGROUND: Laugier's hernia is a very rare atypical femoral hernia and is challenging to diagnose preoperatively. Herein, we report a rare case of inguinal and Laugier's hernias treated with laparoscopic transabdominal preperitoneal repair. CASE PRESENTATION: A 63-year-old man was admitted to our hospital with right groin swelling for 4 years. Computed tomography revealed an indirect inguinal hernia with protrusion of the small intestine. The preoperative diagnosis was right indirect inguinal hernia; Laugier's hernia was unknown. The patient underwent laparoscopic transabdominal preperitoneal repair. During the surgery, part of the perivesical adipose tissue penetrated the lacunar ligament. It was located medial to the typical site of a femoral hernia. Thus, Laugier's hernia was diagnosed. Finally, laparoscopic transabdominal preperitoneal repair was performed for Laugier's hernia and inguinal hernia. The postoperative course was good, without recurrence. CONCLUSIONS: To our knowledge, this is the first reported case of inguinal and Laugier's hernia treated with laparoscopic transabdominal preperitoneal repair. Surgeons should be mindful that inguinal hernias can occur concurrently with other types of hernias, such as femoral hernias, including atypical variants like Laugier's hernia. Additionally, they should actively consider laparoscopic approaches such as transabdominal preperitoneal for femoral hernias. These approaches are beneficial for precise diagnosis, confirming the presence of other hernias, and simultaneously treating all coexisting inguinal hernias.

Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial.

BACKGROUND: Trastuzumab deruxtecan has shown encouraging activity in patients with treatment-refractory HER2-positive, RAS wild-type and BRAF wild-type metastatic colorectal cancer. Dose optimisation and further antitumour assessments in patients with RAS mutations and those with previous anti-HER2 therapy are warranted. We aimed to evaluate two doses of trastuzumab deruxtecan (5·4 mg/kg and 6·4 mg/kg) to establish the recommended dose in patients with pretreated HER2-positive, RAS wild-type or mutant metastatic colorectal cancer. METHODS: DESTINY-CRC02 was a multicentre, randomised, two-stage, two-arm, phase 2 study done in 53 research hospitals and medical centres in Australia, Belgium, France, Italy, Japan, South Korea, Spain, Taiwan, the UK, and the USA. Eligible patients were aged 18 years and older or 20 years and older (depending on region) with pretreated pathologically documented, unresectable, recurrent, or metastatic HER2-positive, and RAS wild-type or mutant colorectal cancer. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and have received previous chemotherapy, and anti-EGFR, anti-VEGF, or anti-PD-L1 therapy, if clinically indicated. In stage 1, patients were randomly assigned (1:1), via a secure interactive response technology system, to receive 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan administered intravenously every 21 days. Stratification factors were ECOG performance status, HER2 status, and RAS status. In stage 2, patients were assigned into the 5·4 mg/kg treatment group only. The primary endpoint was confirmed objective response rate by blinded independent central review, assessed in all patients for whom treatment was assigned (full analysis set). Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04744831, and is ongoing (not recruiting). FINDINGS: Between March 5, 2021, and March 29, 2022, 135 patients were centrally screened, 122 of whom were enrolled. In stage 1, 40 patients each were randomly assigned to receive trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg. In stage 2, an additional 42 patients were enrolled in the 5·4 mg/kg group. 64 (52%) participants were male and 58 (48%) were female. The median duration of follow-up was 8·9 months (IQR 6·7-10·5) in the 5·4 mg/kg group and 10·3 months (5·9-12·7) in the 6·4 mg/kg group. The confirmed objective response rate by blinded independent central review was 37·8% (31/82 [95% CI 27·3-49·2]) in the 5·4 mg/kg group and 27·5% (11/40 [14·6-43·9]) in the 6·4 mg/kg group. 34 (41%) of 83 patients in the 5·4 mg/kg group and 19 (49%) of 39 in the 6·4 mg/kg group had grade 3 or worse drug-related treatment-emergent adverse events. The most common grade 3 or worse drug-related treatment-emergent adverse events were neutrophil count decreased (13 [16%] of 83 patients), anaemia (six [7%]), nausea (six [7%]), and white blood cell count decreased (five [6%]) in the 5·4 mg/kg group; and were neutrophil count decreased (10 [26%] of 39 patients), anaemia (eight [21%]), platelet count decreased (four [10%]), and white blood cell count decreased (four [10%]) in the 6·4 mg/kg group. Drug-related serious adverse events occurred in 11 (13%) of 83 patients in the 5·4 mg/kg group and six (15%) of 39 patients in the 6·4 mg/kg group; the most common in the 5·4 mg/kg group was nausea (three [4%] patients) and the most common in the 6·4 mg/kg group were fatigue (two [5%] patients), neutropenia (two [5%]), and thrombocytopenia (two [5%]). A drug-related treatment-emergent adverse event related to death occurred in one (1%) patient in the 5·4 mg/kg group (due to hepatic failure). Adjudicated drug-related interstitial lung disease or pneumonitis events were observed in seven (8%) patients in the 5·4 mg/kg group (all grade 1 or 2) and in five (13%) patients in the 6·4 mg/kg group (four grade 1 or 2; one grade 5). INTERPRETATION: The promising antitumour activity and favourable safety profile support trastuzumab deruxtecan 5·4 mg/kg as the optimal single-agent dose for patients with pretreated HER2-positive metastatic colorectal cancer, including those with RAS mutations, previous anti-HER2 therapy, or both. FUNDING: Daiichi Sankyo and AstraZeneca.

Novel ERBB2 Variant Potentially Associated with Resistance against Anti-HER2 Monoclonal Antibody-Based Therapy in ERBB2-Amplified Metastatic Colorectal Cancer.

PURPOSE: HER2-targeted therapies in ERBB2-amplified metastatic colorectal cancer (mCRC) are effective; however, a notable portion of patients do not respond to treatment, and secondary resistance occurs in most patients receiving these treatments. The purpose of this study was to investigate determinants of treatment efficacy and resistance in patients with ERBB2-amplified mCRC who received HER2-targeted therapy by analyzing multiomics data. EXPERIMENTAL DESIGN: We investigated genomic data from a nationwide large cancer genomic screening project, the SCRUM-Japan project. We analyzed paired genome and transcriptome data of tissue and genomic data of ctDNA collected pre- and postprogression in patients enrolled in the related trial, TRIUMPH, in ERBB2-amplified mCRC. RESULTS: In 155 patients with ERBB2-amplified solid tumors who received HER2-targeted therapy based on the SCRUM-Japan project, the objective response rate was 50%, 51%, and 35% in ERBB2 wild-type, variant of unknown significance, and pathogenic variant groups, respectively. In the paired genome and transcriptome data analyses in TRIUMPH, we identified the novel splicing-associated variant c.644-66_-2del in one of the 11 patients with paired whole-exome sequencing and whole-transcriptome sequencing data sets, which lacks the binding domain of pertuzumab, in progressed metastatic tumor as a variant with potential pathogenicity. The time-course ctDNA analysis detected c.644-66_-2del as an acquired variant. CONCLUSIONS: This study highlighted the importance of ERBB2 genomic status when evaluating the efficacy of HER2-targeted therapies in ERBB2-amplified mCRC. The identification of a novel splicing-associated variant may provide insights into potential mechanisms of treatment resistance. Furthermore, we demonstrated the utility of ctDNA to follow the acquired genomic status of mCRC tumors.

Improvement in Quality of Life after Laparoscopic or Robotic-assisted Sacrocolpopexy with a Single Anterior Mesh in Patients with Pelvic Organ Prolapse: A Retrospective Analysis from a Single Institution.

Objectives: Pelvic organ prolapse (POP) is a significant health-care problem for older women. We have treated POP surgically using laparoscopic sacrocolpopexy (LSC) or robotic-assisted sacrocolpopexy (RSC). The original LSC and RSC procedures were done with anterior and posterior meshes; however, the use of the single mesh procedure is increasing because of its simplicity and safety. There have been few reports about the change in quality of life (QOL) using the single mesh procedure. Therefore, the present study aimed to retrospectively evaluate the change in QOL by LSC and RSC using a single anterior mesh for women without posterior compartment prolapse. Materials and Methods: We performed LSC or RSC using a single anterior mesh in 52 patients who had POP without posterior vaginal wall prolapse between August 2018 and October 2022. We assessed the QOL before and after surgery using prolapse-QOL (P-QOL) questionnaires. Results: All patients who received LSC or RSC with a single anterior mesh left the hospital as scheduled without severe perioperative complications. There were no instances of wound infection or vaginal mesh extrusion. The recovery rate of questionnaires was 63.5% (33/52). All QOL score domains improved significantly, and there were no questionnaire parameters that worsened. Conclusion: LSC or RSC using only a single anterior mesh improves P-QOL with a low incidence of surgical complications for POP patients who did not have posterior vaginal wall prolapse. LSC or RSC with a single anterior mesh may be a prospective new procedure for POP.

Mixbiotic society measures: Assessment of community well-going as living system.

Social isolation and fragmentation represent global challenges, with the former stemming from a lack of interaction and the latter from exclusive mobs-both rooted in communication issues. Addressing these challenges, the philosophical realm introduces the concept of the "mixbiotic society." In this framework, individuals with diverse freedoms and values mix together in physical proximity with diverse mingling, recognizing their respective "fundamental incapacities" and uniting in solidarity. This study aims to provide novel measures to balance freedom and solidarity, specifically the intermediate between isolation and mobbing, within a mixbiotic society. To achieve this, we introduce simplified measures to evaluate dynamic communication patterns. These measures complement traditional social network analysis of static structures and conventional entropy-based assessments of dynamic patterns. Our specific hypothesis posits that the measures corresponding to four distinct phases are established by representing communication patterns as multidimensional vectors. These measures include the mean of Euclidean distance to quantify "mobism" for fragmentation, the relative distance change for "atomism" indicating isolation, and a composite measure derived from multiplying the mean and variance of cosine similarity for "mixism," reflecting the well-going state of a mixbiotic society. Additionally, nearly negligible measures correspond to "nihilism." Through the evaluation of seven real-society datasets (high school, primary school, workplace, village, conference, online community, and email), we demonstrate the utility of the "mixism" measure in assessing freedom and solidarity in society. These measures can be employed to typify communities on a radar chart and a communication trajectory graph. The superiority of the measures lies in their ability to evaluate dynamic patterns, ease of calculation, and easily interpretable meanings compared to conventional analyses. As a future development, alongside additional validation using diverse datasets, the mixbiotic society measures will be employed to analyze social issues and applied in the fields of digital democracy and platform cooperativism.

Postoperative venous thromboembolism after surgery for locally recurrent rectal cancer.

BACKGROUND: Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. METHODS: From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. RESULTS: Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). CONCLUSIONS: This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.

Effects of Longitudinal Changes in Anemia Status on Clinical Outcomes in Patients With Non-Valvular Atrial Fibrillation　- Analysis From the Hokuriku-Plus AF Registry.

BACKGROUND: Anemia, a common comorbidity in older patients with heart failure (HF) and atrial fibrillation (AF), is associated with an increased risk of adverse events. This study evaluated the prognostic effects of longitudinal changes in anemia status on clinical outcomes in patients with AF. METHODS AND RESULTS: We prospectively evaluated data of 1,388 patients with AF from the Hokuriku-Plus AF Registry (1,010 men; mean [±SD] age 72.3±9.7 years) and recorded the incidence of death, HF, thromboembolism, and major bleeding. Of these patients, the 1,233 for whom hemoglobin levels were available at baseline and at the 1-year follow-up were further evaluated. Patients were categorized into 3 groups based on longitudinal changes in 1-year anemia status: Group 1, AF without anemia; Group 2, AF with improved anemia; and Group 3, AF with sustained or new-onset anemia. Over the 1-5 years of follow up, the incidences of death, HF, thromboembolism, and major bleeding were significantly higher among patients with than without anemia. In addition, the incidence of death or HF was significantly higher in Group 3 than in Groups 1 and 2. Multivariate analysis revealed no anemia or improvement in anemia in 1 year as an independent predictor for a favorable prognosis for cardiovascular death and HF. CONCLUSIONS: Recovery from anemia may be associated with a favorable clinical course of AF.

Origin of O2 Generation in Sulfide-Based All-Solid-State Batteries and its Impact on High Energy Density.

The cathode surface of sulfide-based all-solid-state batteries (SBs) is commonly coated with amorphous-LiNbO3 in order to stabilize charge-discharge reactions. However, high-voltage charging diminishes the advantages, which is caused by problems with the amorphous-LiNbO3 coating layer. This study has investigated the degradation of amorphous-LiNbO3 coating layer directly during the high-voltage charging of SBs. O2 generation via Li extraction from the amorphous-LiNbO3 coating layer is observed using electrochemical gas analysis and electrochemical X-ray photoelectron spectroscopy. This O2 leads to the formation of an oxidative solid electrolyte (SE) around the coating layer and degrades the battery performance. On the other hand, elemental substitution (i.e., amorphous-LiNbxP1- xO3) reduces O2 release, leading to stable high-voltage charge-discharge reactions of SBs. The results have emphasized that the suppression of O2 generation is a key factor in improving the energy density of SBs.

Clinical features associated with NeoRAS wild-type metastatic colorectal cancer A SCRUM-Japan GOZILA substudy.

"NeoRAS WT" refers to the loss of RAS mutations (MTs) following first-line treatment in metastatic colorectal cancer (mCRC). We evaluate the incidence and clinicopathological characteristics of NeoRAS WT mCRC using next-generation sequencing of plasma circulating tumor DNA. Patients with mCRC enrolled in the GOZILA study initially diagnosed with tissue RAS MT mCRC and received subsequent systemic therapy are eligible. NeoRAS WT is defined as the absence of detectable RAS MT in plasma and assessed in all eligible patients (Group A) and in a subgroup with at least one somatic alteration detected in plasma (Group B). Overall, 478 patients are included. NeoRAS WT prevalence is 19.0% (91/478) in Group A and 9.8% (42/429) in Group B. Absence of liver or lymph node metastasis and tissue RAS MTs other than KRAS exon 2 MTs are significantly associated with NeoRAS WT emergence. Overall, 1/6 and 2/6 patients with NeoRAS WT treated with anti-EGFR monoclonal antibodies (mAbs) show partial response and stable disease for ≥6 months, respectively. NeoRAS WT mCRC is observed at a meaningful prevalence, and anti-EGFR mAb-based therapy may be effective.

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

BACKGROUND: The significance of resection of para-aortic lymph node metastasis in colorectal cancer is controversial. OBJECTIVE: To clarify the prognosis of colorectal cancer after para-aortic lymph node metastasis resection. DESIGN: Multicenter retrospective study. SETTINGS: Thirty-six institutions in Japan participated in this study. Database and medical records at each institution were used for data collection. PATIENTS: Patients with resected and pathologically proven para-aortic lymph node metastasis of colorectal cancer between 2010 and 2015 were included. MAIN OUTCOME MEASURES: Overall survival after para-aortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of para-aortic 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% 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 HR: 1.91, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.98, p = 0.005), time to metastases (synchronous vs metachronous adjusted HR: 2.02, p = 0.02), and the number of para-aortic lymph node metastasis (3 or more vs less than 3, adjusted HR: 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, adjusted HR: 4.77, p = 0.01; rectum vs right-sided colon, adjusted HR: 5.27, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.90, p = 0.03), number of para-aortic lymph node metastases (3 or more vs less than 3, adjusted HR: 2.20, p = 0.001), and hospital volume (less than 10 vs 10 or more, adjusted HR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Para-aortic 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 3 para-aortic lymph node metastases were a favorable prognostic factor for overall and recurrence-free survival. However, para-aortic lymph node metastases were considered to be a systemic disease, and the significance of resection was limited. See Video Abstract . RESULTADO A LARGO PLAZO POSTERIOR A LA RESECCIN QUIRRGICA DE METSTASIS EN GANGLIOS LINFTICOS PARAARTICOS DE CNCER COLORRECTAL UN ESTUDIO RETROSPECTIVO MULTICNTRICO: ANTECEDENTES:La importancia de la resección de metástasis en los ganglios linfáticos paraaórticos (PALNM) en el cáncer colorrectal (CCR) es controvertida.OBJETIVO:Aclarar el pronóstico del CCR después de la resección PALNM.DISEÑO:Estudio retrospectivo multicéntrico.ENTORNO CLINICO:Treinta y seis instituciones en Japón participaron en este estudio.PACIENTES:Pacientes con PALNM de CCR resecado y patológicamente probado entre 2010 y 2015.FUENTES DE DATOS:Base de datos y registros médicos de cada institución.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general (SG) después de la resección PALNM, supervivencia libre de recurrencia (SLR) y patrones de recurrencia después de la resección R0 de PALNM.RESULTADOS:Se incluyó un total de 133 pacientes en la población de análisis primario de este estudio. La tasa de SG a 5 años (intervalo de confianza [IC] del 95 %) fue del 41,0 % (32,0, 49,8) y la mediana de supervivencia (IC del 95 %) fue de 4,1 (3,4, 4,7) años. Los factores de pronóstico independientes para la SG fueron el estadio T patológico (pT4 vs. pT1-3, índice de riesgo ajustado [aHR]: 1,91, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,98, p = 0,005), tiempo hasta las metástasis (síncronas vs. metacrónicas, aHR: 2,02, p = 0,02) y número de PALNM (≥3 vs. <3, aHR: 2,13, p = 0,001). La tasa de SLR a 5 años (IC del 95%) fue del 21,1% (13,5, 29,7), con una mediana (IC del 95%) de 1,2 (0,9, 1,4) años. La ubicación del tumor primario (colon del lado izquierdo vs. derecho, aHR: 4,77, p = 0,01; recto vs. colon del lado derecho, aHR: 5,27, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,90, p = 0,03), el número de PALNM (≥3 vs. <3, aHR: 2,20, p = 0,001) y el volumen hospitalario (<10 vs. ≥10, aHR: 2,18, p = 0,02) se identificaron como independientes factores pronósticos del SLR. La recurrencia de los ganglios linfáticos paraaórticos fue la más común con un 33,3%.LIMITACIONES:No se puede descartar un sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:Menos de tres PALNM fue un factor pronóstico favorable tanto para la SG como para la SLR. Sin embargo, las PALNM se consideraron una enfermedad sistémica y la importancia de la resección fue limitada. (Traducción- Dr. Francisco M. Abarca-Rendon ).

QUATTRO-II randomized trial: CAPOXIRI+bevacizumab vs. FOLFOXIRI+bevacizumab as first-line treatment in patients with mCRC.

BACKGROUND: The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC). METHODS: In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80 < HR < 1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes. FINDINGS: Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met its primary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9 months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR 1.114 [0.80 < HR < 1.25], p = 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%). CONCLUSION: CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC. FUNDING: Chugai Pharmaceutical Co., Ltd.

Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes. METHODS: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values. RESULTS: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight. CONCLUSIONS: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120.

Evaluation of Deeply Infiltrating Endometriosis by Preoperative Magnetic Resonance Imaging in Patients with Adenomyosis.

Objectives: Before endometriosis surgery, it is important to identify deep infiltrating endometriosis (DIE) to assess the surgical difficulty. Preoperative magnetic resonance imaging (MRI) was used to determine which findings are useful in predicting DIE. Materials and Methods: Between 2008 and 2016, 54 patients with adenomyosis underwent total laparoscopic hysterectomy at our hospital. We retrospectively evaluated the intraoperative findings and magnetic resonance imaging (MR) images. The MR images were scored based on the presence of five findings: retroflexed uterus, elevated posterior vaginal fornix, intestinal tethering in the direction of the uterus, faint strands between the uterus and intestine, and fibrotic nodules covering the serosal surface of the uterus. Results: Of the five findings, intestinal tethering and faint strands between the uterus and intestine showed a sensitivity of 73% and a specificity of 91%-100%, indicating the usefulness of these findings for detecting deep endometriosis lesions. However, finding a retroflexed uterus did not contribute to DIE lesion detection. The sensitivities of an elevated posterior fornix and fibrotic nodules covering the surface of the uterus were as low as 46%-59%, and their specificities were as high as 84%-91%. Conclusion: Preoperative preparation is essential for patients with intestinal tethering or faint strands between the uterus and intestine on preoperative MRI after obtaining appropriate informed consent.

Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.