Genomic Landscape of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens for Immunoprevention.

BACKGROUND & AIMS: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers. METHODS: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays. RESULTS: Mutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced precancers, and 20% of precancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced precancers, and 107 in precancers. No neoAgs were detected in PWOMP. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced precancers, and 29% of precancers. We observed increased levels of naïve CD8+ and memory CD4+ T cells in mismatch repair-deficient cancers and precancers via transcriptomics analysis. CONCLUSIONS: Shared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS precancers and early-stage cancers.

The prognostic impact of tumor deposits in colorectal cancer: More than just N1c.

BACKGROUND: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC. METHODS: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards regression analyses. RESULTS: In total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02-3.22), as it was for each given N category (e.g., N2a and TD-negative [HR, 2.50; 95% CI, 2.37-2.64] vs. N2a and TD-positive [HR, 3.75; 95% CI, 3.49-4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65-3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87-4.82]). CONCLUSIONS: TDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.

Para-aortic Lymph Node Dissection for Colorectal Cancer: Predicting Pathologic Lymph Node Positivity and Optimizing Outcomes.

INTRODUCTION: In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. METHODS: An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). RESULTS: Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. CONCLUSIONS: Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.

The Learning Curve for Robotic Lateral Pelvic Lymph Node Dissection for Rectal Cancer: A View From the West.

BACKGROUND: Lateral pelvic lymph node dissection is performed for selected patients with rectal cancer with persistent lateral nodal disease after neoadjuvant therapy. This technique has been slow to be adopted in the West because of concerns regarding technical difficulty. This is the first report on the learning curve for lateral pelvic lymph node dissection in the United States or Europe. OBJECTIVE: This study aimed to analyze the learning curve associated with robotic lateral pelvic lymph node dissection. DESIGN: Retrospective observational cohort. SETTING: Tertiary academic cancer center. PATIENTS: Consecutive patients from 2012 to 2021. INTERVENTION: All patients underwent robotic lateral pelvic lymph node dissection. MAIN OUTCOME MEASURES: The primary end points were the learning curves for the maximum number of nodes retrieved and urinary retention, which was evaluated with simple cumulative sum and 2-sided Bernoulli cumulative sum charts. RESULTS: Fifty-four procedures were included. A single-surgeon learning curve (n = 35) and an institutional learning curve are presented in the analysis. In the single-surgeon learning curve, a turning point marking the end of a learning phase was detected at the 12th procedure for the number of retrieved nodes and at the 20th procedure for urinary retention. In the institutional learning curve analysis, 2 turning points were identified at the 13th procedure, indicating progressive improvements for the number of retrieved nodes, and at the 27th procedure for urinary retention. No sustained alarm signals were detected at any time point. LIMITATIONS: The retrospective nature, small sample size, and the referral center nature of the reporting institution may limit generalizability. CONCLUSIONS: In a setting of institutional experience with robotic colorectal surgery, including beyond total mesorectal excision resections, the learning curve for robotic lateral pelvic lymph node dissection is acceptably short. Our results demonstrate the feasibility of the acquisition of this technique in a controlled setting, with sufficient case volume and proctoring to optimize the learning curve. See Video Abstract. LA CURVA DE APRENDIZAJE DE LA DISECCIN ROBTICA DE LOS GANGLIOS LINFTICOS PLVICOS LATERALES EN EL CNCER DE RECTO UNA VISIN DESDE OCCIDENTE: ANTECEDENTES:La disección lateral de los ganglios linfáticos pélvicos se realiza en pacientes seleccionados con cáncer de recto con enfermedad ganglionar lateral persistente tras el tratamiento neoadyuvante. La adopción de esta técnica en Occidente ha sido lenta debido a la preocupación por su dificultad técnica. Éste es el primer informe sobre la curva de aprendizaje de la disección de los ganglios linfáticos pélvicos laterales en EE.UU. o Europa.OBJETIVO:El objetivo de este estudio fue analizar la curva de aprendizaje asociada a la disección robótica de los ganglios linfáticos pélvicos laterales.DISEÑO:Cohorte observacional retrospectiva.LUGAR:Centro oncológico académico terciario.PACIENTES:Pacientes consecutivos desde 2012 al 2021.INTERVENCIÓN:Todos los pacientes fueron sometieron a disección robótica de ganglios linfáticos pélvicos laterales.PRINCIPALES MEDIDAS DE RESULTADO:Los criterios de valoración primarios fueron las curvas de aprendizaje tomando en cuenta el mayor número de ganglios recuperados y la retención urinaria que fueron evaluados con gráficos de suma acumulativa simple y de suma acumulativa de Bernoulli de dos caras.RESULTADOS:Fueron incluidos 54 procedimientos. En el análisis se presentan una curva de aprendizaje de un solo cirujano (n = 35) y una curva de aprendizaje institucional. En la curva de aprendizaje de un solo cirujano, se detectó un punto de inflexión que marcaba el final de una fase de aprendizaje en el duodécimo procedimiento para el número de ganglios extraídos y en el vigésimo para la retención urinaria. En el análisis de la curva de aprendizaje institucional, se identificaron dos puntos de inflexión en las intervenciones 13.ª y 26.ª, que indicaron mejoras progresivas en el número de ganglios extraídos, y en la 27.ª en la retención urinaria. No se detectaron señales de alarma sostenidas en ningún momento.LIMITACIONES:La naturaleza retrospectiva, el pequeño tamaño de la muestra y la naturaleza de centro de referencia de la institución informante que pueden limitar la capacidad de generalizarse.CONCLUSIONES:En un entorno de experiencia institucional con cirugía robótica colorrectal incluyendo más allá de las resecciones TME, la curva de aprendizaje para la disección robótica de ganglios linfáticos pélvicos laterales es aceptablemente corta. Nuestros resultados demuestran la viabilidad de la adquisición de esta técnica en un entorno controlado, con un volumen de casos suficiente y una supervisión que puede optimizar la curva de aprendizaje. (Traducción-Dr. Osvaldo Gauto ).

Early Postoperative Prediction of Complications and Readmission After Colorectal Cancer Surgery Using an Artificial Neural Network.

BACKGROUND: Early predictors of postoperative complications can risk-stratify patients undergoing colorectal cancer surgery. However, conventional regression models have limited power to identify complex nonlinear relationships among a large set of variables. We developed artificial neural network models to optimize the prediction of major postoperative complications and risk of readmission in patients undergoing colorectal cancer surgery. OBJECTIVE: This study aimed to develop an artificial neural network model to predict postoperative complications using postoperative laboratory values and compare the accuracy of models to standard regression methods. DESIGN: This retrospective study included patients who underwent elective colorectal cancer resection between January 1, 2016, and July 31, 2021. Clinical data, cancer stage, and laboratory data from postoperative days 1 to 3 were collected. Complications and readmission risk models were created using multivariable logistic regression and single-layer neural networks. SETTING: National Cancer Institute-Designated Comprehensive Cancer Center. PATIENTS: Adult patients with colorectal cancer. MAIN OUTCOME MEASURES: The accuracy of predicting postoperative major complications, readmissions, and anastomotic leaks using the area under the receiver operating characteristic curve. RESULTS: Neural networks had larger areas under the curve for predicting major complications compared to regression models (neural network 0.811; regression model 0.724, p < 0.001). Neural networks also showed an advantage in predicting anastomotic leak ( p = 0.036) and readmission using postoperative day 1 to 2 values ( p = 0.014). LIMITATIONS: Single-center, retrospective design limited to cancer operations. CONCLUSIONS: In this study, we generated a set of models for the early prediction of complications after colorectal surgery. The neural network models provided greater discrimination than the models based on traditional logistic regression. These models may allow for early detection of postoperative complications as early as postoperative day 2. See the Video Abstract . PREDICCIN POST OPERATORIA TEMPRANA DE COMPLICACIONES Y REINGRESO DESPUS DE LA CIRUGA DE CNCER COLORRECTAL MEDIANTE UNA RED NEURONAL ARTIFICIAL: ANTECEDENTES:Los predictores tempranos de complicaciones postoperatorias pueden estratificar el riesgo de los pacientes sometidos a cirugía de cáncer colorrectal. Sin embargo, los modelos de regresión convencionales tienen un poder limitado para identificar relaciones no lineales complejas entre un gran conjunto de variables. Desarrollamos modelos de redes neuronales artificiales para optimizar la predicción de complicaciones postoperatorias importantes y riesgo de reingreso en pacientes sometidos a cirugía de cáncer colorrectal.OBJETIVO:El objetivo de este estudio fue desarrollar un modelo de red neuronal artificial para predecir complicaciones postoperatorias utilizando valores de laboratorio postoperatorios y comparar la precisión de estos modelos con los métodos de regresión estándar.DISEÑO:Este estudio retrospectivo incluyó a pacientes que se sometieron a resección electiva de cáncer colorrectal entre el 1 de enero de 2016 y el 31 de julio de 2021. Se recopilaron datos clínicos, estadio del cáncer y datos de laboratorio del día 1 al 3 posoperatorio. Se crearon modelos de complicaciones y riesgo de reingreso mediante regresión logística multivariable y redes neuronales de una sola capa.AJUSTE:Instituto Nacional del Cáncer designado Centro Oncológico Integral.PACIENTES:Pacientes adultos con cáncer colorrectal.PRINCIPALES MEDIDAS DE RESULTADO:Precisión de la predicción de complicaciones mayores postoperatorias, reingreso y fuga anastomótica utilizando el área bajo la curva característica operativa del receptor.RESULTADOS:Las redes neuronales tuvieron áreas bajo la curva más grandes para predecir complicaciones importantes en comparación con los modelos de regresión (red neuronal 0,811; modelo de regresión 0,724, p < 0,001). Las redes neuronales también mostraron una ventaja en la predicción de la fuga anastomótica ( p = 0,036) y el reingreso utilizando los valores del día 1-2 postoperatorio ( p = 0,014).LIMITACIONES:Diseño retrospectivo de un solo centro limitado a operaciones de cáncer.CONCLUSIONES:En este estudio, generamos un conjunto de modelos para la predicción temprana de complicaciones después de la cirugía colorrectal. Los modelos de redes neuronales proporcionaron una mayor discriminación que los modelos basados en regresión logística tradicional. Estos modelos pueden permitir la detección temprana de complicaciones posoperatorias tan pronto como el segundo día posoperatorio. (Traducción-Dr. Mauricio Santamaria ).

Perioperative and oncological outcomes following robotic en bloc multivisceral resection for colorectal cancer.

AIM: As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative-intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long-term outcomes following robotic extended resection for colorectal cancer. METHOD: We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short- and long-term outcomes, using the Kaplan-Meier method to analyse overall and recurrence-free survival. RESULTS: Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three-year overall survival was 88% and median progression-free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. CONCLUSION: Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer.

[Clinical characteristics and literature review of ectopic gastric mucosa in the small intestine].

The study aims to summarize the clinical characteristics of patients with ectopic gastric mucosa in the small intestine, comparing clinical presentation differences between domestic and foreign patients through literature review. The clinical characteristics of cases diagnosed with ectopic gastric mucosa in the small intestine at Peking Union Medical College Hospital from January 2000 to January 2024 were retrospectively analyzed. By searching databanks, such as PubMed, EMBASE, the Cochrane Library, Wanfang, VIP, CNKI, and etc (the inclusion period was from the establishment of the database to January 1, 2024). The literature review was conducted on ectopic gastric mucosa in the small intestine. A total of 10 cases were included, all male, age [M (Q1, Q3)] was 27 (13-69) years old. Gastrointestinal bleeding was the first manifestation in most cases, with severe cases leading to hemorrhagic shock. Abdominal CT indicated local intestinal wall thickening and luminal narrowing in 3 cases. Four cases lesions were located at the beginning of the jejunum and 6 lesions were located in the end segment of ileum. All cases underwent local lesion resection, with postoperative pathology confirming ectopic gastric mucosa. Symptoms disappeared postoperatively, with a follow-up period of 0.5-3.0 years. Literature review indicates that the main clinical manifestation of gastric mucosa ectopia in the small intestine in China is gastrointestinal bleeding, while foreign patients are often complicated with intestinal duplication and intussusception, with abdominal pain and vomiting as the primary and main symptoms. The occurrence rate of intestinal obstruction in female patients, both domestically and abroad, is higher than that in male patients. The occurrence rate of ileal lesions with intestinal obstruction and small intestinal duplication is higher than that of duodenal lesions in both domestic and foreign patients. Local small intestine resection is an effective treatment method with generally good prognosis. Ectopic small intestinal mucosa is relatively rare, with symptoms of gastrointestinal bleeding and intestinal obstruction being common presentations, which can serve as one of the differential diagnoses for unexplained gastrointestinal bleeding.

[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

Young-onset Rectal Cancer: Unique Tumoral Microbiome and Correlation With Response to Neoadjuvant Therapy.

OBJECTIVE: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology. BACKGROUND: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown. METHODS: YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR. RESULTS: Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P <0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum , Bacteroides dorei, and Ruminococcus bromii (all P <0.001), but MPR in LORC was associated with R. bromii ( P <0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors. CONCLUSIONS: Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.

Hepatectomy Before Primary Tumor Resection as Preferred Approach for Synchronous Liver Metastases from Rectal Cancer.

BACKGROUND: For patients with synchronous liver metastases (LM) from rectal cancer, a consensus on surgical sequencing is lacking. We compared outcomes between the reverse (hepatectomy first), classic (primary tumor resection first), and combined (simultaneous hepatectomy and primary tumor resection) approaches. METHODS: A prospectively maintained database was queried for patients with rectal cancer LM diagnosed before primary tumor resection who underwent hepatectomy for LM from January 2004 to April 2021. Clinicopathological factors and survival were compared between the three approaches. RESULTS: Among 274 patients, 141 (51%) underwent the reverse approach; 73 (27%), the classic approach; and 60 (22%), the combined approach. Higher carcinoembryonic antigen level at LM diagnosis and higher number of LM were associated with the reverse approach. Combined approach patients had smaller tumors and underwent less complex hepatectomies. More than eight cycles of pre-hepatectomy chemotherapy and maximum diameter of LM > 5 cm were independently associated with worse overall survival (OS) (p = 0.002 and 0.027, respectively). Although 35% of reverse-approach patients did not undergo primary tumor resection, OS did not differ between groups. Additionally, 82% of incomplete reverse-approach patients ultimately did not require diversion during follow-up. RAS/TP53 co-mutation was independently associated with lack of primary resection with the reverse approach (odds ratio: 0.16, 95% CI 0.038-0.64, p = 0.010). CONCLUSIONS: The reverse approach results in survival similar to that of combined and classic approaches and may obviate primary rectal tumor resections and diversions. RAS/TP53 co-mutation is associated with a lower rate of completion of the reverse approach.

Germline Cancer Risk Profiles of Patients With Young-Onset Colorectal Cancer: Findings From a Prospective Universal Germline Testing and Telegenetics Program.

BACKGROUND: Colorectal cancer is being increasingly diagnosed in people younger than 50 years. An inheritable cancer predisposition has been reported in 22% of the young-onset cases. Assessment of germline risk is critical for personalized cancer care. OBJECTIVE: The study aimed to implement universal germline cancer risk assessment and testing and to define the germline cancer risk profiles of patients presenting with young-onset disease. DESIGN: This is a prospective cohort study. SETTINGS: This study was conducted at a tertiary-referral academic medical center. PATIENTS: This study included newly diagnosed patients presenting to surgical clinics between September 2019 and February 2021 who were treated on a standardized care pathway including the universal germline risk assessment. INTERVENTIONS: Patients received educational material on young-onset disease, genetic testing, and insurance coverage followed by genetic counseling (either remotely by telegenetics or in person). Consenting patients were assessed on a 47-gene common hereditary cancer panel. MAIN OUTCOME MEASURES: The primary outcome was a proportion of patients with identifiable germline cancer predisposition. RESULTS: Among 500 patients with colorectal cancer, 185 (37%) were 50 years of age or younger (median: 44). A family history was absent for the majority of patients (123; 67%), and in 15 patients, tumors (8.1%) were deficient in DNA mismatch repair. Germline testing was completed in 130 patients (70%); the remainder were pending (7%), deceased (1%), or declined (22%). Pathogenic germline mutations were identified in 25 of 130 (19%) patients: 12 in mismatch repair genes and 13 in other genes. A variant of uncertain significance was found in 23 (18%) patients. Importantly, a pathogenic germline mutation was identified in 12% of the patients without a family history (versus 32% with; p = 0.015) and in 13% of those with proficient mismatch repair colorectal cancers (versus 71% if deficient; p < 0.001). LIMITATIONS: The study is limited by its implementation at a single tertiary academic institution. CONCLUSIONS: One in 5 patients with young-onset disease harbored germline cancer predisposition. This detection rate, coupled with a high level of interest and acceptance from patients and feasibility of implementation, supports universal germline cancer risk assessment in this patient population. See Video Abstract at http://links.lww.com/DCR/B925 . PERFILES DE RIESGO DE CNCER DE LNEA GERMINAL DE PACIENTES CON CNCER COLORRECTAL DE INICIO JOVEN HALLAZGOS DE UN PROGRAMA UNIVERSAL PROSPECTIVO DE PRUEBAS DE LNEA GERMINAL Y TELEGENTICA: ANTECEDENTES:El cáncer colorrectal se diagnostica cada vez más en personas menores de 50 años. Se ha informado una predisposición hereditaria al cáncer en el 22 % de los casos de aparición temprana. La evaluación del riesgo de la línea germinal es fundamental para la atención personalizada del cáncer.OBJETIVO:Implementar la evaluación y las pruebas universales de riesgo de cáncer de línea germinal, y definir los perfiles de riesgo de cáncer de línea germinal de los pacientes que presentan una enfermedad de aparición temprana.DISEÑO:Un estudio de cohorte prospectivo.AJUSTE:Un centro médico académico de referencia terciaria.PACIENTES:Los pacientes recién diagnosticados que se presentaron en clínicas quirúrgicas entre Septiembre de 2019 y Febrero de 2021 fueron tratados en una vía de atención estandarizada que incluye una evaluación de riesgo de línea germinal universal.INTERVENCIÓN:Los pacientes recibieron material educativo sobre enfermedades de aparición temprana, pruebas genéticas y cobertura de seguro, seguido de asesoramiento genético (ya sea a distancia por telegenética o en persona). Los pacientes que dieron su consentimiento fueron evaluados en un panel de cánceres hereditarios comunes de 47 genes.MEDIDA DE RESULTADO PRINCIPAL:Proporción de pacientes con predisposición identificable al cáncer de línea germinal.RESULTADOS:Entre 500 pacientes con cáncer colorrectal, 185 (37%) tenían 50 años o menos (mediana: 44). No había antecedentes familiares en la mayoría (123, 67%) y 15 tumores (8,1%) eran deficientes en la reparación del desajuste de ácido desoxirribonucleico. La prueba de línea germinal se completó en 130 pacientes (70%); el resto estaban pendientes (7%), fallecidos (1%) o declinados (22%). Se identificaron mutaciones patogénicas de la línea germinal en 25 (de 130, 19%) pacientes: 12 en genes de reparación de errores de emparejamiento y 13 en otros genes. Se encontró una variante de significado incierto en 23 (18%) pacientes. Es importante señalar que se identificó una mutación germinal patogénica en el 12% de los pacientes sin antecedentes familiares (frente al 32% con; p = 0,015) y en el 13% de aquellos con cánceres colorrectales competentes en la reparación de errores de emparejamiento (frente al 71% si eran deficientes; p < 0,001).LIMITACIÓN:Implementado en una sola institución académica terciaria.CONCLUSIÓN:Uno de cada cinco pacientes con enfermedad de inicio joven albergaba predisposición al cáncer de línea germinal. Esta tasa de detección, junto con un alto nivel de interés y aceptación por parte de los pacientes y la viabilidad de la implementación, respaldan la evaluación universal del riesgo de cáncer de línea germinal en esta población de pacientes. Consulte el Video Resumen en http://links.lww.com/DCR/B925 . (Traducción-Dr. Yesenia Rojas-Khalil ).

Acupuncture and Chinese herbal medicine for menopausal mood disorder: a randomized controlled trial.

OBJECTIVE: This study aimed to analyze the effectiveness of acupuncture combined with Chinese herbal medicine (CHM) on mood disorder symptoms for menopausal women. METHODS: A total of 95 qualified Chinese participants were randomly assigned to one of three groups: 31 in the acupuncture combined with CHM group (combined group), 32 in the acupuncture combined with CHM placebo group (acupuncture group) and 32 in the CHM combined with sham acupuncture group (CHM group). The patients were treated for 8 weeks and followed up for 4 weeks. The data were collected using the Greene Climacteric Scale (GCS), self-rating depression scale (SDS), self-rating anxiety scale (SAS) and safety index. RESULTS: The three groups each showed significant decreases in the GCS, SDS and SAS after treatment (p < 0.05). Furthermore, the effect on the GCS total score and the anxiety domain lasted until the follow-up period in the combined group (p < 0.05). Within the three groups, there was no difference in GCS and SAS between the three groups after treatment (p > 0.05). However, the combined group showed significant improvement in the SDS, compared with both the acupuncture group and the CHM group at 8 weeks and 12 weeks (p < 0.05). No obvious abnormal cases were found in any of the safety indexes. CONCLUSIONS: The results suggest that either acupuncture, or CHM or combined therapy offer safe improvement of mood disorder symptoms for menopausal women. However, the combination therapy was associated with more stable effects in the follow-up period and a superior effect on improving depression symptoms.

[Survey of Helicobacter pylori levofloxacin and clarithromycin resistance rates and drug resistance genes in Ningxia, 2020-2022].

Objective: To explore the rate of Helicobacter pylori (Hp) resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia, and to assess the concordance between phenotypic resistance and genotypic resistance. Methods: Cross-sectional study. Patients diagnosed with Hp infection in 14 hospitals in Ningxia region from February 2020 to May 2022 were retrospectively selected. Hp strains were isolated from gastric biopsy specimens of Hp-infected patients and subjected to phenotypic drug sensitivity testing and detection of resistance genes to analyze the rate of Hp resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia region; and the concordance rate and Kappa concordance test were used to assess the concordance between phenotypic resistance and genotypic resistance. Results: A total of 1 942 Hp strains were isolated and cultured, and among the infections, 1 069 cases (55.0%) were male and 873 cases (45.0%) were female, aged (50.0±12.5) years (15-86 years). The rates of Hp resistance to levofloxacin and clarithromycin in Ningxia were 42.1% (818/1 942) and 40.1% (779/1 942), respectively, and the rate of dual resistance to both was 22.8% (443/1 942). The rate of resistance to levofloxacin and clarithromycin of Hp strains from female patients was higher than in male patients (levofloxacin: 50.4%(440/873) vs 35.4%(378/1 069); clarithromycin: 44.4%(388/873) vs 36.6%(391/1 069), both P<0.001). Among the GyrA gene mutations associated with levofloxacin resistance, the differences in mutation rate of amino acid at positions 87 and 91 were statistically significant in both drug-resistant and sensitive strains(both P<0.001), except for Asn87Thr. Hp strains were statistically significant for levofloxacin (Kappa=0.834, P<0.001) and clarithromycin (Kappa=0.829, P<0.001) had good concordance in resistance at the phenotypic and genotypic levels. Conclusion: The resistance of Hp to levofloxacin and clarithromycin in Ningxia region is severe, and there is good consistency between genotypic and phenotypic resistance.

[Clinical efficacy and prognostic risk factors of salvage liver transplantation, rehepatectomy, and local ablation in the treatment of postoperative recurrence of hepatocellular carcinoma].

Objective: To investigate and analyze the clinical efficacy of salvage liver transplantation (SLT), rehepatectomy (RH), local ablation (LA), and prognostic risk factors in patients with postoperative recurrence of hepatocellular carcinoma. Methods: Clinical data of 145 patients with recurrent liver cancer in the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2005 to June 2018 were retrospectively collected. SLT group, RH group, and LA group included 25, 44, and 76 cases, respectively. Follow-up and statistics were recorded on the overall survival rate, relapse-free survival rate, and complications of the three groups of patients at 1, 2, and 3 years after surgery. Univariate and multivariate COX analyses were used to analyze the prognostic risk factors in patients with recurrent HCC. Results: The overall survival rates of 1, 2, and 3 years following surgery in the SLT, RH, and LA groups were 100.0%, 84.0%, 72.0%, 95.5%, 77.3%, 65.9%, 90.8%, 76.3%, and 63.2%, respectively, when the recurrence of liver cancer met the Milan criteria. The overall survival rate did not differ statistically between SLT and RH (P = 0.303) or between RH and LA (P = 0.152). There were statistically significant differences in recurrence-free survival between SLT and RH or RH and LA (P = 0.046). There was no statistically significant difference in the incidence of complications between SLT and RH or RH and LA (P > 0.017). Age > 65 years was an independent risk factor affecting the overall survival rate in patients with recurrent HCC. Age > 65 years and recurrence time < 24 months were independent risk factors affecting the recurrence-free survival rate in patients with recurrent HCC. Conclusion: SLT is the best treatment option when the recurrence of HCC meets Milan's criteria. RH and LA are the appropriate treatment plans for recurrent HCC when the liver source is limited.

Financial toxicity impact on younger versus older adults with cancer in the setting of care delivery.

BACKGROUND: Young adults and other working-age adults with cancer are at risk for cancer-related financial toxicity (FT), including material hardships, depletion of coping resources, and psychological burden. This study compares FT domains in young adults (18-39 years old) (YAs), other working-age adults (40-64 years old), and older adults (≥65 years old) receiving cancer care. METHODS: A total of 311 adults were surveyed using the multi-domain Economic Strain and Resilience in Cancer instrument measuring FT (0-10 score indicating least to greatest FT; score ≥5 severe FT). Participants were receiving ambulatory care from March-September 2019. Associations of age with overall FT and material hardship, coping resource depletion, and psychological burden FT domains were tested using Kruskal-Wallis and χ2 tests and multivariable generalized linear models with gamma distribution. RESULTS: YAs (median age, 31.5 years) comprised 9.6% of the sample; other working-age adults comprised 56.9%. Overall, material, coping, and psychological FT scores were worse in younger age adults versus older adults (P < .001 in all multivariable models). Compared with older adults, younger age adults demonstrated worse material hardship (median scores, 3.70 vs 4.80 vs 1.30 for YAs, other working-age, and older adults, respectively; P < .001), coping resource depletion (4.50 vs 3.40 vs 0.80; P < .001), and psychological burden (6.50 vs 7.00 vs 1.00; P < .001). Fifty percent of YAs had severe overall FT versus 40.7% of other working-age adults and 9.6% of older adults (P < .001). CONCLUSIONS: Younger age adults with cancer bore disproportionate FT. Interventions to address unmet needs are critical components for addressing FT in this population.

Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer: A Comparison of Short- and Long-term Oncologic Outcomes.

OBJECTIVE: To evaluate the impact of neoadjuvant multi-agent systemic chemotherapy and radiation (TNT) vs neoadjuvant single-agent chemoradiation (nCRT) and multi-agent adjuvant chemotherapy on overall survival (OS), tumor downstaging, and circumferential resection margin (CRM) status in patients with locally advanced rectal cancer. SUMMARY OF BACKGROUND DATA: Outside of clinical trials and small institutional reports, there is a paucity of data regarding the short and long-term oncologic impact of TNT as compared to nCRT. METHODS: Adult patients with stage II-III rectal adenocarcinoma were identified in the National Cancer Database [2006-2015]. RESULTS: Out of 8,548 patients, 36% received TNT and 64% nCRT. In the cohort, 13% had a pCR and 20% a neoadjuvant rectal (NAR) score <8. In multivariable analysis, as compared to nCRT, TNT demonstrated numerically higher pCR rates ( P = 0.05) but had similar incidence of positive CRM ( P = 0.11). Similar results were observed with NAR scores <8 as the primary endpoint. After adjusting for confounders, OS was comparable between the 2 groups. Additional factors independently associated with lower OS included male gender, uninsured status, low income status, high comorbidity score, poorly differentiated tumors, abdominoperineal resection, and positive surgical margins (all P <0.01). In separate models, both pCR and a NAR score <8 were associated with improved OS. CONCLUSION: In this national cohort, TNT was not associated with better survival and/or CRM negative status in comparison with nCRT, despite numerically higher downstaging rates. Further refinement of patient selection and treatment regimens are needed to establish effective neoadjuvant platforms to improve outcomes of patients with rectal cancer.

Magnetic Resonance Imaging Directed Surgical Decision Making for Lateral Pelvic Lymph Node Dissection in Rectal Cancer After Total Neoadjuvant Therapy (TNT).

OBJECTIVE: Lateral pelvic lymph node (LPLN) metastases are an important cause of preventable local failure in rectal cancer. The aim of this study was to evaluate clinical and oncological outcomes following magnetic resonance imaging (MRI)-directed surgical selection for lateral pelvic lymph node dissection (LPLND) after total neoadjuvant therapy (TNT). METHODS: A retrospective consecutive cohort analysis was performed of rectal cancer patients with enlarged LPLN on pretreatment MRI. Patients were categorized as LPLND or non-LPLND. The main outcomes were lateral local recurrence rate, perioperative and oncological outcomes and factors associated with decision making for LPLND. RESULTS: A total of 158 patients with enlarged pretreatment LPLN and treated with TNT were identified. Median follow-up was 20 months (interquartile range 10-32). After multidisciplinary review, 88 patients (56.0%) underwent LPLND. Mean age was 53 (SD±12) years, and 54 (34.2%) were female. Total operative time (509 vs 429 minutes; P =0.003) was greater in the LPLND group, but median blood loss ( P =0.70) or rates of major morbidity (19.3% vs 17.0%) did not differ. LPLNs were pathologically positive in 34.1%. The 3-year lateral local recurrence rates (3.4% vs 4.6%; P =0.85) did not differ between groups. Patients with LPLNs demonstrating pretreatment heterogeneity and irregular margin (odds ratio, 3.82; 95% confidence interval: 1.65-8.82) or with short-axis ≥5 mm post-TNT (odds ratio 2.69; 95% confidence interval: 1.19-6.08) were more likely to undergo LPLND. CONCLUSIONS: For rectal cancer patients with evidence of LPLN metastasis, the appropriate selection of patients for LPLND can be facilitated by a multidisciplinary MRI-directed approach with no significant difference in perioperative or oncologic outcomes.

Definitive Intensity-Modulated Chemoradiation for Anal Squamous Cell Carcinoma: Outcomes and Toxicity of 428 Patients Treated at a Single Institution.

BACKGROUND: Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers. METHODS: Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan-Meier method. RESULTS: A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity. CONCLUSIONS: Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.

Quality and Location of the Surgical Episode Mediate a Large Proportion of Socioeconomic-Based Survival Disparities in Patients with Resected Stage I-III Colon Cancer.

INTRODUCTION: Lower socioeconomic status (SES) is associated with shorter overall survival (OS) in patients with locoregional colon cancer. We aimed to estimate: (1) the proportion of SES-based OS disparities mediated by disparities in the quality and location of surgical treatment in patients with resected stage I-III colon cancer and (2) the relative importance of components of surgical quality. PATIENTS AND METHODS: We examined patients ages 18-80 years with resected stage I-III colon adenocarcinoma using the 2010-2016 National Cancer Database. SES was defined at the zip code level. Inverse odds weighting mediation analysis was used to estimate the proportion mediated (PM) for nine treatment quality-related and facility-related factors and composite PMs in models including all nine mediators. Models compared high SES patients with each lower SES stratum. RESULTS: Among 171,009 patients, 5-year OS increased from 70.4% in low SES patients to 78.1% in high SES. When high SES patients were compared with low, lower-middle, and upper-middle SES patients, PM ranges among lower SES strata were: minimally invasive surgery 16.0-16.6%, lymph nodes examined 7.7-9.6%, positive margins 3.8-6.5%, length of stay 16.7-28.1%, readmissions insignificant to 3.7%, treatment at > 1 CoC facility 2.7-3.1%, facility type insignificant to 7.3%, facility volume 2.9-8.2%, and adjusted facility 90-day mortality rates 33.2-42.8%. Composite PMs were 76.9% (95% CI 61.3%, 92.4%) for low SES, 68.7% (95% CI 56.4%, 81.1%) for lower-middle SES, and 60.9% (95% CI 43.1%, 78.6%) for upper-middle SES. CONCLUSIONS: These data suggest that improving the quality of the surgical episode for disadvantaged patients undergoing resection for locoregional colon cancer could decrease SES-based survival disparities by over half.

Super-response to guselkumab treatment in patients with moderate-to-severe psoriasis: age, body weight, baseline Psoriasis Area and Severity Index, and baseline Investigator's Global Assessment scores predict complete skin clearance.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease that often leads to a diminished quality of life. Goals of treating patients with psoriasis have shifted with more focus on achieving near or complete clearance of the skin. Guselkumab, a fully human monoclonal antibody targeting interleukin-23, is effective in treating moderate-to-severe psoriasis. OBJECTIVE: To describe the baseline characteristics of patients with moderate-to-severe psoriasis achieving super-response (Psoriasis Area and Severity Index [PASI] 100 response at Weeks 20 and 28) after commencing guselkumab treatment. METHODS: Pooled data from VOYAGE 1 and VOYAGE 2 studies identified super-response; baseline demographic, disease and pharmacokinetic characteristics were compared with non-super-response. A stepwise logistic regression analysis identified which factors were potentially predictive of super-response status, with significance level of 0.1. RESULTS: A subset of patients randomized to guselkumab comprised this post hoc analysis (n = 664); 271 patients achieved super-response vs. 393 with non-super-response. Patient age at study entry and baseline body weight (≤90 kg vs. >90 kg), PASI, and Investigator's Global Assessment (IGA) score were significant predictors of super-response status, with odds ratios (95% confidence intervals) of 0.98 (0.967-0.993; P = 0.003), 1.42 (1.026-1.977; P = 0.034), 0.97 (0.955-0.993; P = 0.007) and 0.66 (0.433-0.997; P = 0.048), respectively. More patients with super-response achieved an early response: Week 2 PASI 75 (5.5% vs. 1.8%) and Week 8 PASI 100 (22.5% vs. 3.3%) vs. non-super-response. Median serum guselkumab concentrations through Week 28 were slightly greater in patients with super-response vs. non-super-response. CONCLUSION: Guselkumab was more likely to achieve early clinical responses (complete skin clearance) in younger patients, less obese patients and patients with less severe psoriasis.