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: The aim of this study was to develop an artificial neural network model to predict postoperative complications using postoperative laboratory values, and compare these models' accuracy 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 day 1 to 3 were collected. Models of complications and readmission risk were created using multivariable logistic regression and single-layer neural networks. SETTING: National Cancer Institute-Designated Comprehensive Cancer Center. PATIENTS: Adult colorectal cancer patients. MAIN OUTCOME MEASURES: Accuracy of predicting postoperative major complication, readmission and anastomotic leak 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 1-2 values (p = 0.014). LIMITATIONS: Single-center, retrospective design limited to cancer operations. CONCLUSIONS: In this study, we generated a set of models for 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 soon as postoperative day 2. See Video Abstract.

Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership.

BACKGROUND: Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS. METHODS: A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis. RESULTS: The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n = 171, 79.9%) and treat >10 extremity sarcoma cases annually (n = 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p < 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background. CONCLUSION: Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.

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 ).

The Value of Anti-Müllerian Hormone in Predicting Ovulation Induced by Aromatase Inhibitors in Women With Polycystic Ovary Syndrome.

OBJECTIVES: This study aimed to evaluate the value of anti-Müllerian hormone (AMH) in predicting ovulation induced by aromatase inhibitors (AI) and pregnancy outcomes in women with polycystic ovary syndrome (PCOS). METHODS: From January 2018 to December 2020, this prospective cohort study enrolled women with PCOS aged between 18 and 45 years who underwent ovulation induction using AI protocol and intrauterine insemination (IUI) for infertility at a Center for Reproductive Endocrinology and Infertility, University Hospital. Receiver operating characteristic curves were used to estimate the chance of ovulation responses and pregnancy outcomes. RESULTS: In total, 64% of 65 women with PCOS were recruited following AI treatment, and the clinical pregnancy rate was 19.4% following IUI. Patients who experienced ovulation had a lower mean serum AMH concentration than non-responders (7.11 ng/mL vs. 8.95 ng/mL, respectively), but the difference was not statistically significant. Between the pregnancy and non-pregnancy groups, statistically significant differences in AMH concentrations were observed (8.71 ng/mL vs. 6.73 ng/mL, respectively, P = 0.040). The area under the curve of the receiver operating characteristic for non-ovulation prediction was 0.445, 95% CI (0.284-0.606) with P = 0.467, and for clinical pregnancy was 0.735, 95% CI (0.561-0.910) with P = 0.104. CONCLUSIONS: In women with PCOS, the AMH level does not predict ovarian responsiveness to AI treatment, but it does predict the success of IUI cycles.

What is the Risk for Peritoneal Metastases and Survival Afterwards in T4 Colon Cancers?

BACKGROUND: Patients with T4 colon adenocarcinomas have an increased risk of peritoneal metastases (PM) but the histopathologic risk factors for its development are not well-described. OBJECTIVE: The purpose of this study was to determine factors associated with PM, time to recurrence, and survival after recurrence among patients with T4 colon cancer. PATIENTS AND METHODS: Patients with pathologic T4 colon cancer who underwent curative resection from 2005 to 2017 were identified from a prospectively maintained institutional database and classified by recurrence pattern: (a) none - 68.8%; (b) peritoneal only - 7.9%; (c) peritoneal and extraperitoneal - 9.9%; and (d) extraperitoneal only - 13.2%. Associations between PM development and patient, primary tumor, and treatment factors were assessed. RESULTS: Overall, 151 patients were analyzed, with a median follow-up of 66.2 months; 27 patients (18%) developed PM (Groups B and C) and 20 (13%) patients recurred at non-peritoneal sites only (Group D). Median time to developing metastases was shorter for Groups B and C compared with Group D (B and C: 13.7 months; D: 46.7 months; p = 0.022). Tumor deposits (TDs) and nodal stage were associated with PM (p < 0.05), and TDs (p = 0.048) and LVI (p = 0.015) were associated with additional extraperitoneal recurrence. Eleven (41%) patients with PM underwent salvage surgery, and median survival after recurrence was associated with the ability to undergo cytoreduction (risk ratio 0.20, confidence interval 0.06-0.70). CONCLUSION: PM risk after resection of T4 colon cancer is independently associated with factors related to lymphatic spread, such as N stage and TDs. Well-selected patients can undergo cytoreduction with long-term survival. These findings support frequent postoperative surveillance and aggressive early intervention, including cytoreduction.

Risks of Hypoparathyroidism After Total Thyroidectomy in Children: A 21-Year Experience in a High-Volume Cancer Center.

BACKGROUND: Hypoparathyroidism occurs relatively frequently after thyroid surgery in children. However, few studies have reported risk factors. We aimed to identify risk factors for hypoparathyroidism that occurred after total thyroidectomy for proven or suspected malignancy in children. METHODS: Children (aged ≤ 18 years) who underwent total thyroidectomy for neoplasm or RET germline mutation at our institution between 1997 and 2018 were included. We retrospectively reviewed demographics, surgical indications, perioperative and follow-up laboratory results, pathologic results, and duration of calcium/calcitriol supplementation. Risk factors for hypoparathyroidism were identified by multivariate analysis. RESULTS: Of 184 consecutive patients, 111 had undergone surgery for neoplasm; these diseases were primarily malignancies (106, 95.5%), predominantly papillary carcinoma (103, 92.8%). The remaining 73 patients had undergone early thyroidectomy for RET germline mutation. Among all patients, 67 (36.4%) had hypoparathyroidism: 61 transient and 6 permanent. In a multivariate analysis, central neck dissection (odds ratio 4.3, 95% confidence interval 2.0-9.1) and gross extrathyroidal extension (odds ratio 4.9, 95% confidence interval 2.0-12.1) predicted overall hypoparathyroidism; however, no significant factors were associated with permanent hypoparathyroidism. Most patients with permanent hypoparathyroidism (5 of 6) had undergone therapeutic central neck dissection. When central neck dissection was performed, younger children had a higher risk of overall hypoparathyroidism. CONCLUSIONS: In pediatric total thyroidectomies, central neck dissection and gross extrathyroidal extension were major predictors for overall hypoparathyroidism. Surgeons performing thyroidectomy in such patients should be aware of the relatively high risk, preserve parathyroid tissue to the extent possible, and be conscientious regarding postoperative calcium monitoring and replacement.

Exploration of the role of anti-Mullerian hormone and LH/FSH ratio in diagnosis of polycystic ovary syndrome.

OBJECTIVE: This study explores the role of anti-Mullerian hormone (AMH) and LH/FSH ratio in diagnosis of polycystic ovary syndrome (PCOS). METHODS: In this multicentre cross-sectional descriptive study, a total of 863 infertile women between 18 and 45 years were evaluated at three infertility centres in Vietnam and were recruited from June 2016 to June 2017. The patients were classified into two groups: Group I included 441 patients with PCOS (based on Rotterdam criteria consensus) and Group II included 422 non-PCOS women. Diagnosis of PCOS was established based on Rotterdam 2003 consensus, and exclusion criteria were ovarian disease (ovary cyst/tumour), history of ovarian surgery and ovarian failure. RESULTS: At an optimum cut-off level of 32.79 pmol/L, AMH showed sensitivity and specificity of 78.50% and 75.83%, respectively, with the AUC 0.852 (95% CI: 0.826-0.875). The LH/FSH ratio had a similar AUC at the optimum cut-off of 1.33 (AUC = 0.867, 95% CI 0.842-0.889), which demonstrated a similar diagnosis value to AMH (P = 0.340). By using multiple logistic regression analysis, 1 ng/mL increase in AMH levels was associated with an increased risk of PCOS (OR = 1.63, 95% CI: 1.506-1.764; P < 0.001). Similarly, one unit increase in LH/FSH ratio was associated with 14.433 times increased (95% CI: 9.302-22.395; P < 0.001) risk of PCOS. There were no significant differences between values of AMH and LH/FSH ratio in PCOS diagnosis, as the difference between the two AUCs was 0.013, 95% CI: -0.024 to 0.028 and P = 0.897. CONCLUSION: The value of serum AMH concentration has been found not significantly superior to LH/FSH ratio in PCOS diagnosis. Although these biomarkers separately are not adequate for PCOS diagnosis based on their own value, the combination of different endocrine factors including AMH, LH and LH/FSH ratio together with BMI and other anthropometric and clinical characteristics may offer extra value to establish the diagnosis of PCOS.

Defining polycystic ovary syndrome phenotype in Vietnamese women.

AIM: This study aimed to evaluate the unique phenotype of the Vietnamese polycystic ovarian syndrome (PCOS) population. METHODS: In this multicenter cross-sectional descriptive study, a total of 901 reproductive-age women were recruited at three medical centers in Vietnam from June 2016 to May 2018. Group I included 479 patients with PCOS (Rotterdam 2003 consensus) and Group II included 422 non-PCOS women, consisted of women with regular menstrual cycle, collected at the same time of PCOS recruitment, without ovarian disease or ovarian failure. Main outcome measures were anthropomorphic, serum hormone, ultrasound and physical characteristics of PCOS. RESULTS: The Vietnamese PCOS population was lean, but with a higher weight and body mass index compared to controls. About 34.4% of PCOS subjects had hirsutism, primarily confined to the leg, arm and pubis. The PCOS population had higher serum luteinizing hormone (LH), LH : follicle stimulating hormone ratio, anti-Mullerian hormone and testosterone. The PCOS population had double the ovarian volume compared to controls. PCOS subjects had no increase in metabolic disease history and had on average optimal serum markers for low metabolic disease risk. Group D (O + polycystic ovary morphology [PCOM]) was the most prevalent phenotype noted in our Vietnamese PCOS cohort (67.6%). Modified Ferriman-Gallwey, levels of LH, testosterone and anti-Mullerian hormone were highest in Group A (O + H + PCOM) and lowest in Group D (O + PCOM). CONCLUSION: The Vietnamese PCOS population is characterized by a lean body type, nonfacial hirsutism, anovulatory, enlarged ovaries and typical PCOS serum hormone markers, low risk factors for metabolic syndrome. Nonclassical phenotypes for PCOS were more frequent than the classic phenotype.

Oncologic Outcomes of Extended Robotic Resection for Rectal Cancer.

BACKGROUND: Surgery for locally advanced rectal cancers beyond the plane of total mesorectal excision (TME) or extramesorectal nodal involvement should include complete resection. This study evaluated the oncologic feasibility and safety of robot-assisted surgery for rectal cancer beyond the TME plane. METHODS: The study analyzed the operative, perioperative, and oncologic outcomes for all patients who underwent robot-assisted extended rectal cancer surgery from April 2009 to February 2015. RESULTS: Of 36 patients, 22 underwent multivisceral en bloc resection, and 18 underwent extramesorectal lymph node (EMRLN) dissection. The median tumor location was 5 cm [interquartile range (IQR), 2.2-9.0 cm] from the anal verge. A total of 32 patients underwent neoadjuvant chemoradiation therapy. The median body mass index of the patients was 26.8 kg/m(2) (IQR, 24.0-31.9 kg/m(2)). Conversion was required for one patient because of inability to tolerate the Trendelenburg position. All the resections were R0, and there were no incomplete TMEs. The vagina and prostate or periprostatic structures were the most commonly resected (n = 13/22), and the lateral pelvic nodes were the most common EMRLNs (n = 16/18). The median numbers of examined mesorectal lymph nodes and EMRLNs were respectively 20 (IQR, 18.0-28.0) and 2.5 (IQR, 1.0-6.0). The median hospital stay was 4 days (IQR, 3.0-5.5 days). Six patients experienced Clavien-Dindo grade 3 complications, the most common of which was deep abscess (n = 5, 13.8 %). The 5-year actuarial local recurrence rate was 3.6 %. CONCLUSIONS: Minimally invasive resection for rectal cancer can be performed with extended lymph node dissection or en bloc multivisceral resection using the surgical robot in selected patients. This technique is feasible and has acceptable morbidity.

Impact of ileostomy-related complications on the multidisciplinary treatment of rectal cancer.

BACKGROUND: Radical resection is the primary treatment for rectal cancer. When anastomosis is possible, a temporary ileostomy is used to decrease morbidity from a poorly healed anastomosis. However, ileostomies are associated with complications, dehydration, and need for a second operation. We sought to evaluate the impact of ileostomy-related complications on the treatment of rectal cancer. METHODS: We conducted a retrospective study of patients who underwent sphincter-preserving surgery between January 2005 and December 2010 at a tertiary cancer center. The primary outcome was the overall rate of ileostomy-related complications. Secondary outcomes included complications related to ileostomy status, ileostomy closure, anastomotic complications at primary resection, rate of stoma closure, and completion of adjuvant chemotherapy assessed by multivariate logistic regression. RESULTS: Of 294 patients analyzed, 32% (n = 95) were women. Two hundred seventy-one (92%) received neoadjuvant chemoradiation. The median tumor distance from the anal verge was 7 cm (interquartile range 5-10 cm). Two hundred eighty-one (96%) underwent stoma closure at a median of 7 months (interquartile range 5.4-8.3 months). The most common complication related to readmission was dehydration (n = 32-11%). Readmission within 60 days of primary resection was associated with delay in initiating adjuvant chemotherapy (odds ratio 3.01, 95% confidence interval 1.42-6.38, p = 0.004). CONCLUSIONS: Diverting ileostomies created during surgical treatment of rectal cancers are associated with morbidity; however, this is balanced against the risk of anastomosis-related morbidity at rectal resection. Given the potential benefit of fecal diversion, patient-oriented interventions to improve ostomy management, particularly during adjuvant chemotherapy, can be expected to yield marked benefits.

Dry eye rate and its relationship with disease stage in patients with primary hypertension: a cross-sectional study in Vietnam.

AIM: To determine the dry eye (DE) rate and its relationship with disease stage in patients with primary hypertension. METHODS: A cross-sectional study included 432 patients with primary hypertension (with an equal number of patients in each group: 144 in stage I, II, and III hypertension) and 144 healthy subjects as a control group. The Ocular Surface Disease Index (OSDI) and Schirmer I test without anesthetics were conducted on all 576 subjects. Subjects with OSDI scores <13 and Schirmer I values equal to or under 10 mm were diagnosed with DE. RESULTS: The ratio of DE in hypertension patients was higher than in the control group (41.7% versus 18.8%; P<0.001). The proportion of patients with DE increased gradually according to the hypertension stage: 27.1% in stage I, 40.3% in stage II, and 57.6% in stage III, P<0.001. Age, duration of hypertension, plasma urea, creatinine, and high-sensitivity C-reactive protein (CRP-hs) levels in hypertension patients with DE were higher than those without DE, P<0.001. Advanced age, a long duration of hypertension, diabetes mellitus, elevated plasma creatinine, and CRP-hs levels were independent factors associated with DE in primary hypertension patients, P<0.001. CONCLUSION: DE is a common disorder associated with advanced age, a long duration of hypertension, diabetes mellitus, elevated plasma CRP-hs, and creatinine levels in patients with primary hypertension.

Dry Eye and Some Related Factors in Patients with Type 2 Diabetic Nephropathy: A Cross-Sectional Study in Vietnam.

Aim: To determine the prevalence of dry eye (DE) and some related factors in patients with type 2 diabetic nephropathy (T2DN). Methods: We performed a cross-sectional study on 338 people, who were divided into 2 groups: 169 T2DN patients and 169 patients diagnosed with type 2 diabetic mellitus (T2DM) without renal complications as a control group. The Ocular Surface Disease Index (OSDI) and test fluorescein tear-film break-up time (TBUT) were done in all 338 subjects. Patients with OSDI scores < 13 and TBUT values equal to or under 10 seconds were diagnosed with dry eye. Results: The prevalence of DE in T2DN patients was significantly higher than T2DM group (55.6% versus 37.3%). The T2DN groups with dry eye had a median duration of DM, the proportion of hypertension, peripheral nerve complications, anemia, proportion of using insulin, and concentration of plasma glucose, HbA1C, urea, creatinine, CRP-hs significantly higher than those of T2DN without dry eye. Advanced age, high HbA1C level, and decreased eGFR were independent factors associated with dry eye in T2DN patients. Conclusion: Dry eye was a common condition associated with advanced age, high HbA1C levels, and decreased GFR in T2DN patients.

A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

Comparative analysis of lymph node metastases in patients with ypT0-2 rectal cancers after neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy before total mesorectal excision for rectal cancer is associated with improved local tumor control, primary tumor regression, and pathologic downstaging. Therefore, tumor response in the bowel wall has been proposed to be used to identify patients for organ-preserving strategies. OBJECTIVE: The aim of this study was to determine the rate of residual lymph node involvement following neoadjuvant chemoradiotherapy among patients with ypT0-2 residual bowel wall tumor and to comparatively assess their oncologic outcomes following total mesorectal excision. DESIGN: This is a retrospective consecutive cohort study, 1993 to 2008. SETTING AND PATIENTS: Patients with stage cII to III rectal carcinoma treated with preoperative chemoradiotherapy and total mesorectal excision were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the rate of lymph node metastasis by ypT stage, recurrence-free survival, and the frequencies of distant metastasis and local recurrence. RESULTS: Among all 406 ypT0-2 patients, 66 (16.3%) had lymph node metastasis: 20.8% among ypT2, 17.1% among ypT1, and 9.1% among ypT0 patients. Local recurrences (2.0% vs 5.5%; p = 0.038) but not distant metastases (9.3% vs 13.5%; p = 0.38) occurred more frequently in ypN+ than in ypN0 patients. Recurrence-free survival was 85.2% among ypT0-2N0 and 79.6% for ypT0-2N+ patients (p = 0.28). The lack of difference in recurrence-free survival persisted after covariate adjustment (HR, 1.29; 95% CI, 0.77-2.16; p = 0.37). However, among ypT3-4 patients, 5-year recurrence-free survival was significantly lower with lymph node metastasis (HR, 1.51; 95% CI, 1.07-2.12; p = 0.019). LIMITATIONS: Low local recurrence event rate limited further comparison by ypT0-2 subgroups. CONCLUSIONS: Residual mesorectal lymph node metastasis risk remains high even with good neoadjuvant chemoradiotherapy response within the bowel wall. Complete removal of the mesorectal burden results in excellent disease control. Given the uniquely good outcomes with standard therapy among patients with ypT0-2 disease, the use of ypT stage to stratify patients for local excision risks undertreatment of an unacceptably high proportion of patients.

Investigating the antibacterial mechanism of Ampelopsis cantoniensis extracts against methicillin-resistant Staphylococcus aureus via in vitro and in silico analysis.

Methicillin-resistant Staphylococcus aureus (MRSA) is a critical pathogen responsible for a wide variety of serious infectious diseases in humans. The accelerated phenomena of drug tolerance, drug resistance, and dysbacteriosis provoked by antibiotic misuse are impeding the effectiveness of contemporary antibiotic therapies primarily used to treat this common worldwide pathogen. In this study, the antibacterial activity of 70% ethanol extract and multiple polar solvents of Ampelopsis cantoniensis were measured against the clinical MRSA isolate. The agar diffusion technique was employed to determine the zone of inhibition (ZOI), accompanied by the use of a microdilution series to identify the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Our results revealed that the ethyl acetate fraction exhibited the most significant antibacterial activity, which was determined to be bacteriostatic based on the MBC/MIC ratio 8. A list of compounds isolated from A. cantoniensis was computationally studied to further investigate the mechanism of action with the bacterial membrane protein PBP2a. The combination of molecular docking and molecular dynamics methods showed that the main compound, dihydromyricetin (DHM), is expected to bind to PBP2a at allosteric site. In addition, DHM was identified as the major compound of ethyl acetate fraction, which accounts for 77.03 ± 2.44% by high performance liquid chromatography (HPLC) analysis. As a concluding remark, our study addressed the antibacterial mechanism and suggested the prioritization of natural products derived from A. cantoniensis as a potential therapy for MRSA.Communicated by Ramaswamy H. Sarma.

Multimodality salvage of recurrent disease after local excision for rectal cancer.

BACKGROUND: Local excision, alone or in combination with chemoradiation, is increasingly considered for rectal cancer. Higher risks of disease recurrence have been demonstrated after local excision. OBJECTIVE: The aim of this study was to examine the outcomes of current-era multimodality salvage for recurrent rectal cancer after local excision. DESIGN: This was a single-institutional retrospective study. SETTINGS: This study was conducted at a tertiary-referral cancer center between 1993 and 2011. PATIENTS: Forty-six patients with recurrent rectal cancer after initial local excision were included. INTERVENTION: Multimodality salvage treatment was performed as appropriate. MAIN OUTCOME MEASURES: The primary outcomes measured were the pattern of disease recurrence, salvage treatments, and resultant overall and re-recurrence-free survival. RESULTS: After the initial local excision, recurrent disease was diagnosed after a median interval of 1.9 years: local/regionally in 67%, distantly in 18%, and both in 15%. Four patients (9%) had recurrence that was unsalvageable, 2 (4%) declined treatment, and 40 (87%) underwent surgical salvage. Preoperative chemoradiation was given in 30 (75%) patients. The R0 resection rate was 80%, requiring multivisceral resection (33%), total pelvic exenteration (5%), and metastasectomy (25%). The rate of sphincter preservation was 33%, and perioperative morbidity was 50%. The first site of failure after salvage was distant in 38% and was local only in 10%. The 5-year overall and 3-year re-recurrence-free survival were 63% and 43%. Pathologic stage at initial local excision, receipt of neoadjuvant chemoradiation before local excision, recurrence pattern after local excision, pathologic stage at salvage, and R0 resection at salvage influenced re-recurrence-free survival. LIMITATIONS: This study was limited by the referral and selection biases inherent in a small study cohort. CONCLUSIONS: Failure after local excision for rectal cancer may not be salvageable. When feasible, multimodality treatment, including multivisceral resection, pelvic irradiation, and chemotherapy, was associated with potentially lasting treatment-related morbidities and only modest success in long-term disease control. These findings should be compared with the expected stage-specific outcomes of standard proctectomy for early-stage rectal cancer, when local excision is being considered.

Reverse-hybrid robotic mesorectal excision for rectal cancer.

PURPOSE: The robotic system offers potential technical advantages over laparoscopy for total mesorectal excision with radical lymphadenectomy for rectal cancer. However, the requirement for fixed docking limits its utility when the working volume is large or patient repositioning is required. The purpose of this study was to evaluate short-term outcomes associated with a novel setup to perform total mesorectal excision and radical lymphadenectomy for rectal cancer by the use of a "reverse" hybrid robotic-laparoscopic approach. METHODS: This is a prospective consecutive cohort observational study of patients who underwent robotic rectal cancer resection from January 2009 to March 2011. During the study period, a technique of reverse-hybrid robotic-laparoscopic rectal resection with radical lymphadenectomy was developed. This technique involves reversal of the operative sequence with lymphovascular and rectal dissection to precede proximal colonic mobilization. This technique evolved from a conventional-hybrid resection with laparoscopic vascular control, colonic mobilization, and robotic pelvic dissection. Perioperative and short-term oncologic outcomes were analyzed. RESULTS: Thirty patients underwent reverse-hybrid resection. Median tumor location was 5 cm (interquartile range 3-9) from the anal verge. Median BMI was 27.6 (interquartile range 25.0-32.1 kg/m). Twenty (66.7%) received neoadjuvant chemoradiation. There were no conversions. Median blood loss was 100 mL (interquartile range 75-200). Total operation time was a median 369 (interquartile range 306-410) minutes. Median docking time was 6 (interquartile range 5-8) minutes, and console time was 98 (interquartile range 88-140) minutes. Resection was R0 in all patients; no patients had an incomplete mesorectal resection. Six patients (20%) underwent extended lymph node dissection or en bloc resection. CONCLUSIONS: Reverse-hybrid robotic surgery for rectal cancer maximizes the therapeutic applicability of the robotic and conventional laparoscopic techniques for optimized application in minimally invasive rectal surgery.

A Cross-Sectional Study on Potential Ovarian Volume and Related Factors in Women with Polycystic Ovary Syndrome from Infertile Couples.

PURPOSE: This study was designed to explore the value of ovarian volume (OV) measured by transvaginal ultrasound and its relationship with anthropometry and serum hormonal levels in a polycystic ovary syndrome (PCOS) population. PATIENTS AND METHODS: A total of 119 women with PCOS from infertile couples were recruited in this cross-sectional study. On days 2-4 of the menstrual cycle, transvaginal ultrasound examinations were performed, and hormonal profiles were measured. PCOS diagnosis was based on the Rotterdam 2003 criteria and classified into four phenotype groups. The PCOS group (study group) and the non-PCOS group (control group) were compared. RESULTS: The mean age of the participants was 32.66±4.10 years compared to 33.99±4.78 years in 273 cases (69.6%) without PCOS. The mean OV was statistically larger in the PCOS group than in the non-PCOS group (7.65±3.23 mL vs 6.08±3.67 mL, p < 0.001) and positively correlated with serum anti-Mullerian (AMH) and luteinizing hormone (LH) levels (r=0.30; p < 0.001 and r=0.23; p < 0.001, respectively), and weakly and inversely correlated with age (-0.182, p < 0.001). The area under the receiver operating characteristic (ROC) curve of OV in the diagnosis of PCOS was 0.613 (0.557-0.670, 95% CI). CONCLUSION: The enlarged OV is remarkable in women with PCOS and is related to AMH and LH concentrations. Although the diagnostic potential of PCOS is substantially low, OV alone may contribute to predicting the severity of PCOS and better performance for the diagnosis of PCOS phenotypes.

Development of Genotype-Specific Anti-Bovine Rotavirus A Immunoglobulin Yolk Based on a Current Molecular Epidemiological Analysis of Bovine Rotaviruses A Collected in Japan during 2017-2020.

Bovine rotavirus A (RVA), a major causative pathogen of diarrhea in dairy and Japanese beef calves, has led to severe economic losses in numerous countries. A dual genotyping system based on genomic segments encoding VP7 (G genotype) and VP4 (P genotype), comprising the outer layer of the virion, has been used to understand the epidemiological dynamics of RVAs at the national and global levels. This study aimed to investigate occurrence frequency of G and P genotypes for multiple bovine RVAs from calf diarrheic samples collected in Japan from 2017 to 2020. After we produced anti-bovine RVA immunoglobulin yolks (IgYs) from hens immunized with the two RVAs with different genotypes (G6P[5] and G10P[11]) selected on the basis of the current epidemiological survey, we investigated cross-reactivity against bovine RVAs with different G and P combinations owing to establish a useful strategy to protect calves from RVA infections using the two IgYs. Consequently, the two produced anti-bovine IgYs showed strong cross-reactivity against bovine RVAs with the same G and/or P genotypes in neutralization assay, respectively. Therefore, our data suggest the possibility of a passive immunization to protect calves from a bovine RVA infections epidemic in Japan via oral administration of the two IgYs into calves. The findings presented herein will provide important information that IgY is one of the effective tools to prevent infections of various pathogens.