Risk factors for the failure of endoscopic balloon dilation to manage anastomotic stricture from colorectal surgery: retrospective cohort study.

BACKGROUND: An anastomotic stricture after colorectal surgery is principally managed by endoscopic balloon dilation (EBD). Although this intervention is effective, however, subsequent procedures or surgical interventions are often required. This study aimed to assess the long-term outcomes of EBD for anastomotic stricture arising from colorectal cancer surgery. MATERIALS AND METHODS: We analyzed 173 patients who received curative surgery for colorectal cancer at our hospital between January 2000 and December 2022 and had undergone EBD to manage anastomotic stricture. The medical records of these cases were retrospectively reviewed to assess the outcomes and risk factors for restenosis and permanent stoma. RESULTS: Of the 173 study patients, 41 (23.7%) presented with restenosis with a median time to recurrence of 49 [37-150] days. The restenosis group was significantly younger (55.6 years versus 60.8 years), with a more prominent rectal location (80.5% versus 57.6%), a higher incidence of hand-sewn anastomosis (24.4% versus 5.3%), and a higher percentage of neoadjuvant radiotherapy (34.1% versus 5.3%, P < 0.001). Multivariable analysis indicated neoadjuvant radiotherapy (adjusted HR 2.48; 95% CI 1.03-5.95) and cerebral vascular disease (adjusted HR 6.97; 95% CI 2.15-22.54) as independent prognostic factors for restenosis. Fourteen patients (8.1%) required a permanent stoma due to treatment failure. All cases needing a permanent stoma were male (14 patients, 100%, P = 0.007) and this group had a higher rate of neoadjuvant radiotherapy, adjuvant chemotherapy, and hand-sewn anastomosis. CONCLUSION: Patients receiving neoadjuvant radiotherapy are most prone to restenosis after an EBD intervention to manage an anastomotic stricture. Neoadjuvant radiotherapy is also a strong risk factor for requiring a permanent stomas due to treatment failure.

Influence of additional prophylactic oral antibiotics during mechanical bowel preparation on surgical site infection in patients receiving colorectal surgery.

BACKGROUND: Prophylactic antibiotics (PAs) are standard for preventing surgical site infections (SSIs) post-colorectal surgery. This study aims to compare the effect of additional empiric oral antibiotics (OAs) alongside routine PAs to identify SSI risk factors. METHODS: A retrospective observatory analysis was conducted from January 2019 to December 2022 at Asan Medical Center, Seoul, Korea. The cohort was divided into two groups: PA given 1 h before surgery and discontinued within 24 h, and OA administered empiric OAs during mechanical bowel preparation in addition to PA. RESULTS: From a total of 6736 patients, 3482 were in the PA group and 3254 in the OA group. SSI incidence showed no significant intergroup difference (p = 0.374) even after propensity score matching (p = 0.338). The multivariable analysis revealed male sex [odds ratio (OR): 2.153, 95% confidence interval (CI): 1.626-2.852, and p = 0.001], open surgery (OR: 3.335, 95% CI: 2.456-4.528, and p = 0.001), dirty wound (OR: 2.171, 95% CI: 1.256-3.754, and p = 0.006), and an operation time of more than 145 min (OR: 2.110, 95% CI: 1.324-3.365, and p = 0.002) as SSI risk factors. In rectal surgery subgroup, OA demonstrated a protective effect against SSI (OR: 0.613, 95% CI: 0.408-0.922, and p = 0.019) and in laparoscopic approach (OR: 0.626, 95% CI: 0.412-0.952, and p = 0.028). CONCLUSIONS: OA did not affect SSI incidence in colorectal surgeries. Male sex, open surgery, dirty wounds, and longer operation time were risk factors for SSI. However, for rectal and laparoscopic surgery, OA was a protective factor for SSI.

Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site.

Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at α/ß-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the α/ß-tubulin-GB1 complex.

Molecularly imprinted polymer-based extended-gate field-effect transistor chemosensors for selective determination of antiepileptic drug.

Ultrathin molecularly imprinted polymer (MIP) films were deposited on the surfaces of ZnO nanorods (ZNRs) and nanosheets (ZNSs) by electropolymerization to afford extended-gate field-effect transistor sensors for detecting phenytoin (PHT) in plasma. Molecular imprinting efficiency was optimized by controlling the contents of functional monomers and the template in the precursor solution. PHT sensing was performed in plasma solutions with various concentrations by monitoring the drain current as a function of drain voltage under an applied gate voltage of 1.5 V. The reliability and reproducibility of the fabricated sensors were evaluated through a solution treatment process for complete PHT removal and PHT adsorption-removal cycling, while selectivity was examined by analyzing responses to chemicals with structures analogous to that of PHT. Compared with the ZNS/extracted-MIP sensor and sensors with non-imprinted polymer (NIP) films, the ZNR/extracted-MIP sensor showed superior responses to PHT-containing plasma due to selective PHT adsorption, achieving an imprinting factor of 4.23, detection limit of 12.9 ng/mL, quantitation limit of 53.0 ng/mL, and selectivity coefficients of 3-4 (against tramadol) and ~ 5 (against diphenhydramine). Therefore, we believe that the MIP-based ZNR sensing platform is promising for the practical detection of PHT and other drugs and evaluation of their proper dosages.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

Comparative Cost Analysis Between Endoscopic Resection and Surgery for Submucosal Colorectal Cancer.

BACKGROUND: There are few studies analyzing the cost of endoscopic resection and surgical resection in the treatment of submucosal colorectal cancer. OBJECTIVE: The objective was to perform a detailed cost analysis of endoscopic resection and surgical resection for submucosal colorectal cancer. DESIGN: This was a retrospective observational study. SETTING: This study was conducted at a tertiary academic center. PATIENTS: Medical records of 484 patients with submucosal colorectal cancer who underwent endoscopic resection or surgical resection between July 2003 and July 2015 were reviewed. MAIN OUTCOME MEASUREMENTS: The total costs during index admission and follow-up as well as clinical outcomes between the 2 groups were compared in the whole cohort and propensity score-matched cohort. RESULTS: In the propensity score-matched analysis ( n = 155 in each group), the endoscopic resection and surgical resection groups did not show significant differences in the rates of procedure-related adverse events (6.5% vs 3.9%; p = 0.304) and recurrence (0.6% vs 1.3%; p > 0.99). Readmission was more common in the endoscopic resection group (40.6% vs 11.0%; p < 0.001) because 64 (41.3%) patients underwent additional surgery for endoscopic noncurative resection. The endoscopic resection group had a lower cost during the index admission (1335.6 vs 6698.4 USD; p < 0.001), whereas the surgical resection group had a lower cost during follow-up (2488.7 vs 5035.7 USD; p < 0.001). The total cumulative cost was lower in the endoscopic resection group (6371.3 vs 9187.1 USD; p < 0.001). The same trend was observed in the whole cohort without propensity score matching. LIMITATIONS: A limitation of this study was the retrospective nature of analysis. CONCLUSIONS: The total cumulative cost for treatment and follow-up for submucosal colorectal cancer was lower in the endoscopic resection group, which had comparable oncologic outcomes as the surgical resection group. Endoscopic resection can be considered a cost-effective option for initial treatment for submucosal colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B881 . ANLISIS COMPARATIVO DE COSTOS ENTRE LA RESECCIN ENDOSCPICA Y LA CIRUGA PARA EL CNCER COLORRECTAL SUBMUCOSO: ANTECEDENTES: Existen pocos estudios que analizan el costo de la resección endoscópica y la resección quirúrgica en el tratamiento del cáncer colorrectal submucoso.OBJETIVO: El objetivo fue realizar un análisis detallado de costos tanto de la resección endoscópica y la resección quirúrgica para el cáncer colorrectal submucoso.DISEÑO: Este fue un estudio observacional retrospectivo.AJUSTE: Este estudio se realizó en un centro académico terciario.PACIENTES: Se revisaron las historias clínicas de 484 pacientes con cáncer colorrectal submucoso que fueron sometidos a resección endoscópica o resección quirúrgica entre julio de 2003 y julio de 2015.PRINCIPALES MEDICIONES DE RESULTADOS: Los costos totales durante la admisión índice y el seguimiento, así como los resultados clínicos entre los dos grupos, fueron comparados en toda la cohorte y la cohorte emparejada por puntuación de propensión.RESULTADOS: En el análisis emparejado por puntuación de propensión ( n = 155 en cada grupo), los grupos de resección endoscópica y resección quirúrgica no mostraron diferencias significativas en las tasas de eventos adversos relacionados con el procedimiento (6,5% vs 3,9%, p = 0,304) y recurrencia (0,6% vs 1,3%, p > 0,99). La readmisión fue más común en el grupo de resección endoscópica (40,6% vs 11,0%, p < 0,001) porque 64 (41,3%) pacientes fueron sometidos a una cirugía adicional para lograr la resección en aquellos casos en que la resección endoscópica no fue curativa. El grupo de resección endoscópica tuvo un costo menor durante el ingreso índice (1335.6 vs 6698.4 USD, p < 0.001), mientras que el grupo de resección quirúrgica tuvo un costo menor durante el seguimiento (2488.7 vs 5035.7 USD, p < 0.001). El costo total acumulado fue menor en el grupo de resección endoscópica (6371,3 vs 9187,1 USD, p < 0,001). La misma tendencia se observó en toda la cohorte sin emparejamiento por puntuación de propensión.LIMITACIONES: La naturaleza retrospectiva del análisis.CONCLUSIONES: El costo total acumulado para el tratamiento y seguimiento del cáncer colorrectal submucoso fue menor en el grupo de resección endoscópica, que tuvo resultados oncológicos comparables a los del grupo de resección quirúrgica. La resección endoscópica puede considerarse una opción rentable para el tratamiento inicial del cáncer colorrectal submucoso. Consulte Video Resumen en http://links.lww.com/DCR/B881 . (Traducción-Dr Osvaldo Gauto ).

Optimal surgical management of duodenal fistula in Crohn's disease: a Korean multicenter cohort study.

PURPOSE: Duodenal fistula in Crohn's disease (CDF) is a rare condition with an unclear optimal surgical management approach. We reviewed a Korean multicenter cohort of CDF surgery cases and assessed their perioperative outcomes to evaluate the effectiveness of the surgical interventions. METHODS: The medical records of patients who underwent CD surgery between January 2006 and December 2021 from three tertiary medical centers were retrospectively reviewed. Only CDF cases were included in this study. The demographic and preoperative characteristics, perioperative details, and postoperative outcomes were analyzed. RESULTS: Among the initial population of 2149 patients who underwent surgery for CD, 23 cases (1.1%) had a CDF operation. Fourteen of these patients (60.9%) had a history of previous abdominal surgery, and 7 had duodenal fistula at the previous anastomosis site. All duodenal fistulas were excised and primarily repaired via a resection of the originating adjacent bowel. Additional procedures such as gastrojejunostomy, pyloric exclusion, or T-tube insertion were performed in 8 patients (34.8%). Eleven patients (47.8%) experienced postoperative complications including for anastomosis leakages. Fistula recurrence was noted in 3 patients (13%) of which one patient required a re-operation. Biologics administration was associated with fewer adverse events by multivariable analysis (P = 0.026, odds ratio = 0.081). CONCLUSION: Optimal perioperative conditioning of patients receiving a primary repair of a fistula and resection of the original diseased bowel can successfully cure CDF. Along with primary repair of the duodenum, other complementary additional procedures should be considered for better postoperative outcomes.

Determination of ovalbumin sensing response of protein-imprinted bilayered hydrogel strips via measurement of mechanically driven bending angles based on swelling-induced deformation.

Novel detection method has been developed to explore changes in mechanical bending angles on a bilayer of polyethylene terephthalate (PET) and molecularly imprinted polymer (MIP). For an ovalbumin (OVA)-imprinted hydrogel layer, functional monomers were employed to achieve sufficient binding effect in the polymer matrix. The OVA amount added in the MIP precursor solution and the dimensions of OVA-imprinted hydrogel (MIH) strips were controlled to maximize the change in bending angles as an OVA sensing response within a valid detection range. The sensing behaviors were determined by monitoring the difference in the bending angles via protein adsorption based on the swelling-induced deformation of the OVA-extracted hydrogel (E-MIH) strip. The equilibrium adsorption capacity of the E-MIH strip was calculated via the Bradford protein assay. The detection limit, quantification limit, and imprinting factor were calculated. To compare the selectivity coefficients, the adsorption behaviors of three proteins were investigated. Finally, the reusability of the E-MIH strip was explored via repeated adsorption and extraction. Based on the results, the E-MIH strips demonstrated a promising protein sensing platform monitoring mechanical bending angles affected by swelling deformation.

Clinical Implication of Perineural and Lymphovascular Invasion in Rectal Cancer Patients Who Underwent Surgery After Preoperative Chemoradiotherapy.

BACKGROUND: Lymphovascular and perineural invasion are well-known negative prognostic indicators in rectal cancer, but previous studies on their significance are not consistent. OBJECTIVE: This study assessed the prognostic value of lymphovascular and perineural invasion in rectal cancer patients who received preoperative chemoradiotherapy followed by curative resection. DESIGN: This is a retrospective analysis. SETTING: This study was performed at a tertiary cancer center. PATIENTS: Rectal cancer patients who underwent curative resection after preoperative chemoradiotherapy between January 2000 and December 2010. MAIN OUTCOME MEASURES: The primary outcomes were disease-free survival and overall survival. The survival rates were estimated using Kaplan-Meier analysis, and group comparisons were conducted using a log-rank test. RESULTS: Of the 1156 included patients, 109 (9.4%) presented with lymphovascular invasion and 137 (11.9%) presented with perineural invasion. Lymphovascular and perineural invasion were associated with T and N downstaging after preoperative chemoradiotherapy ( p < 0.001). In the ypN0 patients, the 5-year disease-free survival rates were 70.8% and 78.5% ( p = 0.150) for the lymphovascular invasion and absent groups, respectively. In the perineural invasion group, the 5-year disease-free survival rate was 59.0% compared to 80.2% in the absent group ( p = 0.001). Among the ypN+ patients, the 5-year disease-free survival rates were 36.9% and 44.4% for the lymphovascular invasion and absent groups, respectively ( p = 0.211). The perineural invasion group had a poorer 5-year disease-free survival rate compared to the absent group (29.7% vs 46.7%; p = 0.011). By multivariable analyses, perineural invasion correlated with a poor disease-free survival (HR 1.412, 95% CI 1.082-1.843; p = 0.011) and also in ypN0 subgroup analysis (HR 1.717, 95% CI 1.093-2.697; p = 0.019). LIMITATIONS: This study was a retrospective study conducted at a single center. CONCLUSIONS: Perineural invasion is a reliable independent predictor of recurrence in rectal cancer patients treated with preoperative chemoradiotherapy. Patients with perineural invasion should be considered for closer surveillance even with ypN0 status. See Video Abstract at http://links.lww.com/DCR/B833 .IMPLICACIÓN CLÍNICA DE LA INVASIÓN PERINEURAL Y LINFOVASCULAR EN PACIENTES CON CÁNCER DE RECTO SOMETIDOS A CIRUGÍA DESPUÉS DE QUIMIORRADIOTERAPIA PREOPERATORIA. ANTECEDENTES: La invasión linfovascular y perineural en cancer de recto, son indicadores pronósticos negativos bien conocidos, pero estudios previos sobre su significancia, no son consistentes. OBJETIVO: El estudio evaluó el valor pronóstico de la invasión linfovascular y perineural en pacientes con cáncer de recto sometidos a quimiorradioterapia preoperatoria seguida de resección curativa. DISEO: Es un análisis retrospectivo. ENTORNO CLINICO: El estudio se realizó en un centro oncológico terciario. PACIENTES: Pacientes con cáncer de recto sometidos a resección curativa después de quimiorradioterapia preoperatoria entre enero de 2000 y diciembre de 2010. PRINCIPALES MEDIDAS DE VALORACION: Los resultados primarios fueron la supervivencia libre de enfermedad y la supervivencia general. Las tasas de supervivencia se estimaron mediante el análisis de Kaplan-Meier y las comparaciones de grupos se realizaron mediante una prueba de rango logarítmico. RESULTADOS: De los 1156 pacientes incluidos, 109 (9,4%) presentaron invasión linfovascular y 137 (11,9%) invasión perineural. La invasión linfovascular y perineural se asoció con reducción del estadio de T y N después de la quimiorradioterapia preoperatoria ( p < 0,001). En los pacientes ypN0, las tasas de supervivencia libre de enfermedad a 5 años fueron del 70,8% y el 78,5% ( p = 0,150) para los grupos con y sin invasión linfovascular, respectivamente. En el grupo de invasión perineural, la tasa de supervivencia libre de enfermedad a 5 años fue del 59,0%, en comparación con el 80,2% en el grupo ausente ( p = 0,001). Entre los pacientes ypN +, las tasas de supervivencia sin enfermedad a 5 años fueron del 36,9% y 44,4% para los grupos con y sin invasión linfovascular, respectivamente ( p = 0,211). El grupo de invasión perineural mostró una tasa de supervivencia libre de enfermedad a 5 años menor, en comparación con el grupo ausente (29,7% versus 46,7%, p = 0,011). Mediante análisis multivariable, la invasión perineural se correlacionó con una pobre tasa de supervivencia de enfermedad (índice de riesgo 1,412; intervalo de confianza del 95%: 1,082-1,843; p = 0,011) y también en el análisis de subgrupos ypN0 (índice de riesgo 1,717; intervalo de confianza del 95%: 1,093-2,697; p = 0,019). LIMITACIONES: Estudio retrospectivo realizado en un solo centro. CONCLUSIONES: La invasión perineural es un predictor independiente y confiable de recurrencia en pacientes con cáncer de recto tratados con quimiorradioterapia preoperatoria. Los pacientes con invasión perineural deben considerarse para una vigilancia más estrecha incluso con estadio ypN0. Consulte Video Resumen en http://links.lww.com/DCR/B833 . (Traducción-Dr. Fidel Ruiz Healy ).

Comparative survival risks in patients undergoing abdominoperineal resection and sphincter-saving operation for rectal cancer: a 10-year cohort analysis using propensity score matching.

PURPOSE: Abdominoperineal resection (APR) has been considered to have a higher risk of local recurrence and poorer survival outcome than sphincter-saving operation (SSO) in patients with rectal cancer. This study compared long-term oncologic outcomes and prognostic parameters in propensity score-matched patients who underwent APR and SSO. METHODS: This study analyzed 958 consecutive patients with lower rectal cancer who underwent preoperative chemoradiotherapy followed by APR or SSO between 2005 and 2015. Propensity score matching analysis was performed to adjust baseline characteristics, including clinical stage, tumor distance from the anal verge, and tumor size. RESULTS: In the entire cohort, the APR group had larger and lower tumors and showed significantly shorter 5-year disease-free survival (DFS) than the SSO group (64.5% vs. 75.8%, p = 0.01). After propensity score matching, there were no significant between-group differences in local (9.5% vs. 8.0%, p = 0.59) and systemic (27.9% vs. 23.4%, p = 0.3) recurrence rates, and 5-year DFS (67.5% vs. 69.9%, p = 0.49) and overall survival (80.8% vs. 82.9%, p = 0.65) rates. A lower number of lymph nodes retrieved was independently associated with recurrence and survival outcomes in the APR group, whereas poorly differentiated histology was an independent associated parameter in the SSO group. Advanced stage and perineural invasion were identified as independent prognostic parameters in both groups. CONCLUSIONS: This study indicated that the long-term oncologic outcomes of APR were comparable to those of SSO. Because prognostic parameters associated with oncologic outcomes differed between the respective procedures, correctable parameters could be ameliorated through complete total mesorectal excision and personalized systemic treatment.

The COVID Positive Pathway: a collaboration between public health agencies, primary care, and metropolitan hospitals in Melbourne.

OBJECTIVES: To assess the capacity of the COVID Positive Pathway, a collaborative model of care involving the Victorian public health unit, hospital services, primary care, community organisations, and the North Western Melbourne Primary Health Network, to support people with coronavirus disease 2019 (COVID-19) isolating at home. DESIGN, SETTING, PARTICIPANTS: Cohort study of adults in northwest Melbourne with COVID-19, 3 August - 31 December 2020. MAIN OUTCOME MEASURES: Demographic and clinical characteristics, and social and welfare needs of people cared for in the Pathway, by care tier level. RESULTS: Of 1392 people referred to the Pathway by the public health unit, 858 were eligible for enrolment, and 711 consented to participation; 647 (91%) remained in the Pathway until they had recovered and isolation was no longer required. A total of 575 participants (81%) received care in primary care, mostly from their usual general practitioners; 155 people (22%) received care from hospital outreach services, and 64 (9%) needed high tier care (hospitalisation). Assistance with food and other basic supplies was required by 239 people in the Pathway (34%). CONCLUSIONS: The COVID Positive Pathway is a feasible multidisciplinary, tiered model of care for people with COVID-19. About 80% of participants could be adequately supported by primary care and community organisations, allowing hospital services to be reserved for people with more severe illness or with risk factors for disease progression. The principles of this model could be applied to other health conditions if regulatory and funding barriers to information-sharing and care delivery by health care providers can be overcome.

Oncological outcomes according to the treatment modality based on the size of rectal neuroendocrine tumors: a single-center retrospective study.

BACKGROUND: Owing to an increased number of colonoscopy screenings, the incidence of diagnosed rectal neuroendocrine tumors (NETs) has also increased. Tumor size is one of the most frequently regarded factors when selecting treatment; however, it may not be the determinant prognostic variable. We aimed to evaluate oncological outcomes according to the treatment modality based on the size of rectal NETs. METHODS: A retrospective analysis was performed on patients who were treated for rectal NETs between March 2000 and January 2016 at the Asan Medical Center, Seoul, Korea. Patients who underwent endoscopic removal, local surgical excision, and radical resection were included. The primary outcome was recurrence-free survival (RFS). Data were specified and analyzed following the 2019 World Health Organization classification (WHO). RESULTS: A total of 644 patients were categorized under three groups according to the treatment modality used: endoscopic removal (n = 567), surgical local excision (n = 56), and radical resection (n = 21). Of a total of 35 recurrences, 27 were local, whereas eight were distant. The RFS rate did not differ significantly between the treatment groups in the same tumor-size group ([Formula: see text]1 cm group: P = .636, 1-2 cm group: P = .160). For T1 tumors, RFS rate was not different between local excision and radical resection ([Formula: see text]1 cm group: P = .452, 1-2 cm group: P = .700). Depth of invasion, a high Ki-67 index, and margin involvement were confirmed as independent risk factors for recurrence. Among patients treated with endoscopic removal, endoscopic biopsy was a significant factor for worse RFS (P < .001), while tumor size did not affect the RFS. CONCLUSION: The current guideline recommends treatment options according to tumor size. However, more oncologically important prognostic factors include muscularis propria invasion and a higher Ki-67 index.

COVID-19 pandemic 2020: a tertiary Melbourne hospital's experience.

BACKGROUND: The COVID-19 pandemic has affected different parts of Australia in distinct ways across 2020 and 2021. In 2020, Melbourne was the epicentre of COVID-19. As one of the key tertiary centres caring for the patients affected by the outbreaks, the Royal Melbourne Hospital (RMH) managed the majority of the Victorian inpatient caseload. AIMS: To review the demographics, management and outcomes of patients with COVID-19 cared for by the RMH services in 2020. METHODS: A single health service retrospective cohort analysis of demographics, interventions and outcomes was conducted to characterise the RMH experience in 2020. RESULTS: From January to December 2020, 433 patients required admission more than 24 h. The demographics of affected patients and outcomes changed over the course of the study. Overall, 47% (203/433) required oxygen, most frequently (36%; 154/433) with low-flow devices (nasal prongs or hudson mask), and 11% (47/433) of patients required admission to intensive care. We recorded a 30-day mortality of 24% (104/433) mortality overall, rising to over 50% in patients aged over 80 years. CONCLUSIONS: The experience of this health service in 2020 demonstrated changing demographics over time, with associated differences in outcomes; notably marked mortality in older populations, frequent complications and limited inter-site transfer possible with mobilised resources.

Distribution pattern of tumor infiltrating lymphocytes and tumor microenvironment composition as prognostic indicators in anorectal malignant melanoma.

Anorectal malignant melanoma (ARMM) is a rare disease with poor prognosis. Determining ARMM prognosis precisely is difficult due to the lack of proper assessment techniques. Immunotherapy has proven effective against cutaneous malignant melanoma and may show efficacy in ARMM. Herein, we assessed the immune profile of ARMM to identify possible prognostic biomarkers. Twenty-two ARMM formalin-fixed and paraffin-embedded samples were evaluated using an nCounter® PanCancer Immune Profiling Panel. Validation was performed through immunohistochemical staining for CD3, CD8, Foxp3, CD68, CD163, and PD-L1. RNA analysis revealed significantly decreased scores for pathways involved in cell regulation and function, as well as chemokines, in recurrent patients compared to nonrecurrent patients. In cell-type profiling, the recurrent cases displayed significantly low tumor infiltrating lymphocyte (TIL) scores. Recurrence/death prediction models were defined using logistic regression and showed significantly lower scores in recurrent and deceased patients (all, P < 0.001) compared to those in nonrecurrent and surviving patients. The high total TIL and tumor-associated macrophage (TAM) groups had significantly better overall survival outcomes compared to the low total TIL and TAM groups (P = 0.007 and P = 0.035, respectively). In addition, the presence of CD3 + TILs in the invasion front was an independent favorable prognostic indicator (P = 0.003, hazard ratio = 0.21, 95% confidential interval, 0.01-0.41). Patients with inflamed or brisk-infiltration type tumors also had a significantly better overall survival than that of patients with immune-desert/excluded and absent/non-brisk type tumors (P = 0.03 and P = 0.0023, respectively). In conclusion, TILs have a strong prognostic value in ARMM, and the quantification of TILs and an analysis of the TIL phenotype and infiltration pattern during pathological diagnosis are essential to guide treatment strategies and accurate prognosis in ARMM.

Re-evaluation of controversial issues in the treatment of cT3N0-2 rectal cancer: a 10-year cohort analysis using propensity-score matching.

BACKGROUND: Although neoadjuvant treatment is thought to provide optimal local control for stage II and III rectal cancers, many patients have been reported cured by total mesorectal excision (TME), alone or with additional chemotherapy (CTX). METHODS: This study retrospectively evaluated outcomes in 2643 patients with cT3N0-2 rectal cancers undergoing curative TME during 2005-2015. Recurrence and survival outcomes were measured in three propensity-score matched groups, consisting of patients who underwent preoperative chemoradiotherapy (CRT) with postoperative CTX (NAPOC), postoperative CRT (POCRT), and exclusively postoperative CTX (EPOCT). RESULTS: Near-complete or complete TME was conducted in more than 95.9% of patients and 80% of scheduled dose of postoperative CTX was completed in 99%. Except for higher SR rate in the POCRT group than the NAPOC group (p = 0.008), 5-year cumulative local and systemic recurrence (LR and SR) rates were 4.9% and 15.2% for cT3N0, and 4.2% and 21% for cT3N1-2 patients (LR, p = 0.703; SR, 0.065), respectively, with no significant differences associated with treatment exposure (p = 0.11-1). The 5-year cumulative disease-free (75.6% vs 65.7%, p = 0.018) and overall survival (87.1% vs 79.4%, p = 0.018 each) rates were higher in the NAPOC group than the POCRT group with cT3N1-2. However, any significant survival differences were not identified between the NAPOC and EPOCT groups according to tumor sub-stages or locations (p = 0.395-0.971). CONCLUSIONS: We found any treatment modalities including competent TME and postoperative adjuvant CTX efficiently reducing LR generating robust survival outcome in the propensity-matched cohorts, demanding further randomized controlled trials by clinical sub-stages II-III.

Characteristics and Prognosis of Colorectal Cancer after Liver or Kidney Transplantation.

BACKGROUND: The purpose of this study was to evaluate the characteristics and prognosis of de novo CRC patients who underwent liver or kidney transplantation. METHODS: We retrospectively reviewed the medical records of 66 de novo CRC patients selected from 8,734 liver transplant (LT) or kidney transplant (KT) recipients. We analyzed characteristics and survival outcomes of de novo CRC patients and sporadic CRC patients who underwent radical surgery with stage I-III in Asan Medical Center between 2005 and 2016. Survival outcomes were analyzed via the 1:4 matching method. RESULTS: The standard incidence ratio (SIR) of de novo CRC in KT recipients is 1.67 in men and 2.54 in women. That in LT recipients is 3.10 in men and 2.25 in women. Compared with sporadic CRC patients, de novo CRC patients had more colon cancer than rectal cancer (p=0.041). In 9 patients (13.6%), CRC was diagnosed within one year after transplantation, 21 patients (31.8%) were diagnosed between 1-5 years, and the remaining 36 patients (54.6%) were diagnosed thereafter. There were no significant differences in recurrence-free survival and overall survival between the two groups (p=0.211 and p=0.324, respectively). CONCLUSIONS: The risk of developing de novo CRC in transplant recipients was higher than in the general population. The survival outcome of de novo CRC was no different compared with the sporadic CRC. Therefore, regular surveillance is essential for timely diagnosis and treatment for transplantation patients. A large prospective study for an intense CRC surveillance program in transplantation patients is needed.

Evaluation of Serological Tests for SARS-CoV-2: Implications for Serology Testing in a Low-Prevalence Setting.

BACKGROUND: Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little premarket validation. METHODS: Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT). RESULTS: Sensitivities for PoCT ranged from 51.8% (95% confidence interval [CI], 43.1%-60.4%) to 67.9% (95% CI, 59.4%-75.6%), and specificities from 95.6% (95% CI, 89.2%-98.8%) to 100.0% (95% CI, 96.1%-100.0%). ELISA sensitivity for IgA or IgG detection was 67.9% (95% CI, 59.4%-75.6%), increasing to 93.8% (95% CI, 85.0%-98.3%) for samples >14 days post symptom onset. sVNT sensitivity was 60.9% (95% CI, 53.2%-68.4%), rising to 91.2% (95% CI, 81.8%-96.7%) for samples >14 days post symptom onset, with specificity 94.4% (95% CI, 89.2%-97.5%). CONCLUSIONS: Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.

Radioiodine ablation in thyroid cancer patients: renal function and external radiation dose rate at discharge according to patient preparation.

BACKGROUND: An elevated thyroid stimulating hormone (TSH) level is essential for the uptake of radioiodine into thyroid remnants and residual thyroid cancer in patients undergoing high-dose radioiodine therapy (HD-RIT). Recently, the use of recombinant human thyroid stimulating hormone (rh-TSH) has increased in preference over the conventional method of thyroid hormone withdrawal (THW). However, the clinical influences of the two methods, aside from the therapeutic effects, have not been widely evaluated. The aim of this work was to investigate the influences of the two methods, particularly on the renal function and external radiation dose rate (EDR) from patients undergoing HD-RIT. METHODS: From February 2012 to November 2016, 667 patients (M:F=138:529, mean age: 47.7±11.8 years), who underwent first HD-RIT (120, 150, or 180 mCi, 1 mCi=37 MBq) for ablation of remnant thyroid tissue or residual thyroid cancer, were enrolled. Patients who were proven to have distant metastasis to lung or bone were excluded. Low- to high-risk patients based on 2015 American thyroid association management guidelines who underwent first HD-RIT in our department were included. The period from total thyroidectomy to HD-RIT was limited within 12 months. The following parameters were collected and evaluated: age, gender, histology type and TNM stage of thyroid cancer, glomerular filtration rate on the admission day for total thyroidectomy (baseline GFR), GFR on the day of HD-RIT (follow-up GFR), thyroglobulin (Tg) and TSH levels on the day of HD-RIT, and EDR on the discharge day after HD-RIT. RESULTS: There were 386 patients using the THW method and 281 patients choosing the rh-TSH method. The baseline GFR of the THW group (106±16 mL/min/1.73 m2) and that of the rh-TSH group (104±17 mL/min/1.73 m2) were within normal limits and there was no significant difference. However, follow-up GFR of the THW group (84±17 mL/min/1.73 m2) was much lower than that of the rh-TSH group (104±16 mL/min/1.73 m2) (P=0.000). In the THW group, the follow-up GFR decreased significantly (P=0.000), yet the follow-up GFR of the rh-TSH group was not statistically different when compared with its baseline GFR (P=0.142). EDRs were lower in all rh-TSH subgroups compared to those of THW subgroups with statistical significance. Tg and TSH levels were not different between the two groups, excluding a few small-sized subgroups analyses. CONCLUSIONS: In this retrospective analysis of renal function and EDR, the use of rh-TSH appears to help maintain renal function and finally decrease EDR in contrast to the THW method when undergoing HD-RIT.

Pandemic printing: a novel 3D-printed swab for detecting SARS-CoV-2.

OBJECTIVES: To design and evaluate 3D-printed nasal swabs for collection of samples for SARS-CoV-2 testing. DESIGN: An iterative design process was employed. Laboratory evaluation included in vitro assessment of mock nasopharyngeal samples spiked with two different concentrations of gamma-irradiated SARS-CoV-2. A prospective clinical study compared SARS-CoV-2 and human cellular material recovery by 3D-printed swabs and standard nasopharyngeal swabs. SETTING, PARTICIPANTS: Royal Melbourne Hospital, May 2020. Participants in the clinical evaluation were 50 hospital staff members attending a COVID-19 screening clinic and two inpatients with laboratory-confirmed COVID-19. INTERVENTION: In the clinical evaluation, a flocked nasopharyngeal swab sample was collected with the Copan ESwab and a mid-nasal sample from the other nostril was collected with the 3D-printed swab. RESULTS: In the laboratory evaluation, qualitative agreement with regard to SARS-CoV-2 detection in mock samples collected with 3D-printed swabs and two standard swabs was complete. In the clinical evaluation, qualitative agreement with regard to RNase P detection (a surrogate measure of adequate collection of human cellular material) in samples collected from 50 hospital staff members with standard and 3D-printed swabs was complete. Qualitative agreement with regard to SARS-CoV-2 detection in three pairs of 3D-printed mid-nasal and standard swab samples from two inpatients with laboratory-confirmed SARS-CoV-2 was also complete. CONCLUSIONS: Using 3D-printed swabs to collect nasal samples for SARS-CoV-2 testing is feasible, acceptable to patients and health carers, and convenient.

Latifolin Inhibits Oxidative Stress-Induced Senescence via Upregulation of SIRT1 in Human Dermal Fibroblasts.

Latifolin, a natural flavonoid found in Dalbergia odorifera T. Chen, has been reported to exhibit anti-inflammatory and anticarcinogenic activities in vitro. However, the anti-aging effects of latifolin are unknown. In this study, we selected a model in vitro system, hydrogen peroxide (H2O2)-induced senescence in human dermal fibroblasts (HDFs), to examine the protective effects of latifolin against senescence and the detailed molecular mechanisms involved. Latifolin reversed the senescence-like phenotypes of the oxidant-challenged model, including senescence-associated ß-galactosidase (SA-ß-gal) staining, cell proliferation, and the expression of senescence-related proteins, such as caveolin-1, ac-p53, p21Cip1/WAF1, p16Ink4α, pRb, and cyclinD1. We also found that latifolin induced the expression of silent information regulator 1 (SIRT1) in a concentration- and time-dependent manner, and the anti-senescence effect of latifolin was abrogated by SIRT1 inhibition. Latifolin also suppressed the activation of Akt and S6K1 and attenuated the increase in SA-ß-gal activity after H2O2 exposure. Our results indicate that latifolin exerts protective effects against senescence in HDFs and that induction of SIRT1 and inhibition of the mammalian target of rapamycin (mTOR) pathway are key mediators of its anti-aging effects.