The Role of Tumor Location on Endoscopic and Surgical Management of Malignant Colon Polyps.

BACKGROUND: Endoscopic polypectomy could be an appropriate, definitive treatment for pathologic T1 (pT1) colon polyps without high-risk features. Prior studies suggested worse prognosis for proximal versus distal advanced-stage colon cancers following curative treatment. However, there is limited evidence on the prognostic impact of tumor location for pT1s. PATIENTS AND METHODS: This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results database to identify adults with T1NxMx or T1N0-3M0/x colon adenocarcinoma from 2000 to 2019. RESULTS: A total of 3398 patients underwent endoscopic polypectomy (17% proximal) and 28,334 had a partial colectomy (49% proximal) for pT1 adenocarcinoma. Following endoscopic polypectomy, 5-year overall and cancer-specific survival rates were 64% and 91% for proximal versus 83% and 96% for distal polyps, compared with 82% and 95% for proximal versus 88% and 97% for distal tumors after colectomy. In multivariable models, there was a greater difference in overall survival between proximal and distal polyps for those who underwent endoscopic versus surgical resection [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.49-2.02 vs. HR 1.13, 95% CI 1.08-1.18]. Patients with proximal versus distal polyps who underwent polypectomy also exhibited increased cancer-specific mortality (HR 1.94, 95% CI 1.37-2.75). However, cancer-specific survival variations based on tumor location were no longer observed in patients undergoing partial colectomy (HR 1.09, 95% CI 0.98-1.21). CONCLUSIONS: Proximal tumor location was independently associated with worse overall and cancer-specific survival following endoscopic polypectomy. However, after colectomy, the cancer-specific disparity based on tumor laterality was mitigated. These findings suggest that proximal location may be considered a high-risk feature in endoscopic polypectomy.

Pathologic Complete Response, Total Neoadjuvant Therapy and the Survival Paradox in Locally Advanced Rectal Cancer.

BACKGROUND: Pathologic complete response (pCR) after preoperative chemoradiation (nCRT) correlates with improved overall survival for patients with locally advanced rectal cancers (LARCs). Escalation protocols including total neoadjuvant therapy (TNT), which delivers multi-agent chemotherapy and chemoradiation before surgery, are associated with increased complete response rates. However, TNT is not associated with improved overall survival. The authors hypothesized that the route to pCR may be an important predictor of oncologic outcome. METHODS: Adults with LARC between 2006 and 2017 were identified in the National Cancer Database. The cohort was limited to those who received neoadjuvant radiation (45-70 Gy) and underwent proctectomy. RESULTS: Of 25,880 patients, 16 % received TNT and 84 % had nCRT followed by either multi-agent (27 %), single-agent (14 %), or no adjuvant chemotherapy (44 %). Overall, 18 % achieved pCR, with higher rates in the TNT cohort than in the nCRT (18 %) or multi-agent (14 %) chemotherapy cohorts. With control for covariates, the OS in the pCR cohort was similar for the patients that received single-agent therapy and those that received multi-agent adjuvant therapy, and superior to the TNT and no adjuvant therapy cohorts. Conversely, among the patients who did not achieve pCR, those who received single-agent chemotherapy had OS comparable with those who had multi-agent adjuvant therapy and TNT, which was better than no adjuvant therapy. CONCLUSION: Patients achieving pCR after TNT had worse OS than those who had CRT alone, suggesting that the neoadjuvant route by which pCR is achieved is prognostically relevant. Therefore, in the era of neoadjuvant therapy escalation, pCR does not necessarily portend a uniformly favorable prognosis.

Conditional Overall Survival After Diagnosis of Non-Metastatic Colon Cancer: Impact of Laterality, MSI, and KRAS Status.

BACKGROUND: The prognostic relevance of laterality, microsatellite instability (MSI), and KRAS status in colon cancer has been established. However, their effect on conditional overall survival (COS) remains unknown. METHODS: COS is the probability of surviving additional years after a time from diagnosis. The National Cancer Database (2010-2017) was queried for adults with non-metastatic colon cancer and known mutation status undergoing curative resection. COS was investigated at 2 years. RESULTS: Of 4838 patients, 3716 survived at least 2 years: 15% had stage I, 38% stage II, and 46% stage III disease. Fifty-nine percent had a right-sided tumor, 16% were MSI-high, and 37% were mutated KRAS (mKRAS). The proportion of patients alive at 2 years was higher for stage I compared with stage II and III (65 vs. 61 vs. 54%). The 5-year overall survival for stage I-III was 80, 76, and 67% for the initial cohort, and 90, 88, and 86% for those alive at 2 years. After adjustment, higher pathologic T and N stage, tumor deposits, and no chemotherapy were associated with worse COS (p < 0.01). While laterality and MSI status were not associated with COS, mKRAS was independently associated with decreased COS (HR 1.35, 95% CI 1.12-1.62). CONCLUSION: Patients with mKRAS had worse COS, suggesting that these mutations confer an aggressive biologic behavior, with patients remaining at higher risk of death 2 years after diagnosis. Routine evaluation of KRAS status should be considered in patients with non-metastatic disease for prognostication and to identify those who might benefit from modified surveillance protocols.

A Multinational, Multi-Institutional Study Assessing the Impact of Diabetes Mellitus on the Prognosis of Patients with Non-Muscle Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin.

The study aimed to examine the impact of diabetes mellitus type 2 (DMII) on the oncological outcomes of non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) using comprehensive real-world data. We performed an analysis of data on NMIBC patients treated with BCG from the United States (US) National Phase II BCG/Interferon (IFN) trial database (125 centers) and pooled databases from three tertiary care institutions: France (FR), Lebanon (LB) (2000-2021), and the US (University of Iowa) (2011-2021). There were 867 patients from the Phase II trial, 1232 from the FR/LB cohort, and 233 from the US (Iowa) cohort (n = 2332). DM II was reported in 13% of the Phase II trial cohort, 14.4% of the FR/LB cohort, and 33.5% of the US (Iowa) cohort. The median follow-up was 24 months in the Phase II trial cohort, 25 months in the FR/LB cohort, and 48 months in the US (Iowa) cohort. In multivariable Cox regression analyses, DMII was not significantly associated with recurrence or progression of the tumor in any of the cohorts included in this study. DMII may not be a clinical prognostic factor for NMIBC patients treated with BCG. Prospective evaluation is needed.

Prognostic role of the neutrophil/lymphocyte ratio in high-risk BCG-naïve non-muscle-invasive bladder cancer treated with intravesical gemcitabine/docetaxel.

OBJECTIVES: To investigate the role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in the prediction of response to sequential intravesical therapy, gemcitabine and docetaxel (Gem/Doce), given to patients with bacille Calmette-Guérin (BCG)- naïve high-risk non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A retrospective analysis was conducted on 115 patients who received intravesical Gem/Doce for high-risk NMIBC between January 2011 and December 2021. Data were computed as the median (interquartile range [IQR]) or mean (standard deviation [sd]). Cox regression analysis was performed to determine if neutrophilia, NLR, platelet counts, and PLR before instillation therapy were predictive of recurrence-free survival (RFS) and overall survival (OS). Predictive performance was estimated using Uno's C-statistic. RESULTS: The median (IQR) follow-up for the overall cohort was 23 (13-36) months. The mean (sd) values for NLR, PLR and platelet counts were 3.4 (2.3), 142.2 (85.5), and 225.2 (75.1) × 109/L, respectively. NLR was associated with RFS, with a hazard ratio of 1.32 (95% confidence interval CI 1.19-1.46). Concordance analysis showed that NLR had a good ability to predict RFS (C-index: 0.7, P < 0.01). The PLR and platelet count were not associated with RFS and did not predict recurrence. In terms of OS, none of these cellular inflammatory markers showed any prediction value. CONCLUSION: Pre-treatment NLR provides some predictive accuracy for RFS in high-risk BCG-naïve patients receiving Gem/Doce. Further prospective trials are needed to validate this finding.

Transplant versus no transplant in myelodysplastic syndrome and acute myeloid leukemia with TP53 mutation; a referral center experience.

A remarkably high rate of post-transplant relapse in patients with TP53-mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT (N = 38) versus non-HSCT (N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs. 72) while patients in the non-HSCT cohort more commonly had complex karyotype with chromosome 17 aberrancy and 5q deletion (p < .01). A total of 69 TP53 variants including 64 pathogenic variants, and 5 variants of undetermined significance were detected. Nine patients (4 in HSCT and 5 in non-HSCT) had multi-hit TP53 variants. After induction: 57.9% versus 56.6% in the HSCT versus non-HSCT cohort achieved morphologic complete remission. Median time to HSCT was 6 months and median follow-up was 15.1 months for HSCT and 5.7 months for non-HSCT. Median disease-free survival (DFS) and overall survival (OS) were 11.7 and 15.9 months for HSCT, and 4.1 and 5.7 months for non-HSCT cohorts, respectively. Non-relapse mortality at 12 months was 22% versus 44% for HSCT versus non-HSCT. In the HSCT cohort, the rate of grade II-IV acute and chronic graft-versus-host disease (GVHD) was 55% and 18%, respectively. None of the patients from the non-HSCT cohort were alive while four patients from the HSCT cohort were alive, in remission, and without GVHD (GRFS) at the time of abstraction. Better treatment strategies for patients with TP53-mutated MDS/AML remain an area of unmet clinical need.

Modern Trends in Surgical Site Infection Rates for Colorectal Surgery: A National Surgical Quality Improvement Project Study 2013-2020.

BACKGROUND: Few studies have investigated trends in global surgical site infection rates in colorectal surgery in the past decade. OBJECTIVE: This study seeks to describe changes in rates of different surgical site infections from 2013 to 2020, identify risk factors for surgical site infection occurrence, and evaluate the association of minimally invasive surgery and infection rates in colorectal resections. DESIGN: A retrospective analysis of the National Surgical Quality Improvement Program database 2013-2020 identifying patients undergoing open or laparoscopic colorectal resections by procedure codes was performed. Patient demographic information, comorbidities, procedures, and complications data were obtained. Univariable and multivariable logistic regression analyses were performed. SETTING: This was a retrospective study. PATIENTS: A total of 279,730 patients received colorectal resections from 2013 to 2020. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of surgical site infection, divided into superficial, deep incisional, and organ space infections. RESULTS: There was a significant decrease in rates of superficial infections ( p < 0.01) and deep incisional infections ( p < 0.01) from 5.9% in 2013 to 3.3% in 2020 and from 1.4% in 2013 to 0.6% in 2020, respectively, but a rise in organ space infections ( p < 0.01) from 5.2% in 2013 to 7.1% in 2020. Minimally invasive techniques were associated with decreased odds of all surgical site infections compared to open techniques ( p < 0.01) in multivariate analysis, and adoption of minimally invasive techniques increased from 59% in 2013 to 66% in 2020. LIMITATIONS: The study is limited by its retrospective nature and variables available for analysis. CONCLUSIONS: Superficial and deep incisional infection rates have significantly decreased, likely secondary to improved adoption of minimally invasive techniques and infection prevention bundles. Organ space infection rates continue to increase. Additional research is warranted to clarify current recommendations for mechanical bowel preparation and oral antibiotic use as well as to study novel interventions to decrease postoperative infection occurrence. See Video Abstract . TENDENCIAS MODERNAS EN LAS TASAS DE INFECCIN DEL SITIO QUIRRGICO PARA CIRUGA COLORRECTAL UN ESTUDIO DEL PROYECTO NACIONAL DE MEJORA DE LA CALIDAD QUIRRGICA: ANTECEDENTES:Hay pocos estudios que investiguen las tendencias en las tasas globales de infección del sitio quirúrgico en cirugía colorrectal en la última década.OBJETIVO:Este estudio busca describir cambios en las tasas de diferentes infecciones del sitio quirúrgico entre 2013 y 2020, identificar factores de riesgo para la aparición de ISQ y evaluar la asociación de la cirugía mínimamente invasiva y las tasas de infección en resecciones colorrectales.DISEÑO:Se realizó un análisis retrospectivo de la base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica 2013-2020 que identifica a los pacientes sometidos a resecciones colorrectales abiertas o laparoscópicas mediante códigos de procedimiento. Se obtuvo información demográfica de los pacientes, comorbilidades, procedimientos y datos de complicaciones. Se realizó regresión logística univariable y multivariable.AJUSTE:Este fue un estudio retrospectivo.PACIENTES:Un total de 279,730 pacientes recibieron resección colorrectal entre 2013 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:La medida de resultado primaria fue la tasa de infección del sitio quirúrgico, dividida en infecciones superficiales, incisionales profundas y del espacio de órganos.RESULTADOS:Hubo una disminución significativa en las tasas de infecciones superficiales (p < 0,01) e infecciones incisionales profundas ( p < 0,01) del 5,9% en 2013 al 3,3% en 2020 y del 1,4% en 2013 al 0,6% en 2020, respectivamente. pero un aumento en las infecciones del espacio de los órganos ( p < 0,01) del 5,2 % en 2013 al 7,1 % en 2020. El uso de técnicas mínimamente invasivas se asoció con una disminución de las probabilidades de todas las infecciones del sitio quirúrgico en comparación con las técnicas abiertas ( p < 0,01) en el análisis multivariado y la adopción de técnicas mínimamente invasivas aumentó del 59% en 2013 al 66% en 2020.LIMITACIONES:El estudio está limitado por la naturaleza retrospectiva y las variables disponibles para el análisis.CONCLUSIONES:Las tasas de infección superficial y profunda han disminuido significativamente, probablemente debido a una mejor adopción de técnicas mínimamente invasivas y esquemas de prevención de infecciones. Las tasas de infección del espacio de los órganos continúan aumentando. Se justifica realizar investigaciones adicionales para aclarar las recomendaciones actuales para la preparación intestinal mecánica y el uso de antibióticos orales, así como para estudiar intervenciones novedosas para disminuir la aparición de infecciones posoperatorias. (Traducción-Dr. Yolanda Colorado ).

A Population-Level Validation of the New 9th Edition of the American Joint Commission on Cancer Staging System for Anal Squamous Cell Carcinoma.

BACKGROUND AND OBJECTIVES: The staging system for anal squamous cell carcinoma (ASCC) was recently revised, downstaging selected node-positive patients and upstaging some with larger tumors. We aimed to validate this staging system using a population-based cohort. METHODS: The Surveillance, Epidemiology, and End Results database was analyzed to identify adult ASCC patients. Patients were staged according to the American Joint Committee on Cancer (AJCC) 8th and 9th edition systems. Survival probabilities were estimated using Kaplan-Meier curves. Cox regression models were utilized to estimate the effect of stage on overall (OS) and cancer-specific survival (CSS). RESULTS: A total of 2117 patients were identified and staged based on the two AJCC classifications. At 24 months when comparing stage IIB versus stage IIIA, the 8th edition revealed an improved OS (79% vs. 88%) and CSS (84% vs. 91%) for stage IIIA disease, while the 9th edition restored the hierarchical OS (IIB 88% vs. IIIA 78%) and CSS (91% vs. 82%) order. CONCLUSIONS: The hierarchical increase of the OS HRs, and nearly all CSS HRs, across disease stages validated the updated edition of the AJCC classification. Although this change may not have significant implication on the management of ASCC, it does provide better prognostication.

Romiplostim for Treatment of Children and Young Adults With Severe Aplastic Anemia and Myelodysplastic Syndrome.

Thrombopoietin receptor agonists (TPO-RAs) induce trilineage hematopoiesis under conditions with acquired hematopoietic failure. We evaluated safety, tolerability, and preliminary efficacy of a TPO-RA, romiplostim (Nplate), with or without standard-of-care immunosuppressive therapy (±IST) for children (ages < 21 y) with newly diagnosed and relapsed/refractory severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS). Data were collected from an observational study and a single arm interventional pilot study. The safety outcome was treatment-related adverse events (AEs). Efficacy was evaluated by complete hematopoietic response (CHR) at week 24. Romiplostim was commenced at 5 µg/kg/week, with dose escalation of 2.5 µg/kg/week (maximum, 20 µg/kg/dose) based on platelet response. Romiplostim was continued until CHR was observed. Ten subjects (SAA, 9 [IST, 4; without IST, 5]; MDS, 1) completed the study (median age: 9.2 y). Median romiplostim dose was 10 µg/kg/week (range: 5 to 17.5 µg/kg/week). The cumulative incidence of CHR was 70.4% (95% CI, 20.2%-92.6%). Among 21 AEs (Grade 1 to 3), 3 were attributed to romiplostim. At a median posttherapy follow-up of 10.9 months (range: 0.7 to 77.5), no clonal evolution, bone marrow fibrosis or mortality was reported. This proof-of-concept study provides data about short-term safety, tolerability, and preliminary efficacy of romiplostim (±IST) for treatment of pediatric SAA/MDS.

Site-Specific knockdown of microglia in the locus coeruleus regulates hypervigilant responses to social stress in female rats.

BACKGROUND: Women are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking. METHODS: Microglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3 µg/side, n = 5-6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25 µg/side, n = 13-14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance. RESULTS: Intra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1ß (IL-1ß). Further, the efficacy and selectivity of microinjected m-CLD was fully characterized. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1ß. Intra-central amygdala m-CLD had no effect on WS-evoked behavior. CONCLUSIONS: These studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses.

Responding to distress in cancer care: Increasing access to psycho oncology services through integrated collaborative care.

OBJECTIVE: Despite increased attention to the utility of collaborative care models for promoting whole-person care in cancer populations, there is a paucity of empirical research testing the impact of these care models on effectively identifying and serving highly distressed cancer patients. This study sought to experimentally test the effectiveness of a year-long collaborative care program on referral rates to psycho-oncology services for patients with moderate to high distress. METHODS: Data for this study consisted of 11,467 adult patients with cancer who were screened for psychosocial distress 6-months prior to, and following, the integrated collaborative care intervention. Psychosocial referral rates pre-, peri- and post- intervention were analyzed. RESULTS: Findings indicated high distress patients were at 3.76 (95% CI [2.40, 5.87]), 5.03 (95% CI [3.25, 7.76]), and 7.62 (95% CI [5.34, 10.87]) times increased odds of being referred during the pre-intervention, peri-intervention, and post-intervention, respectively, when compared to low distress patients, and these differences across time were significantly different (p = 0.04). CONCLUSION: Findings from this study suggest that the successful initiation of a collaborative care model within a comprehensive cancer center contributed to significantly greater referral rates of cancer patients with moderate to high distress to psycho-oncology services. This study contributes to the growing consensus that collaborative care models can positively impact the care of complex medical patients.

Use of subgroup-specific hematopoietic stem cell collection efficiencies to improve truncation calculations for large-volume leukapheresis procedures.

PURPOSE: A critical component of optimizing peripheral blood (PB) hematopoietic stem cell (HSC) collections is accurately determining the processed blood volume required to collect the targeted number of HSCs. Fundamental to most truncation equations employed to determine this volume is the procedure's estimated collection efficiency (CE), which is typically applied uniformly across all HSC collections. Few studies have explored the utility of using different CEs in subpopulations of donors that have substantially different CEs than the institutional average. METHODS: Initial procedures from 343 autologous and 179 allogeneic HSC collections performed from 2018 to 2021 were retrospectively analyzed. Predictive equations were developed to determine theoretical truncation rates in various donor subgroups. RESULTS: Quantitative variables (pre-procedure cell counts) and qualitative variables (relatedness to recipient, gender, method of venous access, and mobilization strategy) were found to significantly impact CE. However, much of the variability in CE between donors could not be explained by the variables assessed. Analyses of procedures with high pre-collection PB cell counts identified lower CE values for these donors' truncation equations which still allow truncation but minimize risk of collecting less CD34+ cells than requested. CONCLUSIONS: Individualized CE does not substantially improve truncation volume calculations over use of a fixed CE and adds complexity to these calculations. The optimal fixed CE varies between autologous and allogeneic donors, and donors with high pre-collection PB cell counts in either of these groups. This model will be clinically validated and continuously refined through analysis of future HSC collections.

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.

Sequential Intravesical Valrubicin and Docetaxel for the Salvage Treatment of Non-Muscle-Invasive Bladder Cancer.

PURPOSE: Intravesical gemcitabine-docetaxel has emerged as an efficacious and well-tolerated salvage therapy for non-muscle-invasive bladder cancer. However, further rescue therapies are needed for subsequent recurrences or intolerance, particularly when cystectomy is refused or precluded. Valrubicin is a U.S. Food and Drug Administration-approved agent for bacillus Calmette-Guérin unresponsive disease, yet as monotherapy has demonstrated poor efficacy. We report our experience with sequential intravesical valrubicin and docetaxel as a rescue therapy for non-muscle-invasive bladder cancer. MATERIALS AND METHODS: We retrospectively identified all patients with recurrent non-muscle-invasive bladder cancer treated with valrubicin and docetaxel between April 2013 and June 2021. Patients received weekly sequential intravesical instillations of 800 mg valrubicin and 37.5 mg docetaxel for 6 weeks. If disease-free at first follow-up, monthly maintenance of 2 years was initiated. The primary outcome was recurrence-free survival, assessed using the Kaplan-Meier method. RESULTS: The analysis included 75 patients with median follow-up of 21 months (IQR: 13-37). Twelve patients with low-grade disease had a 73% recurrence-free survival at 2 years. Sixty-three patients with recurrent high-grade disease had a 38% 2-year high-grade recurrence-free survival. Forty-two (56%) patients had carcinoma in situ present; recurrence-free survival was similar for those with and without carcinoma in situ (P = .63). Two patients died of metastatic bladder cancer while 10 underwent cystectomy. Among patients with high-grade disease, overall, cancer-specific, and cystectomy-free survivals were 87%, 96%, and 84% at 2 years, respectively. Adverse events included bladder spasms (n = 18), urinary frequency (n = 10), and dysuria (n = 8). Two patients could not tolerate valrubicin and docetaxel induction. CONCLUSIONS: In a heavily pretreated population, our results suggest valrubicin and docetaxel is an effective rescue treatment for patients with recurrent non-muscle-invasive bladder cancer. Further prospective evaluation is needed.

Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer.

PURPOSE: Bacillus Calmette-Guérin (BCG) is currently recommended as adjuvant therapy following complete transurethral resection of bladder tumor for high-risk nonmuscle-invasive bladder cancer (NMIBC). In response to the BCG shortage, gemcitabine plus docetaxel (Gem/Doce) has been utilized at our institution in the BCG-naïve setting. We report the outcomes of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce. MATERIALS AND METHODS: We retrospectively reviewed patients with BCG-naïve high-risk NMIBC treated with Gem/Doce from May 2013 through April 2021. Patients received 6 weekly intravesical instillations of sequential 1 gm gemcitabine and 37.5 mg docetaxel after complete transurethral resection of bladder tumor. Monthly maintenance of 2 years was initiated if disease-free at first followup. The primary outcome was recurrence-free survival. Survival was assessed with the Kaplan-Meier method, indexed from the first Gem/Doce instillation. Adverse events were reported using CTCAE (Common Terminology Criteria for Adverse Events) v5 (National Cancer Institute, Bethesda, Maryland). Differences were assessed with the log-rank test. RESULTS: There were 107 patients with a median followup of 15 months included in the analysis. Patients had high-risk characteristics including 47 with any carcinoma in situ and 55 with T1 disease. Recurrence-free survival was 89%, 85% and 82% at 6, 12 and 24 months, respectively. Recurrence rates were similar between patients with or without carcinoma in situ (p=0.42). No patient had disease progression or died of bladder cancer. One patient underwent cystectomy due to end-stage lower urinary tract symptoms. Overall survival was 84% at 24 months. There were 92 adverse events (1 ≥grade 3), and 4 (4%) patients were unable to receive a full induction course. CONCLUSIONS: Gem/Doce is an effective and well-tolerated therapy for BCG-naïve NMIBC. Further investigation is warranted.

Analysis of the Understanding and Worry about Lymphedema of Patients with Breast Cancer.

BACKGROUND: Lymphedema is a potential lifelong sequela of breast cancer treatment. We sought to: (1) evaluate the worry and knowledge of patients about lymphedema, (2) quantify patients reporting lymphedema education and screening, and (3) determine willingness to participate in lymphedema screening and prevention programs. PATIENTS AND METHODS: A survey evaluating lymphedema-related knowledge and worry was sent to patients treated for stage 0-III breast cancer. Exclusion criteria included > 10 years since diagnosis, missing clinical staging, and those without axillary surgery. Responses were linked with clinicopathologic information. RESULTS: Of 141 patients meeting inclusion criteria, 89% of those without lymphedema were not at all or slightly worried about lymphedema. Higher levels of worry were associated with clinical stage II-III disease [odds ratio (OR) 2.63, p = 0.03], a history of axillary lymph node dissection (ALND) (OR 4.58, p < 0.01), and employment (OR 2.21, p = 0.05). A total of 102 (72%) patients recalled receiving lymphedema education. Lymphedema knowledge was limited, with < 25% of respondents answering > 50% of the risk factor questions correctly. Worry and knowledge were not significantly associated. Of patients without lymphedema, 36% were interested in learning more about lymphedema and 64% were willing to participate in or learn more about a screening program. Most (66%) felt that lymphedema information should be provided before and after cancer treatment. DISCUSSION: A majority of our breast cancer survivors had limited knowledge about lymphedema risk factors. While most patients were not worried about developing lymphedema, higher worry was seen in patients with a higher clinical stage at diagnosis, ALND, and employment. Our findings suggest potential targets and timing for patient-centered educational interventions.

Superficial versus deep inguinal nodal dissection for vulvar cancer staging.

OBJECTIVE: The objective of this study was to compare the rate of groin recurrence among women undergoing superficial or deep inguinal lymph node dissections in suspected early-stage vulvar carcinoma. Secondary objectives included comparison of overall survival and post-operative morbidity between the study groups. METHODS: A retrospective cohort of 233 patients with squamous cell carcinoma (SCC) of the vulva who underwent an inguinal lymph node dissection at two major academic institutions from 1999 to 2017 were analyzed. Demographic, surgical, recurrence, survival, and post-operative morbidity data were collected for 233 patients, resulting in a total of 400 groin node dissections analyzed. RESULTS: Rates of overall primary recurrence of disease between superficial and deep inguinal LND (42.5 vs. 39.8%, p = 0.70) and rates of inguinal recurrence (3.4 vs. 8.3%, p = 0.16) were similar. Overall rates of postoperative morbidity were significantly higher in the cohort undergoing deep LND (70.3% vs 44.3%, p < 0.01). Rates of lymphedema (42.4 vs 15.9%, p < 0.01), readmission (26.3 vs 6.8%, p < 0.01), and infection (40.7 vs 14.8%, p < 0.01) were all significantly higher among patients undergoing deep LND. There was no significant difference noted in overall survival between the study groups when adjusting for stage and age (HR 1.08, p = 0.84). CONCLUSION: Superficial inguinal LND had no significant difference in rate of recurrence or overall survival when compared to deep inguinal LND in patients with vulvar SCC. Those who received a deep LND had a significant increase in overall morbidity, including lymphedema, readmission, and infection. For patients who cannot undergo or fail sentinel lymph node mapping, a superficial inguinal lymph node dissection may have similar outcomes in recurrence and overall survival with a reduction in overall morbidity as compared to a complete, or deep, lymph node dissection.

Male gender, smoking, younger age, and preoperative pain found to increase postoperative opioid requirements in 592 elective colorectal resections.

PURPOSE: With increased awareness of the opioid epidemic, understanding contributing factors to postoperative opioid use is important. The purpose of this study was to evaluate patient and perioperative factors that contribute to postoperative opioid use after colorectal resections and their relation to pre-existing pain conditions and psychiatric diagnoses. METHODS: A retrospective review was conducted identifying adult patients who underwent elective colorectal resection at a single tertiary center between 2015 and 2018. Patient demographics, preoperative factors, surgical approach, and perioperative pain management were evaluated to determine standard conversion morphine milligram equivalents required for postoperative days 0 to 3 and total hospital stay. RESULTS: Five hundred and ninety-two patients: 46% male, median age 58 years undergoing colorectal resections for indications including cancer, inflammatory bowel disease, and diverticulitis were identified. Less opioid use was found to be associated with female gender (ß = - 42), patients who received perioperative lidocaine infusion (ß = - 30), and older adults (equivalents/year) (ß = - 4, all p < 0.01). Preoperative opioid use, preoperative abdominal pain, epidural use, and smoking were all independently associated with increased postoperative opioid requirements. CONCLUSIONS: In this study of patients undergoing elective colorectal resection, factors that were associated with higher perioperative opioid use included male gender, smoking, younger age, preoperative opioid use, preoperative abdominal pain, and epidural use. Perioperative administration of lidocaine was associated with decreased opioid requirements. Understanding risk factors and stratifying postoperative pain regimens may aid in improved pain control and decrease long-term dependency.

Decreased testosterone recovery after androgen deprivation therapy for prostate cancer.

INTRODUCTION Androgen deprivation therapy (ADT) is often used in the treatment of prostate cancer. Specific factors affecting testosterone recovery after cessation of ADT have not been well-characterized in existing literature. MATERIALS AND METHODS: We retrospectively reviewed patients at our institution who received ADT between 1999 and 2018. Patients with at least one course of ADT and subsequent testosterone level within 12 months of cessation of ADT were included. Patients received at least one of the following four agents: leuprolide, goserelin, triptorelin, and degarelix. Cox regression models were utilized to estimate the effect of patient and treatment characteristics on time to testosterone recovery(≥ 240 ng/dL) after ADT cessation. Patients without testosterone recovery were censored at last testosterone evaluation. To account for the possible dependency between multiple ADT courses within a patient, we used a robust sandwich variance estimate. RESULTS: Severty-six patients were included. Mean age was 64 +/- 8 years. Median duration of ADT was 15 months, with a median time to recovery of 19 months. On univariable analysis, age and duration of ADT were significant; a trend towards significance was noted for hypertension, diabetes, peripheral vascular disease, goserelin and bicalutamide. Patient age, duration of ADT, and treatment with the agent goserelin were significantly associated with prolonged hypogonadism on multivariable analysis (p < 0.01). CONCLUSIONS: Increasing age and duration of ADT therapy are associated with decreased likelihood to recover normal testosterone levels after cessation of therapy. The use of the ADT agent goserelin was also associated with decreased testosterone recovery for unclear reasons.

Multimodal perioperative pain protocol for gynecologic laparotomy is associated with reduced hospital length of stay.

OBJECTIVES: The primary objective was to evaluate the impact of a multimodal perioperative pain regimen on length of hospital stay for patients undergoing laparotomy with a gynecologic oncologist. METHODS: We compared 52 patients who underwent laparotomy with a gynecologic oncologist at a single institution between 2017 and 2018, after implementation of a multimodal perioperative pain regimen, to a historic cohort of 94 patients (2016-2017). The multimodal pain regimen included pre- and post-operative administration of oral acetaminophen, gabapentin, and celecoxib, in addition to standard narcotics and optional epidural analgesia. Demographic, surgical, and post-operative data were collected. RESULTS: On multivariable analysis, bowel resection, stage, surgery length, age, and cohort group were retained as significant independent predictors of length of stay. Patients undergoing laparotomy prior to the pain protocol had a length of stay 1.26 times longer than patients during the post-implementation period (p < 0.01). For complex surgical patients, this translated into a reduction in length of hospital stay of 1.73 days. There was a significant reduction in pain scale score on post-operative day zero from 5 to 3 (p = 0.02) and a non-significant overall reduction of post-operative morphine equivalents, with similar adverse outcomes. CONCLUSION: Implementation of a multimodal perioperative pain regimen in patients undergoing gynecologic oncology laparotomy was associated with a significant reduction of length of hospital stay and improved patient-perceived pain, even in the absence of a complete Enhanced Recovery After Surgery (ERAS) protocol.