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

BACKGROUND: There are few studies investigating trends in global surgical site infection rates in colorectal surgery in the last decade. OBJECTIVE: This study seeks to describe changes in rates of different surgical site infections from 2013-2020, identify risk factors for SSI 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 were performed. SETTING: This was a retrospective study. PATIENTS: A total of 279,730 patients received colorectal resection from 2013 - 2020. MAIN OUTCOME MEASURES: Primary outcome measure was 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. Use of minimally invasive techniques was 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: Study is limited by retrospective nature and variables available for analysis. CONCLUSIONS: Superficial and deep 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 prep and oral antibiotic use as well as to study novel interventions to decrease postoperative infection occurrence. See Video Abstract.

Repeat Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors: A NET Center of Excellence Experience.

INTRODUCTION: The available data for the safety and efficacy of repeat peptide receptor radionuclide therapy (PRRT) are almost exclusively from European centers. We present an updated experience with repeat PRRT in a cohort of US patients with neuroendocrine tumors (NETs) at our NET center of excellence. METHODS: We used our single-center longitudinal NET registry to identify patients who had been previously treated with at least one dose of PRRT (PRRT 1, either 177Lu DOTATATE or 90Y DOTATOC) and following radiographic disease progression were re-treated with a second course of PRRT (PRRT 2). We reviewed patient, tumor and treatment characteristics, objective response rates, and toxicities after PRRT 1 and PRRT 2. RESULTS: A total of 11 patients were included in the analysis. 45.5% (5/11) of patients received 177Lu DOTATATE PRRT only, both for PRRT1 and PRRT 2, while 54.5% (6/11) of patients received 90Y DOTATOC PRRT for PRRT1. At first restaging scan after PRRT2 (3-6 months), 18.2% (2/11), 36.4% (4/11), and 27.3% (3/11) of patients had PR, SD, and PD, respectively; 2/11 patients (18.2%) died before the first restaging scan. Therefore, 5/11 (45.5%) patients were noted to have disease progression. Median PFS for PRRT1 was 25.4 months and median PFS for PRRT2 was 13.1 months (p = 0.0001). We did not find a statistically significant difference between the occurrence of short and long-term hematological toxicities as well as renal toxicity after PRRT1 and PRRT2. CONCLUSION: We show that repeat PRRT may benefit select patients and have an acceptable safety profile. In our cohort, PFS was significantly lower after PRRT2 as compared to PRRT1.

Longitudinal Outcomes of Malignant Ureteral Obstruction Secondary to Ovarian Cancer: Predictors of Resolution and the Role of Surgical Management.

OBJECTIVE: To review the management of ovarian cancer (OCa) associated hydronephrosis (HN). Specifically, we aim to identify optimal management of HN in the acute setting, predictors of HN resolution, and the role of surgery (tumor debulking/(+/-)ureterolysis/hysterectomy). MATERIALS/METHODS: The study cohort included OCa patients managed at our institution from 2004-2019 that developed OCa-associated HN. Initial HN management was recorded as none, retrograde ureteral stent (RUS) or percutaneous nephrostomy tube (PCN). Primary outcomes included (1) HN management failure, (2) HN management complications, and (3) HN resolution. Patient, cancer, and treatment predictors of outcomes were assessed using logistic regression and fine-Gray competing risk models. RESULTS: Of 2580 OCa patients, 190 (7.4%) developed HN. HN was treated in 121; 90 (74.4%) with RUS, 31 (25.6%) with PCN. Complication rates were similar between PCN and RUS (83% vs 85.1%; P = .79; all Clavian Grade I/II). Initial HN treatment failure occurred in 28 patients, predicted by renal atrophy (hazard ratios (HR) 3.27, P <.01). HN resolution occurred in only 52 (27%) patients and was predicted by lower International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO III/IV HR 0.42, P <.01) and surgical tumor debulking/ureterolysis (HR 2.83, P = .02). CONCLUSION: Resolution of HN associated with malignant obstruction from OCa is rare and is most closely associated with tumor debulking and International Federation of Gynecology and Obstetrics (FIGO) stage. Initial endoscopic treatment modality was not significantly associated with complications or resolution, though RUS failures were slightly more common. Ureteral reconstruction at time of debulking/ureterolysis is potentially underutilized.

Venetoclax-based therapy in treatment-naïve and relapsed/refractory acute myeloid leukemia.

Combining venetoclax with the hypomethylating agents azacitidine or decitabine has shown high complete response rates (60-70 %) in newly diagnosed (ND) acute myeloid leukemia (AML). However, studies addressing the efficacy of this approach in relapsed/refractory (R/R) AML remain limited. We conducted a retrospective analysis on patients treated with venetoclax-based therapy at a single institution. Objective response rates (ORR) and overall survival (OS) were assessed using logistic regression and Cox regression models, respectively. The total study population exhibited an ORR of 64 % with a complete remission at 34 %, complete remission with incomplete count recovery at 19%, and morphologic leukemia free state at 11 %. Patients with ND AML had a better ORR (71 %) compared to R/R AML (55 %), but the difference was not statistically significant. Median OS for the overall population was 14.4 months (range: 2-26 months). In the ND group, patients had a longer 6-month OS (82 % vs. 55 % in R/R AML), while both cohorts showed similar 12- and 24-month OS. Factors such as the hypomethylating agent chosen, adverse cytogenetics, TP53 mutations, prior hypomethylating agent use, and stem cell transplant status did not significantly affect ORR or OS. These findings support the effectiveness of venetoclax-based treatments in ND and R/R AML.

Immediate gemcitabine bladder instillation following bladder closure during robotic-assisted radical nephroureterectomy: a multi-institutional report of feasibility and initial outcomes.

Background: Bladder recurrence after radical nephroureterectomy (RNU) is common and randomized data supports utilization of prophylactic intravesical mitomycin to reduce recurrence. Recently, gemcitabine has been shown to be safe and effective at reducing recurrence following transurethral resection of bladder tumors. We sought to evaluate the safety and efficacy of a single, intraoperative gemcitabine instillation immediately following bladder cuff closure during RNU, and to compare outcomes with non-gemcitabine intravesical chemotherapy agents. Methods: We retrospectively reviewed all patients from two high volume centers who underwent robotic-assisted RNU between 2016-2020 and received either 2 g intravesical gemcitabine immediately following bladder cuff closure or non-gemcitabine intravesical chemotherapies [40 mg mitomycin C (MMC) or 50 mg doxorubicin] at the beginning of the procedure. Clinicopathologic factors were compared between cohorts. Bladder recurrence rates were evaluated using the Kaplan-Meier method and log-rank test. Results: During RNU, 24 patients received gemcitabine and 31 patients received non-gemcitabine chemotherapy. In total, 35% (19/55) of patients experienced a bladder cancer recurrence. There was no significant difference in estimated bladder recurrence-free survival (bRFS) between gemcitabine and non-gemcitabine patient cohorts (P=0.64). By 12 months post-surgery, 25% of patients had experienced bladder recurrence. The estimated 1-year bladder RFS survival was 73% for gemcitabine and 76% for non-gemcitabine chemotherapy. Overall survival and cancer-specific survival did not differ between cohorts. No adverse events potentially attributable to the use of gemcitabine were noted within 30 days postoperatively. Conclusions: Gemcitabine instilled immediately following bladder cuff closure during RNU has similar bRFS rates compared to established chemotherapy agents instilled at the start of surgery.

Retrospective study of testosterone deficiency and symptom burden in patients with pancreatic cancer.

Background: Pancreatic cancer patients have poor quality of life. Testosterone deficiency is associated with constitutional symptoms and sexual dysfunction which may contribute to poor quality of life. We investigated the prevalence of screening for and presence of testosterone deficiency in male pancreatic cancer patients. Methods: To determine the frequency of screening for testosterone deficiency in pancreatic cancer patients, our institution's electronic medical record system was queried for male patients diagnosed with a pancreatic mass between 2006 and 2020 and an available testosterone level. In a separate analysis, total testosterone was measured in serum samples from a cohort of 89 male pancreatic ductal adenocarcinoma (PDAC) patients. Low serum testosterone was defined as <300 ng/dL. Results: One thousand five hundred and sixty-six male patients were identified with a pancreatic mass, and 35 (2.2%) also had a testosterone level. In our analysis cohort, 44 of 89 patients (49.4%) were found to have low serum testosterone. Symptoms consistent with testosterone deficiency were documented for 70% of these patients, with fatigue being the most common. Testosterone level had no significant association with progression-free survival (PFS) (P=0.66) or overall survival (OS) (P=0.95). Conclusions: Testosterone deficiency is common but rarely assessed in male patients with pancreatic cancer. Further studies are warranted to explore the possibility of testosterone supplementation to improve quality of life in this patient population.

Association of Patient Proximity to Dermatologic Care With Melanoma Stage at Diagnosis and Outcome.

This cohort study evaluates the association of proximity to dermatologic clinicians with stage at diagnosis and cancer-specific survival among adults with cutaneous melanoma in Iowa.

Patient reported quality of life in young adults with sarcoma receiving care at a sarcoma center.

Background: Sarcomas are a diverse group of neoplasms that vary greatly in clinical presentation and responsiveness to treatment. Given the differences in the sites of involvement, rarity, and treatment modality, a multidisciplinary approach is required. Previous literature suggests patients with sarcoma suffer from poorer quality of life (QoL) especially physical and functional wellbeing. Adolescent and young adult (AYA) patients are an underrepresented population in cancer research and have differing factors influencing QoL. Methods: Retrospective analysis of Young Adult patients (age 18-39) enrolled in the Sarcoma Tissue Repository at University of Iowa. QoL was assessed using the self-report FACT-G questionnaire at enrollment and 12 months post-diagnosis; overall scores and the 4 wellbeing subscales (Physical, Emotional, Social, Functional) were calculated. Linear mixed effects models were used to measure the association between the rate of change in FACT-G subscale scores and baseline clinical, comorbidity, and treatment characteristics. Results: 49 patients were identified. 57.1% of patients had a malignancy involving an extremity. Mean FACT-G scores of overall wellbeing improved from baseline to 12 months (76.4 vs. 85.4, p < 0.01). Social and emotional wellbeing did not differ significantly between baseline and 12 months. Physical wellbeing (18.8 vs. 23.9, p < 0.01) and functional wellbeing (16.8 vs. 20.0, p< 0.01) scores improved from baseline to 12 months. No difference was seen for FACT-G overall scores for age, sex, laterality, marital status, performance status, having children, clinical stage, limb surgery, chemotherapy, or tumor size. A difference was demonstrated in physical wellbeing scores for patients with baseline limitation (ECOG 1-3) compared to those with no baseline limitation (ECOG 0) (p = 0.03). A difference was demonstrated in social wellbeing based on anatomical site (p = 0.02). Conclusion: Young adults with sarcoma treated at a tertiary center had improvements in overall reported QoL at 12 months from diagnosis. Overall baseline QoL scores on FACT-G were lower than the general adult population for YA patients with sarcoma but at 12 months became in line with general population norms. The improvements seen merit further investigation to evaluate how these change over the continuum of care. Quality of life changes may be useful outcomes of interest in sarcoma trials.

Characterizing Early Changes in Quality of Life in Young Women With Breast Cancer.

Introduction: Younger age at diagnosis is a risk factor for poor health-related quality of life (HRQOL) in long-term breast cancer survivors. However, few studies have specifically addressed HRQOL in young adults with breast cancer (i.e., diagnosed prior to age 40), nor have early changes in HRQOL been fully characterized. Methods: Eligible female patients with breast cancer were identified through our local cancer center. To establish HRQOL, patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) around diagnosis and 12 months later. Sociodemographic factors, genetic susceptibility to cancer, tumor- and treatment-related factors, and comorbidities (e.g., depression/anxiety) were abstracted from medical records and the local oncology registry. Mixed-effects models were used to identify changes in FACT-B scores during the first year of treatment and to determine whether any demographic/treatment-related factors modulated changes in scores. Results: Health-related quality of life in young patients with breast cancer was within normal limits at baseline, with a FACT-B overall well-being score of 108.5 (95% confidence limits [CI] = 103.7, 113.3). Participants reported slight improvements over a 12-month period: FACT-B overall well-being scores increased 6.6 points (95% CI = 2.1, 11.1, p < 0.01), functional well-being improved 3.0 points (95% CI = 2.0, 4.1, p < 0.01), emotional well-being improved 1.9 points (95% CI = 0.9, 2.8, p < 0.01), and physical well-being improved 1.5 points (95% CI = 0.2, 2.8, p = 0.03), on average. Participants with anxiety/depression at baseline reported greater improvements in FACT-B overall well-being (change: 12.9, 95% CI = 6.4, 9.5) and functional well-being (change: 5.2, 95% CI = 3.5, 6.9) than participants who did not have anxiety/depression at baseline (change in FACT-B overall well-being: 4.9, 95% CI = 0.2, 9.7; change in functional well-being: 2.3, 95% CI = 1.1, 3.4). Marital status, reconstructive surgery, and baseline clinical staging were also significantly associated with changes in aspects of HRQOL, although their impact on change was relatively minimal. Conclusion: Young women with breast cancer do not report HRQOL concerns during the first year of treatment. Improvements in HRQOL during the first year of treatment may be attributable to a sense of relief that the cancer is being treated, which, in the short run, may outweigh the negative late effects of treatment.

Does Antimicrobial Prophylaxis in Patients with Specific Comorbidities Reduce the Risk of Infection after Simple Cystourethroscopy?

INTRODUCTION: We evaluated whether antimicrobial prophylaxis decreases rates of post-procedural infection (urinary tract infection or sepsis) after simple cystourethroscopy for patients with specific comorbidities. METHODS: We utilized Epic® reporting software to conduct a retrospective review of all simple cystourethroscopy procedures performed by providers in our urology department from August 4, 2014 to December 31, 2019. Data collected included patient comorbidities, antimicrobial prophylaxis administration and incidence of post-procedural infection. Mixed effects logistic regression models were utilized to estimate the effects of antimicrobial prophylaxis and patient comorbidities on the odds of post-procedural infection. RESULTS: Antimicrobial prophylaxis was given for 7,001 (78%) of 8,997 simple cystourethroscopy procedures. Overall, 83 (0.9%) post-procedural infections occurred. The estimated odds of post-procedural infection were lower when antimicrobial prophylaxis was given compared to those without prophylaxis (OR 0.51, 95% CI 0.35-0.76; p <0.01). The number needed to treat with antimicrobial prophylaxis to prevent 1 post-procedural infection was 100. None of the comorbidities evaluated showed significant benefit from antimicrobial prophylaxis for prevention of post-procedural infection. CONCLUSIONS: Overall, the rate of post-procedural infection after simple office cystourethroscopy was low (0.9%). Though antimicrobial prophylaxis decreased the odds of post-procedural infection overall, the number needed to treat was high (100). Antibiotic prophylaxis was not shown to significantly reduce the risk of post-procedural infection in any of the comorbidity groups we evaluated. These findings suggest that the comorbidities evaluated in this study should not be used to recommend antibiotic prophylaxis for simple cystourethroscopy.

Characterizing academic performance in pediatric acute lymphoblastic leukemia with population-based achievement tests.

BACKGROUND: Recent shifts from radiation to chemotherapy-based treatment for acute lymphoblastic leukemia (ALL) have contributed to reduced long-term morbidity. Despite this, ALL survivors remain at increased risk for long-term cognitive impairments. AIM: To identify demographic and treatment factors associated with school performance in pediatric survivors of ALL. METHODS: We collected standardized test scores for reading, math, and science obtained in a school setting from grades 3-11 in 63 ALL survivors (46.0% boys). Most participants were assessed across multiple grades (median number of grades n = 5, range 1-7), and 269 observations were considered in the analyses. Treatment exposures were extracted from medical records. Socio-economic status was estimated using participation in free/reduced lunch programs at school. Mixed effects linear regression models were conducted to determine factors associated with school performance. RESULTS: ALL survivors' scores were comparable to state norms on reading, math, and science performances. On multivariable analysis, participation in free/reduced lunch programs was significantly associated with lower reading scores (ß = -12.52; 95% CI -22.26:-2.77, p = .01). Exposure to radiation during treatment was also associated with lower reading test scores (ß = -30.81, 95% CI -52.00:-9.62, p = .01). No significant associations between demographics and treatment parameters were observed for math and science test scores. CONCLUSIONS: We utilized population-based achievement tests conducted from grades 3-11 to characterize school performance in ALL survivors. Our results imply that survivors with low socio-economic status and those exposed to radiation during treatment could benefit from early monitoring and intervention to maximize academic success.

A novel Iowa-Mayo validated composite risk assessment tool for allogeneic stem cell transplantation survival outcome prediction.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for many hematologic conditions and is associated with considerable morbidity and mortality. Therefore, prognostic tools are essential to navigate the complex patient, disease, donor, and transplant characteristics that differentially influence outcomes. We developed a novel, comprehensive composite prognostic tool. Using a lasso-penalized Cox regression model (n = 273), performance status, HCT-CI, refined disease-risk index (rDRI), donor and recipient CMV status, and donor age were identified as predictors of disease-free survival (DFS). The results for overall survival (OS) were similar except for recipient CMV status not being included in the model. Models were validated in an external dataset (n = 378) and resulted in a c-statistic of 0.61 and 0.62 for DFS and OS, respectively. Importantly, this tool incorporates donor age as a variable, which has an important role in HSCT outcomes. This needs to be further studied in prospective models. An easy-to-use and a web-based nomogram can be accessed here: https://allohsctsurvivalcalc.iowa.uiowa.edu/ .

Longitudinal Outcomes from Conservative Management of Cervical Cancer Associated Ureteral Obstruction.

OBJECTIVE: To identify predictors of hydronephrosis (HN) resolution and HN treatment failure. HN is a common comorbid condition with cervical cancer (CCa). Treatments for CCa continue to improve and long-term management strategies of HN are becoming increasingly necessary. METHODS: A query of a single hospital (2004 - 2019) ICD-9 and CPT codes was made to develop a cohort of CCa patients with HN. A retrospective review was performed. The effects of patient, renal/HN, and cancer covariates on time to HN treatment failure, treatment complications and time to HN resolution were evaluated using logistic regression and competing risk Cox regression models. RESULTS: Of the 1670 women treated for CCa during the study period, 179 (10.7%) developed HN (n = 72 (40%) bilateral), 78 (44%) at time of CCa diagnosis and 101 (56%) as a result of treatment, of which 145 (81%) underwent initial treatment with a PCN (n = 77, 53%) or US (n = 68, 47%). Complication rates were similar between PCN (56%) and US (61%) when adjusting for treatment time. Initial treatment failure was more likely with US vs PCN (HR 3.2, P <0.01). HN resolution (n = 32, 22%) without reconstruction was predicted by HN concurrent with CCa diagnosis (HR 3.1, P <0.01) and bilateral HN (HR 0.2, P <0.01). CONCLUSION: CCa associated HN has a resolution rate of only 19% at 12 months. Those presenting with HN after CCa treatment are less likely to resolve without reconstruction. PCN and US have similar complication rates but initial US placement has a nearly three times increased risk of failing than PCN.

Outcomes of patients with stage III non-small cell lung cancer (NSCLC) that harbor a STK11 mutation.

BACKGROUND: STK11 mutation (STK11m ) in patients (pts) with stage IV non-small cell lung cancer (NSCLC) is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11m in stage III NSCLC pts treated with concurrent chemoradiation (CCRT) with or without consolidation ICI is unknown. METHODS: Stage III NSCLC patients who received CCRT and had known STK11 mutational status were included in this retrospective study. The data on the STK11m pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 (STK11w ) from the University of Iowa served as a comparison group. Patient demographics and clinical characteristics were collected. Cox regression models were used to explore the effect of STK11 mutation on survival. RESULTS: 75 pts with stage III NSCLC who had known STK11 mutational status were identified. 16/75 (21%) had STK11m . 5/16 with STK11 m did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11m and 59 STK11w pts were not statistically different (STK11m vs. STK11w ): mean age: 57 vs. 64 yrs, non-squamous histology: 8/11 (73%) vs. 37/59 (63%), KRAS mutation: 3/11 (27%) vs. 11/59 (19%), TP53 mutation: 6/11 (55%) vs. 15/59 (25%), PD-L1 ≥50%: 1/8 (13%) vs. 10/32 (31%), and consolidation ICI 6/11 (55%) vs. 17/59 (29%). Regarding the 6 STK11m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 6 (range, 1-25) in the 17 pts with STK11w who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11m pts was significantly worse than STK11 w pts (HR =2.25; 95% CI, 1.03-4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11m vs. STK11w patients (HR 1.47, 95% CI, 0.49-4.38, P=0.49). CONCLUSIONS: In stage III NSCLC patients who received CCRT, STK11m was associated with worse PFS compared to STK11w . Larger studies are needed to further explore the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.