Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Development and multicentre validation of the FLEX score: personalised preoperative surgical risk prediction using attention-based ICD-10 and Current Procedural Terminology set embeddings.

BACKGROUND: Preoperative knowledge of surgical risks can improve perioperative care and patient outcomes. However, assessments requiring clinician examination of patients or manual chart review can be too burdensome for routine use. METHODS: We conducted a multicentre retrospective study of 243 479 adult noncardiac surgical patients at four hospitals within the Mass General Brigham (MGB) system in the USA. We developed a machine learning method using routinely collected coding and patient characteristics data from the electronic health record which predicts 30-day mortality, 30-day readmission, discharge to long-term care, and hospital length of stay. RESULTS: Our method, the Flexible Surgical Set Embedding (FLEX) score, achieved state-of-the-art performance to identify comorbidities that significantly contribute to the risk of each adverse outcome. The contributions of comorbidities are weighted based on patient-specific context, yielding personalised risk predictions. Understanding the significant drivers of risk of adverse outcomes for each patient can inform clinicians of potential targets for intervention. CONCLUSIONS: FLEX utilises information from a wider range of medical diagnostic and procedural codes than previously possible and can adapt to different coding practices to accurately predict adverse postoperative outcomes.

Early C-reactive protein after colorectal surgery is not predictive of anastomotic leak: a retrospective cohort study.

PURPOSE: Prior studies suggest postoperative C-reactive protein (CRP) trends are sensitive for predicting anastomotic leak (AL) after elective colorectal surgery. However, in the setting of enhanced recovery pathways, multi-day CRP trends may not be feasible. This study aimed to assess the realistic and clinical utility of CRP in prediction of AL. METHODS: A retrospective review of patients who underwent elective colectomy or proctectomy from January 2019 to October 2020 at a single institution was performed. Comorbidities, operative characteristics, and perioperative outcomes were recorded. CRP was checked routinely on POD1 and on a clinical basis subsequently. The association between 10-point change in CRP-POD1 and AL was evaluated using multivariable logistic regression. The relationships between CRP-POD3, CRP-POD1, and AL were assessed using exploratory analyses. RESULTS: Among 332 patients, 23 (6.9%) developed AL, of which 9 cases (39%) were diagnosed upon readmission. AL was not associated with mortality. Median length of stay was 3 days (IQR 2-5). Median days to AL diagnosis was 7 (IQR 4-15). Adjusting for diverting stoma, steroid use, diagnosis, and open surgery, each 10-point increase in CRP was associated with increased odds of AL (OR 1.12, 95% CI 1.03-1.21, p=0.008). CRP-POD1 had poor discriminant utility for detecting AL (AUC 0.62, 95% CI = 0.494-0.746; p=0.061). CONCLUSION: CRP on POD1 is not a reliable method to predict a leak, and trending CRP may not be practical with decreasing lengths of stay in colorectal surgery.

Diagnostic Impact of Adrenal Vein Sampling in Adrenal Cushing's Syndrome.

BACKGROUND: Adrenal Cushing's syndrome is characterized by ACTH-independent hypercortisolism. Adrenal vein sampling (AVS) is not routinely employed prior to management decisions, and few studies have investigated the value of AVS in this population. We assessed whether AVS provides a diagnostic benefit for treatment planning. MATERIALS AND METHODS: Six patients with imaging and biochemical evidence of adrenal Cushing's syndrome undergoing AVS at our institution from 2015 to 2020 were analyzed retrospectively, including demographic and clinical characteristics. AVS lateralization index was determined by comparing the (cortisol/ipsilateral reference hormone) ratios of both adrenal veins. lateralization index of 2 or greater was considered diagnostic of unilateral disease. Post-management clinical improvement was defined as serum cortisol normalization, symptomatic improvement, or both. RESULTS: Cross-sectional imaging noted bilateral adrenal enlargement or nodules in three patients, and unilateral nodules in three patients. AVS results were discordant with imaging in three patients. Treatment included medical management in two patients, percutaneous radiofrequency ablation in one patient, and laparoscopic adrenalectomy in two patients. One patient was lost to follow up. AVS results aided management planning in five patients, definitively changing treatment from surgery to medical management in one patient. All five patients demonstrated clinical improvement. CONCLUSIONS: AVS offered useful information for determining appropriate management of adrenal Cushing's syndrome, especially distinguishing unilateral from bilateral disease. Even in bilateral disease, AVS may show a dominant gland, potentially allowing a staged unilateral adrenalectomy, before assessing the need for completion adrenalectomy or medical management. Larger studies are needed to better establish whether AVS offers significant benefit for this population.

Colitis-Associated Colorectal Cancer Survival is Comparable to Sporadic Cases after Surgery: a Matched-Pair Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) confers an increased lifetime risk of colorectal cancer (CRC). The pathogenesis of colitis-associated CRC is considered distinct from sporadic CRC, but existing is mixed on long-term oncologic outcomes. This study aims to compare clinicopathological characteristics and survival between colitis-associated and sporadic CRC. METHODS: Data was retrospectively extracted and analyzed from a single institutional database of patients with surgically resected CRC between 2004 and 2015. Patients with IBD were identified as having colitis-associated CRC. The remainder were classified as sporadic CRC. Propensity score matching was performed. Univariate and survival analyses were carried out to estimate the differences between the two groups. RESULTS: Of 2275 patients included in this analysis, 65 carried a diagnosis of IBD (2.9%, 33 Crohn's disease, 29 ulcerative colitis, 3 indeterminate colitis). Average age at CRC diagnosis was 62 years for colitis-associated CRC and 65 for sporadic CRC. The final propensity score matched cohort consisted of 65 colitis-associated and 130 sporadic CRC cases. Patients with colitis-associated CRC were more likely to undergo total proctocolectomy (p < 0.01) and had higher incidence of locoregional recurrence (p = 0.026) compared to sporadic CRC patients. There were no significant differences in time to recurrence, tumor grade, extramural vascular invasion, perineural invasion, or rate of R0 resections. Overall survival and disease-free survival did not differ between groups. On multiple Cox regression, IBD diagnosis was not a significant predictor of survival. CONCLUSIONS: Patients with colitis-associated CRC who undergo surgical resection have comparable overall and disease-free survival to patients with sporadic CRC.

Sociability development in mice with cell-specific deletion of the NMDA receptor NR1 subunit gene.

Social affiliative behavior is an important component of everyday life in many species and is likely to be disrupted in disabling ways in various neurodevelopmental and neuropsychiatric disorders. Therefore, determining the mechanisms involved in these processes is crucial. A link between N-methyl-d-aspartate (NMDA) receptor function and social behaviors has been clearly established. The cell types in which NMDA receptors are critical for social affiliative behavior, however, remain unclear. Here, we use mice carrying a conditional allele of the NMDA R1 subunit to address this question. Mice bearing a floxed NMDAR1 (NR1) allele were crossed with transgenic calcium/calmodulin-dependent kinase IIα (CaMKIIα)-Cre mice or parvalbumin (PV)-Cre mice targeting postnatal excitatory forebrain or PV-expressing interneurons, respectively, and assessed using the three-chambered Social Approach Test. We found that deletion of NR1 in PV-positive interneurons had no effect on social sniffing, but deletion of NR1 in glutamatergic pyramidal cells resulted in a significant increase in social approach behavior, regardless of age or sex. Therefore, forebrain excitatory neurons expressing NR1 play an important role in regulating social affiliative behavior.

Self-Reported Exercise Trends in Parkinson's Disease Patients.

OBJECTIVE: To examine trends in type, frequency, and effectiveness of different modes of exercise in patients with Parkinson's Disease (PD). BACKGROUND: Exercise has been shown to improve symptoms in PD patients. Recent studies suggest that dance may be a particularly helpful exercise option. However, it remains unclear how the benefits of various forms of exercise compare to dance and to each other. Information on these trends can help inform future exercise programs for PD patients. METHOD: 55 PD patients completed a survey on their exercise frequency, the impact of exercise on their symptoms, and whether they exercise alone or in groups. 9 PD patients who attend dance therapy classes completed an extended survey with additional questions comparing the benefit of dance therapy to traditional forms of exercise. RESULTS: Of the 64 patients surveyed, 67% of patients exercised at least twice a week for at least 30 minutes at a time, and 28% of patients exercised alone only. Walking was most commonly reported (77%), followed by stretching (52%), and weights (28%). 97% of patients who exercised noted mitigation of their PD symptoms. Additionally, a significantly greater percentage of patients who exercised in groups reported symptomatic improvements compared to patients who only exercised alone (p = 0.03). CONCLUSION: More patients who participated in group exercise reported symptomatic improvement compared to those who exercised strictly alone. This suggests that the psychosocial and cognitive component of group therapy, such as dance, may confer additional benefits to PD patients.