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.

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.

Association Between Female Sex and Better Survival in Gastroenteropancreatic Neuroendocrine Tumors.

INTRODUCTION: Studies conflict on whether sex influences survival in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). GEP-NETs express receptors and genes responsive to female hormones. We hypothesized that women would have improved survival and this difference would be greater in premenopausal age women compared to older women. MATERIALS AND METHODS: The National Cancer Database from 2004 to 2016 was queried for patients with GEP-NETs based on histologic code. Demographic, tumor, treatment, and socioeconomic characteristics were compared between men and women and age ≤45 or >65 y using Fisher's exact and Wilcoxon tests as appropriate. The primary endpoint was overall survival (OS), assessed by Kaplan-Meier survival analysis. RESULTS: Included in the study were 73,521 patients with small bowel neuroendocrine tumors (SBNETs), gastric neuroendocrine tumors (GNETs), or pancreas neuroendocrine tumors (36,197 female, 37,324 male). Women lived longer regardless of primary site, with the largest difference in GNETs (median OS 139 versus 85 mo) and smallest in SBNETs (121 versus 116, P < 0.001 for both). While male patients more often had high grade and metastatic disease, female sex remained independently associated with improved OS after adjusting for confounders (hazard ratio 0.84, P < 0.001). In GNETs and SBNETs, female sex had a larger beneficial effect on OS in premenopausal than postmenopausal patients. CONCLUSIONS: Women with GEP-NETs have improved survival over men, especially in the premenopausal age group. This may be due to a protective effect of female hormones; however, further studies are necessary to uncover the biologic basis of this difference.

Liver resection is superior to tumor ablation in patients with multifocal hepatocellular carcinoma.

INTRODUCTION: The management of T2 multifocal hepatocellular carcinoma (MHCC) is controversial, and the comparative impact of liver resection (LR) versus tumor ablation (TA) on survival continues to be debated. The aim of our study was to examine short- and long-term survival for LR and TA in a nationally representative cohort. We hypothesized that patients who underwent LR would have improved survival. METHODS: We utilized the National Cancer Database (2004-2015) to identify patients diagnosed with non-metastatic T2 MHCC. Kaplan-Meier survival curves were generated to compare 10-year overall survival (OS) between LR and TA patients. Kaplan-Meier analysis with stratification was also performed based on lymphovascular invasion, resection margin status, and Charlson-Deyo score. Cox proportional hazard models were used in multivariable analyses. RESULTS: A total of 1225 patients met the inclusion criteria. 991 patients received LR, and 234 received TA. The majority of patients were male, White, and older than ≥60 years old. Clinicodemographic characteristics were generally similar between LR and TA patients. Among patients who underwent LR, 84% had negative margins, and 17% had lymphovascular invasion. Mortality at 30 days was significantly higher among LR patients compared to TA patients (5.4% vs 0.0%, p < 0.001), with those having a Charlson-Deyo score ≥2 facing the highest risk at 7.3%. Nevertheless, 10-year OS for the LR cohort was 27.5% (95% confidence interval [CI]: 24.4%-30.8%) versus 14.7% (95% CI: 9.8%-20.7%, p < 0.001) for TA patients. In stratified analysis, survival benefit was statistically significant only among those with negative resection margin, no lymphovascular invasion, and Charlson-Deyo score ≤1. In multivariable Cox analysis, LR was independently associated with improved survival compared to TA (hazard ratio: 0.80; 95% CI = 0.67-0.95). CONCLUSION: LR poses a higher long-term survival benefit than TA. Prospective studies are warranted to confirm these findings. Although our study patients are a highly selected group of multifocal T2 patients, it gives us a good insight into the fact that LR provides better outcomes if a transplant option is unavailable.

Evaluation of association between center colorectal neuroendocrine neoplasm volume and survival among patients with colorectal neuroendocrine carcinoma.

BACKGROUND: Although correlation between center volume and survival has been reported for several complex cancers, it remains unknown if this is true for colorectal neuroendocrine carcinomas (CRNECs). We hypothesized that higher center annual volume of colorectal neuroendocrine neoplasm resections would be associated with overall survival (OS) for patients with CRNECs. METHODS: Patients in the National Cancer Database diagnosed with stages I-III CRNEC between 2006 and 2018 and who underwent surgical resection were identified. The mean annual colorectal neuroendocrine neoplasm resection volume threshold associated with significantly worse mortality hazard was determined using restricted cubic splines. Kaplan-Meier (KM) method was used to compare OS, while Cox proportional hazards model was used for multivariable analysis. RESULTS: There were 694 patients with CRNEC who met inclusion criteria across 1229 centers. Based on the cubic spline, centers treating fewer than one colorectal neuroendocrine neoplasm patient every 3 years on average had worse outcomes. Centers below this threshold were classified as low-volume (LV) centers corresponding with 42% of centers and about 15% of the patient cohort. In unadjusted survival analysis, LV patients had a median OS of 14 months (95% confidence interval [CI]: 10-19) while those treated at HV centers had a median OS of 33 months (95% CI: 25-49). In multivariable analysis, resection at a LV center was associated with increased risk of mortality (1.42 [95% CI: 1.01-2.00], p = 0.04). CONCLUSION: CRNEC patients have a dire prognosis; however, treatment at an HV center may be associated with decreased risk of mortality.

Care Patterns and Outcomes for Intrahepatic Cholangiocarcinoma by Rurality of Patient Residence in a Midwestern State.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy of the liver and has the worst prognosis of any tumor arising from the liver, with a 5-year survival as low as 10%. However, whether the rurality of a patient's residence impacts care received and survival has not been well studied. We aimed to assess differences in care patterns associated with the rurality of patient's residences and their impact on survival outcomes, hypothesizing that patients in rural areas would experience lower survival. METHODS: Adult patients diagnosed with ICC between 2010 and 2020 were identified in the Iowa Cancer Registry. Chi-square tests were used to compare values categorical variables by rural/urban status. Cox proportional hazards regression was used to determine associations with cancer-specific mortality. RESULTS: Of 672 patients diagnosed with ICC during the study period, 53%, 27%, and 21% resided in metropolitan, micropolitan, and rural areas, respectively. There were no significant differences in age, sex, stage at diagnosis, the proportion receiving chemotherapy within 12 weeks of diagnosis, and undergoing surgery across all groups. Additionally, the proportion receiving definitive care at a National Cancer Institute (NCI) designated center was comparable across the three groups (37% metro vs. 43% micro vs. 35% rural). However, rural residents had the highest proportion of traveling ≥ 50 miles for definitive care (22% metro vs. 41% micro vs. 56% rural). In multivariable analysis of patients with Stage 1-3 disease, younger age, receipt of chemotherapy, surgery, and definitive care at an NCI center were independently associated with decreased mortality risk. However, rural residence was not significantly associated with survival (HR: 0.64 [95% CI: 0.38-1.06]). CONCLUSION: Similar to other complex cancer diagnoses, we found that definitive care at an NCI center was associated with decreased mortality risk for patients with ICC. Although rural residence was not independently associated with survival in this cohort, rural residents traveled significantly longer distances to access definitive care. This highlights a crucial need to improve access to specialized centers for complex cancer care.

Peritoneal Metastases After Intraductal Papillary Mucinous Neoplasm Resection: How Common are They?

INTRODUCTION: Peritoneal metastases (PMs) following resection of pancreatic intraductal papillary mucinous neoplasms (IPMNs) are rare. Consequently, prevalence, risk factors, and prognosis are not well known. We reviewed our institution's experience and published literature to further characterize the scope of this phenomenon. METHODS: All pancreatectomy cases (556 patients) performed at a tertiary care center between 2010 and 2020 were reviewed to identify IPMN diagnoses. Patients with adenocarcinoma not arising from IPMN, or a history of other malignancies were excluded. RESULTS: Seventy-eight patients underwent pancreatectomy with IPMN on final pathology at our institution; 51 met inclusion criteria. Of these, there were five cases of PMs (4:1 females:males). Four had invasive carcinoma arising from IPMN and one had high-grade dysplasia at the index operation. Female sex and invasive histology were significantly associated with PM (P < 0.05). PM rates by sex were 3% (95% confidence interval [CI]: 0.5-15) in males and 22% (95% CI: 9-45) in females. Rates by histology were 2.9% (95% CI: 0.5-15) for noninvasive IPMN, and 23.5% (95% CI: 9.5-47) for invasive carcinoma arising from IPMN. Median interval from surgery to PMs was 7 mo (range: 3-13). CONCLUSIONS: PMs following IPMN resection are rare but may be more common in patients with invasive histology. Although rare, PMs can arise in patients with noninvasive IPMNs. Further studies on pathophysiology and risk factors of PM following IPMN resection are needed and may reinforce adherence to guidelines recommending long-term surveillance.

Management of Duodenal Neuroendocrine Tumors: Surgical versus Endoscopic Mucosal Resection.

BACKGROUND: Management of duodenal neuroendocrine tumors (DNETs) is not standardized, with smaller lesions (< 1-2 cm) generally treated by endoscopic mucosal resection (EMR) and larger DNETs by surgical resection (SR). This study reviewed how patients were selected for treatment and compared outcomes. PATIENTS AND METHODS: Patients with DNETs undergoing resection were identified through institutional databases, and clinicopathologic data recorded. χ2 and Wilcoxon tests compared variables. Survival was determined by Kaplan-Meier, and Cox regression tested association with survival. RESULTS: Among 104 patients, 64 underwent EMR and 40 had SR. Patients selected for SR had larger tumor size, younger age, and higher T, N, and M stage. There was no difference in progression-free (PFS) or overall survival (OS) between SR and EMR. In 1-2 cm DNETs, there was no difference in PFS between SR and EMR [median not reached (NR), P = 0.1]; however, longer OS was seen in SR (median NR versus 112 months, P = 0.03). In 1-2 cm DNETs, SR patients were more likely to be node-positive and younger. After adjustment for age, resection method did not correlate with survival. Comparison of surgically resected DNETs versus jejunoileal NETs revealed longer PFS (median NR versus 73 months, P < 0.001) and OS (median NR versus 119 months, P = 0.004) DISCUSSION: In 1-2 cm DNETs, there was no difference in survival between EMR and SR after adjustment for age. Recurrences could be salvaged, suggesting that EMR is a reasonable strategy. Compared with jejunoileal NETs, DNETs treated by SR had improved PFS and OS.

Comparative outcomes of treatment modalities in nonagenarians with nonmetastatic pancreatic adenocarcinoma.

BACKGROUND: There has been an increase in the elderly patient population seeking care for pancreatic ductal adenocarcinoma (PDAC). This study aimed to delineate the effectiveness of therapeutic options in nonagenarians (aged 90-99 years) diagnosed with resectable PDAC. METHODS: This study used the National Cancer Database to identify patients with nonmetastatic PDAC (stage I-III) from 2004 to 2021. The study compared median overall survival (mOS) using Kaplan-Meier curves among 5 treatment categories: surgery, surgery along with chemoradiation, chemotherapy alone, radiotherapy alone, and chemoradiation alone. Cox proportional hazards regression was used in multivariate analyses. RESULTS: Of 459,174 patients, 793 aged ≥ 90 years had nonmetastatic PDAC. Of 793 patients, 245 (30.9 %) underwent chemotherapy alone, 296 (37.3 %) underwent radiotherapy alone, 162 (20.4 %) underwent chemoradiation alone, 58 (7.3 %) underwent curative-intent resection, and 32 (4.0 %) underwent surgery combined with chemoradiation. The mOS estimates in different treatment modalities were 9.5 months (95 % CI, 6.7-14.5) for surgery alone, 19.1 months (95 % CI, 2.4-64.3) for surgery combined with chemoradiation, 8.2 months (95 % CI, 7.2-9.2) for chemotherapy alone, 8.4 months (95 % CI, 7.6-9.6) for radiotherapy alone, and 11.2 months (95 % CI, 8.7-12.9) for chemoradiation alone (P < .001). In multivariate analysis, the odds of survival were better for patients who underwent surgery alone than for those who underwent chemotherapy alone, although the odds of survival did not significantly differ between patients who underwent radiotherapy alone and those who underwent chemoradiation alone. Nonetheless, surgery combined with chemoradiation was associated with decreased mortality risk compared with surgery alone (hazard ratio, 0.46; 95 % CI, 0.25-0.87; P = .02). Operative 30-day mortality rate was 8.8 %, and 90-day mortality rate was 17.8 %. CONCLUSION: Surgery combined with chemoradiation improved the survival of nonagenarians with PDAC compared with other therapies. However, only 1 in 25 patients received all 3 treatment components. Moreover, our study highlights a very high operative mortality rate in nonagenarians.

Epidemiology and survival outcomes of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinoma.

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasms are a rare subtype of neuroendocrine neoplasm consisting of ≥30% each of neuroendocrine and non-neuroendocrine differentiation. Neuroendocrine carcinomas are poorly differentiated neuroendocrine tumors. The epidemiology and prognosis of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas are not clearly defined in the literature. We sought to examine the presentation, patterns of care, and outcomes of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. METHODS: We identified patients diagnosed with stage I-III colorectal (excluding appendix) mixed neuroendocrine-non-neuroendocrine neoplasms or neuroendocrine carcinomas with only one-lifetime cancer diagnosis who underwent surgical resection between 2010 and 2018 from the National Cancer Database. We performed bidirectional selection to identify variables to include in a multivariable Cox proportional hazards model. RESULTS: We identified 189 patients with a diagnosis of stage I to III colorectal mixed neuroendocrine-non-neuroendocrine neoplasms, 66% of whom had poorly differentiated tumors and 482 with neuroendocrine carcinomas. Among patients with stage III disease, 68% of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and 54% of patients with neuroendocrine carcinomas received adjuvant chemotherapy. The median survival for the overall patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas cohorts were 38 and 42 months, respectively (P = .22), and the median survival for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas with stage III disease were 30 and 25 months, respectively (P = .27). In multivariable analysis, fewer number of positive nodes and receipt of adjuvant chemotherapy were independently associated with decreased risk of mortality for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. CONCLUSION: Adjuvant chemotherapy is associated with improved survival in stage III mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. Future studies are warranted to identify subsets of patients benefiting most from adjuvant therapy.

NSQIP 5-factor modified frailty index and complications after ileal anal pouch anastomosis for ulcerative colitis.

Background: Frailty has been associated with worse postoperative outcomes. The 5-factor modified frailty index (mFI-5) is an objective measure although its validity in measuring frailty in patients undergoing ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (CUC) has not been reported. Methods: This study used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted proctectomy database. The mFI-5 was calculated by five preoperative diagnoses: insulin-dependent or noninsulin-dependent diabetes, congestive heart failure, hypertension, chronic obstructive pulmonary disease, and dependent or partially dependent functional status. The impact of mFI-5 on minor and major postoperative morbidity in CUC patients undergoing IPAA was analyzed. Results: The cohort included 1454 patients (median age 38 years, median body mass index [BMI] 26 kg/m2) of which 87 % had a mFI-5 = 0, 11 % had a mFI-5 = 1, and 2.5 % a mFI-5 ≥ 2. In multivariable logistic regression, mFI-5 ≥ 2 was significantly associated with minor complications (OR = 2.29, 95 % CI [1.00-5.22], p = 0.049), but not with major complications (p = 0.860). Conclusion: IPAA for CUC is associated with high postoperative morbidity, however, the mFI-5 alone has limited utility in determining which patients are at a higher risk of complications due to frailty. These observations suggest there is a need for more relevant instruments to measure frailty in this patient cohort.

Liver transplant versus liver resection in patients with multifocal hepatocellular carcinoma.

BACKGROUND: The optimal surgical option in patients with multifocal hepatocellular carcinoma (MHCC) is an area of active research. The preference varies based on geographic variations and institutional policies. We sought to determine long-term outcomes in patients with MHCC based on surgical treatment-liver transplant (LT) vs resection (LR). METHODS: We performed a retrospective analysis of the National Cancer Database (2004-2015) and identified patients with MHCC within Milan criteria. Patients with α-fetoprotein ≥ 1000 ng/mL and those who underwent ablation were excluded. The primary outcome measure was long-term survival in patients undergoing LT vs LR. The secondary aim of our study was to determine clinicodemographic factors associated with the receipt of LT and LR. RESULTS: A total of 1546 patients were included, of whom 1211 received LT and 335 underwent LR. Patients who were non-Hispanic White (70.8% vs 54.9%; P < .01), privately insured (53.7% vs 36.7%; P < .01), and treated at academic centers (85.4% vs 71.6%; P < .01) were more likely to receive an LT. Multivariable Cox analysis revealed LT was associated with improved survival compared with LR (hazard ratio, 0.34; 95% CI, 0.28-0.42). CONCLUSION: We described clinical and sociodemographic differences in LT and LR patients and found LT to be associated with a decreased mortality risk compared with LR. The study's findings should be interpreted in the context of several limitations, including the selection of MHCC criteria within Milan criteria.

Patterns of care and outcomes for hepatocellular carcinoma and pancreatic cancer based on rurality of patient's residence in a rural midwestern state.

BACKGROUND: Although advancements in surgical planning and multidisciplinary care have improved the survival of patients with hepatopancreatic cancers in recent years, the impact of the rurality of patient residence on care received and survival is not well known. We aimed to assess the association between the rurality of a patient's residence and cancer-specific survival outcomes among patients with hepatocellular carcinoma (HCC) and pancreatic cancer (PC) in Iowa, hypothesizing that patients in rural areas would experience lower survival. METHODS: Adult patients diagnosed with HCC or PC between 2010 and 2020 were identified using the Iowa Cancer Registry. Chi-square tests were used to compare categorical variables by rural/urban status. Logistic regression was used to examine factors associated with receiving surgery. Multivariable-adjusted Cox proportional hazards regression was used to determine associations with cancer-specific mortality. RESULTS: Of 1877 patients with HCC, 58%, 27%, and 16% resided in metropolitan, micropolitan, and rural areas, respectively. Approximately 70% of patients in rural areas traveled ≥50 miles for definitive care. Additionally, those residing in rural areas had the highest proportion of patients receiving definitive care at non-Commission on Cancer (CoC) centers (12.6% metro vs 14% micro vs 22.2% rural, P < .001). In a multivariable-adjusted analysis of patients with stage I to III disease, definitive care at a non-CoC center was independently associated with lower odds of surgery (odds ratio [OR] = 0.23; 95% CI, 0.12-0.45; P < .0001) and higher mortality risk (OR = 1.39; 95% CI, 1.07-1.79; P = .01), though rural residence was not. For PC, 5465 patients were diagnosed, and 51%, 28%, and 20% resided in metropolitan, micropolitan, and rural areas, respectively. Similar to HCC, although rural residence was neither associated with odds of surgery nor with mortality risk, receiving definitive care at non-CoC accredited centers was associated with significantly lower odds of receiving surgery (OR = 0.17; 95% CI, 0.11-0.26; P < .0001) and higher mortality risk (OR = 1.48; 95% CI, 1.23-1.77; P < .0001). CONCLUSION: Rural residents with hepatopancreatic cancer have the highest proportion of patients receiving definitive care at non-CoC centers, which is associated with lower odds of receiving surgery and higher odds of mortality. This highlights the importance of standardizing complex cancer care and the need to foster collaboration between specialized and non-specialized centers.

A framework to improve retention of Black surgical trainees: A Society of Black Academic Surgeons white paper.

Attrition is high among surgical trainees, and six of ten trainees consider leaving their programs, with two ultimately leaving before completion of training. Given known historically and systemically rooted biases, Black surgical trainees are at high risk of attrition during residency training. With only 4.5% of all surgical trainees identifying as Black, underrepresentation among their peers can lend to misclassification of failure to assimilate as clinical incompetence. Furthermore, the disproportionate impact of ongoing socioeconomic crisis (e.g., COVID-19 pandemic, police brutality etc.) on Black trainees and their families confers additional challenges that may exacerbate attrition rates. Thus, attrition is a significant threat to medical workforce diversity and health equity. There is urgent need for surgical programs to develop proactive approaches to address attrition and the threat to the surgical workforce. In this Society of Black Academic Surgeons (SBAS) white paper, we provide a framework that promotes an open and inclusive environment conducive to the retention of Black surgical trainees, and continued progress towards attainment of health equity for racial and ethnic minorities in the United States.

Equivalency of short-term perioperative outcomes after open, laparoscopic, and robotic ileal pouch anal anastomosis. Does procedure complexity override operative approach?

Background: Ileal pouch anal anastomosis is the treatment of choice for patients with chronic ulcerative colitis and familial adenomatous polyposis undergoing a proctocolectomy and desiring bowel continuity. It is a technically complex operation associated with significant morbidity and may be performed by an open, laparoscopic, or robotic approach. However, there is a paucity of data regarding the comparative perioperative outcomes between these 3 techniques outside of institutional studies. Methods: The NSQIP targeted proctectomy data set was used to identify patients who underwent open, laparoscopic, and robotic ileal pouch anal anastomosis between 2016 and 2019. Thirty-day outcomes between different surgical approaches were compared using univariate and multivariable analysis. Results: During the study period, 1,067 open, 971 laparoscopic, and 341 robotic ileal pouch anal anastomosis were performed. The most frequent indications were inflammatory bowel disease (64%), malignancy (18%), and familial adenomatous polyposis (7%). Mean age of the cohort was 43 ±â€¯15 years with 43% female and 76% with body mass index ≤ 30 kg/m2. Overall morbidity was 26.8% for the entire cohort with 4% anastomotic leak, 6% reoperation, 21% ileus, and 21% readmission rate. After adjusting for available confounders, operative approach was not associated with better short-term outcomes, including length of stay, overall morbidity, anastomotic leak, reoperation, incidence of ileus, and 30-day readmissions. Conclusion: Ileal pouch anal anastomosis continues to be associated with significant postoperative morbidity regardless of operative approach. Patient-related advantages in terms of perioperative outcomes for laparoscopic and robotic platforms compared to open surgery are less pronounced in complex operations such as ileal pouch anal anastomosis.

Congenital intrathoracic accessory spleen is a very rare trick of nature: a case report.

BACKGROUND: Congenital intrathoracic accessory spleen (CIAS) refers to a developmental anomaly resulting in the presence of splenic tissue within the chest. The differential diagnoses for the resulting mass are pulmonary malformations, or lesions with malignant potential. To our knowledge, only four cases of presumed CIAS have been described in literature to date, and no cases were reported in the United States. CASE PRESENTATION: We report on a 14-year-old Caucasian female with a left chest mass discovered incidentally on a CT scan performed following an all-terrain vehicle accident. Following resection, the mass was diagnosed as a CIAS. CONCLUSIONS: From our review of literature, we found that CIAS can pose a diagnostic dilemma as it is rare, difficult to distinguish from pulmonary sequestration, or malignancy, and biopsy is often inconclusive. Resection is required to rule out malignancy and determine the diagnosis. Pediatric thoracic surgeons should consider CIAS in their differential for an intrathoracic mass with an inconclusive biopsy.

Preoperative bleeding requiring transfusion: An under-reported indication for hemorrhoidectomy.

BACKGROUND: Though hemorrhoids commonly cause minor gastrointestinal bleeding, major hemorrhage requiring blood transfusion is believed to be rare. We sought to identify the prevalence and risk factors for preoperative transfusion in surgical hemorrhoidectomy patients. METHODS: Patients undergoing surgical hemorrhoidectomy at a single institution (2012-2017) were evaluated for preoperative bleeding requiring transfusion. Bivariate analysis compared patients requiring transfusion to those who did not, and multivariable analysis evaluated for independent risk factors for transfusion. RESULTS: Out of 520 patients, 7.3% experienced hemorrhoidal bleeding requiring transfusion, and 80.6% reported bleeding. On multivariable analysis, the use of either an anticoagulant or non-aspirin antiplatelet agent was associated with transfusion (OR 3.08, p = 0.03). Patients requiring transfusion had extensive preoperative workups, including colonoscopy (94.7%), flexible sigmoidoscopy (7.89%), upper endoscopy (50%) and capsule endoscopy (26.3%). CONCLUSIONS: Bleeding requiring transfusion is an under-reported complication of hemorrhoids. Increased recognition could lead to expeditious surgical treatment and less costly diagnostic workup.

Adjuvant composition and delivery route shape immune response quality and protective efficacy of a recombinant vaccine for Entamoeba histolytica.

Amebiasis caused by Entamoeba histolytica is the third leading cause of parasitic mortality globally, with some 100,000 deaths annually, primarily among young children. Protective immunity to amebiasis is associated with fecal IgA and IFN-γ in humans; however, no vaccine exists. We have previously identified recombinant LecA as a potential protective vaccine antigen. Here we describe the development of a stable, manufacturable PEGylated liposomal adjuvant formulation containing two synthetic Toll-like receptor (TLR) ligands: GLA (TLR4) and 3M-052 (TLR7/8). The liposomes stimulated production of monocyte/macrophage chemoattractants MCP-1 and Mip-1ß, and Th1-associated cytokines IL-12p70 and IFN-γ from human whole blood dependent on TLR ligand composition and dose. The liposomes also demonstrated acceptable physicochemical compatibility with the recombinant LecA antigen. Whereas mice immunized with LecA and GLA-liposomes demonstrated enhanced antigen-specific fecal IgA titers, mice immunized with LecA and 3M-052-liposomes showed a stronger Th1 immune profile. Liposomes containing GLA and 3M-052 together elicited both LecA-specific fecal IgA and Th1 immune responses. Furthermore, the quality of the immune response could be modulated with modifications to the liposomal formulation based on PEG length. Compared to subcutaneous administration, the optimized liposome adjuvant composition with LecA antigen administered intranasally resulted in significantly enhanced fecal IgA, serum IgG2a, as well as systemic IFN-γ and IL-17A levels in mice. The optimized intranasal regimen provided greater than 80% protection from disease as measured by parasite antigen in the colon. This work demonstrates the physicochemical and immunological characterization of an optimized mucosal adjuvant system containing a combination of TLR ligands with complementary activities and illustrates the importance of adjuvant composition and route of delivery to enhance a multifaceted and protective immune response to amebiasis.

The effects of indoor and outdoor dust exposure on the growth, sensitivity to oxidative-stress, and biofilm production of three opportunistic bacterial pathogens.

Within the last decade, many studies have highlighted the radical changes in the components of indoor and outdoor dust. For example, agents like automobile emitted platinum group elements and different kinds of organic phthalates and esters have been reported to be accumulating in the biosphere. Humans consistently face dermal, respiratory, and dietary exposures to these particles while indoors and outdoors. In fact, dust particulate matter has been associated with close to 500,000 deaths per year in Europe and about 200,000 deaths per year in the United States. To date, there has been limited examination of the physiological impact of indoor and outdoor dust exposure on normal flora microbes. In this study, the effect of indoor- and outdoor-dust exposure on three opportunistic bacterial species (Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa) was assessed. Specifically, bacterial growth, oxidative stress resistance, and biofilm production were measured following indoor- and outdoor-dust exposures. Studies were conducted in nutritionally-rich and -poor environments typically encountered by bacteria. Surprisingly, indoor-dust (200µg/mL), enhanced the growth of all three bacterial species in nutrient-poor conditions, but slowed growth in nutrient-rich conditions. In nutrient-rich medium, 100µg/mL exposure of either indoor- or outdoor-dust resulted in significantly reduced oxidative stress resistance in E. coli. Most interestingly, dust (indoor and outdoor), either in nutrient-rich or -poor conditions, significantly increased biofilm production in all three bacterial species. These data suggest that indoor and outdoor dust, can modify opportunistic bacteria through altering growth, sensitivity to oxidative stress, and their virulence potential through enhanced biofilm formation.