A retrospective single-institution review of the impact of COVID-19 on severity of biliary disease.

BACKGROUND: The COVID-19 pandemic possessed far-reaching health implications beyond the public health impact that have yet to be fully elucidated. We hypothesized that the COVID-19 pandemic led to an increase in biliary disease complexity and incidence of emergency cholecystectomy. METHODS: We reviewed our institutional experience with cholecystectomy from February 2019-February 2021, n = 912. Pre COVID-19 pandemic patients were compared to patients after the onset of the pandemic. Baseline characteristics were compared between groups. A Cochran-Armitage test for trend assessed the temporal impact of COVID-19 on emergency presentation and gallbladder disease complexity. RESULTS: We identified 442 patients pre-pandemic and 470 patients during the pandemic. No significant differences were noted in demographics. COVID-19 significantly impacted emergency presentation (43.2% vs. 56.8%, p= <0.01), cholecystitis (53.2% vs 61.8%; p=<0.01), and gangrenous cholecystitis (2.8% vs 6.1%; p=<0.01). Both groups had similar clinical outcomes. CONCLUSIONS: The COVID-19 pandemic affected an increased incidence of emergency presentation and complexity of gallbladder disease but did not significantly impact clinical outcomes. These findings may have broader implications for other diseases possibly affected by COVID-19.

High dose vitamin D supplementation does not rescue bone loss following Roux-en-Y gastric bypass in female rats.

Postoperative bone loss and increased fracture risk associated with Roux-en-Y gastric bypass (RYGB) have been attributed to vitamin D/calcium malabsorption and resultant secondary hyperparathyroidism (HPT). Adequate vitamin D supplementation (VDS), particularly in an older female population, reduces incidence of secondary HPT but the effect on bone loss and fracture risk remains unclear. To investigate whether VDS corrects the RYGB bone phenotype, 41 obese adult female rats were randomized to RYGB with 1000 IU (R1000) or 5000 IU (R5000) vitamin D/kg food or a sham surgical procedure with either paired (PF) or ad libitum (AL) feeding. Bone turnover markers, urinary calcium/creatinine ratio (CCR), and serum calciotropic and gut hormones were assessed throughout a 14-week postoperative period. Femurs were analyzed by micro-computed tomography (µCT), three-point bending test, and histomorphometry. 1000 IU animals had low 25­hydroxyvitamin D (25(OH)D), high serum parathyroid hormone (PTH), and very low urine CCR levels. 5000 IU corrected the 25(OH)D and secondary HPT but did not increase urine CCR or serum levels of 1,25­dihydroxyvitamin D (1,25(OH)D) significantly between RYGB groups. Compared to sham animals at 14 weeks, RYGB animals had significantly higher serum osteocalcin (OCN) and C-terminal telopeptide (CTX) levels. The gut hormone peptide tyrosine tyrosine hormone (PYY) was higher in the RYGB groups, and leptin was lower. µCT and biomechanical testing revealed RYGB females had decreased cortical and trabecular bone volume and weaker, stiffer bone than controls. Histomorphometry showed decreased bone volume and increased osteoid volume with increased mineral apposition rate in RYGB compared to controls. No differences in bone phenotype were identified between 1000 IU and 5000 IU groups, and osteoclast numbers were comparable across all four groups. Thus, in our model, 5000 IU VDS corrected vitamin D deficiency and secondary HPT but did not rescue RYGB mineralization rate nor the osteomalacia phenotype. Longer studies in this model are required to evaluate durability of these detrimental effects. Our findings not only underscore the importance of lifelong repletion of both calcium and vitamin D but also suggest that additional factors affect skeletal health in this population.

Bariatric surgery is associated with renal function improvement.

INTRODUCTION: Weight loss after bariatric surgery improves both blood pressure and glycemic control following surgery. The effect of bariatric surgery on renal function is not well characterized. In this study, we sought to quantify the change in renal function over time following surgery. METHODS: We retrospectively reviewed all patients who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between 2012 and 2014 at our institution. The glomerular filtration rate (GFR, mL/min) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Body mass index (BMI, kg/m2) and percent weight loss (%WL) were calculated following the surgery. RESULTS: A total of 149 patients who underwent bariatric surgery were included in this study: LRYGB (n = 86 and LSG (n = 63). In LRYGB group, baseline BMI (kg/m2, ±SD) and GFR (mL/min, ±SD) were 48.5 ± 6.8 and 94.7 ± 23.8, respectively. In comparison, BMI and GFR were 49.1 ± 11.9 kg/m2 and 93.1 ± 28.0 mL/min in the LSG group, respectively. Over the follow-up period (19.89 ± 10.93 months), the patients who underwent LRGYB lost a larger percentage of weight as compared to those in the LSG group (29.9 ± 11.7% vs 22.3 ± 10.7%; p = <0.0001). Overall, GFR improved in both LRYGB (101.0 ± 25.8 mL/min) and LSG groups (97.9 ± 25.8 mL/min) and was not significantly different between the two groups. Of patients with a GFR < 90 mL/min prior to weight loss surgery (n = 62), 42% had improvement of their GFR to > 90 mL/min postoperatively (p < 0.001). There was no relationship between weight loss percentage and GFR improvement (p = 0.8703). CONCLUSIONS: Bariatric surgery was associated with improvement in postoperative renal function at almost two years following surgery but was not different for LRYGB versus LSG. The gain in GFR was independent of percentage of weight lost suggesting an alternate mechanism in the improvement of renal function other than weight loss alone.

Emotional intelligence in surgery is associated with resident job satisfaction.

BACKGROUND: Emotional intelligence (EI) has been associated with improved work performance and job satisfaction in several industries. We evaluated whether EI was associated with higher measures of work performance and job satisfaction in surgical residents. METHODS: We distributed the validated Trait EI Questionnaire and job satisfaction survey to all general surgery residents at a single institution in 2015. EI and job satisfaction scores were compared with resident performance using faculty evaluations of clinical competency-based surgical milestones and standardized test scores including the United States Medical Licensing Examination (USMLE) and American Board of Surgery In-Training Examination (ABSITE). Statistical comparison was made using Pearson correlation and simple linear regression adjusting for postgraduate year level. RESULTS: The survey response rate was 68.9% with 31 resident participants. Global EI was associated with scores on USMLE Step 2 (r = 0.46, P = 0.01) and Step 3 (r = 0.54, P = 0.01) but not ABSITE percentile scores (r = 0.06, P = 0.77). None of the 16 surgical milestone scores were significantly associated with global EI or EI factors before or after adjustment for postgraduate level. Global EI was associated with overall job satisfaction (r = 0.37, P = 0.04). Of the facets of job satisfaction, global EI was significantly associated with views of supervision (r = 0.42, P = 0.02) and nature of work (r = 0.41, P = 0.02). CONCLUSIONS: EI was associated with job satisfaction and USMLE performance but not ACGME competency-based milestones or ABSITE scores. EI may be an important factor for fulfillment in surgical training that is not currently captured with traditional in-training performance measures.

Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology.

Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap), is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap) gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA), glucose tolerance testing (GTT), insulin tolerance testing (ITT), microcomputed tomography (µCT), and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research.

Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF-α, which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.

Stromal regulation of human gastric dendritic cells restricts the Th1 response to Helicobacter pylori.

BACKGROUND & AIMS: Mucosal dendritic cells (DCs) play a key role in initiating the T-helper (Th)1 response to Helicobacter pylori. To further elucidate the mucosal response to H pylori, we examined whether gastric stromal factors condition DCs to support tolerance to H pylori, analogous to intestinal stromal factor-driven macrophage tolerance to commensal bacteria. METHODS: To model mucosal DC development, we isolated and cultured cell-depleted human stroma/extracellular matrix from fresh gastric and intestinal mucosa to generate stroma-conditioned media. We then analyzed the capacity of stroma-conditioned media-treated monocyte-derived DCs and primary human gastric and intestinal DCs pulsed in vitro with H pylori to induce T-cell proliferation and interferon gamma secretion. RESULTS: Stromal factors in gastric mucosa suppressed H pylori-stimulated DC activation and the ability of DCs to drive a Th1 proliferative and cytokine response to H pylori. The ability of gastric stromal factors to down-regulate DC function was similar to that of intestinal stromal factors and was independent of transforming growth factor ß, prostaglandin E2, interleukin (IL)-10, and thymic stromal lymphopoietin. Stroma-conditioned media-induced reduction in DC-stimulated Th1 responses was associated with reduced DC release of IL-12. CONCLUSIONS: Gastric stromal factors down-regulate DC responsiveness to H pylori, resulting in a dampened gastric Th1 response. We speculate that stroma-induced down-regulation of DC function contributes to the permissiveness of both gastric and intestinal mucosa to colonization by persistent residential microbes.

Minimally invasive Heller's myotomy in children: safe and effective.

PURPOSE: The aim of the study was to review a single institution experience of minimally invasive Heller's myotomy in pediatric patients with achalasia. METHODS: An institutional review board-approved retrospective review from 1999 to 2005 identified patients 18 years old and younger who underwent a minimally invasive Heller's myotomy for achalasia. RESULTS: Twenty-six patients were identified with a mean age of 15 (range, 4-18 years). There were 11 female and 15 male patients. There were 3 intraoperative complications (2 esophageal mucosal injuries and 1 aspiration). There was no mortality. All 26 surgeries were completed laparoscopically. Two patients had Dor fundoplication, whereas 23 patients had Toupet fundoplication. Average length of hospital stay was 2.7 days (range, 1-4 days) excluding the 3 patients with intraoperative complications and 3.5 days for all patients (range, 1-17 days). Postoperative follow-up ranged from 0 to 75 months (mean, 20 months). Postoperatively, one patient developed reflux symptoms (incidence 4%). Seven patients (27%) had recurrence of symptoms at a mean of 13 months (range, 1-66 months) after their operation. CONCLUSIONS: Laparoscopic Heller's myotomy with fundoplication is a safe and effective treatment of symptomatic achalasia in the pediatric population. Complications were low in this group of patients and comparable to other published reports in the literature.

Outcome of adrenocortical tumors in children.

PURPOSE: This study reviews adrenocortical tumors in children to determine factors that significantly affect outcome. METHODS: An institutional review board-approved retrospective review from 1976 to 2005 identified 23 patients younger than 19 years old with histologic confirmation of adrenocortical carcinoma (ACC) and adenomas. RESULTS: The mean age of the 23 children was 9.0 +/- 1.6 years; girls predominated (female-to-male ratio = 1.9:1) as did cancers (ACC 16, adenoma 7); tumor hormone production (74%); and advanced stage for disease (66%). All malignancies were more than 2.5 cm. Adrenalectomy, including en bloc resection of adjacent structures (35%) achieved grossly negative margins in 70% of patients. Three patients received chemotherapy or chemoradiation as primary treatment without surgery. There was no perioperative mortality; morbidity was 10% (pneumothorax, acute renal failure, chylous ascites, and thrombocytosis). Surgical cure without adjuvant therapy was achieved for all adenomas and ACC stages I and II. For ACC stage III and IV, median survival was 21 months, 5-year survival was 0%. All advanced-staged ACC received adjuvant therapy. Surgically negative margins conferred a survival advantage. CONCLUSIONS: Children, especially females with ACC present with large advanced-staged tumors. Surgically negative margins with or without en bloc resection improves survival. The high percentage of children with functioning tumors suggests earlier detection is possible.

Outcomes of primary liver cancer in children: an appraisal of experience.

INTRODUCTION: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most common primary liver cancers in children. Recent advances in management of pediatric liver cancer have improved disease-specific survival (DSS). This is a review of our experience with childhood liver malignancy over the past 3 decades. MATERIALS AND METHODS: A retrospective chart review from 1975 to 2005 identified patients who were 18 years old or younger with a histologically confirmed diagnosis of primary liver cancer. Patients were staged according to the Children's Cancer Group and Pediatric Oncology Group (CCG/POG) system. Patients were followed up prospectively through clinic visits and mail correspondence. Standard statistical methods were used for comparison, risk, and survival analyses. RESULTS: Fifty-two patients were confirmed to have primary liver cancers, where 24 (46%) patients had HB, 22 (42%) had HCC, 3 (6%) had sarcomas, and 3 (6%) had other histologies. Mean ages at presentation for HB and HCC were 3.2 and 13.1 years old, respectively. The most common presentations were abdominal mass (67%) and pain (40%). Most patients underwent major liver resection (n = 45, 87%), including: lobectomy (n = 25, 48%), and trisegmentectomy (n = 11, 21%). Three patients underwent liver transplantation (n = 3, 6%) for advanced local disease. Forty-five (87%) received primary or neoadjuvant and/or adjuvant chemotherapy. Patients had the following CCG/POG stages: I (n = 31, 60%), II (n = 6, 11.5%), III (n = 9, 17%), and IV (n = 6, 11.5%). Complete gross resection (stage I and II) was achieved in 37 (71%) patients. The perioperative mortality and morbidity rates were 0% and 29%, respectively. Patients with complete resection had significantly better 5-year DSS and median survival compared with incomplete gross resection: 62% vs 9% and 216 vs 18 months, P < .001. Patients treated during the period 1995-2005 had better 5-year DSS and median survival compared with those treated during 1975-1994: 68% vs 32% and 117 vs 27 months, P = .032. All 3 patients who underwent transplantation for conventionally unresectable disease are alive without disease recurrence (follow-up period, 1-15 years). CONCLUSION: Complete resection of the pediatric primary liver tumors remains the cornerstone of treatment to achieve cure. Major liver resection can be performed with minimal perioperative mortality and morbidity. Patients with HB appeared to have better survival compared with patients with HCC, and there was significant improvement in the DSS of children treated in the recent decade. Liver transplantation in conjunction with chemotherapy may have an increasing role in the management of locally advanced primary liver cancers.