Pancreaticogastrostomy as a fistula mitigating strategy for a high-risk pancreatic anastomosis following pancreaticoduodenectomy.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) has been associated with soft gland texture and/or small pancreatic duct. We hypothesized that selective use of pancreaticogastrostomy (PG) over pancreaticojejunostomy (PJ) in those scenarios would decrease the rate of CR-POPF. METHODS: Review of prospective database of all PD's performed at a single institution between 2009 and 2019 was performed. The pancreatic remnant was deemed "high risk" if soft gland and/or small duct were present. RESULTS: PJ was performed in 199 (147 "low-risk" and 52 "high-risk") cases, and 110 patients (all "high-risk") had a PG. Overall CR-POPF rate was 11.9% with no difference between the groups. Risk-stratified analysis within PJ group showed CR-POPF rate of 5.4% versus 36% in "low-risk" versus "high risk" scenarios, respectively; the use of PG significantly decreased CR-POPF rate (9.1%, p < 0.0001). Gastrointestinal bleeding was more likely to occur following PG than PJ. Soft gland texture and gastrointestinal bleeding were the strongest predictors of CR-POPF in PJ and PG groups, respectively. CONCLUSION: Selective use of PG after PD in "high-risk" scenarios mitigates the risk of CR-POPF. Increased rate of gastrointestinal bleeding calls for further refinement of the technique and heightened postoperative vigilance.

COVID-19 Pandemic and Indigenous Representation in Public Health Data.

Public Health 3.0 calls for the inclusion of new partners and novel data to bring systemic change to the US public health landscape. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has illuminated significant data gaps influenced by ongoing colonial legacies of racism and erasure. American Indian and Alaska Native (AI/AN) populations and communities have been disproportionately affected by incomplete public health data and by the COVID-19 pandemic itself. Our findings indicate that only 26 US states were able to calculate COVID-19‒related death rates for AI/AN populations. Given that 37 states have Indian Health Service locations, we argue that public health researchers and practitioners should have a far larger data set of aggregated public health information on AI/AN populations. Despite enormous obstacles, local Tribal facilities have created effective community responses to COVID-19 testing, tracking, and vaccine administration. Their knowledge can lead the way to a healthier nation. Federal and state governments and health agencies must learn to responsibly support Tribal efforts, collect data from AI/AN persons in partnership with Indian Health Service and Tribal governments, and communicate effectively with Tribal authorities to ensure Indigenous data sovereignty. (Am J Public Health. 2021;111(S3): S208-S214. https://doi.org/10.2105/AJPH.2021.306415).

Modern Elective Laparoscopic Cholecystectomy Carries Extremely Low Postoperative Infection Risk.

BACKGROUND: The studies that established historical rates of surgical infection after cholecystectomy predate the modern era of laparoscopy and routine prophylactic antibiotics. Newer studies have reported a much lower incidence of infections in "low-risk" elective, outpatient, laparoscopic cholecystectomies. We investigated the current rate of postoperative infections in these cases within a large, U.S. METHODS: We retrospectively reviewed elective laparoscopic cholecystectomies from the 2016-2017 American College of Surgeons National Surgical Quality Improvement Program database. Our primary outcome was postoperative surgical site infection; secondary was Clostridium difficile infection. Logistic models evaluated the associations of patient and operation characteristics with these outcomes. RESULTS: Surgical infection occurred in 1.0% of cases (293/30,579). Cdifficile infection occurred in 0.1% (31 cases). In our adjusted multivariable models, other/unknown race/ethnicity, diabetes, hypertension, smoking, American Society of Anesthesiologists >2, operative minutes, and wound class 4 were associated with a significantly higher odds of surgical infection; no covariates were significantly associated with Cdifficile infection. CONCLUSIONS: In the setting of modern U.S. surgical practice, the incidence of infection after elective laparoscopic cholecystectomy is very low, on par with clean cases. Our study identified several patient characteristics that were strongly associated with surgical infection. Many of these are not included as risk factors in current guidelines for antibiotic prophylaxis and may help to identify those at higher risk for this rare complication.

APOBEC3F expression in triple-negative breast cancer is associated with tumor microenvironment infiltration and activation of cancer immunity and improved survival.

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) causes a point mutation from cytidine to uracil in DNA and/or RNA. The role of APOBEC3A and APOBEC3B in breast cancer has been well described, whereas that of APOBEC3F remains unknown. To investigate the clinical relevance of APOBEC3F expression, we analyzed a total of 3000 breast cancer cases from multiple independent large patient cohorts including METABRIC, TCGA, GSE75688, and GSE114725. High expression of APOBEC3F was associated with improved disease-specific and overall survival in triple negative breast cancer (TNBC). APOBEC3F is not usually a reflection of cancer cell biology in TNBC or luminal breast cancer, except for homologous recombination deficiency in TNBC. In the TNBC homologous recombination deficiency group, APOBEC3F expression was not consistently associated with intratumor heterogeneity, mutation rates, or neoantigens. APOBEC3F expression did not correlate with response to any of the drugs tested in breast cancer cell lines in vitro. However, high APOBEC3F expression was associated with enrichment of several immune-related gene sets and immune activity. High APOBEC3F expression also accompanied higher infiltration of anti-cancer immune cell infiltration in TNBC. However, in luminal breast cancer, high APOBEC3F tumor significantly enriched not only immune-related gene sets, but also cell proliferation-, metastasis-, and apoptosis-related gene sets. Analysis of single-cell transcriptomes showed APOBEC3F exclusively expressed in immune cells and significantly associated with cytolytic activity of the immune cells, immune response, and immune cell proliferation. Expression of immune checkpoint genes was uniformly elevated in APOBEC3F-high tumors. We conclude that APOBEC3F is exclusively expressed in immune cells and this expression is associated with enhanced anti-cancer immune response as well as improved survival in TNBC.

Transoral Minimally Invasive Tracheoplasty Technique for Cervical Tracheomalacia.

We report a case of cervical tracheomalacia successfully treated by tracheoplasty. The resection of redundant posterior tracheal tissue was performed with a novel minimally invasive transoral approach.

MELK expression in breast cancer is associated with infiltration of immune cell and pathological compete response (pCR) after neoadjuvant chemotherapy.

In experimental settings, maternal embryonic leucine zipper kinase (MELK), an apical member of the snf1/AMPK serine-threonine kinases family, plays a role in tumor growth. We investigated the clinical relevance of MELK expression by performing silico analyses of 7,135 breast cancer patients using multiple independent large cohorts. In triple negative breast cancer (TNBC) found that elevated MELK expression significantly correlates with Nottingham histologic grade and tumor growth according to American Joint Committee Cancer (AJCC) stage. High MELK tumor enriched cell proliferation-related gene sets as well as DNA repair, unfolded protein response, and MTORC signaling gene sets. In two independent cohorts a high mutation rate and worse survival was significantly associated with high MELK tumor. In immune-related gene sets including, allograft rejection, interferon (IFN)-α response, and IFN-γ response, high MELK tumor significantly enriched. Pro-cancer regulatory T cells, T helper type 2 cells and anti-cancer immune cells including CD4+ memory T cells, T helper type1 cells, CD8+ T cells, M1 macrophages, gamma-delta T cells, and dendritic cells with high levels of cytolytic activity (CYT) were highly infiltrated. MELK expression did not correlate with the responses to any of the drugs tested in cell lines. However, pathologic complete response was significantly associated with high MELK following NAC in both TNBC and ER-positive plus HER2-negative breast cancer. In conclusion, cell proliferation, immune response, and NAC breast cancer response was associated with MELK expression.

Abundance of Microvascular Endothelial Cells Is Associated with Response to Chemotherapy and Prognosis in Colorectal Cancer.

The generation of pathologic, immature, and dysfunctional vessels by angiogenesis is a mechanism of metastasis that has been a therapeutic target for colorectal cancer (CRC). In this study, we investigated the clinical relevance of intra-tumoral microvascular endothelial (mvE) cells in CRC using the xCell algorithm on transcriptome. A total of 1244 CRC patients in discovery and validation cohorts were analyzed. We found that an abundance of mvE cells did not mirror angiogenesis but reflected mature blood vessels because it was significantly associated with a high expression of vascular stability-related genes, including sphingosine-1-phosphate receptor genes and pericytes. Epithelial-mesenchymal transition and myogenesis gene sets were enriched in mvE cell abundant CRC, while mvE cell-less CRC enriched cell proliferation, oxidative phosphorylation, and protein secretion gene sets. mvE cell abundant CRC was associated with infiltration of M2 macrophages, dendritic cells, and less gamma-delta T cells (all p < 0.001), but not with the interferon-γ response. mvE cell abundant CRC was significantly associated with worse patient survival in CRC. Interestingly, mvE cell abundant CRC was significantly associated with a high response rate to chemotherapy (p = 0.012) and worse patient survival for those that did not receive chemotherapy. However, there was no survival difference in patients who underwent chemotherapy. In conclusion, we estimated the abundance of mvE cells using the xCell algorithm on tumor transcriptome finding its association with the number of mature blood vessels in a tumor microenvironment and its ability to predict response to chemotherapy, thereby patient survival in CRC.

Low expression of miR-29a is associated with aggressive biology and worse survival in gastric cancer.

Advanced gastric cancer (GC) is one of the most lethal cancer types, thus a better understanding of its biology in patients is urgently needed. MicroRNA (miR)-29a is a known tumor suppressive miR that is related to metastasis, but its clinical relevance in GC remains ambiguous. Here, using a large GC patient cohort we hypothesized that low expression of miR-29a in GC is associated with aggressive cancer biology and worse survival. We demonstrated that low miR-29a GC enriched cell proliferation, apoptosis, metastasis, and angiogenesis related gene sets, as well as the higher expression of related genes. Low miR-29a GC was associated with less anti-cancer immune cell infiltration as well as immune related scoring. Low miR-29a GC demonstrated a worse overall survival (OS) as well as disease specific survival (DSS) compared with high expressing miR-29a GC. Notably, low miR-29a expression was the only factor, other than residual tumor status, to be an independent prognostic biomarker of worse OS and DSS. In conclusion, low miR-29a GC was associated with aggressive cancer biology and worse OS as well as DSS. Additionally, low expression of miR-29a was an independent prognostic biomarker of OS and DSS in gastric cancer patients.

Experience with a Nonopioid Protocol in Ambulatory Breast Surgery: Opioids are Rarely Necessary and Use is Surgeon-Dependent.

CONTEXT: Surgeons write 1.8% of all prescriptions and 9.8% of all opioid prescriptions. Even small doses prescribed for short-term use can lead to abuse; thus, surgeons are uniquely able to combat the opioid epidemic by changing prescribing practices. As part of a department wide quality improvement project, we initiated a nonopioid protocol for all patients undergoing ambulatory breast surgery. OBJECTIVE: To determine the feasibility of a nonopioid protocol for patients undergoing ambulatory breast surgery and to determine if patient-related factors contribute to surgeon adherence to a nonopioid protocol in ambulatory breast surgery. DESIGN: Retrospective chart review of a prospectively collected database, with χ2 analysis and a multiple logistic regression model with the surgeon as the random effect. MAIN OUTCOME MEASURE: Protocol adherence. RESULTS: A total of 180 patients, with a median age of 63 years (range = 18-95 years), were included. Of these, 127 (70.6%) did not receive opioids; in this group there were 2 hematomas (1.6%), and 3 patients required an opioid prescription (2.4%). Fifty-three (29.4%) were prescribed opioids against protocol; in this group, there was 1 hematoma (1.9%). The operating surgeon was the only variable independently correlated with protocol adherence (p < 0.0001). Age, race/ethnicity, surgery type, and history of long-term opioid use were not. CONCLUSION: Ambulatory breast surgery patients tolerated a nonopioid pain regimen well. Surgeons' decisions, rather than patient characteristics, primarily drove the choice of pain management in our study. We believe our protocol can be improved with stricter implementation and education, which must be balanced with practitioner independence.