Immune cells are increased in normal breast tissues of BRCA1/2 mutation carriers.

PURPOSE: Breast cancer risk is elevated in pathogenic germline BRCA 1/2 mutation carriers due to compromised DNA quality control. We hypothesized that if immunosurveillance promotes tumor suppression, then normal/benign breast lobules from BRCA carriers may demonstrate higher immune cell densities. METHODS: We assessed immune cell composition in normal/benign breast lobules from age-matched women with progressively increased breast cancer risk, including (1) low risk: 19 women who donated normal breast tissue to the Komen Tissue Bank (KTB) at Indiana University Simon Cancer Center, (2) intermediate risk: 15 women with biopsy-identified benign breast disease (BBD), and (3) high risk: 19 prophylactic mastectomies from women with germline mutations in BRCA1/2 genes. We performed immunohistochemical stains and analysis to quantitate immune cell densities from digital images in up to 10 representative lobules per sample. Median cell counts per mm2 were compared between groups using Wilcoxon rank-sum tests. RESULTS: Normal/benign breast lobules from BRCA carriers had significantly higher densities of immune cells/mm2 compared to KTB normal donors (all p < 0.001): CD8 + 354.4 vs 150.9; CD4 + 116.3 vs 17.7; CD68 + 237.5 vs 57.8; and CD11c + (3.5% vs 0.4% pixels positive). BBD tissues differed from BRCA carriers only in CD8 + cells but had higher densities of CD4 + , CD11c + , and CD68 + immune cells compared to KTB donors. CONCLUSIONS: These preliminary analyses show that normal/benign breast lobules of BRCA mutation carriers contain increased immune cells compared with normal donor breast tissues, and BBD tissues appear overall more similar to BRCA carriers.

Low utilization of adult-to-adult LDLT in Western countries despite excellent outcomes: International multicenter analysis of the US, the UK, and Canada.

BACKGROUND & AIMS: Adult-to-adult living donor liver transplantation (LDLT) offers an opportunity to decrease the liver transplant waitlist and reduce waitlist mortality. We sought to compare donor and recipient characteristics and post-transplant outcomes after LDLT in the US, the UK, and Canada. METHODS: This is a retrospective multicenter cohort-study of adults (≥18-years) who underwent primary LDLT between Jan-2008 and Dec-2018 from three national liver transplantation registries: United Network for Organ Sharing (US), National Health Service Blood and Transplantation (UK), and the Canadian Organ Replacement Registry (Canada). Patients undergoing retransplantation or multi-organ transplantation were excluded. Post-transplant survival was evaluated using the Kaplan-Meier method, and multivariable adjustments were performed using Cox proportional-hazards models with mixed-effect modeling. RESULTS: A total of 2,954 living donor liver transplants were performed (US: n = 2,328; Canada: n = 529; UK: n = 97). Canada has maintained the highest proportion of LDLT utilization over time (proportion of LDLT in 2008 - US: 3.3%; Canada: 19.5%; UK: 1.7%; p <0.001 - in 2018 - US: 5.0%; Canada: 13.6%; UK: 0.4%; p <0.001). The 1-, 5-, and 10-year patient survival was 92.6%, 82.8%, and 70.0% in the US vs. 96.1%, 89.9%, and 82.2% in Canada vs. 91.4%, 85.4%, and 66.7% in the UK. After adjustment for characteristics of donors, recipients, transplant year, and treating transplant center as a random effect, all countries had a non-statistically significantly different mortality hazard post-LDLT (Ref US: Canada hazard ratio 0.53, 95% CI 0.28-1.01, p = 0.05; UK hazard ratio 1.09, 95% CI 0.59-2.02, p = 0.78). CONCLUSIONS: The use of LDLT has remained low in the US, the UK and Canada. Despite this, long-term survival is excellent. Continued efforts to increase LDLT utilization in these countries may be warranted due to the growing waitlist and differences in allocation that may disadvantage patients currently awaiting liver transplantation. LAY SUMMARY: This multicenter international comparative analysis of living donor liver transplantation in the United States, the United Kingdom, and Canada demonstrates that despite low use of the procedure, the long-term outcomes are excellent. In addition, the mortality risk is not statistically significantly different between the evaluated countries. However, the incidence and risk of retransplantation differs between the countries, being the highest in the United Kingdom and lowest in the United States.

Robotic Resection of Type I Hilar Cholangiocarcinoma with Intrapancreatic Bile Duct Dissection.

BACKGROUND: Type I hilar cholangiocarcinoma is a malignancy of the extrahepatic bile duct for which margin-negative resection with sufficient lymphadenectomy may provide curative treatment. The aim of this video is to highlight the advantages of optical magnification, articulating instruments, and indocyanine green fluorescent cholangiography to demonstrate extrahepatic bile duct resection from the biliary confluence to the intrapancreatic bile duct with comprehensive hilar lymphadenectomy for pathologic staging. METHODS: A 58-year-old male presented with obstructive jaundice and was found to have a biliary stricture arising from the cystic duct and bile duct junction. Endoscopic biopsy of the bile duct confirmed adenocarcinoma. His case was presented at a multidisciplinary tumor conference where consensus was to proceed with upfront robotic en bloc extrahepatic bile duct resection with hilar lymphadenectomy and Roux-en-Y hepaticojejunostomy. RESULTS: Final pathology demonstrated margin-negative resection of moderately differentiated adenocarcinoma, 1 out of 12 lymph nodes involved with disease, and pathologic stage T2N1M0 (stage IIIC). The patient had no postoperative complications and was discharged home on postoperative day 5. At 6 weeks from his operative date, he was initiated on four cycles of adjuvant gemcitabine/capecitabine, followed by 50 Gray external beam radiation therapy with capecitabine, then four cycles of gemcitabine/capecitabine, completed after 6 months of therapy. CONCLUSIONS: Robotic extrahepatic bile duct resection, hilar lymphadenectomy, and biliary enteric reconstruction is feasible and should be considered for selected cases of bile duct resection.

Robotic Isolated Caudate Lobectomy for Solitary Colorectal Liver Metastasis.

BACKGROUND: Safety of liver resection for colorectal adenocarcinoma continues to improve due to decreased morbidity of resection. Minimally invasive techniques contribute greatly to this morbidity reduction. Isolated caudate lobectomy presents a unique technical challenge because of proximity to major vasculature. The video aims to review nuances of robotic isolated caudate lobectomy for metastatic colon adenocarcinoma.

Cellular Immunoprofile of Peritoneal Environment During a HIPEC Procedure.

BACKGROUND: We characterized the peritoneal immune cellular profile during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in this pilot study. METHODS: We prospectively performed flow cytometric analysis of peritoneal fluid collected at laparotomy and during HIPEC at 0, 30, 60, and 90 min. Analysis consisted of standard flow cytometric leukocyte gating and the use of antibodies for stem cells, B lymphocytes, T-helper, T-suppressor, and natural killer (NK) cells. RESULTS: The mean peritoneal carcinomatosis index (PCI) score was 19.8 ± 11.5 (median 19). Twelve patients had a completeness of cytoreduction (CCR) score of 0-1, and three patients had a CCR score of ≥ 2 (20%). The proportion of peritoneal NK cells remained stable (p = 0.655) throughout perfusion. The CD4/CD8 ratio (p = 0.019) and granulocyte/lymphocyte ratio (p = 0.018) evolved during cytoreduction, with no further change during HIPEC. Two distinct temporal patterns of peritoneal T lymphocytes became evident (the 'high' and 'low' CD4/CD8 ratio groups) and patients maintained their high versus low peritoneal CD4/CD8 ratio status throughout the duration of HIPEC. High CD4/CD8 was associated with longer cytoreduction (p = 0.019) and borderline higher PCI score (p = 0.058). No association was identified with age (p = 0.131), sex (p = 1.000), CCR status (p = 0.580), occurrence of complication (p = 0.282), or ascites volume (p = 0.713). CONCLUSION: The cellular immunoprofile of peritoneal fluid during HIPEC is stable but changes during cytoreduction. Two distinct immune groups emerged, based on CD4/CD8 ratios in the peritoneal perfusate. Further studies are warranted to evaluate peritoneal immunity and the clinical significance of novel peritoneal immune phenotype.

Minimally invasive hepatectomy is associated with decreased morbidity and resource utilization in the elderly.

BACKGROUND: The aim of this study was to evaluate whether elderly patients undergoing elective hepatectomy experience increased morbidity/mortality and whether these outcomes could be mitigated by minimally invasive hepatectomy (MIH). METHODS: 15,612 patients from 2014 to 2017 were identified in the Hepatectomy Targeted Procedure Participant Use File of the American College of Surgeons National Surgical Quality Improvement Program. Multivariable logistic regression models were constructed to examine the effect of elderly status (age ≥ 75 years, N = 1769) on outcomes with a subgroup analysis of elderly only patients by open (OH) versus MIH (robotic, laparoscopic, and hybrid, N = 4044). Propensity score matching was conducted comparing the effect of MIH to OH in elderly patients to ensure that results are not the artifact of imbalance in baseline characteristics. RESULTS: Overall, elderly patients had increased risk for 30-day mortality, major morbidity, prolonged length of hospital stay, and discharge to destination other than home. In the elderly subgroup, MIH was associated with decreased major morbidity (OR 0.71, P = 0.031), invasive intervention (OR 0.61, P = 0.032), liver failure (OR 0.15, P = 0.011), bleeding (OR 0.46, P < 0.001), and prolonged length of stay (OR 0.46, P < 0.001). Propensity score-matched analyses successfully matched 4021 pairs of patients treated by MIH vs. OH, and logistic regression analyses on this matched sample found that MIH was associated with decreased major complications (OR 0.69, P = 0.023), liver failure (OR 0.14, P = 0.010), bile leak (OR 0.46, P = 0.009), bleeding requiring transfusion (OR 0.46, P < 0.001), prolonged length of stay (OR 0.46, P < 0.001), and discharge to destination other than home (OR 0.691, P = 0.035) compared to OH. CONCLUSION: MIH is associated with decreased risk of major morbidity, liver failure, bile leak, bleeding, prolonged length of stay, and discharge to destination other than home among elderly patients in this retrospective study. However, MIH in elderly patients does not protect against postoperative mortality.

Hyaline fibrous involution of breast lobules: a histologic finding associated with germline BRCA mutation.

We describe the histology and the frequency of a histologic entity that we term "hyaline fibrous involution", which is characterized by symmetric and regular deposition of basal lamina-like periacinar hyaline material in association with atrophic epithelium, in breast samples from patients with either benign breast disease or germline BRCA mutation. Women with germline BRCA mutation (n = 93) who underwent prophylactic mastectomy (BRCA group) were compared to an age-matched sample of women who underwent biopsy for benign breast disease (n = 93). Median age was 45 years (range, 25-72 years). A single H&E section of each subject's benign breast tissue was reviewed. The total number of terminal duct lobular units and the number of terminal duct lobular units with hyaline fibrous involution were recorded for each case. The presence of any hyaline fibrous involution lobules and the within-sample proportion of hyaline fibrous involution lobules relative to total lobules were compared between groups. Presence of any hyaline fibrous involution was significantly more frequent in the BRCA group compared to the benign breast disease group, 47% vs. 15% (p < 0.0001, adjusted for total lobules). In women with any hyaline fibrous involution lobules, these unusual lobules were similarly rare in both groups, with median proportion of hyaline fibrous involution-positive lobules relative to all lobules of 0.03 in BRCA specimens (n = 44) and 0.03 in the benign breast disease group (n = 14). Within the BRCA group, frequency of any hyaline fibrous involution present was significantly higher in the perimenopausal age group (45-55 years: 63%) compared to other age groups (<45 years, 44%; >55 years, 15%; p = 0.05 and p = 0.02, respectively). Increased presence of hyaline fibrous involution in the setting of BRCA mutation suggests that it may represent a pathologic entity, possibly reflecting abnormal involution or an abnormal response to DNA damage.

CD56+ immune cell infiltration and MICA are decreased in breast lobules with fibrocystic changes.

PURPOSE: While the role of natural killer (NK) cells in breast cancer therapy has been investigated, little information is known about NK cell function and presence in nonmalignant and premalignant breast tissue. Here, we investigate and quantify NK cell marker CD56 and activating ligand MICA in breast tissue with benign breast disease. METHODS: Serial tissue sections from 88 subjects, 44 with benign breast disease (BBD) who remained cancer-free, and 44 with BBD who later developed cancer, were stained with H&E, anti-MICA, and anti-CD56. Up to ten representative lobules were identified on each section. Using digital image analysis, MICA and CD56 densities were determined for each lobule, reported as percent of pixels in the lobule that registered as stained by each antibody. Analyses were performed on a per-subject and per-lobule basis. RESULTS: Per-subject multivariate analyses showed associations of CD56 and MICA with age: CD56 was increased in older subjects (p = 0.03), while MICA was increased in younger subjects (p = 0.005). Per-lobule analyses showed that CD56 and MICA levels were both decreased in lobules with fibrocystic change, with median levels of CD56 and MICA staining, respectively, at 0.31 and 7.0% in fibrocystic lobules compared to 0.76 and 12.2% in lobules without fibrocystic change (p < 0.001 for each). Among fibrocystic lobules, proliferative/atypical lobules showed significantly lower expression compared to nonproliferative lobules for MICA (p = 0.02) but not for CD56 (p = 0.80). CONCLUSION: Levels of CD56+ NK cells and activating ligand MICA were decreased in breast lobules with fibrocystic change, and MICA levels showed a significant stepwise decrease with increasing histopathologic abnormality. MICA levels were also significantly decreased in older subjects, who generally have higher risk of developing cancer. These findings advance a model in which MICA promotes cytotoxic activity in CD56+ NK cells to protect against tumorigenesis in breast lobules, and suggest further research is warranted.

Multivariate model to identify women at low risk of cancer upgrade after a core needle biopsy diagnosis of atypical ductal hyperplasia.

PURPOSE: Atypical ductal hyperplasia (ADH) identified on percutaneous breast biopsy represents a high-risk lesion, upgrading to cancer with surgical excision in ~7-45.8% of cases. Routine excision is questioned due to potential overtreatment and cost. This study evaluates clinical, imaging, and histologic features to predict the risk of upgrade. METHODS: With IRB approval, a single-institution retrospective review was performed of patients who underwent surgical excision of ADH diagnosed by core biopsy from June 2005 to June 2013. We reviewed electronic medical records, breast imaging, and biopsy slides. Multiple imputation was used for missing data. Association of various features with cancer upgrade was assessed using logistic regression. RESULTS: Among 399 cases, the upgrade rate to cancer was 16.0%, (95% CI: 12.8-20.0%), with nine invasive cancers and 55 ductal carcinoma in situ (DCIS) only. Via a logistic regression approach, we defined a subgroup with low risk for upgrade: women whose biopsies showed no individual cell necrosis, and either a) 1 focus of ADH with ≥50% removal, or b) 2-3 foci with ≥90% removal. Cases meeting these criteria had an upgrade rate of 4.9% (95% CI: 1.0-8.9%), compared to 21.4% (16.4-26.3%) in cases that did not meet this low-risk definition. CONCLUSIONS: ADH on core biopsy with low risk of upgrade to cancer is defined by lack of individual cell necrosis, number of foci of ADH, and percent of imaging lesion removed. If these findings are validated, women whose biopsies meet low-risk criteria might be considered for prevention therapy and surveillance without surgical excision.

Securing a Chest Tube Properly: A Simple Framework for Teaching Emergency Medicine Residents and Assessing Their Technical Abilities.

BACKGROUND: Quality-improvement efforts at our institution have identified chest tube dislodgement as a preventable complication of tube thoracostomy. Because proper fixation techniques are not well described in the literature and are seldom formally taught, techniques vary among residents. OBJECTIVE: Our aim was to develop and test a framework for teaching and assessing chest tube securement. METHODS: A repeated-measures study design was used. At baseline, 19 emergency medicine residents (program years 1-3) placed and secured a chest tube in a cadaver. After a 45-min proficiency-based teaching session using a low-cost chest tube simulator (approximate cost, $5), each resident again placed and secured a chest tube in a cadaver, followed by 3-month retention testing. All securements were evaluated by two raters using a four-point checklist and a five-point global assessment scale (GAS). The checklist addressed suture selection, tying knots down to the tube, wound approximation, and tube displacement relative to skin. RESULTS: After the initial educational intervention, median scores for the group improved significantly over baseline for the GAS (p < 0.001), checklist (p < 0.001), and amount of displacement (p = 0.01). At 3 months, GAS, checklist, and displacement scores did not differ significantly from the immediate post-test scores. Inter-rater reliability was substantial, with weighted κ values of .77 for the GAS and .70 for the checklist. CONCLUSIONS: Quality of chest tube securement by emergency medicine residents can be significantly improved with an inexpensive chest tube simulator and a brief workshop. The four-point checklist served as a reliable and effective means for teaching and assessing chest tube securement.

Tube Thoracostomy: A Structured Review of Case Reports and a Standardized Format for Reporting Complications.

INTRODUCTION: Although seemingly straightforward, tube thoracostomy (TT) has been associated with complication rates as high as 30 %. A lack of a standardized nomenclature for reporting TT complications makes comparison and evaluation of reports impossible. We aim to develop a classification method in order to standardize the reporting of complications of TT and identify all reported complications of TT and time course in which they occurred to validate the reporting method. METHODS: A systematic search of MEDLINE, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews from each databases inception through November 5, 2013 was conducted. Original articles written in the English language reporting TT complications were searched. This review adhered to preferred reporting items for systematic reviews and meta-analyses (PRISMA) standards. Duplicate reviewers abstracted case reports for inclusion. Cases were then sorted into one of the five complication categories by two reviewers, and in case of disagreements, settled by a third reviewer. RESULTS: Of 751 papers reporting TT complications, 124 case reports were included for analysis. From these reports, five main categories of TT complications were identified: insertional (n = 65); positional (n = 36); removal (n = 11); infective and immunologic (n = 7); and instructional, educational, or equipment related (n = 5). Placement of TT has occurred in nearly every soft tissue and vascular structure in the thoracic cavity and intra-abdominal organs. CONCLUSION: Our classification method provides further clarity and systematic standardization for reporting TT complications.

Immune cell quantitation in normal breast tissue lobules with and without lobulitis.

While the immune microenvironment has been investigated in breast cancers, little is known about its role in non-malignant breast tissues. Here we quantify and localize cellular immune components in normal breast tissue lobules, with and without visible immune infiltrates (lobulitis). Up to ten representative lobules each in eleven normal breast tissue samples were assessed for B cells (CD20), cytotoxic T cells (CD8), helper T cells (CD4), dendritic cells (CD11c), leukocytes (CD45), and monocytes/macrophages (CD68). Using digital image analysis, immune cell densities were measured and compared between lobules with/without lobulitis. 109 lobules in 11 normal breast tissue samples were evaluated; 31 with lobulitis and 78 without. Immune cells showed consistent patterns in all normal samples, predominantly localized to lobules rather than stroma. Regardless of lobulitis status, most lobules demonstrated CD8+, CD11c+, CD45+, and CD68+ cells, with lower densities of CD4+ and CD20+ cells. Both CD11c+ and CD8+ cells were consistently and intimately associated with the basal aspect of lobule epithelium. Significantly higher densities of CD4+, CD8+, CD20+, and CD45+ cells were observed in lobules with lobulitis. In contrast, densities of monocytes/macrophages and dendritic cells did not vary with lobulitis. In normal breast tissue, myeloid and lymphoid cells are present and localized to lobules, with cytotoxic T and dendritic cells directly integrated with epithelium. Lobules with lobulitis have significantly more adaptive immune (B and T) cells, but no increase in dendritic cells or monocytes/macrophages. These findings indicate an active and dynamic mucosal immune system in normal breast tissue.

Randomized trial of drain antisepsis after mastectomy and immediate prosthetic breast reconstruction.

BACKGROUND: In this 2-site randomized trial, we investigated the effect of antiseptic drain care on bacterial colonization of surgical drains and infection after immediate prosthetic breast reconstruction. METHODS: With IRB approval, we randomized patients undergoing bilateral mastectomy and reconstruction to drain antisepsis (treatment) for one side, with standard drain care (control) for the other. Antisepsis care included both: chlorhexidine disc dressing at drain exit site(s) and irrigation of drain bulbs twice daily with dilute sodium hypochlorite solution. Cultures were obtained from bulb fluid at 1 week and at drain removal, and from the subcutaneous drain tubing at removal. Positive cultures were defined as ≥1+ growth for fluid and >50 CFU for tubing. RESULTS: Cultures of drain bulb fluid at 1 week (the primary endpoint) were positive in 9.9 % of treatment sides (10 of 101) versus 20.8 % (21 of 101) of control sides (p = 0.02). Drain tubing cultures were positive in 0 treated drains versus 6.2 % (6 of 97) of control drains (p = 0.03). Surgical site infection occurred within 30 days in 0 antisepsis sides versus 3.8 % (4 of 104) of control sides (p = 0.13), and within 1 year in three of 104 (2.9 %) of antisepsis sides versus 6 of 104 (5.8 %) of control sides (p = 0.45). Clinical infection occurred within 1 year in 9.7 % (6 of 62) of colonized sides (tubing or fluid) versus 1.5 % (2 of 136) of noncolonized sides (p = 0.03). CONCLUSIONS: Simple and inexpensive local antiseptic interventions with a chlorhexidine disc and hypochlorite solution reduce bacterial colonization of drains, and reduced drain colonization was associated with fewer infections.

Transcolonic peritoneoscopy by using submucosal endoscopy with mucosal flap for the detection of peritoneal bead targeting in the porcine survival model: a feasibility and effectiveness study.

BACKGROUND: Staging peritoneoscopy is typically done by laparoscopy in the operating room. Natural orifice transluminal endoscopic surgery peritoneoscopy is an appealing alternative to the current approach. Transcolonic submucosal endoscopy with mucosal flap (SEMF) may provide natural orifice transluminal endoscopic surgery peritoneoscopy. OBJECTIVE: The aim was to verify the feasibility and safety of transcolonic peritoneoscopy with SEMF (TCPS) in a porcine survival model. DESIGN: Survival study. SETTING: Animal research unit. INTERVENTION: Seven target beads were placed in the peritoneal cavity by laparoscopy in each of 6 animals, and TCPS was performed to identify and touch beads to simulate biopsy. Animals were euthanized after 1 week, at which time, laparotomy was performed and the SEMF site was resected for histological analysis. MAIN OUTCOME MEASUREMENTS: The number of beads identified and touched during peritoneoscopy, rate of successful completion of TCPS, procedure time, mortality equivalent 1 week after TCPS, adverse event rate, histological assessment of SEMF site. RESULTS: All 7 beads in all 6 pigs were identified and touched during TCPS. The success rate of TCP was 100%. No major adverse events occurred during the procedure. The median procedure times for the creation of a submucosal tunnel, peritoneoscopy, closure of mucosal incision, and entire procedure were 19.5, 17, 9.5, and 45 minutes, respectively. All pigs survived until euthanasia, and there was no evidence of peritonitis or severe infection. LIMITATIONS: Animal study, single endoscopist, small sample size. CONCLUSION: Results of this study indicate that TCPS is feasible and safe in a porcine survival model.

National practice patterns in preoperative and postoperative antibiotic prophylaxis in breast procedures requiring drains: survey of the American Society of Breast Surgeons.

BACKGROUND: To assess national practice patterns regarding use of perioperative antibiotics by surgeons performing breast operations requiring drainage tubes. METHODS: The members of the American Society of Breast Surgeons (ASBrS) were surveyed regarding use of perioperative antibiotics for breast operations requiring drains, with or without immediate tissue expander or implant reconstruction. RESULTS: Of 2,857 ASBrS members contacted, 917 (32 %) responded; all self-identified as surgeons. Of 905 evaluable respondents, most described themselves as general surgeons (46 %) or breast surgeons (46 %). For cases in which drains are anticipated, most respondents (86 %) reported routine use of preoperative prophylactic antibiotics, with 99 % selecting cephalosporins. Use of antibiotic >24 h postoperatively varied by whether or not reconstruction was performed. In nonreconstruction cases, the majority (76 %) reported "never/almost never" prescribing antibiotics beyond the 24-h postoperative period, but 16 % reported "always/almost always." In reconstruction cases, the majority (58 %) reported routine antibiotic use beyond 24 h, and the primary driver of the decision to use antibiotics was reported to be the plastic surgeon (83 %). Among those reporting use at >24 h, the duration recommended for nonreconstruction cases was "up to 1 week" in 38 % and "until drains removed" in 39 %; this was similar for reconstruction cases. CONCLUSIONS: Cephalosporins are utilized uniformly as preoperative antibiotic prophylaxis in breast operations requiring drains. However, use of postoperative antibiotic prophylaxis is strongly dependent on the presence of immediate breast reconstruction. Consensus is lacking on the role of postoperative antibiotic prophylaxis in breast operations utilizing drains.

Oncologic and surgical outcomes for gastric cancer patients undergoing gastrectomy differ by race in the United States.

INTRODUCTION: Gastric adenocarcinoma lymph node retrieval during gastrectomy and survival differ significantly between Asian and Western studies. It is unclear whether such disparities are the result of surgical technique, patient population, or other factors. In this observational study, we aimed to determine whether lymph node retrieval and outcomes differ between White, Black, and Asian American patients undergoing gastrectomy for adenocarcinoma. MATERIALS AND METHODS: 47,217 cases of gastric resection for gastric adenocarcinoma and its subtypes were identified in the National Cancer Data Base (2000-2015). Differences in demographics, lymph node retrieval, operative outcomes, and survival were compared by self-reported race (White, Black, and Asian). RESULTS: Asians had greater median lymph node retrieval (17) compared to White (15) and Black (16) patients, P < 0.001. Lymph node ratio was lowest in Asian (0.03) compared to White (0.05) and Black (0.09) patients, P < 0.001. Postoperative mortality was lowest in Asian patients on multivariable analysis (90-day mortality adjusted odds ratio of 0.54, P < 0.001). Median survival was not yet reached for Asian patients but was 39.5 months for White and 43.0 months for Black patients (P < 0.001). Differences in survival by race persisted on multivariable analysis (Asian adjusted hazard ratio was 0.64, 95% CI: 0.59-0.70, P < 0.001). CONCLUSIONS: Asian-American patients with gastric cancer undergoing gastrectomy have greater lymph node retrieval, decreased lymph node ratio, decreased postoperative mortality, and increased long-term survival compared to White or Black Americans. Data suggest factors other than surgical technique and oncologic care may be responsible for gastric adenocarcinoma outcome differences seen between Asian and Western studies.

Randomized Trial of Perioperative Probiotics Among Patients Undergoing Major Abdominal Operation.

BACKGROUND: We investigated the utility and safety of short-course oral probiotics among patients undergoing major abdominal operations. Perioperative probiotics can decrease length of stay and lower rates of infectious complications. We assessed whether perioperative probiotics decrease major complications among patients undergoing high-risk gastrointestinal operations in a pragmatic randomized trial. STUDY DESIGN: This double-blind trial randomized 135 patients undergoing elective major gastrointestinal operations to perioperative oral probiotic VSL#3 taken just before operation and twice daily up to 15 total doses (n = 67) or placebo (n = 68). The primary outcomes measure was 30-day composite end point of death, unplanned readmission, or any infection. RESULTS: Primary end point occurred among 17 patients in the placebo group (25.0%) vs 22 patients in the probiotic group (32.8%; p = 0.315). Thirty-day mortality was 2 (2.9%) in the placebo group compared with 1 (1.5%) in the probiotic group (p = 1.000). The placebo group patients experienced lower 30-day readmission rate (3 of 68 [4.4%]) compared with the probiotic group (11 of 67 [16.4%]; p = 0.022). None of the placebo patients were readmitted for dehydration, but 5 of 11 probiotic group patients (45%; p = 0.049) were readmitted for dehydration as a consequence of diet intolerance and/or diarrhea. There was no difference in 30-day infection rate between the groups (15 or 68 [22%] in the placebo group vs 15 of 67 [22.4%] in the probiotic group; p = 0.963). CONCLUSIONS: Perioperative use of VSL#3 probiotic did not affect 30-day composite end point of mortality, readmission, and infection rate. A significantly higher readmission rate was observed among those exposed to probiotics. Additional studies remain warranted.

Macrophagic "Crown-like Structures" Are Associated with an Increased Risk of Breast Cancer in Benign Breast Disease.

In breast adipose tissue, macrophages that encircle damaged adipocytes form "crown-like structures of breast" (CLS-B). Although CLS-B have been associated with breast cancer, their role in benign breast disease (BBD) and early carcinogenesis is not understood. We evaluated breast biopsies from three age-matched groups (n = 86 each, mean age 55 years), including normal tissue donors of the Susan G. Komen for the Cure Tissue Bank (KTB), and subjects in the Mayo Clinic Benign Breast Disease Cohort who developed cancer (BBD cases) or did not develop cancer (BBD controls, median follow-up 14 years). Biopsies were classified into histologic categories, and CD68-immunostained tissue sections were evaluated for the frequency and density of CLS-B. Our data demonstrate that CLS-B are associated with BBD: CLS-B-positive samples were significantly less frequent among KTB biopsies (3/86, 3.5%) than BBD controls (16/86 = 18.6%, P = 0.01) and BBD cases (21/86 = 24%, P = 0.002). CLS-B were strongly associated with body mass index (BMI); BMI < 25: 7% CLS-B positive, BMI 25-29: 13%, and BMI ≥ 30: 29% (P = 0.0005). Among BBD biopsies, a high CLS-B count [>5 CLS-B/sample: 10.5% (BBD cases) vs 4.7% (BBD controls), P = 0.007] conferred a breast cancer OR of 6.8 (95% CI, 1.4-32.4), P = 0.02, after adjusting for adipose tissue area (cm2), histologic impression, and BMI. As high CLS-B densities are independently associated with an increased breast cancer risk, they may be a promising histologic marker of breast cancer risk in BBD. Cancer Prev Res; 11(2); 113-9. ©2017 AACR.

Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development.

Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD).Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm2 for CD4+ T cells, CD8+ T cells, CD20+ B cells, and CD68+ macrophages and quantification of positive pixel measure for CD11c (dendritic cells).Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8+ T cells, CD11c+ dendritic cells, CD20+ B cells, and CD68+ macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20+ cell density (P = 0.04). Nearly 42% of BBD cases had no CD20+ B cells in evaluated lobules compared with 28% of BBD controls (P = 0.02). The absence of CD20+ cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk.Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945-52. ©2017 AACR.

Assimilating endocrine anatomy through simulation: a pre-emptive strike!

BACKGROUND: We sought to determine if endocrine anatomy could be learned with the aid of a hands-on, low-cost, low-fidelity surgical simulation curriculum and pre-emptive 60-second YouTube video clip. METHODS: A 3-hour endocrine surgery simulation session was held on back-to-back Fridays. A video clip was made available to the 2nd group of learners. A comprehensive 40-point test was administered before (pre-test) and after (post-test) the sessions. RESULTS: General surgery interns (n = 26) participated. The video was viewed 19 times by 80% (12 of 15) of interns with access. Viewers outperformed nonviewers on subsequent post-testing (mean [SD], 29.7 [1.3] vs 24.4 [1.6]; P = .015). Mean scores on the anatomy section of the post-test were higher among viewers than nonviewers (mean [SD] 14.2 [.9] vs 10.3 [1.0]; P = .012). CONCLUSIONS: Low-cost simulation models can be used to teach endocrine anatomy. Pre-emptive viewing of a 60-second video may have been a key factor resulting in higher post-test scores compared with controls, suggesting that the video intervention improved the educational effectiveness of the session.