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BackgroundObservational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer.MethodsWe used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype.ResultsOverall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant.ConclusionsHigher BMI is associated with adverse survival among the majority of women with ovarian cancer.

We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n=675) and controls (n=1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs-PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616-were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-alleleor=0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele=0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04-1.24) p=0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Purpose: Previous studies have examined the association between ABO blood group and ovarian cancer risk, with inconclusive results.Methods: In eight studies participating in the Ovarian Cancer Association Consortium, we determined ABO blood groups and diplotypes by genotyping 3 SNPs in the ABO locus. Odds ratios and 95 % confidence intervals were calculated in each study using logistic regression; individual study results were combined using random effects meta-analysis.Results: Compared to blood group O, the A blood group was associated with a modestly increased ovarian cancer risk: (OR: 1.09; 95 % CI: 1.01-1.18; p = 0.03). In diplotype analysis, the AO, but not the AA diplotype, was associated with increased risk (AO: OR: 1.11; 95 % CI: 1.01-1.22; p = 0.03; AA: OR: 1.03; 95 % CI: 0.87-1.21; p = 0.76). Neither AB nor the B blood groups were associated with risk. Results were similar across ovarian cancer histologic subtypes.Conclusion: Consistent with most previous reports, the A blood type was associated modestly with increased ovarian cancer risk in this large analysis of multiple studies of ovarian cancer. Future studies investigating potential biologic mechanisms are warranted. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) screening remains underutilized in the United States. We conducted a national survey of CRC screening education, prioritization, and self-perceived preparedness among resident physicians in Family Practice (FP), Internal Medicine (IM), and Obstetrics and Gynecology (OB/GYN) training programs.Methods: Directors/administrators from 1085 FP, IM, and OB/GYN training programs were contacted by e-mail with a request to forward an invitation to participate in our Web-based CRC screening education survey to all residents in their program. Willing residents submitted responses in anonymous fashion. Data were analyzed using chi2 tests and analysis of variance methods.Results: In total, 243 program directors/administrators forwarded our invitation, and 835 residents responded (384 FP, 266 IM, 177 OB/GYN, 8 undesignated specialty). Nearly all resident responders (89%) had received CRC screening education, but few content delivery methods were reported. Most felt at least somewhat comfortable or somewhat knowledgeable with respect to advising patients about CRC screening (90%), currently endorsed CRC screening guidelines (89%), and criteria used to identify familial CRC syndromes (50%). However, substantially fewer respondents reported feeling very comfortable or very knowledgeable in these areas (45%, 23%, and 5%, respectively). Program specialty, level of training, and gender were the strongest indicators of self-perceived preparedness.Conclusions: Although based on a relatively small sample of all FP, IM, and OB/GYN residents, these data suggest tangible opportunities to improve the CRC screening curriculum in primary care residency programs. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) screening in the United States is suboptimal. We conducted a national survey to learn about CRC screening perceptions and practices among trainees who perform CRC screening tests including those enrolled in Gastroenterology and Hepatology (GIH), General and Colorectal Surgery, and Diagnostic and Abdominal Radiology training programs.Methods: Program directors/administrators (PDs/PAs) from 642 programs were contacted by e-mail with an invitation to forward our survey to trainees in their programs. Participating trainees then completed an anonymous, Web-based questionnaire.Results: A total of 130/642 (20%) PDs/PAs forwarded our survey to their trainees, with responses received from 476 trainees (80 GIH, 261 surgery, 135 radiology). Colonoscopy was felt to be the best CRC screening test at reducing CRC mortality, with patient-related factors perceived as greater barriers than system-related factors. No single guideline was deemed very influential on CRC screening practices by most trainees. A total of 2 of 5 above-average risk patient profiles were not recognized by most trainees. Colonoscopy was selected as the preferred follow-up test for a positive CRC screening test by most trainees. However, 34% of respondents chose an option other than colonoscopy alone for follow-up of a positive fecal occult blood test.Conclusions: Based on data from this national survey of gastroenterology, surgery, and radiology trainees, opportunities exist for curricular changes that may help enhance current perceptions and practices of trainees who perform CRC screening tests. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that adequate dietary folate may attenuate the risk of breast cancer associated with intake of alcohol. However, patients with breast cancer have been commonly treated with antifolate chemotherapies. The present analysis was performed to test the hypothesis that high folate intake may diminish the effectiveness of chemotherapy and, therefore, adversely influence survival. Women at risk of postmenopausal breast cancer (n = 37,105) participated in the Iowa Women's Health Study. Total folate intake (diet + supplements) was estimated from a food frequency questionnaire administered at baseline in 1986 and categorized into tertiles. From all incident breast cancer cases ascertained in the cohort, we selected those with a diagnosis between 1986 and 1994, chemotherapy as first course of treatment, and adequate diet assessment. Mortality was determined through the State Health Registry of Iowa and the National Death Index. Cox regression was used to estimate survival while adjusting for important covariates. Through 14 yr of follow-up, 80 deaths occurred among the 177 breast cancer cases treated with chemotherapy. Among these patients, high folate intake was not associated with worse survival. After adjustment for age, extent of disease, total calories, alcohol, and estrogen receptor status, women with total folate intake in the highest tertile had a mortality risk ratio of 0.88 (95% confidence interval = 0.44-1.76) compared with cases in the lowest tertile of folate. These findings, although preliminary, afford some reassurance that folate supplementation is unlikely to have a significant adverse effect on survival after chemotherapy for breast cancer. [ABSTRACT FROM AUTHOR]

The Women's Health Alliance Intervention Study is a quasi-experimental intervention designed to test if county-based coalitions can increase breast and cervical cancer screening compliance among women aged 40 years and older living in rural communities. A number of interventions were designed and implemented by coalitions in four counties in north-central Wisconsin during a 2-year period. Four control counties in southwestern Wisconsin were identified for comparison. Judging from the results of this study, community-based intervention efforts can increase breast and cervical cancer screening compliance significantly among women living in rural communities. [ABSTRACT FROM AUTHOR]

Background: The nuclear factor-kappaB (NF-kappaB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of kappaB (IkappaB) prevent NF-kappaB activation by sequestering NF-kappaB proteins in the cytoplasm until IkappaB proteins are phosphorylated and degraded.Methods: We used a case-control study to evaluate the association between single nucleotide polymorphisms (SNPs) in NFKBIA and NFKBIB (the genes encoding IkappaBalpha and IkappaBbeta, respectively) and risk of epithelial ovarian cancer. We queried 19 tagSNPs and putative-functional SNPs among 930 epithelial ovarian cancer cases and 1,037 controls from two studies.Results: The minor allele for one synonymous SNP in NFKBIA, rs1957106, was associated with decreased risk (p = 0.03).Conclusion: Considering the number of single-SNP tests performed and null gene-level results, we conclude that NFKBIA and NFKBIB are not likely to harbor ovarian cancer risk alleles. Due to its biological significance in ovarian cancer, additional genes encoding NF-kappaB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association of cigarette smoking before first pregnancy with risk of postmenopausal breast cancer in a large population-based cohort. PATIENTS AND METHODS: The Iowa Women's Health Study is a prospective cohort study of 55- to 69-year-old women at baseline in 1986. In January 1986, a questionnaire was mailed to 99,826 postmenopausal women to Identify risk factors for cancer and other chronic diseases; 41,836 women responded (42.7% response rate). The primary analyses examined the associations among smoking, parity, age at first birth, and postmenopausal breast cancer. RESULTS: Of the 37,105 women in the cohort at risk, 7095 (19%) and 4186 (11%) initiated smoking before and after first pregnancy, respectively, and 2017 breast cancers were identified before December 31, 1999. Compared with parous women who never smoked, women who began smoking after their first full-term pregnancy were not at increased risk of postmenopausal breast cancer (multivariate-adjusted risk ratio, 1.03; 95% confidence interval, 0.88-1.21). However, women who began smoking before their first pregnancy had a slightly elevated risk of breast cancer (risk ratio, 1.21; 95% confidence Interval, 1.07-1.37). Results were not attenuated by adjustment for age at first pregnancy or number of live births. CONCLUSION: These data suggest that cigarette smoking is associated with a slightly greater risk of postmenopausal breast cancer for women who started smoking before their first full-term pregnancy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the seroprevalence of varicella antibody among recent Somali refugees living in Olmsted County, Minnesota, and to estimate the risk of varicella-zoster virus (VZV) infection in this group. SUBJECTS AND METHODS: We obtained blood samples from the study subjects, along with demographic information, immunization records, and vaccine-preventable disease history. Serum samples were tested using a whole-virus IgG VZV-specific commercial enzyme-linked immunosorbent assay kit. This study was completed in 1998. RESULTS: Overall, 200 Somali refugees, comprising 33 extended families, were interviewed, with 193 providing adequate blood samples. Thirty-five subjects (18%) were seronegative for varicelia. Males had a significantly higher seronegativity rate (25% [n = 23]) compared with females (12% [n = 12]; P = .02); however, this association disappeared after adjustment for age and varicella infection history. Five percent (5/92) of adults were seronegative compared with 30% (30/101) of all children (P < .001). Eight percent (5/61) of the adult females were seronegative, whereas none (0/31) of the adult males were seronegative. Conversely, 38% (23/60) of male children were seronegative compared with 17% (7/41) of female children (P < .001). CONCLUSION: These results demonstrate a high prevalence of varicella seronegativity among Somali refugees who have immigrated to an endemic area. We recommend instituting improved education regarding varicella among Somali communities and increasing vaccine uptake or routine testing for serum varicella antibody to prevent VZV-related morbidity and mortality, particularly in adolescents, adult refugees, and women of childbearing age. [ABSTRACT FROM AUTHOR]

Background: There has been a shift in the treatment of fistula-in-ano towards a focus on preservation of continence while simultaneously eradicating disease. Utilization of radially emitting diode laser catheters to ablate fistula tracks has been described since 2011 with heterogenous studies publishing success rates ranging from 20% to 89%., Objective: Present our experience managing solitary transsphincteric fistulas of cryptoglandular origin with radially emitting diode laser., Design: Prospective non-randomized single center trial with 12-month follow-up., Settings: Quaternary referral academic healthcare center., Patients: Forty-six adults with transsphincteric fistula-in-ano., Interventions: All underwent radially emitting diode laser closure of fistula-in-ano., Main Outcome Measures: Clinical healing and fistula recurrence., Results: Forty-six patients with a median age of 48 years (range, 26-85) underwent diode laser closure. Most were men (n = 28/60%). Twenty-four (52%) had previous fistula repairs with a median of 1.5 (range, 1-7) repairs per patient. All were followed for 12 months. Successful closure following one laser treatment occurred in 43%. Thirteen of 26 failures (50%) were able to undergo a delayed fistulotomy secondary to an anatomic change with the fistula becoming more superficial moving out of internal sphincter muscle following laser ablation, all of which healed. No patients experienced new or worsening (preexisting) fecal incontinence. Two (8%) continued treatment for abscesses / fistula branching. One (3%) experienced migration of the fistula from the base of the left labia to the introitus of the vagina and 1 experienced recurrence and worsening of their disease process with subsequent involvement of the coccyx (previous deep postanal space abscess)., Limitations: Limitations to our study include its non-randomized prospective nature, single center and surgeon experience, and small patient sample size., Conclusions: Radially emitting diode laser closure is a continence preserving option to consider when treating transsphincteric fistula-in-ano. When the procedure fails it does not fail poorly (open wounds, retracted flaps, incontinence, etc.), and can be repeated. Complications can include abscess formation and fistula migration to adjacent anatomic locations (vagina). Even if not successful, following treatment the fistula can anatomically migrate distally becoming more superficial and thus providing the opportunity to proceed with a delayed fistulotomy. See Video Abstract., (Copyright © The ASCRS 2024.)

Purpose: To characterize associations of microcalcifications (calcs) with benign breast disease lesion subtypes and assess whether tissue calcs affect risks of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC)., Methods: We analyzed detailed histopathologic data for 4,819 BBD biopsies from a single institution cohort (2002-2013) followed for DCIS or IBC for a median of 7.4 years for cases (N = 338) and 11.2 years for controls. Natural language processing was used to identify biopsies containing calcs based on pathology reports. Univariable and multivariable regression models were applied to assess associations with BBD lesion type and age-adjusted Cox proportional hazard regressions were performed to model risk of IBC or DCIS stratified by the presence or absence of calcs., Results: Calcs were identified in 2063 (42.8%) biopsies. Calcs were associated with older age at BBD diagnosis (56.2 versus 49.0 years; P < 0.001). Overall, the risk of developing IBC or DCIS did not differ significantly between patients with calcs (HR 1.13, 95% CI 0.90, 1.41) as compared to patients without calcs. Stratification by BBD severity or subtype, age at BBD biopsy, outcomes of IBC versus DCIS, and mammography technique (screen-film versus full-field digital mammography) did not significantly alter association between calcs and risk., Conclusion: Our analysis of calcs in BBD biopsies did not find a significant association between calcs and risk of breast cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Type II endoleaks (T2ELs) are the most common cause of reintervention after endovascular aneurysm repair (EVAR). Although most resolve spontaneously, the long-term implications of T2ELs remain elusive. We aim to evaluate the impact of persistent and late T2ELs on clinical outcomes after EVAR., Methods: This was a single-institution retrospective review of patients who underwent EVAR for degenerative infrarenal abdominal aortic aneurysm between January 2010 and June 2022 with no type I (T1EL) or III (T3EL) endoleak seen at EVAR completion. Patients were categorized based on T2EL status. Group 1 included patients with never detected or transient T2ELs (detected at EVAR completion but not after). Group 2 encompassed persistent T2ELs (seen at EVAR completion and again during follow-up) and late T2ELs (detected for the first time at any point during follow-up). Time-to-event analysis was conducted using a time-dependent approach to T2EL status. Primary outcomes included freedom from sac enlargement (SE), aneurysm-related reinterventions, and overall survival., Results: A total of 803 patients met inclusion criteria. Group 1 included 418 patients (52%), of which 85% had no T2ELs and 15% had transient T2ELs. Group 2 had 385 patients; 23% had persistent T2ELs, and 77% developed a new T2EL. Patients in group 1 had a higher prevalence of smoking (88% vs 83%; P < .001), chronic obstructive pulmonary disease (33% vs 25%; P = .008), chronic kidney disease (13% vs 8%; P = .021), and a higher mean Society for Vascular Surgery score (7 vs 6 points; P = .049). No differences were found in aneurysm diameter or morphology. Mean follow-up was 5 years for the entire cohort. In Group 2, 58 patients (15%) underwent T2EL treatment, most commonly transarterial embolization. At 10 years after EVAR, Group 2 was associated with lower freedom from SE (P < .001) and abdominal aortic aneurysm-related reinterventions (P < .001) and comparable overall survival (P = .42). More T1ELs were detected during follow-up in Group 2 (6 [1%] vs 20 [5%]; P = .004), with 15 (75%) of these detected at a median of 3 years after the T2EL. No difference between groups was observed in explant (0.7% vs 2.1%; P = .130) or aneurysm rupture (0.5% vs 1.3%; P = .269) rates., Conclusions: One-half of patients treated with infrarenal EVAR developed persistent/late T2ELs, which are associated with a higher risk of SE and reinterventions. No difference in overall survival or aneurysm rupture risk was seen at 10 years, based on T2EL status or T2EL intervention. A conservative approach to T2ELs may be appropriate for most patients with absent T1ELs or T3ELs., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Gastric polyposis is common in familial adenomatous polyposis. However, the incidence and risk factors for gastric cancer are unclear. We aimed to evaluate the incidence of gastric cancer and associated risk factors in a large familial adenomatous polyposis population., Methods: Retrospective review of patients with familial adenomatous polyposis undergoing upper endoscopy at Mayo Clinic from 1989 to 2023. Cumulative incidence of gastric cancer(95% confidence intervals) were calculated using Kaplan-Meier survival approaches. Associations of clinical characteristics with development of gastric cancer were examined using Cox proportional hazards regression., Results: 337 patients underwent 2,502 endoscopies with a median of 10.4 (IQR 3.9-17.2) years of endoscopic surveillance. At any time during surveillance, 294 (87%) patients had gastric polyps, 200 (59%), fundic gland polyps; 116 (34%), low-grade dysplasia; and 11 (3.3%), high-grade dysplasia. Amongst these, only 6 (2%) patients developed gastric cancer; 5 with high-grade dysplasia (3 (50%) on prior endoscopy, 2 (33%) at time of cancer diagnosis; and 1 (16%) had low-grade dysplasia on prior endoscopy. The 10-year cumulative incidence of gastric cancer is 0% with no polyps, 1% with polyps, 6% with low-grade dysplasia, 11% with polyps >2cm, and 20% with high-grade dysplasia. Both high-grade dysplasia and polyps >2cm had a strong association with the development of gastric cancer (p<0.001)., Conclusion: While the overall risk of gastric cancer in familial adenomatous polyposis is low, outcomes remain poor. Gastric cancer can be predicted by endoscopic findings and specific GC surveillance guidelines are imperative to improve detection rates and guide timely intervention., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Low-grade appendiceal mucinous neoplasms (LAMNs) can progress to pseudomyxoma peritonei (PMP). The incidence and risk factors for recurrence are unclear, and there is a lack of consensus on the need and duration of surveillance imaging., Methods: Patients at the Mayo Clinic in Rochester, Minnesota, with a histologic diagnosis of LAMNs confined to the appendix and limited involvement of the right lower quadrant from 1992 to 2023 were included. Associations between recurrence and risk factors were assessed using Kaplan-Meier curves and Cox proportional hazards regression., Results: A total of 125 patients with LAMNs underwent abdominal imaging surveillance for a median of 51.2 months (IQR, 26-92). Of note, 5 patients (4%) recurred, all of which were PMP. Overall, the 5- and 10-year cumulative recurrence incidence rates were 3% and 6%, respectively. The median time to recurrence was 24 months (IQR, 23-87). Only LAMNs limited to the right lower quadrant and LAMN tumor size of <2 cm were associated with recurrence (P < .05). The 5- and 10-year cumulative recurrence risks were 12% and 30%, respectively, for the 21 patients with either risk factor. Only 1% of patients without these 2 risk factors developed a recurrence at 10 years., Conclusion: The overall recurrence risk of LAMN after resection is low. Appendectomy is sufficient for LAMN. Select patients with acellular mucin confined to the right lower quadrant and a tumor size of <2 cm are at higher risk of recurrence. Thus, long-term surveillance is recommended for high-risk individuals. Conversely, LAMNs without risk factors can be safely observed expectantly., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC)., Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss., Results: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1., Conclusions: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation., (©2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: The aims of the Advocate-BREAST project are to study and improve the breast cancer (BC) patient experience through education and patient-centered research., Methods: In December 2021, an electronic REDCap survey was circulated to 6,918 BC survivors (stage 0-4) enrolled in the Mayo Clinic Breast Disease Registry. The questionnaire asked about satisfaction with BC care delivery, and education and support receive(d) regarding BC linked concerns. Patients also ranked Quality Improvement (QI) proposals., Results: The survey received 2,437 responses. 18% had Ductal Carcinoma in Situ, 81% had early breast cancer (EBC), i.e. stage 1-3, and 2% had metastatic breast cancer (MBC). Mean age was 64 (SD 11.8), and mean time since diagnosis was 93 months (SD 70.2). 69.3% of patients received all care at Mayo Clinic. The overall experience of care was good (> 90%). The main severe symptoms recalled in year 1 were alopecia, eyebrow/eyelash thinning, hot flashes, sexual dysfunction, and cognitive issues. The main concerns recalled were fear of BC recurrence/spread; loved ones coping; fear of dying, and emotional health. Patients were most dissatisfied with information regarding sexual dysfunction, eyebrow/eyelash thinning, peripheral neuropathy, and on side effects of immunotherapy/targeted therapies. Top ranking QI projects were: i) Lifetime access to concise educational resources; ii) Holistic support programs for MBC and iii) Wellness Programs for EBC and MBC., Conclusions: Patients with early and advanced BC desire psychological support, concise educational resources, and holistic care., Implications: Focused research and QI initiatives in these areas will improve the BC patient experience., (© 2024. The Author(s).)

Background: Ulcerative colitis, total colectomy and tofacitinib have all been associated with increased risk of venous thromboembolism., Objective: To determine if preoperative tofacitinib exposure increases venous thromboembolism or other postoperative complications among patients with ulcerative colitis undergoing subtotal colectomy, total colectomy or total proctocolectomy., Design: Retrospective, case-control study at a single institution., Settings: A tertiary referral center., Patients: Adult patients with ulcerative colitis undergoing subtotal colectomy, total colectomy or total proctocolectomy after 2018 who were taking tofacitinib within 30 days of surgery (n = 56) were compared to age and sex-matched patients with ulcerative colitis undergoing the same surgeries but who were not exposed to tofacitinib (n = 56)., Main Outcome Measure: The primary outcome was differences in the incidence of venous thromboembolism within 90 days of surgery based on tofacitinib exposure. Secondary outcomes were 90-day postoperative complications., Results: Groups were well matched for age (non-tofacitinib: mean 35.2 years [SD 12.0], tofacitinib: 35.9 [SD 12.1], p = 0.36) and sex (41% female in each group, p = 1.00). Medical characteristics were similar between groups except for biologic medication exposure 30 days before surgery (non-tofacitinib: 66%, tofacitinib: 36%, p = 0.004). Surgical characteristics did not differ between groups. Most patients were discharged on extended venous thromboembolism prophylaxis (non-tofacitinib: 80% and tofacitinib: 77%). Adjusted for biologic exposure, there were no statistically significant differences in venous thromboembolism (non-tofacitinib exposed: 14%, tofacitinib-exposed: 4%, p = 0.09) or other postoperative outcomes., Limitation: Retrospective, single institutional study., Conclusion: Among patients with ulcerative colitis undergoing total colectomy or proctocolectomy, exposure to tofacitinib was not associated with an increased risk of venous thromboembolism or other postoperative complications. See Video Abstract., Competing Interests: Financial Disclosures: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Colon and Rectal Surgeons.)

Introduction: Although Hispanic White (HW) females have a lower incidence of breast cancer than non-Hispanic White (NHW) females, breast cancer risk is unclear for HW females after benign breast disease (BBD)., Methods: We compared BBD characteristics and subsequent breast cancer risk among HW and NHW females in New Mexico using a population-based collection of benign breast biopsies (1996-2007). BBD was categorized as nonproliferative disease (NPD), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). Breast cancer risk was assessed as absolute risk (AR) using cumulative incidence and RR by comparing the number of breast cancer events in BBDs to non-BBD., Results: This study included 3,684 HW and 6,587 NHW females with BBD. HW females had similar proportions of NPD (58.6% vs. 54.3%), PDWA (21.4% vs. 23.5%), and AH (3.6% vs. 3.3%) as NHW females. Breast cancer risk among all females with BBD was higher than population-based expected rates (RR, 1.87) and was similar for HW and NHW subgroups (RR = 1.99 vs. 1.84). As expected, breast cancer risk increased with increasing BBD severity, both overall [RR, 1.81 (NPD), 1.85 (PDWA), and 3.10 (AH)] and in the HW and NHW subgroups. Adjusted AR of breast cancer at 5 years also increased with the severity of BBD (HW vs. NHW; NPD: 1.4% vs. 2.1%; PDWA: 1.5% vs. 2.7%; AH: 6% vs. 4.8%)., Conclusions: We found similar breast cancer RRs and ARs in HW and NHW. Risk counseling should ensure that HW females receive breast cancer clinical management warranted by their similar absolute risks., Impact: The present population-based provides evidence for the clinical management of HW females with BBD for the prevention of breast cancer., (©2024 American Association for Cancer Research.)

Background: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥80 years (P80+). Identifying and addressing unmet needs are critical., Aims: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80-)., Methods: In 12/2021, a REDCap survey was electronically circulated to 6918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care., Results: Overall, 2437 participants responded (35% response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80- ( p < 0.01). Notably, P80+ were significantly less satisfied with information about the short and long-term side effects of BC therapies and managing toxicities. P80+ were also less likely to have participated in a clinical trial ( p < 0.001) or to want to do so in the future ( p = 0.0001)., Conclusions: Although P80+ experienced less anxiety and symptom-related distress compared with P80-, they were significantly less satisfied with information regarding the side effects of BC therapies and their management. P80+ were significantly less likely to have participated in a clinical trial or be open to considering this option. Future studies should address educational needs pertaining to side effects and barriers to research participation in P80+.

Objective: To perform a retrospective, multicenter, external validation of the Cleveland Clinic malignancy probability prediction model for incidental pulmonary nodules., Patients and Methods: From July 1, 2022, to May 31, 2023, we identified 296 patients who underwent tissue acquisition at Mayo Clinic (MC) (n=198) and Loyola University Medical Center (n=98) with histopathology indicating malignant (n=195) or benign (n=101). Data was collected at initial radiographic identification (point 1) and at the time of intervention (point 2). Point 3 represented the most recent data. The areas under the receiver operating characteristics were calculated for each model per time point. Calibration was evaluated by comparing the predicted and observed rates of malignancy., Results: The areas under the receiver operating characteristics at time points 1, 2, and 3 for the MC model were 0.67 (95% CI, 0.61-0.74), 0.67 (95% CI, 0.58-0.77), and 0.70 (95% CI, 0.63-0.76), respectively. The Cleveland Clinic model (CCM) was 0.68 (95% CI, 0.61-0.74), 0.75 (95% CI, 0.65-0.84), and 0.72 (95% CI, 0.66-0.78), respectively. The mean ± SD estimated probability for malignant pulmonary nodules (PNs) at time points 1, 2, and 3 for the CCM was 64.2±25.9, 65.8±24.0, and 64.7±24.4, which resembled the overall proportion of malignant PNs (66%). The mean estimated probability of malignancy for the MC model at each time point was 38.3±27.4, 36.2±24.4, and 42.1±27.3, substantially lower than the observed proportion of malignancies., Conclusion: The CCM found discrimination similar to its internal validation and good calibration. The CCM can be used to augment clinical and shared decision-making when evaluating high-risk PNs., Competing Interests: Dr Reisenauer reports research grant from Intuitive, royalties from Imvana, lazarro, Mediview, consulting fees for active consulting from elucent and noah, honoraria for lectures from Astra Zenec, and participated on the Mauna Kea Advisory board. The other authors report no competing interests., (© 2024 The Authors.)

Purpose: The autosomal dominant cancer predisposition disorders hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are genetic conditions for which early identification and intervention have a positive effect on the individual and public health. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC and LS., Methods: Participants were recruited from three geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; Jacksonville, FL). Participants underwent Exome+ sequencing (Helix Inc, San Mateo, CA) and return of results for specific genetic findings: HBOC ( BRCA1 and BRCA1 ) and LS ( MLH1 , MSH2 , MSH6 , PMS2 , and EPCAM ). Chart review was performed to collect demographics and personal and family cancer history., Results: To date, 44,306 participants have enrolled in Tapestry. Annotation and interpretation of all variants in genes for HBOC and LS resulted in the identification of 550 carriers (prevalence, 1.24%), which included 387 with HBOC (27.2% BRCA1 , 42.8% BRCA2 ) and 163 with LS (12.3% MSH6 , 8.8% PMS2 , 4.5% MLH1 , 3.8% MSH2 , and 0.2% EPCAM ). More than half of these participants (52.1%) were newly diagnosed carriers with HBOC and LS. In all, 39.2% of HBOC/LS carriers did not satisfy National Comprehensive Cancer Network (NCCN) criteria for genetic evaluation. NCCN criteria were less commonly met in underrepresented minority populations versus self-reported White race (51.5% v 37.5%, P = .028)., Conclusion: Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have LS and HBOC cancer predisposition syndromes.

Background: Virtual surgical planning (VSP) for composite microvascular free flaps has become standard of care for oncologic head and neck reconstruction. Controversy remains as to the use of three-dimensional (3D)-printed patient-specific titanium implants (PSIs) versus hand-bent stock reconstruction plates. Proponents of PSIs cite improved surgical accuracy, reduced operative times, and improved clinical outcomes. Detractors purport increased cost associated with PSIs and presumed equivalent accuracy with less expensive stock plates., Purpose: The study purpose was to measure and compare the 3D-volumetric accuracy of PSI versus stock reconstruction plates among subjects undergoing VSP-guided mandibular fibular free flap reconstruction., Study Design, Setting, Sample: A retrospective cohort study of subjects undergoing VSP-guided fibular free flap reconstructions at Mayo Clinic between 2016 and 2023 was performed. Subjects were excluded for non-VSP guidance, midfacial reconstruction, nonfibular free flaps, and lack of requisite study variables., Predictor Variable: The primary predictor was the type of reconstruction plate utilized (PSI vs stock plate)., Main Outcome Variable: The main outcome was volumetric surgical accuracy of the final reconstruction compared to the preoperative surgical plan by root mean square error (RMSE) calculation. Lower RMSE values indicated a higher surgical accuracy., Covariates: Covariates included age, sex, race, smoking status, American Society of Anesthesiologists (ASA) Physical Status Classification System, Charlson Comorbidity Index, preoperative diagnosis, and number of fibular segments., Analyses: Differences in surgical accuracy were assessed between preoperative and postoperative segmented scans using volumetric overlays from which RMSE values were calculated. Univariate and multivariate modeling of plate type to RMSE calculation was performed. Statistical significance set to P < .05., Results: Total of 130 subjects were identified, 105 PSI and 25 stock plates. Calculated mean RMSE in millimeters (mm) for stock plates was 1.46 (standard deviation: 0.33) and 1.15 (standard deviation: 0.36) for PSIs. Univariate modeling demonstrated a statistically significant difference in RMSE of 0.31 (95% confidence interval: 0.16-0.47) (P < .001) equating to a 21.2% (P < .001) improved volumetric surgical accuracy for PSIs. The association of improved volumetric accuracy with PSIs has been maintained in all multivariate models controlling for confounding., Conclusion and Relevance: In modern era VSP-guided head and neck fibular free flap reconstruction, patient-specific 3D-printed titanium implants confer a statistically significant improvement in volumetric surgical accuracy over stock reconstruction plates., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10 -8 ) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10 -5 ). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to identify trends in hospital length of stay (HLOS) and intensive care unit length of stay (ICULOS), and the relationship with cerebrospinal fluid drainage (CSFD) protocols in patients undergoing fenestrated-branched endovascular aortic repair (FB-EVAR) of thoracoabdominal aortic aneurysms (TAAAs)., Methods: A retrospective review of patients who underwent elective FB-EVAR for extent I to IV TAAAs between 2008 and 2023 at a single aortic center of excellence was conducted. Patient demographics, cardiovascular comorbidities, surgical risk, technical details, CSFD strategy (prophylactic or therapeutic), procedural success, and perioperative outcomes were collected. Patients were divided into two groups based on CSFD protocol. Group 1 included patients treated before 2020 when prophylactic CSFD was performed widely, and Group 2 consisted of patients treated since 2020 with therapeutic CSFD. Primary end points were HLOS, ICULOS, major adverse events, and perioperative mortality., Results: FB-EVAR was performed in 702 patients; 412 underwent elective TAAA repair and were included in the analysis. Mean age was 73 ± 8 years and 68% were male. Patient-specific manufactured devices were used in 252 patients (61%), physician-modified endografts in 110 (27%), and 50 patients (12%) were treated with off-the-shelf devices. Demographics, aneurysm extent, major adverse events (including spinal cord ischemia [SCI]), and mortality were similar in both groups. A significant reduction in mean HLOS between the groups (9 ± 9 vs 6 ± 5 days; P = .02) coincided with decreased use of prophylactic CSFD (70% vs 1.2%; P < .001), with similar rates of SCI (7.6% vs 4.9%; P = .627) and ICULOS (3 ± 3 vs 2.5 ± 3; P = .19). Patients in the therapeutic drainage cohort (group 2) had a higher incidence of congestive heart failure (24% vs 11%; P = .003), hypercholesterolemia (91% vs 80%; P = .015), chronic obstructive pulmonary disease (55% vs 37%; P = .004), and peripheral artery disease (39% vs 19%; P < .001) compared with group 1, suggesting treatment of a more complex patient cohort. On adjusted multivariable analysis accounting for American Society of Anesthesiologists score, comorbidities, and device type, the difference in HLOS remained statistically significant (P = .01)., Conclusions: HLOS decreased over time in patients undergoing FB-EVAR for TAAA after transition from a prophylactic to a therapeutic CSFD protocol. This transition was the only modifiable, independent risk factor for a shorter HLOS, without an increase in SCI, albeit with similar ICULOS., Competing Interests: Disclosures B.C.M. receives consulting fees and research support from Cook Medical and W. L. Gore & Associates. He is an aortic advisor for Cook Medical, W. L. Gore & Associates, and Medtronic. All fees are paid to Mayo Clinic. G.S.O. receives consulting, speaking, and/or scientific advisory fees from Centerline Biomedical, Cook Medical, GE Healthcare, and W. L. Gore & Associates; receives research grant support from GE Healthcare and W. L. Gore & Associates paid to the University of Texas Health Science Center at Houston; and has a Global Principal Investigator agreement with Cook Medical. interest., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To develop and analyze a risk-adjusted cumulative sum (RA-CUSUM) chart as a potential method to monitor individual surgeon performance in robotic total mesorectal excision (TME) for rectal cancer., Summary Background Data: Currently, surgeons lack real-time tools to monitor and enhance their performance beyond residency completion. While national quality programs exist, granular, individual-level data is crucial for continuous improvement. Previous studies suggest CUSUM charts hold promise in identifying performance trends and outliers., Methods: This retrospective study analyzed data from 640 robotic TME cases performed by 12 surgeons at two institutions. RA-CUSUM charts were generated for three outcomes: complications, operative time, and length of stay., Results: The overall RA-CUSUM curves for operative time and complications showed an initial learning phase followed by a plateau or downward slope, indicating proficiency or improvement. However, individual surgeon curves revealed significant heterogeneity. Three surgeons consistently excelled in operative time, while five minimized complications most effectively. Potential quality improvement could be implemented to drive performance toward positive outliers. No differences were found in unadjusted outcomes, including conversion, number of lymph nodes harvested, and positive circumferential margins., Conclusions: The RA-CUSUM chart is a promising method for identifying individual surgeon performance in robotic TME. It could help surgeons, teams, and leaders identify improvement areas and benchmark themselves against positive outliers. Further studies are needed to explore the potential of RA-CUSUM for implementing interventions to improve surgical quality., Competing Interests: Conflicts of interest: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe long-term quality of life (QOL) and gastrointestinal (GI) symptoms in patients who underwent pancreatoduodenectomy for pancreatic cancer in the modern era., Background: As advances in pancreatic cancer management improve outcomes, it is essential to assess long-term patient-reported outcomes after surgery., Methods: Patients who underwent curative intent pancreatoduodenectomy for pancreatic cancer between January 2011 and June 2019 from a single center were identified. Patients alive ≥3 years after surgery were considered long-term survivors (LTS). LTS who were alive in June 2022 received a 55-question survey to assess their QOL (EORTC-QLQ-C30) and GI symptoms (EORTC-PAN26 and Problem Areas in Diabetes Questionnaire). Responses were compared against population norms. Clinicodemographic characteristics in LTS versus non-LTS and survey completion were compared., Results: Six hundred seventy-two patients underwent pancreatoduodenectomy for pancreatic cancer; 340 were LTS. One hundred thirty-seven patients of the 238 eligible to complete the survey responded (response rate: 58%). Compared to the US general population, LTS reported significantly higher QOL (75 vs 64; P <0.001), less nausea/vomiting, pain, dyspnea, insomnia, appetite loss, and constipation, but more diarrhea (all P <0.001). Most patients (n=136/137, 99%) reported experiencing postoperative GI symptoms related to pancreatic insufficiency (n=71/135, 53%), reflux (n=61/135, 45%), and delayed gastric emptying (n=31/136, 23%). Most patients (n=113/136, 83%) reported that digestive symptoms overall had little to no impact on QOL, and 91% (n=124/136) would undergo surgery again., Conclusions: Despite known long-term complications following pancreatoduodenectomy, cancer survivors appear to have excellent QOL. Specific long-term gastrointestinal symptoms data should be utilized for preoperative education and follow-up planning., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Multiple scores validate long-term type-2 diabetes mellitus (T2DM) remission after metabolic and bariatric surgery (MBS). However, studies comparing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have not adequately controlled for certain parameters, which may influence procedure selection., Methods: We conducted a multicenter retrospective review of patients with T2DM who underwent RYGB or SG between 2008 and 2017. Data on demographics, clinical, laboratory, and metabolic values were collected annually for up to 14 years. Each eligible RYGB patient was individually matched to an eligible SG patient based on diabetes severity, weight loss, and follow-up duration., Results: Among 1149 T2DM patients, 467 were eligible for matching. We found 97 matched pairs who underwent RYGB or SG. RYGB showed significantly higher T2DM remission rates (46.4%) compared to SG (33.0%) after matching. SG patients had higher insulin usage (35.1%) than RYGB patients (20.6%). RYGB patients also experienced greater decreases in HbA1c levels and diabetes medication usage than SG patients., Conclusions: RYGB demonstrates higher efficacy for T2DM remission compared to SG, regardless of baseline characteristics, T2DM severity, weight loss, and follow-up duration. Further studies are needed to understand the long-term metabolic effects of MBS and the underlying pathophysiology of T2DM remission after MBS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Pearl Ma is a consultant for Ethicon, Medtronic and Intuitive. Dr Andres Acosta reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study; holding stock in Gila Therapeutics and Phenomix Sciences; and serving as a consultant for Rhythm Pharmaceuticals, General Mills, and Amgen Pharmaceuticals outside the submitted work. Dr Barham Abu Dayyeh has received consulting fee from Endogenex, Endo-TAGSS, Metamodix, and BFKW; consulting fee and grant/research support from USGI, Cairn Diagnostics, Aspire Bariatrics, Boston Scientific; speaker honorarium from Olympus, Johnson and Johnson; speaker honorarium and grant/research support from Medtronic, Endogastric solutions; and research support/grant from Apollo Endosurgery, and Spatz Medical. Dr Kelvin Higa is a consultant for Medtronic and Ethicon. Dr Karl Hage, Dr Wissam Ghusn, Kayla Ikemiya, Robert A. Vierkant, and Dr Omar M. Ghanem declare no conflict of interest.