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1.
Ann Surg ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38939968

RESUMEN

OBJECTIVE: To investigate the association between workload and pregnancy outcomes among US surgical faculty and trainees. SUMMARY BACKGROUND DATA: Despite the increased risk of pregnancy associated complications among surgeons, most US institutions do not have formalized support to help sustain a healthy pregnancy in surgeons. METHODS: An anonymous self-administered Qualtrics survey was distributed electronically to US surgeons across all surgical specialties. Female surgical trainees/faculty with current or previous pregnancy were invited to participate. Data pertaining to demographics, workload, and pregnancy outcomes were collected for each individual pregnancy resulting in live birth. Multivariate analysis was used to assess for workload and outcomes, controlling for age, race, gravidity, and use of assisted reproductive technology. A significance level of 0.0056 was used for each outcome (Bonferroni multiple-testing adjustment 0.05/9). RESULTS: 817 surgeons experiencing 1348 pregnancies resulting in live birth were included. The mean (SD) age at first live birth was 32(4). The most prevalent major and neonatal complications included preeclampsia/gestational hypertension (n=196, 14.5%) and preterm delivery (n=179, 12.8%), respectively. Most institutions did not have a policy regarding workload modification (n=1189, 88.5%). Most surgeons did not modify their workload (n=862, 63.9%). When looking at individual workload metrics, feeling overworked during the last week of pregnancy correlated with risk of major complication (P=0.0001), preeclampsia/gestational hypertension (P=0.0003), and intra/post-partum complication (P=0.0001). Association with unplanned cesarean section (P=0.0096) and preterm delivery (P=0.0036) reached nominal significance. CONCLUSIONS: Most surgeons do not modify their workload during pregnancy, potentially contributing to feeling overworked and peri-partum complications. There is an urgent need for a cultural shift and institutional policies to safeguard the health and wellbeing of pregnant surgeons.

2.
Am Surg ; 90(6): 1800-1802, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38565170

RESUMEN

Laparoscopic subtotal cholecystectomy (LSC) is utilized to prevent complications in the difficult cholecystectomy. Medium-term outcomes are poorly studied for fenestrating and reconstituting operative techniques. A single-institution retrospective review was undertaken of all LSCs. A telephone survey was used to identify complications addressed at other institutions. We performed subgroup analyses by operative approach and of patients requiring postoperative endoscopic intervention (ERC). 28 patients met inclusion criteria. The median follow-up was 32.7 months. There were no bile duct injuries or reoperations. 21% of patients required a postoperative ERC and 50% were discharged home with a drain. Bile leaks were found to be more prevalent in the fenestrating LSC group (38% vs 0%, P = .003). The case series suggested more severe recurrent biliary disease in patients undergoing reconstituting LSC. Laparoscopic subtotal cholecystectomy appears to have satisfactory medium-term outcomes. The reconstituting LSC group trends toward more severe recurrent disease which warrants further investigation.


Asunto(s)
Colecistectomía Laparoscópica , Alta del Paciente , Complicaciones Posoperatorias , Humanos , Colecistectomía Laparoscópica/métodos , Colecistectomía Laparoscópica/efectos adversos , Estudios Retrospectivos , Femenino , Masculino , Estudios de Seguimiento , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Adulto , Resultado del Tratamiento , Anciano , Recurrencia , Reoperación/estadística & datos numéricos
3.
J Surg Res ; 295: 41-46, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37980827

RESUMEN

BACKGROUND: Interest in general surgery has steadily decreased among medical students due to negative perceptions of surgeons, a lack of meaningful clerkship involvement, and inadequate mentorship. We implemented a novel mentorship-based surgery clerkship (MBSC) in which each student was matched with a resident mentor with the goals of enhancing student learning experience, meaningfulness, and interest in surgery. We hypothesized that students participating in the MBSC would report increased confidence in surgical competencies, exposure to surgical faculty, and positive perception of surgery, with no detriment to clerkship grades. METHODS: Mentors were instructed to provide the following when asked by the student: (1) weekly feedback; (2) personalized goals; (3) daily cases; (4) specific videos; (5) presentation subjects; (6) operating room skills coaching. A 5-point Likert Scale survey was distributed to the students pre and post clerkship, and median differences in Likert Scale Score pre and post mentorship were compared between mentored and control groups using the unpaired Wilcoxon's test. This was a two-arm, nonrandomized trial comparing traditional curriculum with the mentored program. RESULTS: The total sample size was n = 84. When comparing mentored to control, Wilcoxon's analysis showed greater post clerkship increases in confidence in operating room etiquette (P = 0.03), participating in rounds (P = 0.02), and suturing (P < 0.01). There were greater increases in perceived surgeon compassion (P = 0.04), respectfulness (P < 0.01), and teaching ability (P < 0.01). Median scores for meaningfulness overall (P = 0.01) and as measured as a feeling of positively impacting a patient (P = 0.02) were also increased when comparing mentored to control. More students were encouraged by a surgeon to pursue surgery (P = 0.01) and consider a surgery career themselves (P = 0.02). CONCLUSIONS: An MBSC increases meaningfulness, confidence, skills, and exposure in various surgical competencies. Compared to nonmentored students, MBSC students have more positive perceptions of surgeons and are more likely to pursue surgery.


Asunto(s)
Prácticas Clínicas , Cirugía General , Estudiantes de Medicina , Cirujanos , Humanos , Cirugía General/educación , Mentores , Estudios Prospectivos
4.
Surg Endosc ; 37(8): 6445-6451, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37217683

RESUMEN

BACKGROUND: Revisional bariatric surgeries are increasing for weight recurrence and return of co-morbidities. Herein, we compare weight loss and clinical outcomes following primary Roux-en-Y Gastric Bypass (P-RYGB), adjustable gastric banding to RYGB (B-RYGB), and sleeve gastrectomy to RYGB (S-RYGB) to determine if primary versus secondary RYGB offer comparable benefits. METHODS: Participating institutions' EMRs and MBSAQIP databases were used to identify adult patients who underwent P-/B-/S-RYGB from 2013 to 2019 with a minimum one-year follow-up. Weight loss and clinical outcomes were assessed at 30 days, 1 year, and 5 years. Our multivariable model controlled for year, institution, patient and procedure characteristics, and excess body weight (EBW). RESULTS: 768 patients underwent RYGB: P-RYGB n = 581 [75.7%]; B-RYGB n = 106 [13.7%]; S-RYGB n = 81 [10.5%]. The number of secondary RYGB procedures increased in recent years. The most common indications for B-RYGB and S-RYGB were weight recurrence/nonresponse (59.8%) and GERD (65.4%), respectively. Mean time from index operation to B-RYGB or S-RYGB was 8.9 and 3.9 years, respectively. After adjusting for EBW, 1 year %TWL (total weight loss) and %EWL (excess weight loss) were greater after P-RYGB (30.4%, 56.7%) versus B-RYGB (26.2%, 49.4%) or S-RYGB (15.6%, 37%). Overall comorbidity resolution was comparable. Secondary RYGB patients had a longer adjusted mean length of stay (OR 1.17, p = 0.071) and a higher risk of pre-discharge complications or 30-day reoperation. CONCLUSION: Primary RYGB offers superior short-term weight loss outcomes compared to secondary RYGB, with decreased risk of 30-day reoperation.


Asunto(s)
Derivación Gástrica , Laparoscopía , Obesidad Mórbida , Adulto , Humanos , Derivación Gástrica/métodos , Obesidad Mórbida/cirugía , Resultado del Tratamiento , Estudios Retrospectivos , Laparoscopía/métodos , Reoperación , Pérdida de Peso/fisiología , Aumento de Peso , Gastrectomía/métodos
5.
Am Surg ; 89(4): 871-874, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34645295

RESUMEN

Dr. Joseph Murray was a plastic surgeon who is best known for performing the first successful human organ transplant. After graduating from Harvard Medical School and completing a surgical internship at Peter Bent Brigham Hospital, Murray enlisted in the US Army Medical Corp and spent 5 years at Valley Forge General Hospital treating World War II soldiers injured in combat. He treated hundreds of burn victims with skin grafts and took an interest in the variable process of graft rejection based on both the patient's relation to the graft donor and the patient's level of immunocompetency. His work at Valley Forge set the stage for his research investigating the feasibility of kidney transplantation and immunosuppression. He went on to perform the first successful kidney transplant between identical twins in 1954, between fraternal twins in 1959, and between an unrelated donor and recipient in 1962. For his efforts, he was awarded the 1990 Nobel Prize in Medicine.


Asunto(s)
Trasplante de Riñón , Trasplante de Órganos , Cirujanos , Masculino , Humanos , Historia del Siglo XX , Terapia de Inmunosupresión , Trasplante de Piel
7.
Surg Endosc ; 37(5): 3974-3981, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36002686

RESUMEN

BACKGROUND: Marginal ulcer (MU) formation is a serious complication following Roux-en-Y Gastric Bypass (RYGB). Incidental data suggested a higher incidence of MU following conversion of Sleeve Gastrectomy to RYGB (S-RYGB). Herein, we evaluate the incidence of MU after primary versus secondary RYGB. METHODS: After IRB approval, each institution's electronic medical record and MBSAQIP database were queried to retrospectively identify adult patients who underwent primary RYGB (P-RYGB), Gastric Banding to RYGB (B-RYGB), or S-RYGB between 2014 and 2019, with minimum 1 year follow-up. Patient demographics, operative data, and post-operative outcomes were compared. Numeric variables were compared via two-sample t test, Wilcoxon test or Kruskal Wallis rank sum test. Two-sample proportion test or Fisher's exact test was employed for categorical and binary variables. p < 0.05 marked statistical significance. RESULTS: 748 patients underwent RYGB: P-RYGB n = 584 [78.1%]; B-RYGB n = 98 [13.1%]; S-RYGB n = 66 [8.8%]. Most patients were female (83.2%). Mean age was 45.7 years. Forty-six (n = 6.1%) patients developed MU, a median of 14 ± 32.2 months (range 0.5-82) post-operatively. Incidence of MU was significantly higher for patients undergoing S-RYGB (n = 9 [13.6%]), compared to P-RYGB (n = 34 [5.8%]) and B-RYGB (n = 3 [3.1%]) (p = 0.023). Median time (months) to MU was significantly shorter for patients who underwent S-RYGB (5 ± 6) compared to P-RYGB or B-RYGB (19 ± 37.5) (p = 0.035). Among those who developed MU, there was no significant difference in H. pylori status, NSAID, steroid, or tobacco use, irrespective of operation performed. CONCLUSION: In this multi-institutional cohort, patients who underwent S-RYGB had a significantly higher incidence of MU than those with P-RYGB or B-RYGB. Further research is needed to elucidate its pathophysiology and prevention strategies.


Asunto(s)
Derivación Gástrica , Obesidad Mórbida , Úlcera Péptica , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Derivación Gástrica/efectos adversos , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Estudios Retrospectivos , Incidencia , Gastrectomía/efectos adversos , Úlcera Péptica/epidemiología , Úlcera Péptica/etiología , Úlcera Péptica/cirugía
8.
Plast Reconstr Surg Glob Open ; 10(12): e4675, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36569246

RESUMEN

The field of plastic surgery, formally organized in 1931 with the founding of the American Society of Plastic and Reconstructive Surgery, was shaped in many ways by a small practice of Philadelphia physicians. At the center of the practice was Warren B. Davis, a Philadelphia otolaryngologist and plastics pioneer whose innovations in cleft palate surgery would lead to significant improvements in functional and cosmetic outcomes in his time. In addition to his own innovations, Davis was responsible for the training of John Reese, the inventor of the Reese dermatome that changed the face of burn medicine during World War II. Aside from his contributions to surgery and the founding of the American Society of Plastic and Reconstructive Surgery, Dr. Davis was also the founder and first editor of the Plastic and Reconstructive Surgery journal which to this day is the premiere, authoritative journal of plastic surgery. Lastly, Dr. Davis established a plastic surgical practice, now Jefferson Plastic Surgery. Unique in its longevity, this practice would continue to shape the field of plastic surgery and continues to improve lives today-109 years after its founding in 1913.

9.
J Surg Res ; 279: 97-103, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35753107

RESUMEN

INTRODUCTION: General Surgery residency programs remain competitive, with over a quarter of US MD seniors failing to match into a categorical program each year. While previous literature has shown the role of mentorship in attracting medical students to surgery, there is a dearth of information demonstrating the role of mentorship in successfully matching those students to surgery programs. METHODS: We implemented a structured mentorship program for medical students interested in applying to general surgery or integrated plastics, vascular, or cardiothoracic residencies over the course of one year, consisting of seven standardized meetings and events spanning the students' MS3 and MS4 years. Following Match Day, we sent students a five-point Likert scale survey to assess the perceived utility of each event and solicited self-reported application information. RESULTS: Of the 22 students at a single institution who attended the structured mentorship program and applied to general surgery residency, 100% matched into a categorical program, significantly higher than the 73% national match rate of US MD seniors into general surgery (P < 0.01). There were no significant differences between the two cohorts in terms of United States Medical Licensing Examination board scores, Alpha Omega Alpha Honor Society status, or median number of publications, research experiences, work experiences, or volunteer experiences. Nineteen of the 22 students responded to the survey, yielding an 86% response rate. Ninety percent of the students attended at least six out of the seven events. Six out of the seven events had median helpfulness scores (out of five) that were significantly higher than a "neutral" baseline (P < 0.05). CONCLUSIONS: A structured mentorship program may play a useful role in successfully matching general surgery applicants to residencies and would be a simple and low-cost program to implement at other medical schools.


Asunto(s)
Internado y Residencia , Estudiantes de Medicina , Selección de Profesión , Humanos , Mentores , Encuestas y Cuestionarios , Estados Unidos
10.
J Surg Res ; 278: 293-302, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35636205

RESUMEN

INTRODUCTION: Achieving satisfactory post-operative pain control for common elective general surgical procedures, while minimizing opioid utilization, remains challenging. Utilizing pre-operative educational strategies, as well as multimodal analgesia, we sought to reduce the post-operative opioid use in elective general surgery cases. METHODS: Between November 2019 and July 2021, patients undergoing elective inguinal hernia repair or cholecystectomy were enrolled in the study. Patients were divided into three cohorts: Control, opioid sparing (OS), or zero-opioid (ZO). Control patients did not have any intervention; OS patients had an opioid reduction intervention protocol applied (patient education and perioperative multimodal analgesia) and were provided an opioid prescription at discharge; the ZO had the same protocol, however, patients were not provided opioid prescriptions at discharge. Two weeks after discharge, patients were interviewed to record opioid consumption, pain scores, and level of satisfaction since discharge. RESULTS: A total of 129 patients were recruited for the study. Eighty-eight patients underwent inguinal hernia repair and 41 patients underwent cholecystectomy. Median post-operative morphine equivalents consumed in the Control cohort (n = 58); 46 (37.5-75) were significantly reduced when the OS protocol was enacted (n = 42); 15 (11-22.5) and further reduced to zero for every patient in the ZO cohort (n = 29) (P = 0.0001). There were no differences in patient-reported average pain scores after discharge (P = 0.08) or satisfaction levels with experience (P = 0.8302). CONCLUSIONS: Our study demonstrates that patient education and preoperative interventions can result in zero opioids prescribed after common general surgery procedures with equivalent patient satisfaction and pain scores.


Asunto(s)
Analgésicos Opioides , Hernia Inguinal , Analgésicos Opioides/uso terapéutico , Hernia Inguinal/cirugía , Humanos , Pacientes Ambulatorios , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Pautas de la Práctica en Medicina , Estudios Prospectivos
12.
Am Surg ; 88(2): 321-324, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33381976

RESUMEN

Dr Nina Braunwald is celebrated for her work as the first female cardiothoracic surgeon and her key role in the design and implementation of the first prosthetic mitral valve. She began her residency at Bellevue Hospital in 1952, a time in the United States where the scope of women's work was limited. Once her training took her to the National Institutes of Health (NIH), her historic flexible leaflet valve was developed and Dr Braunwald paved an innovative step toward the advanced prostheses of today. Afterward, she was recognized by the American Board of Thoracic Surgery in 1963. Her extensive research and educational passion for cardiothoracic surgery led to numerous publications, a leadership role with the NIH, and associate professorship at University of California San Diego and Harvard; leaving behind a significant legacy to be memorialized in awards and fellowships to women in academic cardiac surgery. Her work inspired continued evolution of the prosthetic valve and countless women to pursue surgery as a career before passing away in 1992, leaving behind a new generation of women surgeons. Despite her successful career, she was never promoted to full professor by her academic institutions.


Asunto(s)
Prótesis Valvulares Cardíacas/historia , Válvula Mitral , Médicos Mujeres/historia , Cirugía Torácica/historia , Boston , California , Historia del Siglo XX , Humanos , National Institutes of Health (U.S.) , Diseño de Prótesis/historia , Estados Unidos
15.
Am Surg ; 87(9): 1525-1528, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33502229

RESUMEN

War has the unique ability to intensify obstacles that surgeons face daily in civilian hospitals. After a brief overview of the historical context of the first and second world wars, this article will focus on how those daily challenges, namely limited skill, bleeding, and infection, led to an era of surgical innovation and standardization of surgical education.


Asunto(s)
Difusión de Innovaciones , Cirugía General/historia , Medicina Militar/historia , Segunda Guerra Mundial , Primera Guerra Mundial , Historia del Siglo XX , Humanos
16.
J Am Coll Surg ; 232(1): 55-64, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33098966

RESUMEN

BACKGROUND: Early cholecystectomy (E-CCY; 8 weeks or less) after percutaneous cholecystostomy tube (PCT) placement has been associated with increased postoperative complications, but this finding has not been validated at a national level and PCT-related complications and interventions (PCT-RCIs) were not evaluated. STUDY DESIGN: Adults with PCT for acute cholecystitis subsequently undergoing CCY were identified within the Nationwide Readmission Database (2010-2015) and our institution (2017-2019). Adjusted relative risks (aRRs) of postoperative complications were estimated using Poisson regression comparing E-CCY with delayed cholecystectomy (D-CCY; more than 8 weeks) within the nationwide cohort. Institutional PCT-RCIs, operative data, and postoperative outcomes were compared between E-CCY and D-CCY using chi-square and Kruskal-Wallis tests. RESULTS: Of 6,145 patients from the Nationwide Readmission Database, 32.9% were D-CCY. Risk-adjusted analysis identified no differences between E-CCY and D-CCY in complications (aRR 0.98; 95% CI, 0.89 to 1.07), mortality (aRR 0.88; 95% CI, 0.43 to 1.81), or 30-day readmissions (aRR 1.04; 95% CI, 0.85 to 1.27). Risk-adjusted analyses assessing the association of time to interval cholecystectomy (IC) with morbidity indicated an increased risk of surgical complications in the first month after PCT placement (aRR 1.17; 95% CI, 1.08 to 1.33). In the institutional cohort (E-CCY, n = 23; D-CCY, n = 45), there were no statistically significant differences found in estimated blood loss, length of stay, and postoperative complications. There were increased PCT-RCIs in the D-CCY group (26.9% E-CCY vs 69% D-CCY; p < 0.01) based on our unadjusted analysis. CONCLUSIONS: Increased operative complications when IC is performed within 1 month of PCT placement and increased PCT-RCIs when IC is performed 8 weeks after PCT placement suggest that the most favorable timing for IC is between 4 and 8 weeks after PCT placement.


Asunto(s)
Colecistectomía/métodos , Colecistitis Aguda/cirugía , Colecistostomía/métodos , Anciano , Colecistectomía/efectos adversos , Colecistitis Aguda/terapia , Colecistostomía/instrumentación , Bases de Datos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
17.
Am Surg ; 85(12): 1311-1313, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31912779

RESUMEN

Dr. Orvar Swenson is best remembered for developing the Swenson pull-through, a technique he developed to treat Hirschsprung's disease. After graduating from Harvard Medical School and beginning his residency at Peter Bent Brigham Hospital, Dr. Swenson observed that patients with Hirschsprung's disease and toxic megacolon resumed normal bowel function after placement of transverse colostomies. His observation led to studying the patency of his patients' colons using barium enema contrast studies. At the collapsed portion of the colon, he performed rectal biopsies leading to the discovery that the cause of Hirschsprung's disease is that the collapsed portion of the colon lacks the Auerbach plexus. The Swenson pull-through removes this aganglionic portion of the colon and cures the patient. His career grew from there as he traveled to academic institutions teaching his technique. He is remembered fondly for his contributions to pediatric surgery through the restructuring of pediatric surgery departments, pediatric surgery research, and writing and editing multiple volumes of Pediatric Surgery, the standard textbook for pediatric surgeons. He died peacefully in 2012 at the age of 103 years.


Asunto(s)
Colectomía/historia , Colon/inervación , Enfermedad de Hirschsprung/historia , Niño , Colectomía/métodos , Enfermedad de Hirschsprung/cirugía , Historia del Siglo XX , Humanos , Plexo Mientérico , Especialidades Quirúrgicas/historia , Estados Unidos
18.
J Surg Oncol ; 115(4): 365-370, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28299807

RESUMEN

BACKGROUND: Patients and providers are increasingly interested in the utilization, safety, and efficacy of minimally invasive surgery (MIS). We reviewed 11 years of MIS resections (laparoscopic and robotic) for intra-abdominal malignancies. METHODS: Patients who underwent gastrectomy, distal pancreatectomy, hepatic resection, and colorectal resection between 2004 and 2014 were identified. Cases were categorized as open, laparoscopic, and robotic based on the initial operation approach. Diagnostic laparoscopies were excluded. RESULTS: Of the 10 039 patients who underwent the above procedures, between 2004 and 2014, 2832 (28%) were MIS. In 2004, 12% (100/826) of all resections were performed with MIS approaches, rising to 23% (192/821) of all resections by 2009 and 44% (484/1092) in 2014. The number of open resections has remained largely stable: 726 (88% of all resections) in 2004 and 608 (56% of all resections) in 2014. Initially, laparoscopy experienced incremental adoption. Robotic surgery was implemented in 2009 and is currently the dominant MIS approach, accounting for 76% (368/484) of all MIS resections in 2014. Overall mortality has remained less than 1%. CONCLUSIONS: While maintaining patient safety, utilization of MIS techniques has increased substantially since 2004, particularly for gastric and colorectal resections. Since 2009 robotic surgery is the predominant MIS approach.


Asunto(s)
Neoplasias del Sistema Digestivo/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía/tendencias , Procedimientos Quirúrgicos Robotizados/tendencias , Adenocarcinoma/cirugía , Anciano , Instituciones Oncológicas , Carcinoma Neuroendocrino/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Femenino , Humanos , Laparoscopía/estadística & datos numéricos , Masculino , Persona de Mediana Edad , New York , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Centros de Atención Terciaria
19.
Mol Cancer Res ; 13(3): 439-48, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25336517

RESUMEN

UNLABELLED: Mucin1 (MUC1) is overexpressed in pancreatic ductal adenocarcinoma (PDA) and is associated with tumor aggressiveness, suggesting that MUC1 is a promising therapeutic target for promoter-driven diphtheria toxin A (DTA). Endogenous MUC1 transcript levels were analyzed by quantitative PCR (qPCR) in multiple PDA cells (Capan1, HPAFII, Su.86.86, Capan2, Hs766T, MiaPaCa2, and Panc1). Expression levels were correlated with luciferase activity and cell death after transfection with MUC1 promoter-driven luciferase and DTA constructs. MUC1-positive (+) cells had significantly elevated MUC1 mRNA expression compared with MUC1-negative (-) cells. Luciferase activity was significantly higher in MUC1(+) cells when transfected with MUC1 promoter-driven luciferase and MUC1(+) cells underwent enhanced cell death after transfection with a single dose of MUC1 promoter-driven DTA. IFNγ pretreatment enhanced MUC1 expression in MUC1(-) cells and induced sensitivity to MUC1-DTA therapy. Matched primary and metastatic tumor lesions from clinical specimens revealed similar MUC1 IHC labeling patterns, and a tissue microarray of human PDA biopsies revealed increased immunolabeling with a combination of MUC1 and mesothelin (MSLN) antibodies, compared with either antibody alone. Combining MUC1 with MSLN-targeted DTA enhanced drug efficacy in an in vitro model of heterogeneous PDA. These data demonstrate that MUC1 promoter-driven DTA preferentially kills MUC1-expressing PDA cells and drugs that enhance MUC1 expression sensitize PDA cells with low MUC1 expression. IMPLICATIONS: MUC1 expression in primary and metastatic lesions provides a rationale for the development of a systemic MUC1 promoter-driven DTA therapy that may be further enhanced by combination with other promoter-driven DTA constructs.


Asunto(s)
Carcinoma Ductal Pancreático/terapia , Toxina Diftérica/farmacología , Terapia Molecular Dirigida/métodos , Mucina-1/genética , Neoplasias Pancreáticas/terapia , Fragmentos de Péptidos/farmacología , Regiones Promotoras Genéticas , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Muerte Celular , Línea Celular Tumoral , Toxina Diftérica/genética , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Regulación Neoplásica de la Expresión Génica , Vectores Genéticos/farmacología , Humanos , Interferón gamma/farmacología , Mesotelina , Mucina-1/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fragmentos de Péptidos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología
20.
J Gastrointest Surg ; 19(2): 217-25, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25316483

RESUMEN

BACKGROUND: While many patients experience prolonged survival after pancreatic resection for benign or malignant disease, the long-term risk of pancreatogenic diabetes mellitus (DM) remains poorly characterized. METHODS: One thousand one hundred seven patients underwent pancreatectomy at Thomas Jefferson University between 2006 and 2013. Attempts were made to contact all living patients by telephone and a DM-focused questionnaire was administered. RESULTS: Two hundred fifty-nine of 691 (37 %) surviving patients completed the survey, including 179 pancreaticoduodenectomies (PD), 78 distal pancreatectomies (DP), and 2 total pancreatectomies. In the PD group, 44 (25 %) patients reported having DM prior to resection. Of these, 5 (12 %) had improved glucose control after resection and 21 (48 %) reported escalated DM medication requirements post-resection. Of 135 PD patients without preoperative DM, 24 (18 %) had new-onset DM postoperatively. In the DP group, 23 patients (29 %) had DM preoperatively. None had improved glucose control after resection, while six (26 %) had worse control after resection. Seventeen of 55 DP patients (31 %) without preoperative DM developed new-onset DM postoperatively (p = 0.04 vs. PD). Preoperative HgbA1C >6.0 %, glucose >124 mg/dL, and insulin use >2 units per day were associated with an increased risk of new-onset postoperative DM. CONCLUSIONS: The development or worsening of DM after pancreatic resection is extremely common, with different types of resections conveying different risks for disease progression. DP places patients at a greater risk for the development of new-onset postoperative diabetes when compared to PD. In contrast, patients with preoperative diabetes are more likely to experience worsening of their disease after PD as compared to DP. Patients should be screened prospectively, particularly those at highest risk, and informed of and educated about the potential for post-resection DM.


Asunto(s)
Diabetes Mellitus/etiología , Pancreatectomía/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Diabetes Mellitus/sangre , Diabetes Mellitus/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Pancreatectomía/métodos , Enfermedades Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Periodo Posoperatorio , Índice de Severidad de la Enfermedad , Factores de Tiempo
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