Academic Partnerships in Global Surgery: An Overview American Surgical Association Working Group on Academic Global Surgery.

: Most surgeons from high-income countries who work in global surgery will do so through partnerships between their institutions and institutions in low- and middle-income countries (LMICs). In this article, the American Surgical Association Working Group for Global Surgery lays out recommendations for criteria that contribute to equitable, sustainable, and effective partnerships. These include ethically engaging with the LMIC partner institution by putting its interests first and by proactively seeking to be aware of cultural issues. Formally structuring the partnership with a memorandum of understanding and clearly designating leaders at both institutions are important criteria for assuring long-term sustainability. Needs assessments can be done using existing methods, such as those established for development of national surgical, obstetric, and anesthesia plans. Such assessments help to identify opportunities for partnerships to be most effective in addressing the biggest surgical needs in the LMIC. Examples of successful high-income countries-LMIC partnerships are provided.

Global Surgery: Effective Involvement of US Academic Surgery: Report of the American Surgical Association Working Group on Global Surgery.

: There is an unacceptably high burden of death and disability from conditions that are treatable by surgery, worldwide and especially in low- and middle-income countries (LMICs). The major actions to improve this situation need to be taken by the surgical communities, institutions, and governments of the LMICs. The US surgical community, including the US academic surgical community, has, however, important roles to play in addressing this problem. The American Surgical Association convened a Working Group to address how US academic surgery can most effectively decrease the burden from surgically treatable conditions in LMICs. The Working Group believes that the task will be most successful (1) if the epidemiologic pattern in a given country is taken into account by focusing on those surgically treatable conditions with the highest burdens; (2) if emphasis is placed on those surgical services that are most cost-effective and most feasible to scale up; and (3) if efforts are harmonized with local priorities and with existing global initiatives, such as the World Health Assembly with its 2015 resolution on essential surgery. This consensus statement gives recommendations on how to achieve those goals through the tools of academic surgery: clinical care, training and capacity building, research, and advocacy. Through all of these, the ethical principles of maximally and transparently engaging with and deferring to the interests and needs of local surgeons and their patients are of paramount importance. Notable benefits accrue to US surgeons, trainees, and institutions that engage in global surgical activities.

Racial Disparity in Renal Transplantation: Alemtuzumab the Great Equalizer?

OBJECTIVES: Racial disparity as a barrier to successful outcomes in renal transplants for African Americans has been well described. Numerous unsuccessful attempts have been made to identify specific immunologic and socioeconomic factors. The objective of our study was to determine whether alemtuzumab (AL) induction abolishes this discrepancy and improves allograft survival in African American recipients. METHODS: A retrospective chart review of consecutive adult renal transplants was conducted between 2006 and 2014. Kaplan-Meier analysis and hazard ratios were calculated for the African Americans (AA) and white groups. Multiple linear regressions were performed to assess independent variables (race, retransplant, sex, donor type, induction agent) on allograft survival. RESULTS: A significant difference in allograft survival was identified between whites (n = 272) and AA (n = 445), with AA experiencing more graft losses (18.2% vs 12.1%, P = 0.0351). Induction with AL improved outcomes in all transplant recipients. Multiple linear regression identified that the strongest predictor of allograft failure was induction without AL (P < 0.0001). The data for a subset analysis matched for follow-up length demonstrated that whites compared with AA (n = 157, 67 whites and 90 AA) had lower rates of allograft failure in the absence of AL induction (14.9% vs 44.4%, P = 0.0156, hazard ratio = 2.077). In contrast, AL induction (n = 275, 105 whites and 170 AA) eliminated the racial disparity in allograft failure (5.7% vs 9.4%, P = 0.8248, hazard ratio = 1.504). CONCLUSIONS: This is the first study to describe the effects of AL induction therapy on AA renal transplant recipients beyond the first posttransplant year. Our early results suggest that AL induction therapy abolishes the disparity in renal allograft failure.

Prehospital Emergency Care Education for the Nepal Mountaineering Association.

BACKGROUND: Prehospital emergency care training programs are effective in reducing mortality and disability in low-income countries. Implementation of a specifically designed program in the mountainous regions of Nepal has the potential to benefit local populations, trekking and mountaineering guides, and adventure tourists. OBJECTIVE: Our aims were to survey Nepal Mountaineering Association (NMA) members' past experiences with emergencies and medical training, characterize a geographic-specific prehospital emergency care training program, and evaluate the effectiveness and outcome of the program. METHODS: Sixty-two trekking guides, police officers, and students attended the 2-day training program in Pokhara, Nepal in May 2014. Training curriculum was determined in coordination with the NMA. Instructors included Tulane University faculty, surgical residents, and graduate students. Surveys identified participants' experience with emergencies, confidence in providing emergency care, and interest in future trainings. Multiple modalities were utilized to assess trainees' comprehension. RESULTS: Participants rated the program as valuable and expressed desire for additional trainings. Survey results indicated that participants had prior experience with a myriad of emergencies, were more confident in managing traumatic emergencies than medical or environmental, and showed that few had previously received training in cardiopulmonary resuscitation. Areas of instruction included general first responder and geographic-specific content. Participants achieved the course objectives and documented their abilities to successfully manage simulated clinical problems. CONCLUSIONS: The training program, an international collaboration, was documented to be successful by instructors, NMA leadership, and participants. The training program's content matched the participants' specific needs and abilities. Areas for improvement include providing content related to burns, motorcycle injuries, cold-exposure injuries, fever management, and toxicology emergencies.

Comparison of ultrasound-guided biopsy technique for thyroid nodules with respect to adequacy of cytological material.

BACKGROUND: Ultrasound-guided fine-needle aspiration cytology (FNAC) sampling of the thyroid represents a standard diagnostic procedure in the evaluation of thyroid nodules. The specimen can be acquired using either of two different techniques. In the first, the short axis is used with observation only of the tip of the needle whilst in the nodule. In the second technique, the long axis is used with the observation of the entire length of the needle. The decision to sample utilizing either technique was done randomly. This study is a retrospective review performed to compare these two techniques with regard to specimen adequacy. METHODS: Ultrasound-guided FNACs were performed in 80 thyroid nodules between May 2008 and February 2009. One physician acquired the cytology specimens using one of these two methods after localization. Data on the type of technique and its diagnostic accuracy were collected. RESULTS: Forty-nine of 80 thyroid nodules were sampled using the long-axis technique. The overall and deep-lesion diagnostic adequacies of specimens were significantly higher using this technique (93.9 and 95.1%, respectively, p < 0.01) than the short-axis technique. When comparing the long and short axes for superficial lesions, there was no significant difference in adequacy of the samples (p = 0.92). CONCLUSIONS: This is the first study to compare long- and short-axis techniques with regard to specimen adequacy for thyroid nodules. The long-axis technique decreased the rate of inadequate material and provided more accurate cytological evaluation for deeper lesions.

Megacolon, hypoganglionosis, and cerebrovascular disease.

INTRODUCTION: Gastrointestinal dysmotility has recently been recognized as a sequela of cerebrovascular accident. CASE REPORT: This paper reports the case of a 58-year-old man who presented to an emergency department with severe abdominal pain and distention. He had no prior history of constipation or other symptom of gastrointestinal dysmotility, but did suffer a cerebrovascular accident ten years previously. A diagnosis of colonic volvulus was made. Following partial mechanical decompression, sigmoid colectomy was performed, revealing a severely distended colon with marked wall thickening. Pathology revealed hypogangliosis and disrupted crypt architecture, establishing the diagnosis of idiopathic megacolon with hypogangliosis. DISCUSSION: Chronic gastrointestinal dysmotility has recently been recognized as a sequela of cerebrovascular accident, but is also commonly found following other forms of central nervous system injury. This association likely follows disrupted communication between central autonomic regulatory pathways and intestinal enteric pacemakers. CONCLUSIONS: Gastrointestinal dysmotility is a consequence of neurologic injury, and must be addressed in recommendations for long-term care following a cerebrovascular accident. Current recommendations focus on acute treatment, but do not recommend measures to promote colonic health and gastrointestinal motility.

Plasmacytoma in the thyroid.

OBJECTIVE: The paper presents a case of plasmacytoma unexpectedly found in a goiter. PATIENT MATERIAL AND METHODS: The patient presented with compressive symptoms, including dyspnea and dysphagia and had no documented prior history of multiple myeloma. Physical examination revealed thyromegaly with no specific nodule. Computerized tomographic (CT) scan of the neck and chest showed diffuse homogenous enlargement of both the thyroid lobes extending into the mediastinum. Total thyroidectomy was done because of the compressive symptoms. RESULTS: Pathology revealed evidence of fibrosis surrounding small nodules of residual follicles with massive infiltration by plasma cells. The pathologic diagnosis was plasmacytoma. CONCLUSION: Plasmacytoma should be added to the list of causes of diffuse thyromegaly.

Torsion and gangrene of a Meckel's diverticulum.

A 19-year-old woman presented to the emergency department with intermittent and progressively worsening abdominal pain, nausea, and vomiting. A computed tomographic scan revealed findings consistent with distal small bowel obstruction of unknown etiology. In the operating room, a torsed and gangrenous Meckel's diverticulum with extension of ischemia to adjacent small bowel was discovered and immediately resected. Pathology confirmed the diagnosis of gangrenous Meckel's diverticulum. Torsion and gangrene of a Meckel's diverticulum is a rare complication and often presents with vague and poorly localized signs and symptoms. The preoperative diagnosis is often difficult and presumed to be appendicitis or small bowel obstruction of unclear etiology. Complications of Meckel's diverticulum should be considered in patients with lower abdominal pain and acute abdomen.

Splenic artery embolization and endovascular stapler integrity in a porcine model.

Splenic artery embolization is often used before laparoscopic splenectomy in cases of splenomegaly to reduce blood loss and facilitate the procedure. The aim of this study was to examine the general reliability of endovascular staplers when fired at the site of embolization coil deployment using a porcine model. Ex vivo and in vivo experiments were conducted on porcine abdominal aortas, which are similar in diameter to those of the splenic artery in the human. When the endovascular staplers were fired across the porcine vessels at the area of embolization coil deployment ex vivo, the staple lines all failed. In contrast, in vivo, the staple lines remained intact with no bleeding despite resistance imposed by the intravascular coils. Despite consistent failure in the ex vivo studies, in vivo all staple lines held and permitted safe transection of the vessel. We presume that the hemostatic properties of the coils caused sufficient thrombosis in this model, which mimics the clinical situation, to permit division of the previously embolized splenic vessel.

Effect of Curriculum Changes on Student Performance During General Surgical Clerkship.

INTRODUCTION: Good clinical knowledge of anatomy, taught in medical school, is necessary for practicing physicians. It is a key feature of performance on the United States Medical Licensing Examination Step 1 score. Student performance on anatomy is also an early indicator of overall medical student performance. Unfortunately, curricular time provided for the teaching of anatomy has declined significantly over the last 30 years, leading to growing concerns that the anatomical knowledge of new medical graduates may not be adequate. Data regarding the impact of these changes to the medical school curriculum are lacking, with studies often being limited in number of medical students or time. METHODS: This study examined the anatomy knowledge of students on third-year clinical rotations at Tulane University Medical School. Oral examinations were administered at the conclusion of the junior surgical clerkship. Data on performance were collected over a 5-year period from 690 medical students tested in their knowledge of anatomy, and the other basic sciences collectively considered as pathophysiology. RESULTS: Over the 5-year period, student total scores by year increased in all categories tested. However, during the course of the students' third-year clerkships, the later in the year the students rotated on surgery, the more their scores progressively declined. Unfortunately, this fall was most severe in the knowledge of anatomy. DISCUSSION: Although it is possible to teach anatomy in increasingly shorter periods of time, such that the students achieve high test scores in the standardized short answer examinations, it is clear that their knowledge, as applied to clinical care, rapidly declines the further they get away from Step 1 studying. Further study is necessary to elucidate the weaknesses in the current basic science curricula as they pertain to anatomy and to devise mechanisms to assure retention of this critical science during clinical rotations and beyond into practice.

Double endoscopic technique for operative dilation of esophageal strictures resistant to conventional therapy.

Esophageal strictures are a common problem causing significant morbidity for affected patients. Most can be treated safely and successfully with esophageal dilation. We have treated two patients with post-radiation esophageal strictures so tight that standard dilation technique failed even with an aggressive approach. We utilized a technique for operative dilation of these strictures using both antegrade and retrograde endoscopes. This approach for refractory esophageal strictures has only twice been previously reported. In both patients, a gastrostomy was placed and an endoscope was subsequently passed from the stomach retrograde up to the level of the stricture. Another endoscope was passed from above down to the proximal portion of the stricture. Illuminating the stricture, using fluoroscopy, carefully passing a wire, and grasping and pulling the wire with forceps from the opposite endoscope allowed for safe passage through the stricture. Savary dilators were utilized to effectively dilate the strictures. A method for protection of the lumen for subsequent dilations by passing a small catheter through the stricture was also developed. This technique offers an option for patients with otherwise untreatable strictures, with the major advantage of visualization from above and below.

Choosing Surgery: Identifying Factors Leading to Increased General Surgery Matriculation Rate.

Tulane graduates have, over the past six years, chosen general surgical residency at a rate above the national average (mean 9.6% vs 6.6%). With much of the recent career choice research focusing on disincentives and declining general surgery applicants, we sought to identify factors that positively influenced our students' decision to pursue general surgery. A 50-question survey was developed and distributed to graduates who matched into a general surgery between the years 2006 and 2014. The survey evaluated demographics, exposure to surgery, and factors affecting interest in a surgical career. We achieved a 54 per cent (61/112) response rate. Only 43 per cent considered a surgical career before medical school matriculation. Fifty-nine per cent had strongly considered a career other than surgery. Sixty-two per cent chose to pursue surgery during or immediately after their surgery clerkship. The most important factors cited for choosing general surgery were perceived career enjoyment of residents and faculty, resident/faculty relationship, and mentorship. Surgery residents and faculty were viewed as role models by 72 and 77 per cent of responders, respectively. This study demonstrated almost half of those choosing a surgical career did so as a direct result of the core rotation experience. We believe that structuring the medical student education experience to optimize the interaction of students, residents, and faculty produces a positive environment encouraging students to choose a general surgery career.

Brown bowel syndrome: case report and review.

Brown bowel syndrome is characterized by deposits of lipofuscin in the tunica muscularis of the small intestine. Its etiology is associated with chronic malabsorption resulting in a deficiency of vitamin E. This hypovitaminosis is believed to cause a mitochondrial myopathy secondary to loss of the antioxidant properties of vitamin E, which further worsens the malabsorption and leads to atonic, dilated segments of bowel. Current treatment options involve nutritional supplementation, surgical resection of the affected segments, and intestinal transplantation.

Sensitization of apoptotically-resistant breast carcinoma cells to TNF and TRAIL by inhibition of p38 mitogen-activated protein kinase signaling.

The mitogen-activated protein kinase (MAPK) cascade is a critical component in the regulation of cell survival and proliferation decisions. In breast carcinoma cells, activation of the p38-MAPK member of this family occurs in response to pro-inflammatory cytokines and cellular stress. The involvement of p38-MAPK in the activation of the transcription factor, NF-kappaB, suggests a potential role and mechanism for regulation of cell survival and drug resistance. Generation of the resistant MCF-7 variant (MCF-7TN-R) was achieved by prolonged exposure of MCF-7N cells to increasing concentrations of TNF. Differences in MAPK activation and function in the MCF-7 cell variants were determined. The role of the p38-MAPK pathway in regulation of resistance was determined using pharmacological (SB 203580) or molecular [Dominant Inhibitory (DI)-p38] inhibition. The effect of p38 inhibition on NF-kappaB transcriptional activation was analyzed. As compared to the sensitive MCF-7N parent cell line, the MCF-7TN-R cell line displayed significant resistance to TNF- and TRAIL-induced cell death. Analysis of the expression and phosphorylation of members of the MAPK family revealed an increased basal activation of p38 in the MCF-7TN-R variant. The p38-mediated phosphorylation and transcriptional activity were suppressed by pharmacologic inhibition with SB 230580. Treatment of MCF-7TN-R cells with SB partially restored sensitivity to TNF-induced cell death. In addition, use of a DI-p38 construct with or without the addition to TNF induced cell death, thus restoring TNF-sensitivity to these cells. The ability of p38 inhibition to restore apoptotic sensitivity was correlated with suppression of the TNF-induced cell survival pathway, NF-kappaB. The increased activation of p38-MAPK in MCF-7TN-R cells demonstrates that this signaling pathway through activation of NF-kappaB is an important route for control of resistance to cell death in breast carcinoma. Molecular and pharmacological inhibition of p38-MAPK signaling may represent a mechanism for sensitizing cancer cells to chemotherapeutic regimens and restoration of apoptotic signaling.

Gastrointestinal metastasis to the breast.

BACKGROUND: Although primary breast cancer is common, metastatic disease to the breast, especially primary gastrointestinal cancer, is rare. Routine pathologic examination may be helpful in determining the true diagnosis, but can be misleading. METHODS: To determine whether a signet ring carcinoma was a primary malignancy of the gastrointestinal tract metastatic to the breast or vice versa, histochemical analysis was performed for Her-2/NEU, gross cystic disease fluid protein-15, estrogen receptor, progesterone, carcinoembryonic antigen, cytokeratin 7, and cytokeratin 20. RESULTS: Positive staining for carcinoembryonic antigen and cytokeratin 20 (and negative staining for the breast cancer antigens), and the clinical criteria favors the diagnosis of gastrointestinal carcinoma metastatic to the mammary gland. CONCLUSIONS: Because the prognosis of therapy for metastatic cancer to the breast differs from that of primary breast cancer, it is imperative that the correct diagnosis be established. Immunohistochemistry for carcinoembryonic antigen and cytokeratin 20 are particularly useful. Metastatic gastrointestinal carcinoma to the breast is a rare lesion but needs to be at least included in the differential diagnosis of breast masses, especially in patients with a history of gastrointestinal cancer.

Regulation of estrogen-mediated cell survival and proliferation by p160 coactivators.

BACKGROUND: Estrogen receptor (ER) activity is dependent on coactivator (CoA) proteins. The role of CoA-ER interactions in breast cancer apoptosis remains unexplored. METHODS: Expression vectors for the p160 CoA genes NCOA-1, NCOA-2, or NCOA-3 were transiently transfected into MCF-7 cells. Cell survival was determined by viability and clonogenic survival assays. Effects of CoA expression on estrogen (E2) signaling were determined by estrogen response element (ERE)-luciferase reporter-gene assay. Clonogenic and reporter-gene survival assays were used to examine the molecular inhibition of CoA function (dominant inhibitory [DI]-decoy-CoA) on cell survival. Statistical significance was established at the P < .05 level. RESULTS: Overexpression of NCOA-1, NCOA-2, and NCOA-3 enhanced E2-mediated gene expression by 3.17 +/- 0.51-, 2.33 +/- 0.8-, and 3.65 +/- 0.65-fold, respectively, and enhanced cell survival by suppressing tumor necrosis factor alpha (TNF-alpha)-induced cell death from 80.23% +/- 2.66% viability to 101.5% +/- 8.9%, 86.9% +/- 9.9%, and 95.7% +/- 8.5% viability, respectively. NCOA-1 enhancement of cell survival occurred via suppression of TNF-alpha-induced apoptosis as confirmed by viability and morphologic evaluation. Clonogenic survival and E2-stimulated colony formation in MCF-7 cells were suppressed by expression of DI-decoy-NCOA-1 and DI-decoy-NCOA-3 to 34.4% +/- 7.4% and 54% +/- 5.4% of vector control, but not DI-decoy-NCOA-2. CONCLUSIONS: Overexpression of NCOA-1 and NCOA-3 exerted potent survival effects in breast carcinoma cells. Use of DI-CoA constructs enhanced TNF-alpha-induced cell death and abrogated E2-induced survival. Inhibition of CoA proteins represents a mechanism for enhancing sensitivity therapies in breast carcinoma.