St George's University's Medical Student Research Institute: A Novel, Virtual Programme for Medical Research Collaboration.

OBJECTIVE: Medical student research involvement has evolved to be a core component of medical education and is becoming increasingly vital to success in the United States residency match. We sought to develop a research website allowing students and research faculty to collaborate and complete projects online. METHODS: The Medical Student Research Institute (MSRI) was developed by the St George's University School of Medicine in 2009 to encourage, support, facilitate and centralize medical student research. RESULTS: There are 63 active students in the MSRI (22 students in basic science and 41 students in clinical rotations). The mean GPA for basic science student members was 3.81 ± 0.27 and was 3.80 ± 0.20 for clinical student members. The mean United States Medical Licensing Examination (USMLE) Step 1 score was 241.6 ± 17.5. Since 2009, MSRI students have published 87 manuscripts in 33 different journals and have presented at 14 different national and international conferences. CONCLUSION: A web-based MSRI provides a virtual, entirely online resource for coordinating remote research collaboration between medical students and faculty whose opportunities would be otherwise limited. Initial experiences with the programme have been positive and the framework and concept of the MSRI provides a platform for university and medical schools to provide research opportunities to students who may not have face-to-face access to research faculty.

Aortic valve replacement with and without coronary artery bypass graft surgery in octogenarians: is it safe and feasible?

INTRODUCTION: Octogenarians are often denied complex surgical intervention. We evaluated the rationality of this bias by comparing the outcomes of octogenarians undergoing aortic valve replacement (AVR) with or without coronary artery bypass grafting (CABG), to those of younger patients. METHODS: Data on 476 patients (≥ 80 years) who underwent AVR or AVR/CABG were compared to the Society of Thoracic Surgeons (STS) database. RESULTS: One hundred and seventeen octogenarians underwent AVR and 263 underwent AVR/CABG. Preoperative comorbidity rates were similar between these 2 respective groups, except for diabetes mellitus (18.8 vs. 30.4%, p = 0.02), previous cardiac stent placement (5.1 vs. 17.9%, p = 0.0006) and prior CABG (8.5 vs. 0.8%, p = 0.0002) and mortality did not differ significantly (5.1 vs. 7.6%, p = 0.51). Multivariate analysis identified preoperative chronic renal failure [odds ratio (OR) = 0.09, p < 0.048], postoperative arrhythmia (OR = 0.29, p < 0.022), sepsis (OR =37.38, p < 0.000), pneumonia (OR = 8.29, p < 0.038) and renal failure (OR = 10.16, p < 0.000) with increased rates of in hospital mortality in AVR alone and AVR/CABG. CONCLUSION: AVR alone or AVR/CABG can be safely performed in patients ≥ 80 years with acceptable morbidity/mortality rates. An age of ≥ 80 years is not an independent risk factor predictive of increased in hospital mortality

Near lethal endometriosis and a massive (64 kg) endometrioma: case report and review of the literature.

A 51-year-old morbidly obese, hypertensive, anemic, and amenorrheic female presented with anuria and respiratory symptoms. The patient had a distinctly massive abdomen with necrotic anterior abdominal wall, and laboratory findings revealed a leukocytosis, profound anemia, coagulopathy and renal failure. An abdominal sonogram showed a large, complex intra-abdominopelvic mass and ascites. At surgery, a massive, cystic left ovarian mass, 37 1 of ascitic/cyst fluid, and several peritoneal nodules were removed--a total of 64 kg of tumorous tissue. Histopathological evaluation of the mass revealed an endometrioma. We present this rare case of severe endometriosis in a morbidly obese patient who presented with an exceptionally large endometrioma (64 kg), multifactorial respiratory and renal failure, coagulopathy, and profound anemia.

Bronchobiliary fistula complicating oriental cholangiohepatitis.

Bronchio biliary fistula in adults is a rare event defined by the passage of bile into the bronchus and the sputum (biloptysis).Typically these lesions occur in the congenital form, as a result of thoracoabdominal trauma, or in rare instances as a result of iatrogenic injury or long-standing biliary tract disease and obstruction. In this paper, we report a novel case of a fatal bronchobiliary fistula that developed in a 67-year-old Chinese male with Oriental cholangiohepatitis. To our knowledge, this is the first case report of a bronchobiliary fistula complicating the clinical management of a patient with this disease.

The surgical management of pancreatic neuroendocrine tumors.

NETs of pancreas are rare and may or may not be associated with symptoms of hormone overproduction. Treatment is required for control of tumor growth and for relief of symptoms associated with excess hormone. With advances in the nonsurgical management of many hormone-related symptoms (e.g., proton pump inhibitors or somatostatin analogues), care for many of these patients has shifted toward the control of tumor progression. Complete surgical resection is the only curative treatment for these tumors. With improvements in the preoperative imaging and intraoperative localization techniques, it is hoped that these tumors will be identified and resected for cure with increased frequency. For patients with hepatic metastasis, initial expectant observation and medical management of symptoms is appropriate in view of the long and indolent course of the disease. Hepatic arterial embolization is the preferred mode of palliation for pain and hormonal symptoms. A curative hepatic resection may be possible in selected patients.

Current surgical therapy for carcinoma of the pancreas.

Despite progress in treating many solid tumors, pancreatic cancer continues to be a grave illness. Each year, >29,000 new cases of adenocarcinoma of the pancreas are diagnosed in the United States. Of these patients, only 10-20% have resectable tumors and 25,000 patients (83%) die within 12 months of diagnosis. Until recently, surgery has been the only "effective" therapy available for select patients. Historically, the operative mortality after radical pancreatic resection has been variable, ranging 1-30%, and is both operator- and institution-dependent. Even with a safe and complete surgical resection, the actual 5-year survival after surgery alone is essentially zero, although rates up to 5% have been reported. Despite what would appear to be a dismal outlook, slow progress has occurred in the operative and postoperative care of patients with pancreatic cancer. Advanced imaging techniques and laparoscopy have limited the number of unnecessary laparotomies, and novel adjuvant and neoadjuvant chemotherapy approaches have yielded promising results. This review will summarize the recent literature concerning the surgical therapy and trends in the treatment of carcinoma of the pancreas from 1990 to 1999.

Ileal perforation caused by cytomegalovirus infection in a critically ill adult.

Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract is common and is most often seen in patients with acquired immunodeficiency syndrome (AIDS), inflammatory bowel disease, or those receiving immunosuppressive therapy. CMV infection of the small bowel accounts for only 4.3% of all CMV infections of the GI tract. Isolated cases of small bowel perforation due to CMV have been reported in AIDS patients, and all but one patient has died. This article reports the first case of an ileal perforation due to transfusion-associated CMV infection in a critically-injured non-AIDS patient. Immediate surgical resection and antiviral therapy led to complete recovery. The development of abdominal pain, fever, watery diarrhea, and GI bleeding in a critically ill patient should prompt the clinician to consider the diagnosis of CMV enteritis. If standard stool pathogens and Clostridium difficile toxin studies are nondiagnostic, endoscopic evaluation and CMV serology should be obtained. If CMV infection is confirmed, ganciclovir therapy should be initiated without delay. If bowel perforation occurs. prompt surgical resection is indicated. A heightened level of suspicion for CMV infection in multiply injured trauma victims and other critically ill patients, with earlier recognition of potential small bowel involvement, can hopefully decrease the incidence of bowel perforation, which is usually a fatal event.

Hepatic neuroendocrine metastases: does intervention alter outcomes?

BACKGROUND: In most instances, advanced neuroendocrine tumors follow an indolent course. Hepatic metastases are common, and although they can cause significant pain, incapacitating endocrinopathy, and even death, they are usually asymptomatic. The appropriate timing and efficacy of interventions, such as hepatic artery embolization (HAE) and operation, remain controversial. STUDY DESIGN: The records of 85 selected patients referred for treatment of hepatic neuroendocrine tumor metastases between 1992 and 1998 were reviewed from a prospective database. A multidisciplinary group of surgeons, radiologists, and oncologists managed all patients. Overall survival among this cohort is reported and prognostic variables, which may be predictive of survival, are analyzed. RESULTS: There were 37 men and 48 women, with a median age of 52 years. There were 41 carcinoid tumors, 26 nonfunctional islet cell tumors, and 18 functional islet cell tumors. Thirty-eight patients had extrahepatic metastases, and in 84% of patients, the liver metastases were bilobar. Eighteen patients were treated with medical therapy or best supportive care, 33 patients underwent HAE, and 34 patients underwent hepatic resection. Both the HAE-related mortality and the 30-day operative mortality rates were 6%. By univariate analysis, earlier resection of the primary tumor, curative intent of treatment, and initial surgical treatment were associated with prolonged survival (p < 0.05). On multivariate analysis, only curative intent to treat remained significant (p < 0.04). Patients with bilobar or more than 75% liver involvement by tumor were least likely to benefit from surgical resection. One-, 3-, and 5-year survival rates for the entire group were 83%, 61%, and 53%, respectively. The 1-, 3-, and 5-year survivals for patients treated with medical therapy, HAE, and operation were 76%, 39%, and not available; 94%, 83%, and 50%; and 94%, 83%, and 76%, respectively. CONCLUSIONS: Hepatic metastases from neuroendocrine tumors are best managed with a multidisciplinary approach. Both HAE and surgical resection provide excellent palliation of hormonal and pain symptoms. In select patients, surgical resection of hepatic metastases may prolong survival, but is rarely curative.

Hilar cholangiocarcinoma: a review and commentary.

Hilar cholangiocarcinoma is an uncommon cause of malignant biliary obstruction marked by local tumor spread for which surgery offers the only chance of cure. The diagnostic evaluation and surgical management of this disease continues to evolve. Although direct cholangiography and endoscopic biliary procedures have been used extensively to anatomically define the extent of tumor involvement, establish biliary decompression, and obtain histological confirmation of tumor, reliance on these invasive procedures is no longer necessary, and may be detrimental. Current noninvasive imaging technology permits accurate staging of the primary tumor and has improved patient selection for operative intervention without the need for invasive procedures. Overall survival has improved in accordance with an increasingly aggressive surgical approach. The propensity of this tumor for local invasion has led most experienced hepatobiliary centers to perform a partial hepatectomy in 50% to 100% of cases. Three-year survival rates of 35% to 50% can be achieved when negative histological margins are attained at the time of surgery. When resection is not feasible, either operative bilioenteric bypass or percutaneous transhepatic intubation can achieve significant palliation. There is no effective adjuvant therapy for this disease, and unless clear indications of unresectability exist, most patients should be considered for surgical exploration.

Mucobilia in association with a biliary cystadenocarcinoma of the caudate duct: a rare cause of malignant biliary obstruction.

Mucobilia is a rare condition characterized by the accumulation of abundant mucus within the intra- or extrahepatic biliary tree. A variety of hepatobiliary and pancreatic neoplasms are mucin producing and have been associated with the development of mucobilia including biliary mucinosis, biliary papillomatosis, mucin-producing cholangiocarcinoma (MPCC), or cystic neoplasms of the pancreas or biliary tree (cystadenoma or cystadenocarcinoma). We report the case of 46 year-old male with a biliary cystadenocarcinoma of the caudate lobe which resulted in chronic biliary obstruction and relapsing cholangitis. A review of the literature for both mucobilia and biliary cystadenocarcinoma is provided along with a discussion addressing the clinical presentation, diagnosis, treatment, and prognosis for this rare entity.

Nutritional and metabolic aspects of pancreatic cancer.

Most patients with pancreatic cancer suffer from a variety of severe metabolic and nutritional disturbances. Despite this fact, the role of perioperative nutritional support for these patients remains controversial. This review highlights the results of randomized prospective clinical trials, and meta-analyses that have addressed this issue. The 'current opinion' put forth in this discussion is based on these reviews, and on personal observations in treating more than 500 patients.

Hepatic adenoma associated with recombinant human growth hormone therapy in a patient with Turner's syndrome.

BACKGROUND: Turner's syndrome is a genetic disorder of females with well-described karyotypic abnormalities and phenotypic features. Recombinant human growth hormone (HGH) therapy is one component of a hormonal treatment strategy for these patients and is used to promote sexual maturity and to increase height. METHODS: Literature review of hepatic complications following the initiation of growth hormone therapy for patients with Turner's syndrome, and case report presentation of a 13-year-old female with Turner's syndrome developing a hepatic adenoma following 3 years of HGH treatment. RESULTS: The association between Turner's syndrome and HGH treatment-associated hepatic adenoma has not been described previous to this report. In this patient, surgical resection was contraindicated and the patient was successfully treated by hepatic artery embolization. The unique management issues relating to this case, and a possible association between HGH therapy and the development of hepatic adenoma are discussed. CONCLUSION: This work represents the first documentation of a hepatic adenoma developing in a patient with Turner's syndrome following HGH treatment, and suggests a novel and causal association between HGH treatment and the development of hepatic adenoma in patients with Turner's syndrome.

Innovations and strategies for the development of anticancer vaccines.

In 1893, William Coley reported the spontaneous regression of a soft tissue sarcoma in several patients suffering from acute bacterial infections. Although this observation occurred over a century ago, the concept of anticancer vaccines and the immunotherapy of cancer has only recently seemed plausible. A myriad of specific and non-specific immunostimulatory approaches have been tested throughout the years with only a modicum of success. Most of these approaches were doomed from the outset since they were based on false or inadequate knowledge of tumour immunology. Recent advances in our understanding, most notably the identification of genes encoding for cancer regression antigens, currently permit investigators to pursue a more cogent strategy to develop novel and specific anticancer vaccine approaches. Several of these approaches are currently being tested in clinical trials and have already yielded exciting results. However, a number of immunologic and host obstacles to the successful application of anticancer vaccines remain. This editorial will provide an update on the clinical status of anticancer vaccines and review areas of promising research initiatives.

Nutritional and metabolic aspects of gastrointestinal cancer.

The profound impact of nutrition and nutritional support on the development and clinical outcome of gastrointestinal cancer is undeniable. However, scientific investigation into this area is recent, and many questions remain unanswered. While the importance of 'good nutrition' is unchallenged, details relating to which patients should receive nutritional support, when they should receive it, and what type of support they should receive are not known. Recent prospective randomized clinical trials and meta-analysis have provided conflicting results. This review summarizes the results of the published studies that have addressed these issues, and provides specifics regarding the current role of nutritional support in clinical care, and the prospects for future research.

Carcinoid tumors of the extrahepatic bile duct. A rare cause of malignant biliary obstruction.

BACKGROUND: Carcinoid tumors of the extrahepatic bile duct are rare and account for 0.2-2% of all gastrointestinal carcinoids. Similar to other tumors of the bile duct, these lesions are difficult to diagnose preoperatively and nearly impossible to distinguish from cholangiocarcinoma. METHODS: The authors retrospectively analyzed all reported cases of carcinoid tumor of the bile duct and report on two additional cases. RESULTS: Thirty cases of carcinoid tumor of the bile duct have been reported. Among this group were 20 women and 9 men (female-to-male ratio, 2.2:1) with an overall mean age of 47 years (range, 19-79 years). The most common anatomic sites for extrahepatic carcinoid tumors were the common bile duct (58%), perihilar region (28%), cystic duct (11%), and common hepatic duct (3%). Jaundice was the most common presenting complaint (55%). Sixty-nine percent of patients with extrahepatic biliary carcinoids had disease confined to the bile duct, whereas 31% had evidence of distant metastases. All patients who presented with localized disease remain disease free with a mean follow-up of 32 months (range, 3 months to 20 years). CONCLUSIONS: Carcinoid tumor of the bile duct is a rare form of malignant biliary obstruction. Unlike cholangiocarcinoma, biliary carcinoids occur more commonly in younger patients and in women. Aggressive local invasion by the primary tumor is rare, and metastases occur in less than one-third of patients. All patients who underwent a curative surgical resection were alive and disease free at time of published report, implying a more favorable prognosis. Aggressive surgical resection is recommended.

Prospects for the therapeutic use of anticancer vaccines.

Although a century has passed since initial attempts were made to stimulate the immune system to destroy tumour, the immunotherapy of cancer is still in the early stages. Historically, a variety of specific and nonspecific immunostimulatory strategies have been administered with only modest clinical success. However, recent advances in tumour immunology, most notably the identification of genes encoding for cancer regression antigens, have paved the way for the development of a variety of novel and specific vaccine approaches. These include vaccines based on tumour cells, carbohydrates, peptides and heat-shock proteins, DNA-based vaccination, and the use of recombinant bacteria and viruses to deliver antigens or the DNA coding for them. While several of these approaches have yielded exciting clinical results, a number of immunological and host obstacles to the successful application of cancer vaccines remain. Further research is needed on the optimum choice of antigen, delivery vector, adjuvant and administration regimen.

Apocrine gland carcinoma of the axilla: review of the literature and recommendations for treatment.

Apocrine gland carcinoma is a rare form of sweat gland neoplasm with a distinctive cytologic appearance. Although the region of the axilla remains the most common site for these tumors, apocrine gland carcinoma of the anogenital region, eyelid, ear, chest, wrist, lip, foot, toe, and finger have been reported. Classically, these slow-growing lesions present as painless, colorless or reddish, firm or cystic nodules. More than half of the reported patients with apocrine carcinoma had lymph node metastases at the time of diagnosis. Wide local excision is standard therapy for these lesions. A therapeutic lymph node dissection is indicated for confirmed lymph node metastases and may have a role in the setting of a large or highly aggressive tumor with narrow surgical margins. Although apocrine gland carcinoma responds poorly to chemotherapy, adjuvant radiotherapy may be used in advanced local or regional disease. The authors describe a 69-year-old man with a large recurrent apocrine gland carcinoma of the axilla treated with en bloc excision with axillary dissection and offer a pertinent review of the English literature and recommendations for treatment.

Enterocutaneous fistula in cancer patients: etiology, management, outcome, and impact on further treatment.

Enterocutaneous fistulae that develop in patients with cancer represent a difficult management situation, which is often complicated by prior treatment including surgery, radiation therapy, and chemotherapy. A fistula may in turn delay potentially beneficial treatment of the underlying malignancy. To provide a better understanding of this problem, we reviewed the National Institutes of Health experience with enterocutaneous fistulae in adult patients with cancer. The medical records of patients with cancer who developed a fistula from the gastrointestinal tract during the period 1980 through 1994 were reviewed. Etiology, management, outcome, and impact on further treatment were assessed. Twenty-five patients with gastrointestinal fistulae were identified. The most common primary tumor site was the colon/rectum in males and the ovary in women. The majority of patients had metastatic disease at diagnosis and a history of prior therapy and presented with anorexia and weight loss. The fistula was usually single, most commonly developed from the jejunum/ileum (13 patients) or colon/rectum (6 patients), and occurred postoperatively after procedures on the small bowel (10 patients) or colon (8 patients). Malnutrition and sepsis developed in 60 per cent of patients. Thirty-day mortality was 16 per cent and correlated with prior radiation therapy, location and output from the fistula, and hypoalbuminemia. An enterocutaneous fistula negatively impacted on the provision of further therapy for the majority of patients (63%). Enterocutaneous fistula in the patient with cancer occurs most frequently in the setting of extensive prior therapy and is associated with prolonged morbidity. Identification of high-risk patients and early management of fistulas once they develop may prevent delays in subsequent cancer therapy and decrease morbidity.

Enhancing efficacy of recombinant anticancer vaccines with prime/boost regimens that use two different vectors.

BACKGROUND: The identification of tumor-associated antigens and the cloning of DNA sequences encoding them have enabled the development of anticancer vaccines. Such vaccines target tumors by stimulating an immune response against the antigens. One method of vaccination involves the delivery of antigen-encoding DNA sequences, and a number of recombinant vectors have been used for this purpose. To optimize the efficacy of recombinant vaccines, we compared primary and booster treatment regimens that used a single vector (i.e., homologous boosting) with regimens that used two different vectors (i.e., heterologous boosting). METHODS: Pulmonary tumors (experimental metastases) were induced in BALB/c mice inoculated with CT26.CL25 murine colon carcinoma cells, which express recombinant bacterial beta-galactosidase (the model antigen). Protocols for subsequent vaccination used three vectors that encoded beta-galactosidase--vaccinia (cowpox) virus, fowlpox virus, naked bacterial plasmid DNA. Mouse survival was evaluated in conjunction with antibody and cytotoxic T-lymphocyte responses to beta-galactosidase. RESULTS: Heterologous boosting resulted in significantly longer mouse survival than homologous boosting (all P<.0001, two-sided). Potent antigen-specific cytotoxic T lymphocytes were generated following heterologous boosting with poxvirus vectors. This response was not observed with any of the homologous boosting regimens. Mice primed with recombinant poxvirus vectors generated highly specific antibodies against viral proteins. CONCLUSIONS: The poor efficacy of homologous boosting regimens with viral vectors was probably a consequence of the induction of a strong antiviral antibody response. Heterologous boosting augmented antitumor immunity by generating a strong antigen-specific cytotoxic T-lymphocyte response. These data suggest that heterologous boosting strategies may be useful in increasing the efficacy of recombinant DNA anticancer vaccines that have now entered clinical trials.