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Papers by Annabelle Fonseca

Journal of Clinical Oncology

496 Background: The American Association for the Study of Liver Disease (AASLD) guidelines outlin... more 496 Background: The American Association for the Study of Liver Disease (AASLD) guidelines outline an algorithm regarding the treatment modality of choice for patients with hepatocellular carcinoma (HCC) based on Barcelona Clinic Liver Cancer (BCLC) stage. The AASLD guidelines have several limitations and the adherence rate has been reported to be low. The adherence to AASLD guidelines in treating patients with HCC was explored in this study. Methods: Between 2017 and 2019, 106 patients with HCC were identified. In our cohort, 70 patients (66%) were discussed in the multidisciplinary tumor board (MDTB) and their first-line treatment modality was selected based on consensus recommendations from the MDTB team members. The adherence rate of MDTB recommendations to AASLD guidelines was calculated. Results: Median age was 65 (range 42-90). Males represented 84% while females represented 16%. Caucasians, African Americans and Asians represented 69%, 30% and 1% respectively. BCLC stage 0, ...

Pancreas, Mar 1, 2018

The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the pa... more The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.

The American Surgeon, Apr 1, 2013

Bowel rest, nasogastric (NG) decompression, and intravenous hydration are used to treat small bow... more Bowel rest, nasogastric (NG) decompression, and intravenous hydration are used to treat small bowel obstruction (SBO) conservatively; however, there are no data to support nasogastric tube (NGT) use in patients without active emesis. We aim to evaluate the use of nasogastric decompression in SBO and the safety of managing patients with SBO without the use of a NGT. A retrospective chart review was conducted of adult patients admitted to Yale New Haven Hospital over five years with the diagnosis of SBO. We compared patients who received NG decompression with those who did not. Outcome variables assessed were days to resolution, associated complications, hospital length of stay, and disposition. Of 290 patients who fit the criteria, 190 patients (65.52%) were managed conservatively. Fifty-five patients (18.97%) did not receive NGTs. Sixty-eight patients (23.45%) did not present with emesis; however, nearly 75 per cent of these patients received NGTs. Development of pneumonia and respiratory failure was significantly associated with NGT placement. Time to resolution and hospital length of stay were significantly higher in patients with NGTs. Patients with NG decompression had a significantly increased risk of pneumonia and respiratory failure as well as increased time to resolution and hospital length of stay.

Journal of surgical education, Jan 31, 2015

The American Board of Surgery endoscopy requirements for general surgery training are evolving. I... more The American Board of Surgery endoscopy requirements for general surgery training are evolving. In 2006, the Residency Review Committee in Surgery increased the total number of endoscopy cases required before completion of general surgery residency training. This requirement is set to change further, given the new Flexible Endoscopic Curriculum that would be a requirement for applicants graduating surgical training during or after the 2017 to 2018 academic year. Given these changes, our goal was to evaluate the confidence of senior surgical residents performing flexible endoscopy. A survey was developed and sent to general surgery residents nationally, querying them regarding demographics and program-specific characteristics; additionally they were asked to rate their confidence level in performing flexible upper endoscopy and colonoscopy on a Likert scale of 1 to 5. We then compared those residents who indicated confidence (Likert scale 4-5) to those who did not (Likert scale 1-3)....

Proceedings of the National Academy of Sciences of the United States of America, Jan 31, 2015

Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglyce... more Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglycemia. Exome and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the DNA-binding zinc finger of the transcription factor Yin Yang 1 (YY1). Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that this T372R substitution changes the DNA motif bound by YY1. Global analysis of gene expression demonstrated distinct clustering of tumors with and without YY1(T372R) mutations. Genes showing large increases in expression in YY1(T372R) tumors included ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca(2+) channel); both are expressed at very low levels in normal β-cells and show mutation-specific YY1 binding sites. Both gene products are involved in key pathways regulating insulin secretion. Expression of these genes in rat INS-1 cells demonstrated markedly increased insulin secretion. These findings indicate that YY1(T372R) mutations are neomorp...

Journal of surgical oncology, 2014

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a rising in... more Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a rising incidence in the United States. The increase in medical and locally ablative therapies have improved prognosis, however surgery, either liver resection or transplantation, remains the mainstay of therapy. An increased understanding of liver anatomy, improved imaging modalities and refinements of surgical technique have all led to improved outcomes after surgery. Both resection and transplantation may be used in a complementary manner. Resection remains the treatment of choice for HCC when feasible. Liver transplantation, which removes both the tumor and the underlying diseased liver offers excellent outcomes in patients that meet the Milan criteria. While both these modalities have relatively well defined roles, the treatment of these patients must be tailored individually, using a multidisciplinary approach, to maximize survival, quality of life and allocation of scarce organs.

HPB : the official journal of the International Hepato Pancreato Biliary Association, 2014

Post-operative pancreatic fistula (POPF) formation occurs frequently after a pancreaticoduodenect... more Post-operative pancreatic fistula (POPF) formation occurs frequently after a pancreaticoduodenectomy (PD). Recently, a 10-point Fistula Risk Score (FRS) evaluating the likelihood of clinically relevant POPF (CR-POPF) development has been described and validated. This scheme has yet to be evaluated in PD patients managed without intra-operative drain placement. Among patients undergoing PD at an academic centre since 2003, a retrospective analysis calculating FRS and its correlation with CR-POPF development was evaluated by logistic regression. Secondary analysis examined presentation and management of CR-POPF in undrained PD patients. FRS was calculated for 265 patients; 97.7% were managed without operative drains. The overall incidence of CR-POPF was 7.9%. Logistic regression revealed a 1.6-fold increase in CR-POPF risk per 1-point increase in FRS [95% confidence interval (CI) 1.2-2.0]. The negative predictive value in patients with FRS <3 was 100%, whereas the positive predicti...

Journal of Surgical Education, 2015

General surgical training has changed significantly over the past decade with work-hour restricti... more General surgical training has changed significantly over the past decade with work-hour restrictions, increasing use of minimally invasive techniques, and increasing specialization, leading to decreased resident exposure to open operative techniques. Furthermore, the presence of vascular surgery fellows and the advent of dedicated vascular surgery residencies have had the potential to diminish further the vascular surgery experience of general surgery residents. Given these changes, this study was undertaken to assess the confidence of graduating general surgery residents in performing certain key open vascular maneuvers, approaches that might be required in a general surgery practice, and to determine factors associated with variations in reported confidence. A survey was developed and sent to graduating chief surgical residents nationally. We queried them regarding demographics and program characteristics and asked them to rate their confidence (rated 1-5 on a Likert scale) in performing a vascular anastomosis and 4 specific vascular control maneuvers. We then compared those who indicated confidence with those who did not. We received 653 responses from fifth-year (postgraduate year 5) surgical residents: 69% men, 67.5% from university programs, and 51% from programs affiliated with a Veterans Affairs hospital; additionally, 22% were from small programs, 34% from medium programs, and 44% from large programs. Although 70% of respondents indicated confidence performing a vascular anastomosis, less than 25% indicated confidence performing each of the 4 specified vascular maneuvers. Age, program size, future fellowship plans, surgical volume, estimated percentage of cases performed laparoscopically, and geographic location were all associated with variations in reported confidence. Graduating general surgical residents indicated a significant lack of confidence in performing specific open vascular surgical maneuvers. This decreased confidence varied regionally and was associated with both demographic and program-specific factors.

The American surgeon, 2013

Bowel rest, nasogastric (NG) decompression, and intravenous hydration are used to treat small bow... more Bowel rest, nasogastric (NG) decompression, and intravenous hydration are used to treat small bowel obstruction (SBO) conservatively; however, there are no data to support nasogastric tube (NGT) use in patients without active emesis. We aim to evaluate the use of nasogastric decompression in SBO and the safety of managing patients with SBO without the use of a NGT. A retrospective chart review was conducted of adult patients admitted to Yale New Haven Hospital over five years with the diagnosis of SBO. We compared patients who received NG decompression with those who did not. Outcome variables assessed were days to resolution, associated complications, hospital length of stay, and disposition. Of 290 patients who fit the criteria, 190 patients (65.52%) were managed conservatively. Fifty-five patients (18.97%) did not receive NGTs. Sixty-eight patients (23.45%) did not present with emesis; however, nearly 75 per cent of these patients received NGTs. Development of pneumonia and respi...

Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery, 2014

Objective The aim of this study was to review a single-institution experience with video-assisted... more Objective The aim of this study was to review a single-institution experience with video-assisted thoracoscopic pneumonectomy (VATP). Methods From July 2008 through December 2012, the medical records of all patients undergoing pneumonectomy (total and completion) for lung cancer were reviewed. Clinical parameters were recorded and analyzed. Results During this period, 16% (7/45) of pneumonectomies for malignancy were performed thoracoscopically. Patient selection was performed in the context of a multidisciplinary tumor board. Of the seven VATPs, five were standard (Video 1, available at http://links.lww.com/INNOV/A40 ) and two were completion pneumonectomies (Video 2, available at http://links.lww.com/INNOV/A41 ). Indications were primary lung cancer in six (three adenocarcinoma, one squamous carcinoma, one large cell neuroendocrine carcinoma, and one mixed adenocarcinoma cell and small cell lung carcinoma) and metastatic esophageal cancer in one patient. Preoperative selection was...

Biology, 2012

Adrenocortical tumors are frequently found in the general population, and may 20 be benign adreno... more Adrenocortical tumors are frequently found in the general population, and may 20 be benign adrenocortical adenomas or malignant adrenocortical carcinomas. Unfortunately 21 the clinical, biochemical and histopathological distinction between benign and malignant 22 adrenocortical tumors may be difficult in the absence of widely invasive or metastatic 23 disease, and hence attention has turned towards a search for molecular markers. The study 24 of rare genetic diseases that are associated with the development of adrenocortical 25 carcinomas has contributed to our understanding of adrenocortical tumorigenesis. In 26 addition, comprehensive genomic hybridization, methylation profiling, and genome wide 27 mRNA and miRNA profiling have led to improvements in our understanding, as well as 28 demonstrated several genes and pathways that may serve as diagnostic or prognostic 29 markers. 30 Keywords: (3-10 keywords separated by semi colons) 31 32 Adrenocortical tumors are frequently found in the general population, with an estimated prevalence 34 of 3-7% (1, 2) and are most often discovered incidentally(3). These tumors may be, more commonly, 35 benign adrenocortical adenomas (ACA). Malignant adrenocortical carcinoma (ACC) is a rare 36 malignancy with an estimated incidence of 0.7-2.0 cases per million per year(2-4). 37 Unfortunately the clinical, biochemical and histopathological distinction between ACA and ACC 38 may be difficult in the absence of widely invasive or metastatic disease(5-10). At present the Modified 39 Weiss Score (a histopathologic scoring) is the most widely accepted means of classifying ACC. 40 However, there is significant variation in inter-observer agreement and it does not identify molecular 41 targets for diagnosis and therapeutic intervention. A better method of distinguishing benign from 42 malignant ACTs is therefore needed, and attention has turned towards a search for molecular 43 markers(11). Current understanding of the development of adrenocortical carcinoma in the last decade 44 originated, in large part, due to the study of rare genetic diseases that are associated with the 45 development of ACC(12). In addition, comprehensive genomic hybridization, methylation profiling, 46 and genome wide mRNA and miRNA profiling have, in the more recent past, led to improvements in 47 our understanding, as well as demonstrated several genes and pathways that may serve as diagnostic or 48 prognostic markers (13-17). 49

Nature Genetics, 2013

Users may view, print, copy, download and text and data-mine the content in such documents, for t... more Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Molecular Cancer, 2013

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with high mutational he... more Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with high mutational heterogeneity and a generally poor clinical outcome. Despite implicated roles of deregulated TP53, IGF-2 and Wnt signaling pathways, a clear genetic association or unique mutational link to the disease is still missing. Recent studies suggest a crucial role for epigenetic modifications in the genesis and/or progression of ACC. This study specifically evaluates the potential role of epigenetic silencing of RASSF1A, the most commonly silenced tumor suppressor gene, in adrenocortical malignancy. Results: Using adrenocortical tumor and normal tissue specimens, we show a significant reduction in expression of RASSF1A mRNA and protein in ACC. Methylation-sensitive and-dependent restriction enzyme based PCR assays revealed significant DNA hypermethylation of the RASSF1A promoter, suggesting an epigenetic mechanism for RASSF1A silencing in ACC. Conversely, the RASSF1A promoter methylation profile in benign adrenocortical adenomas (ACAs) was found to be very similar to that found in normal adrenal cortex. Enforced expression of ectopic RASSF1A in the SW-13 ACC cell line reduced the overall malignant behavior of the cells, which included impairment of invasion through the basement membrane, cell motility, and solitary cell survival and growth. On the other hand, expression of RASSF1A/A133S, a loss-of-function mutant form of RASSF1A, failed to elicit similar malignancy-suppressing responses in ACC cells. Moreover, association of RASSF1A with the cytoskeleton in RASSF1A-expressing ACC cells and normal adrenal cortex suggests a role for RASSF1A in modulating microtubule dynamics in the adrenal cortex, and thereby potentially blocking malignant progression. Conclusions: Downregulation of RASSF1A via promoter hypermethylation may play a role in the malignant progression of adrenocortical carcinoma possibly by abrogating differentiation-promoting RASSF1A-microtubule interactions.

Journal of Clinical Oncology

e16609 Background: The Barcelona-Clinic Liver Cancer (BCLC) staging based management proposed by ... more e16609 Background: The Barcelona-Clinic Liver Cancer (BCLC) staging based management proposed by AASLD depends on baseline liver function and performance status of the patient in addition to tumor characteristics. Low adherence to AASLD guidelines, especially in advanced staged tumors, can be ascribed to suboptimal revision/updates of the guidelines reflecting the advancements in hepatocellular carcinoma (HCC) management. Here, in addition to the adherence rate, we explored the overall survival of patients with HCC according to first-line treatment modality compliance to AASLD guidelines. Methods: This is a retrospective study conducted at the University of South Alabama/Mitchell Cancer Institute. Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their compliance with suggested first-line treatment modality according to AASLD guidelines was noted. Overall survival was explored and differ...

Journal of the American College of Surgeons

Abdominal Radiology

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, with... more Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, with an estimated 53,670 new cases diagnosed and an estimated 43,090 deaths in 2017. This high mortality rate is in part due to the small percentage of patients diagnosed with local disease, as well as the biologically aggressive nature of the disease. While only 10-20% of patients will present with surgically resectable disease, this is the only possible curative therapy. Five-year survival of resected pancreatic cancer ranges from 12 to 27%. The National Comprehensive Cancer Network (NCCN) guidelines recommend specific guidelines for imaging modalities used in the diagnosis and staging of pancreatic adenocarcinoma. Indeed, high-quality imaging is not only necessary to accurately stage the disease, but is critical for the determination of key clinical decision branch points such as the determination of surgical resectability. Identification of the lesion within the pancreas, the degree of extra-pancreatic extension, and potential involvement of surrounding vascular structures with the tumor are all findings necessary to classify patients as having resectable, borderline resectable, or with unresectable primary tumors. This article reviews imaging modalities used to evaluate the pancreatic cancer patient from the surgeon&amp;amp;#39;s perspective, with particular emphasis on determination of resectability and preoperative planning, as well as imaging in the postoperative period.

Clinical Endocrinology, 2015

Aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia are important causes of s... more Aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia are important causes of secondary hypertension. Somatic mutations in KCNJ5, CACNA1D, ATP1A1, ATP2B3 and CTNNB1 have been described in APAs. To characterize clinical-pathological features in APAs and unilateral adrenal hyperplasia, and correlate them with genotypes. Retrospective study. Clinical and pathological characteristics of 90 APAs and seven diffusely or focally hyperplastic adrenal glands were reviewed, and samples were examined for mutations in known disease genes by Sanger or exome sequencing. Mutation frequencies were as follows: KCNJ5, 37·1%; CACNA1D, 10·3%; ATP1A1, 8·2%; ATP2B3, 3·1%; and CTNNB1, 2·1%. Previously unidentified mutations included I157K, F154C and two insertions (I150_G151insM and I144_E145insAI) in KCNJ5, all close to the selectivity filter, V426G_V427Q_A428_L433del in ATP2B3 and A39Efs*3 in CTNNB1. Mutations in KCNJ5 were associated with female and other mutations with male gender (P = 0·007). On computed tomography, KCNJ5-mutant tumours displayed significantly greater diameter (P = 0·023), calculated area (P = 0·002) and lower precontrast Hounsfield units (P = 0·0002) vs tumours with mutations in other genes. Accordingly, KCNJ5-mutant tumours were predominantly comprised of lipid-rich fasciculata-like clear cells, whereas other tumours were heterogeneous (P = 5 × 10(-6) vs non-KCNJ5 mutant and P = 0·0003 vs wild-type tumours, respectively). CACNA1D mutations were present in two samples with hyperplasia without adenoma. KCNJ5-mutant tumours appear to be associated with fasciculata-like clear cell predominant histology and tend to be larger with a characteristic imaging phenotype. Novel somatic KCNJ5 variants likely cause adenomas by loss of potassium selectivity, similar to previously described mutations.

World Journal of Endocrine Surgery, 2009

JAMA surgery, 2014

Making an accurate diagnosis of appendicitis in pregnancy is critical for maternal and fetal outc... more Making an accurate diagnosis of appendicitis in pregnancy is critical for maternal and fetal outcomes. To determine whether magnetic resonance (MR) imaging in pregnant patients with suspected appendicitis improves outcomes, minimizes length of stay (LOS), and lowers hospital charges. Retrospective review at a university tertiary referral center of all pregnant patients seen with abdominal pain and suspected appendicitis who were followed up through delivery during an 11-year period. Time to operation, LOS, complications, nontherapeutic exploration, fetal outcomes, and hospital charges. Seventy-nine patients were included in this study, 34 of whom had pathology-confirmed appendicitis. Thirty-one patients underwent MR imaging. A trend toward fewer operations (odds ratio [OR], 0.45; 95% CI, 0.18-1.16; P = .07) was observed in the MR imaging group. Seven nontherapeutic explorations were performed in the non-MR imaging group and 1 nontherapeutic exploration in the MR imaging group (OR, 0...

Journal of Clinical Oncology

496 Background: The American Association for the Study of Liver Disease (AASLD) guidelines outlin... more 496 Background: The American Association for the Study of Liver Disease (AASLD) guidelines outline an algorithm regarding the treatment modality of choice for patients with hepatocellular carcinoma (HCC) based on Barcelona Clinic Liver Cancer (BCLC) stage. The AASLD guidelines have several limitations and the adherence rate has been reported to be low. The adherence to AASLD guidelines in treating patients with HCC was explored in this study. Methods: Between 2017 and 2019, 106 patients with HCC were identified. In our cohort, 70 patients (66%) were discussed in the multidisciplinary tumor board (MDTB) and their first-line treatment modality was selected based on consensus recommendations from the MDTB team members. The adherence rate of MDTB recommendations to AASLD guidelines was calculated. Results: Median age was 65 (range 42-90). Males represented 84% while females represented 16%. Caucasians, African Americans and Asians represented 69%, 30% and 1% respectively. BCLC stage 0, ...

Pancreas, Mar 1, 2018

The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the pa... more The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.

The American Surgeon, Apr 1, 2013

Bowel rest, nasogastric (NG) decompression, and intravenous hydration are used to treat small bow... more Bowel rest, nasogastric (NG) decompression, and intravenous hydration are used to treat small bowel obstruction (SBO) conservatively; however, there are no data to support nasogastric tube (NGT) use in patients without active emesis. We aim to evaluate the use of nasogastric decompression in SBO and the safety of managing patients with SBO without the use of a NGT. A retrospective chart review was conducted of adult patients admitted to Yale New Haven Hospital over five years with the diagnosis of SBO. We compared patients who received NG decompression with those who did not. Outcome variables assessed were days to resolution, associated complications, hospital length of stay, and disposition. Of 290 patients who fit the criteria, 190 patients (65.52%) were managed conservatively. Fifty-five patients (18.97%) did not receive NGTs. Sixty-eight patients (23.45%) did not present with emesis; however, nearly 75 per cent of these patients received NGTs. Development of pneumonia and respiratory failure was significantly associated with NGT placement. Time to resolution and hospital length of stay were significantly higher in patients with NGTs. Patients with NG decompression had a significantly increased risk of pneumonia and respiratory failure as well as increased time to resolution and hospital length of stay.

Journal of surgical education, Jan 31, 2015

The American Board of Surgery endoscopy requirements for general surgery training are evolving. I... more The American Board of Surgery endoscopy requirements for general surgery training are evolving. In 2006, the Residency Review Committee in Surgery increased the total number of endoscopy cases required before completion of general surgery residency training. This requirement is set to change further, given the new Flexible Endoscopic Curriculum that would be a requirement for applicants graduating surgical training during or after the 2017 to 2018 academic year. Given these changes, our goal was to evaluate the confidence of senior surgical residents performing flexible endoscopy. A survey was developed and sent to general surgery residents nationally, querying them regarding demographics and program-specific characteristics; additionally they were asked to rate their confidence level in performing flexible upper endoscopy and colonoscopy on a Likert scale of 1 to 5. We then compared those residents who indicated confidence (Likert scale 4-5) to those who did not (Likert scale 1-3)....

Proceedings of the National Academy of Sciences of the United States of America, Jan 31, 2015

Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglyce... more Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglycemia. Exome and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the DNA-binding zinc finger of the transcription factor Yin Yang 1 (YY1). Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that this T372R substitution changes the DNA motif bound by YY1. Global analysis of gene expression demonstrated distinct clustering of tumors with and without YY1(T372R) mutations. Genes showing large increases in expression in YY1(T372R) tumors included ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca(2+) channel); both are expressed at very low levels in normal β-cells and show mutation-specific YY1 binding sites. Both gene products are involved in key pathways regulating insulin secretion. Expression of these genes in rat INS-1 cells demonstrated markedly increased insulin secretion. These findings indicate that YY1(T372R) mutations are neomorp...

Journal of surgical oncology, 2014

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a rising in... more Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a rising incidence in the United States. The increase in medical and locally ablative therapies have improved prognosis, however surgery, either liver resection or transplantation, remains the mainstay of therapy. An increased understanding of liver anatomy, improved imaging modalities and refinements of surgical technique have all led to improved outcomes after surgery. Both resection and transplantation may be used in a complementary manner. Resection remains the treatment of choice for HCC when feasible. Liver transplantation, which removes both the tumor and the underlying diseased liver offers excellent outcomes in patients that meet the Milan criteria. While both these modalities have relatively well defined roles, the treatment of these patients must be tailored individually, using a multidisciplinary approach, to maximize survival, quality of life and allocation of scarce organs.

HPB : the official journal of the International Hepato Pancreato Biliary Association, 2014

Post-operative pancreatic fistula (POPF) formation occurs frequently after a pancreaticoduodenect... more Post-operative pancreatic fistula (POPF) formation occurs frequently after a pancreaticoduodenectomy (PD). Recently, a 10-point Fistula Risk Score (FRS) evaluating the likelihood of clinically relevant POPF (CR-POPF) development has been described and validated. This scheme has yet to be evaluated in PD patients managed without intra-operative drain placement. Among patients undergoing PD at an academic centre since 2003, a retrospective analysis calculating FRS and its correlation with CR-POPF development was evaluated by logistic regression. Secondary analysis examined presentation and management of CR-POPF in undrained PD patients. FRS was calculated for 265 patients; 97.7% were managed without operative drains. The overall incidence of CR-POPF was 7.9%. Logistic regression revealed a 1.6-fold increase in CR-POPF risk per 1-point increase in FRS [95% confidence interval (CI) 1.2-2.0]. The negative predictive value in patients with FRS <3 was 100%, whereas the positive predicti...

Journal of Surgical Education, 2015

General surgical training has changed significantly over the past decade with work-hour restricti... more General surgical training has changed significantly over the past decade with work-hour restrictions, increasing use of minimally invasive techniques, and increasing specialization, leading to decreased resident exposure to open operative techniques. Furthermore, the presence of vascular surgery fellows and the advent of dedicated vascular surgery residencies have had the potential to diminish further the vascular surgery experience of general surgery residents. Given these changes, this study was undertaken to assess the confidence of graduating general surgery residents in performing certain key open vascular maneuvers, approaches that might be required in a general surgery practice, and to determine factors associated with variations in reported confidence. A survey was developed and sent to graduating chief surgical residents nationally. We queried them regarding demographics and program characteristics and asked them to rate their confidence (rated 1-5 on a Likert scale) in performing a vascular anastomosis and 4 specific vascular control maneuvers. We then compared those who indicated confidence with those who did not. We received 653 responses from fifth-year (postgraduate year 5) surgical residents: 69% men, 67.5% from university programs, and 51% from programs affiliated with a Veterans Affairs hospital; additionally, 22% were from small programs, 34% from medium programs, and 44% from large programs. Although 70% of respondents indicated confidence performing a vascular anastomosis, less than 25% indicated confidence performing each of the 4 specified vascular maneuvers. Age, program size, future fellowship plans, surgical volume, estimated percentage of cases performed laparoscopically, and geographic location were all associated with variations in reported confidence. Graduating general surgical residents indicated a significant lack of confidence in performing specific open vascular surgical maneuvers. This decreased confidence varied regionally and was associated with both demographic and program-specific factors.

The American surgeon, 2013

Bowel rest, nasogastric (NG) decompression, and intravenous hydration are used to treat small bow... more Bowel rest, nasogastric (NG) decompression, and intravenous hydration are used to treat small bowel obstruction (SBO) conservatively; however, there are no data to support nasogastric tube (NGT) use in patients without active emesis. We aim to evaluate the use of nasogastric decompression in SBO and the safety of managing patients with SBO without the use of a NGT. A retrospective chart review was conducted of adult patients admitted to Yale New Haven Hospital over five years with the diagnosis of SBO. We compared patients who received NG decompression with those who did not. Outcome variables assessed were days to resolution, associated complications, hospital length of stay, and disposition. Of 290 patients who fit the criteria, 190 patients (65.52%) were managed conservatively. Fifty-five patients (18.97%) did not receive NGTs. Sixty-eight patients (23.45%) did not present with emesis; however, nearly 75 per cent of these patients received NGTs. Development of pneumonia and respi...

Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery, 2014

Objective The aim of this study was to review a single-institution experience with video-assisted... more Objective The aim of this study was to review a single-institution experience with video-assisted thoracoscopic pneumonectomy (VATP). Methods From July 2008 through December 2012, the medical records of all patients undergoing pneumonectomy (total and completion) for lung cancer were reviewed. Clinical parameters were recorded and analyzed. Results During this period, 16% (7/45) of pneumonectomies for malignancy were performed thoracoscopically. Patient selection was performed in the context of a multidisciplinary tumor board. Of the seven VATPs, five were standard (Video 1, available at http://links.lww.com/INNOV/A40 ) and two were completion pneumonectomies (Video 2, available at http://links.lww.com/INNOV/A41 ). Indications were primary lung cancer in six (three adenocarcinoma, one squamous carcinoma, one large cell neuroendocrine carcinoma, and one mixed adenocarcinoma cell and small cell lung carcinoma) and metastatic esophageal cancer in one patient. Preoperative selection was...

Biology, 2012

Adrenocortical tumors are frequently found in the general population, and may 20 be benign adreno... more Adrenocortical tumors are frequently found in the general population, and may 20 be benign adrenocortical adenomas or malignant adrenocortical carcinomas. Unfortunately 21 the clinical, biochemical and histopathological distinction between benign and malignant 22 adrenocortical tumors may be difficult in the absence of widely invasive or metastatic 23 disease, and hence attention has turned towards a search for molecular markers. The study 24 of rare genetic diseases that are associated with the development of adrenocortical 25 carcinomas has contributed to our understanding of adrenocortical tumorigenesis. In 26 addition, comprehensive genomic hybridization, methylation profiling, and genome wide 27 mRNA and miRNA profiling have led to improvements in our understanding, as well as 28 demonstrated several genes and pathways that may serve as diagnostic or prognostic 29 markers. 30 Keywords: (3-10 keywords separated by semi colons) 31 32 Adrenocortical tumors are frequently found in the general population, with an estimated prevalence 34 of 3-7% (1, 2) and are most often discovered incidentally(3). These tumors may be, more commonly, 35 benign adrenocortical adenomas (ACA). Malignant adrenocortical carcinoma (ACC) is a rare 36 malignancy with an estimated incidence of 0.7-2.0 cases per million per year(2-4). 37 Unfortunately the clinical, biochemical and histopathological distinction between ACA and ACC 38 may be difficult in the absence of widely invasive or metastatic disease(5-10). At present the Modified 39 Weiss Score (a histopathologic scoring) is the most widely accepted means of classifying ACC. 40 However, there is significant variation in inter-observer agreement and it does not identify molecular 41 targets for diagnosis and therapeutic intervention. A better method of distinguishing benign from 42 malignant ACTs is therefore needed, and attention has turned towards a search for molecular 43 markers(11). Current understanding of the development of adrenocortical carcinoma in the last decade 44 originated, in large part, due to the study of rare genetic diseases that are associated with the 45 development of ACC(12). In addition, comprehensive genomic hybridization, methylation profiling, 46 and genome wide mRNA and miRNA profiling have, in the more recent past, led to improvements in 47 our understanding, as well as demonstrated several genes and pathways that may serve as diagnostic or 48 prognostic markers (13-17). 49

Nature Genetics, 2013

Users may view, print, copy, download and text and data-mine the content in such documents, for t... more Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Molecular Cancer, 2013

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with high mutational he... more Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with high mutational heterogeneity and a generally poor clinical outcome. Despite implicated roles of deregulated TP53, IGF-2 and Wnt signaling pathways, a clear genetic association or unique mutational link to the disease is still missing. Recent studies suggest a crucial role for epigenetic modifications in the genesis and/or progression of ACC. This study specifically evaluates the potential role of epigenetic silencing of RASSF1A, the most commonly silenced tumor suppressor gene, in adrenocortical malignancy. Results: Using adrenocortical tumor and normal tissue specimens, we show a significant reduction in expression of RASSF1A mRNA and protein in ACC. Methylation-sensitive and-dependent restriction enzyme based PCR assays revealed significant DNA hypermethylation of the RASSF1A promoter, suggesting an epigenetic mechanism for RASSF1A silencing in ACC. Conversely, the RASSF1A promoter methylation profile in benign adrenocortical adenomas (ACAs) was found to be very similar to that found in normal adrenal cortex. Enforced expression of ectopic RASSF1A in the SW-13 ACC cell line reduced the overall malignant behavior of the cells, which included impairment of invasion through the basement membrane, cell motility, and solitary cell survival and growth. On the other hand, expression of RASSF1A/A133S, a loss-of-function mutant form of RASSF1A, failed to elicit similar malignancy-suppressing responses in ACC cells. Moreover, association of RASSF1A with the cytoskeleton in RASSF1A-expressing ACC cells and normal adrenal cortex suggests a role for RASSF1A in modulating microtubule dynamics in the adrenal cortex, and thereby potentially blocking malignant progression. Conclusions: Downregulation of RASSF1A via promoter hypermethylation may play a role in the malignant progression of adrenocortical carcinoma possibly by abrogating differentiation-promoting RASSF1A-microtubule interactions.

Journal of Clinical Oncology

e16609 Background: The Barcelona-Clinic Liver Cancer (BCLC) staging based management proposed by ... more e16609 Background: The Barcelona-Clinic Liver Cancer (BCLC) staging based management proposed by AASLD depends on baseline liver function and performance status of the patient in addition to tumor characteristics. Low adherence to AASLD guidelines, especially in advanced staged tumors, can be ascribed to suboptimal revision/updates of the guidelines reflecting the advancements in hepatocellular carcinoma (HCC) management. Here, in addition to the adherence rate, we explored the overall survival of patients with HCC according to first-line treatment modality compliance to AASLD guidelines. Methods: This is a retrospective study conducted at the University of South Alabama/Mitchell Cancer Institute. Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their compliance with suggested first-line treatment modality according to AASLD guidelines was noted. Overall survival was explored and differ...

Journal of the American College of Surgeons

Abdominal Radiology

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, with... more Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, with an estimated 53,670 new cases diagnosed and an estimated 43,090 deaths in 2017. This high mortality rate is in part due to the small percentage of patients diagnosed with local disease, as well as the biologically aggressive nature of the disease. While only 10-20% of patients will present with surgically resectable disease, this is the only possible curative therapy. Five-year survival of resected pancreatic cancer ranges from 12 to 27%. The National Comprehensive Cancer Network (NCCN) guidelines recommend specific guidelines for imaging modalities used in the diagnosis and staging of pancreatic adenocarcinoma. Indeed, high-quality imaging is not only necessary to accurately stage the disease, but is critical for the determination of key clinical decision branch points such as the determination of surgical resectability. Identification of the lesion within the pancreas, the degree of extra-pancreatic extension, and potential involvement of surrounding vascular structures with the tumor are all findings necessary to classify patients as having resectable, borderline resectable, or with unresectable primary tumors. This article reviews imaging modalities used to evaluate the pancreatic cancer patient from the surgeon&amp;amp;#39;s perspective, with particular emphasis on determination of resectability and preoperative planning, as well as imaging in the postoperative period.

Clinical Endocrinology, 2015

Aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia are important causes of s... more Aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia are important causes of secondary hypertension. Somatic mutations in KCNJ5, CACNA1D, ATP1A1, ATP2B3 and CTNNB1 have been described in APAs. To characterize clinical-pathological features in APAs and unilateral adrenal hyperplasia, and correlate them with genotypes. Retrospective study. Clinical and pathological characteristics of 90 APAs and seven diffusely or focally hyperplastic adrenal glands were reviewed, and samples were examined for mutations in known disease genes by Sanger or exome sequencing. Mutation frequencies were as follows: KCNJ5, 37·1%; CACNA1D, 10·3%; ATP1A1, 8·2%; ATP2B3, 3·1%; and CTNNB1, 2·1%. Previously unidentified mutations included I157K, F154C and two insertions (I150_G151insM and I144_E145insAI) in KCNJ5, all close to the selectivity filter, V426G_V427Q_A428_L433del in ATP2B3 and A39Efs*3 in CTNNB1. Mutations in KCNJ5 were associated with female and other mutations with male gender (P = 0·007). On computed tomography, KCNJ5-mutant tumours displayed significantly greater diameter (P = 0·023), calculated area (P = 0·002) and lower precontrast Hounsfield units (P = 0·0002) vs tumours with mutations in other genes. Accordingly, KCNJ5-mutant tumours were predominantly comprised of lipid-rich fasciculata-like clear cells, whereas other tumours were heterogeneous (P = 5 × 10(-6) vs non-KCNJ5 mutant and P = 0·0003 vs wild-type tumours, respectively). CACNA1D mutations were present in two samples with hyperplasia without adenoma. KCNJ5-mutant tumours appear to be associated with fasciculata-like clear cell predominant histology and tend to be larger with a characteristic imaging phenotype. Novel somatic KCNJ5 variants likely cause adenomas by loss of potassium selectivity, similar to previously described mutations.

World Journal of Endocrine Surgery, 2009

JAMA surgery, 2014

Making an accurate diagnosis of appendicitis in pregnancy is critical for maternal and fetal outc... more Making an accurate diagnosis of appendicitis in pregnancy is critical for maternal and fetal outcomes. To determine whether magnetic resonance (MR) imaging in pregnant patients with suspected appendicitis improves outcomes, minimizes length of stay (LOS), and lowers hospital charges. Retrospective review at a university tertiary referral center of all pregnant patients seen with abdominal pain and suspected appendicitis who were followed up through delivery during an 11-year period. Time to operation, LOS, complications, nontherapeutic exploration, fetal outcomes, and hospital charges. Seventy-nine patients were included in this study, 34 of whom had pathology-confirmed appendicitis. Thirty-one patients underwent MR imaging. A trend toward fewer operations (odds ratio [OR], 0.45; 95% CI, 0.18-1.16; P = .07) was observed in the MR imaging group. Seven nontherapeutic explorations were performed in the non-MR imaging group and 1 nontherapeutic exploration in the MR imaging group (OR, 0...