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Fifty percent of lung adenocarcinomas harbor somatic mutations in six genes that encode proteins in the EGFR signaling pathway, i.e., EGFR, HER2/ERBB2, HER4/ERBB4, PIK3CA, BRAF, and KRAS. We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis. We analyzed genomic DNA from a total of 261 resected, clinically annotated non-small cell lung cancer (NSCLC) specimens. The coding sequences of 39 genes were screened for somatic mutations via high-throughput dideoxynucleotide sequencing of PCR-amplified gene products. Mutations were considered to be somatic only if they were found in an independent tumor-derived PCR product but not in matched normal tissue. Sequencing of 9MB of tumor sequence identified 239 putative genetic variants. We further examined 22 variants found in RAS family genes and 135 variants localized to exons encoding the kinase domain of respective proteins. We identified a total of 37 non-synonymous somatic mutations; 36 were found collectively in EGFR, KRAS, BRAF, and PIK3CA. One somatic mutation was a previously unreported mutation in the kinase domain (exon 16) of FGFR4 (Glu681Lys), identified in 1 of 158 tumors. The FGFR4 mutation is analogous to a reported tumor-specific somatic mutation in ERBB2 and is located in the same exon as a previously reported kinase domain mutation in FGFR4 (Pro712Thr) in a lung adenocarcinoma cell line. This study is one of the first comprehensive mutational analyses of major genes in a specific signaling pathway in a sizeable cohort of lung adenocarcinomas. Our results suggest the majority of gain-of-function mutations within kinase genes in the EGFR signaling pathway have already been identified. Our findings also implicate FGFR4 in the pathogenesis of a subset of lung adenocarcinomas.

Bronchogenic cysts are foregut-derived developmental anomalies most commonly encountered in the mediastinum and rarely in the abdomen or retroperitoneally. A comprehensive review of the English-language literature of subdiaphragmatic bronchogenic cysts (sBCs) revealed only 48 reported cases of sBC. Although most cases are incidentally discovered, preoperative differential diagnosis often includes tumors with malignant potential and necessitates surgical resection to obtain a definitive diagnosis. Herein, we describe a case of a 46-year-old female presenting with intermittent left flank pain, upon which computed tomography demonstrated a retroperitoneal mass. Upon resection, histopathology revealed the mass to be a thin-walled cystic mass lined by ciliated columnar cells and cartilage, consistent with a subdiaphragmatic bronchogenic cyst. A comprehensive literature review of sBC was also performed.

Appendectomy for appendicitis is one of the most common procedures performed in the United States. Residual tissue left after an initial appendectomy risks the development of stump appendicitis. A comprehensive review of the English-language literature revealed 36 reported cases of stump appendicitis. Typically, patients present with signs and symptoms similar to acute appendicitis; however, due to prior surgery, the diagnosis is difficult and the rate of appendiceal stump perforation is extremely high. Herein, we present a case of a 32-year-old female presenting with right lower quadrant pain, nausea, and fever 5 months after laparoscopic appendectomy. Upon surgery, an appendiceal stump was discovered.

Severe hypophosphatemia (<1.0 mg/dl) is a rarely reported complication of acute pancreatitis; when it does occur, it is typically attributed to alcohol abuse rather than the pancreatitis itself (1-5). In the literature, pancreatitis is not cited as a cause of hypophosphatemia (5, 6-16). Both pancreatitis and hypophosphatemia have widespread ramifications on human physiology, affecting hematologic, neural, hepatic, endocrine, respiratory, and renal systems. Given the possible synergistic consequences of pancreatitis and low serum phosphate, we emphasize the importance of recognizing hypophosphatemia as a complication of pancreatic inflammation.Herein, we report a case of acute pancreatitis unrelated to alcohol abuse associated with severe hypophosphatemia and review the pathophysiology.

Background/Aims: Squamous cell carcinoma of the colon is a rare entity. We report a case of a patient who presented with a perforated squamous cell carcinoma of the sigmoid colon. Results: A 45-year-old female presented with a 2-month history of worsening abdominal pain, bloody diarrhea, and vomiting. She underwent an exploratory laparotomy and was found to have keratinizing squamous cell carcinoma of the sigmoid colon that had perforated forming multiple abscess cavities. The postoperative course was complicated by hypercalcemia and persistent hyperleukocytosis, ultimately resulting in the patient’s death. Conclusions: We present the second reported case of squamous cell carcinoma of the colon associated with hypercalcemia and the first reported case of associated hyperleukocytosis.

Squamous cell carcinoma of the colon is a rare entity. We report a case of a patient who presented with a perforated squamous cell carcinoma of the sigmoid colon. A 45-year-old female presented with a 2-month history of worsening abdominal pain, bloody diarrhea, and vomiting. She underwent an exploratory laparotomy and was found to have keratinizing squamous cell carcinoma of the sigmoid colon that had perforated forming multiple abscess cavities. The postoperative course was complicated by hypercalcemia and persistent hyperleukocytosis, ultimately resulting in the patient's death. We present the second reported case of squamous cell carcinoma of the colon associated with hypercalcemia and the first reported case of associated hyperleukocytosis.

Background Simulators may improve the efficiency, safety, and quality of endoscopic training. However, no objective, reliable, and valid tool exists to assess clinical endoscopic skills. Such a tool to measure the outcomes of educational strategies is a necessity. This multicenter, multidisciplinary trial aimed to develop instruments for evaluating basic flexible endoscopic skills and to demonstrate their reliability and validity. Methods The Global Assessment of Gastrointestinal Endoscopic Skills (GAGES) Upper Endoscopy (GAGES-UE) and Colonoscopy (GAGES-C) are rating scales developed by expert endoscopists. The GAGES scale was completed by the attending endoscopist (A) and an observer (O) in self-assessment (S) during procedures to establish interrater reliability (IRR, using the intraclass correlation coefficient [ICC]) and internal consistency (IC, using Cronbach’s alpha). Instrumentation was evaluated when possible and correlated with total scores. Construct and external validity were examined by comparing novice (NOV) and experienced (EXP) endoscopists (Student’s t -test). Correlations were calculated for GAGES-UE and GAGES-C with participants who had performed both. Results For the 139 completed evaluations (60 NOV, 79 EXP), IRR (A vs. O) was 0.96 for GAGES-UE and 0.97 for GAGES-C. The IRR between S and A was 0.78 for GAGES-UE and 0.89 for GAGES-C. The IC was 0.89 for GAGES-UE, and 0.95 for GAGES-C. There were mean differences between the NOV and the EXP endoscopists for GAGE-UE (14.4 ± 3.7 vs. 18.5 ± 1.6; p  < 0.001) and GAGE-C (11.8 ± 3.8 vs. 18.8 ± 1.3; p  < 0.001). Good correlation was found between the scores for the GAGE-UE and the GAGE-C ( r  = 0.75; n  = 37). Instrumentation, when performed, demonstrated correlations with total scores of 0.84 (GAGE-UE; n  = 73) and 0.86 (GAGE-C; n  = 45). Conclusions The GAGES-UE and GAGES-C are easy to administer and consistent and meet high standards of reliability and validity. They can be used to measure the effectiveness of simulator training and to provide specific feedback. The GAGES results can be generalized to North American and European endoscopists and may contribute to the definition of technical proficiency in endoscopy.

Recommended procedure numbers for upper endoscopy (UE) and colonoscopy (C) are 35 and 50 for surgical residents, and 130 and 140 for gastroenterology fellows, respectively. The purpose of this study was to challenge the methods used to determine proficiency in flexible endoscopy. Global assessment of gastrointestinal endoscopic skills (GAGES) was used to evaluate 139 procedures. Scores for UE were compared using self-reported case numbers and grouped according to requirements for each discipline. C scores were compared using the requirements to define novice and experienced endoscopists. Procedure volumes were plotted against GAGES scores. Three groups were compared for UE based on case volumes: fewer than 35 cases (group 1), 35 to 130 cases (group 2), and more than 130 cases (group 3). There was no difference between group 2 (17.8 ± 1.8) and group 3 (19.1 ± 1.1), but both scored higher than group 1 (14.4 ± 3.7; P < .05). For C, the scores were 11.8 ± 3.8 (novices) and 18.8 ± 1.34 (experienced; P < .001) at a 50-case minimum and 12.4 ± 4.2 and 18.8 ± 1.3 ( P < .001) for a 140-case proficiency cut-off level, respectively. The curve of procedures versus GAGES plateaued at 50 (UE) and 75 (C). The surgical and gastroenterology case recommendations may not represent the experience needed to achieve proficiency. GAGES scores could help define proficiency in basic endoscopy.