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Background: Epidemiologic studies demonstrated higher incidence of thyroid cancer in patients with multinodular goiters compared to the general population. The aim of this study was to evaluate the risk of finding significant thyroid cancer in patients undergoing thyroidectomy for presumed benign disease., Methods: The records of 273 patients operated for indications other than cancer or indeterminate cytology were reviewed and analyzed., Results: 202 (74%) patients had a preoperative fine-needle aspiration (FNA) performed. FNA was benign in 96% of patients and non-diagnostic in 4%. Malignancy was unexpectedly found in 50 (19%) patients. Papillary carcinoma constituted 94% of cancers and 86% of cancers were incidental microcarcinomas. Only 7 (2.6%) patients of the entire cohort had tumors greater than 1 cm, of those only 3 had a previous benign FNA (false-negative rate 1.5%)., Conclusions: The rate of significant thyroid cancer found unexpectedly in resected goiters is extremely low. A negative FNA excludes significant cancer with near certainty.

Background: Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely., Case Report: A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushing's syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease., Conclusion: We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushing's syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently.

Background: We recently reported a grading system for surgical complications. This system proved to have a high sensitivity for recording minor but meaningful complications prolonging hospital stay in patients after colorectal surgery. We aimed to prospectively validate the complication grading system in a general surgery department over 1 year., Methods: All surgical procedures and related complications were prospectively recorded between January 1st and December 31st, 2009. Surgical complications were graded on a severity scale of 1-5. The system classifies short-term outcome by grade emphasizing intensity of therapy required for treatment of the defined complication., Results: During the study period, 2114 patients underwent surgery. Elective and oncological surgeries were performed in 1606 (76%) and 465 (22%) patients, respectively. There were 422 surgical complications in 304 (14%) patients (Grade 1/2: 203 [67%]; Grade 3/4: 90 [29%]; Grade 5: 11 [4%]). Median length of stay correlated significantly with complication severity: 2.3 d for no complication, 6.2 and 11.8 d for Grades 1/2 and 3/4, respectively (P < 0.001). Older age (OR 2.75, P < 0.001), comorbidities (OR 1.44, P = 0.02), American Society of Anesthesiology score >2 (OR 2.07, P < 0.001), contamination Grade (OR 1.85, P = 0.001), oncological (OR 2.82, P < 0.001), open (OR 1.22, P = 0.03), prolonged >120 min (OR 2.08, P < 0.001), and emergency surgery (OR 1.42, P = 0.02) independently predicted postoperative complications., Conclusions: This system of grading surgical complications permits standardized reporting of surgical morbidity according to the severity of impact. Prospective validation of this system supports its use in a general surgery setting as a tool for surgical outcome assessment and quality assurance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Single adenoma is the cause of 80 % of primary hyperparathyroidism (PHPT) resulting in wide acceptance of minimally invasive parathyroidectomy (MIP). The incidence of PHPT increases with age. Little information is available regarding the prevalence of multiglandular disease (MGD) in older patients., Methods: The records of 537 patients that underwent parathyroid surgery between January 2005 and October 2012 at two endocrine surgery referral centers were retrospectively reviewed. Comparison was performed between patients younger than 65 and older than 65 years of age. Clinical variables included preoperative laboratories and imaging, extent of neck exploration, number of glands excised, and intraoperative parathyroid hormone levels during surgery., Results: There were 374 (70 %) patients in the younger age group (YG) and 163 (30 %) patients in the older age group (OG). The mean age was 50 ± 0.5 and 71 ± 0.4 years, respectively. There was no difference between the groups in terms of gender or laboratory results. MGD was significantly more common in the OG (24 % vs. 12 %; p = 0.001) and similarly MIP was less commonly completed in the OG (49 % vs. 68 %; p < 0.001). Cure rates were comparable between the OG and YG (93 % vs. 95 %; p = 0.27). In the OG, patients with MGD had significantly smaller glands as compared to patients with single adenomas in this group (331 ± 67 vs. 920 ± 97 mg; p = 0.006, respectively)., Conclusions: MGD in PHPT was found to be more prevalent in older patients. Planning a bilateral neck exploration should be considered in older patients, especially when a relatively small gland is suggested by imaging or encountered during surgery.

Introduction: Young breast cancer patients undergoing breast-conserving surgery have a significantly higher rate of local recurrence compared with older women. The aim of this study was to assess whether the volume of tissue excised may be associated with the higher local recurrence rate seen in young patients., Methods: Medical records of patients who underwent breast-conserving surgery at a single institution between 1987 and 2001 were reviewed retrospectively. Tumor and specimen volumes were extracted from pathology reports, and specimen-to-tumor-volume ratio (STVR) was calculated. STVR and local recurrence rates were compared for women under 40 and over 50 y of age., Results: Data were available for 97 patients under age 40 and 150 women over age 50. Patients under 40 had significantly more high-grade tumors (57% versus 25%, P < 0.0005). There was no significant difference in average tumor size; however, both specimen volume and STVR (log scale) were lower in younger women: 4.63 versus 5.20, P < 0.001 and 3.81 versus 4.55, P < 0.001, respectively. Younger women also had a significantly higher rate of local recurrence: 17% versus 7%, P = 0.03. On multivariate analysis, lower STVR was significantly associated with a higher recurrence rate for the entire group (P < 0.005) and, to a lesser degree, in younger women (P = 0.05)., Conclusions: The volume of tissue removed in women younger than 40 undergoing breast-conserving therapy tends to be smaller than in older women. This may contribute to the higher local recurrence rates observed in young breast cancer patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Fine needle aspiration biopsy (FNAB) is the most commonly used diagnostic tool to differentiate benign from malignant thyroid nodules. Nevertheless, some FNAB cytology results are not definite. In such cases diagnostic thyroid lobectomy is performed with malignancy rate on final histopathology ranging at 15%-75%. The aim of this study was to improve on the accuracy of FNAB-based cytology by amplification of microRNAs (micro ribonucleic acids [miRs]) from the residual cells left in the FNAB needle after submission for cytology., Methods: Residual cells were collected from the needle cup after FNAB cytology of 77 consecutive patients with thyroid nodules. miR-enriched RNA was extracted for all patients with cytology showing either follicular lesion or suspicion for malignancy (n=11). The expression of miR-21, -31, -146b, -187, -221, and -222 was determined using real-time polymerase chain reaction. Results were compared with final surgical histopathology., Results: RNA was successfully extracted from all FNAB specimens. Five patients had FNAB cytology suspicious for malignancy. The miR panel was positive in all five (100%). Six patients had follicular lesions on FNAB. The miR panel was positive in three of four patients (75%) with confirmed malignancy and was negative in two of two (0%) patients with benign pathology results. This corresponded to a specificity of 100%, sensitivity of 88%, and accuracy of 90%., Conclusions: RNA extraction from FNAB residual cells is feasible, and a miR panel amplified from the extracted RNA seems like a promising diagnostic tool in this limited number of patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Current recommendations for treating acute calculus cholecystitis include the use of intravenous antibiotics, although these recommendations were never tested scientifically. The aim of this study was to evaluate the role of intravenous antibiotic therapy in patients with mild acute calculus cholecystitis., Methods: In this prospective, randomized controlled trial, 84 patients with a diagnosis of mild acute calculus cholecystitis were randomly assigned to supportive treatment only or supportive treatment with intravenous antibiotic treatment (42 patients in each arm). Patients were followed through their index admission and until delayed laparoscopic cholecystectomy was performed., Results: The two study groups did not differ in their demographic data or in the clinical presentation and disease severity. Analysis was conducted on the intent-to-treat basis. Patients in the intravenous antibiotics arm resumed a liquid diet earlier (1.7 vs. 2.2 days, p = 0.02) but did not significantly differ in resumption of regular diet (2.8 vs. 3.2 days, p = 0.16) or hospital length of stay (LOS) (3.9 vs. 3.8 days, p = 0.89). Patients in the intravenous antibiotics arm had rates of percutaneous cholecystostomy tube placement (12 vs. 5 %, p = 0.43), readmissions (19 vs. 13 %, p = 0.73), and perioperative course similar to those not receiving antibiotics. The overall hospital LOS, including initial hospitalization and subsequent cholecystectomy, was similar for both groups (5.6 vs. 5.1 days, p = 0.29). Eight (19 %) patients in the supportive arm were crossed over to the intravenous antibiotic arm during the index admission., Conclusions: Intravenous antibiotic treatment does not improve the hospital course or early outcome in most of the patients with mild acute calculus cholecystitis.

General Surgery is losing its appeal and is facing a critical shortage of surgeons. It therefore has to change and adapt to this new reality and we surgeons are responsible for meeting this challenge. If we want students and residents to embrace surgery we need to show them the rewards and satisfaction that we derive from the profession. A 5 year curriculum is needed to train the "abdominal surgery" or "general surgery specialist," who will maintain and teach comprehensive care of the surgical patient and practice a more limited scope of surgical procedures. In addition, we should train a limited number of disease-oriented specialists by means of 1-2 year fellowships.

Background: Multifocality is an important factor when recommending surgery for papillary thyroid cancer (PTC). The aim of this study is to assess the incidence and characterize the spread pattern of multifocal PTC (mPTC) in patients undergoing total thyroidectomy., Methods: All thyroidectomies performed between 2003 and 2008 were reviewed identifying 289 patients. Data were obtained for demographics, clinical data, and histopathological findings., Results: Of the patients with papillary carcinoma, mPTC was identified in 150 patients (57%), of which 71% had lesions in the contralateral lobe. There were no significant differences in multifocality rate for gender, pathology type, and all tumor size subgroups including ≤1 cm. Pathology examination of representative sections versus the entire gland examination resulted in a significantly lower incidence of contralateral disease (P = .04)., Conclusions: Multifocal and contralateral lesions are common in PTC and their incidence is not related to tumor size. Pathology entire gland examination is strongly recommended to properly assess the rate of mPTC., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC). This study evaluates long-term (10-year) outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV) or 5-FU/Levamisole (5FU+LEV)., Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months., Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02) and gastrointestinal toxicity with 5FU+LV (p=0.03). Female patients treated with 5FU+LEV had improved overall survival., Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

Background: Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms., Methods: The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection., Results: Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively., Conclusions: miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.

Context: Perivascular epithelial cell tumors (PEComas) are a family of rare mesenchymal neoplasms which share cellular, immunohistochemical and ultrastructural characteristics but are found in different visceral and soft tissue sites. PEComas of the pancreas are extremely rare neoplasms., Case Report: We describe a 49-year-old male who was incidentally diagnosed with a pancreatic mass. Endoscopic ultrasound-guided biopsy suggested a PEComa. An uneventful pylorus-preserving pancreaticoduodenectomy was thus performed. The tumor was a solid well-circumscribed mass in the pancreatic head with dilatation of the main pancreatic duct. Histopathology revealed a well-circumscribed and vascularized neoplasm, measuring 32x27x30 mm, composed of epithelioid smooth muscle cells with clear cytoplasm rich in glycogen. The tumor exhibited immunoreactivity to alpha-smooth muscle actin and to melanoma-associated antigen HMB-45., Conclusions: Although rare, pancreatic PEComas should be included in the differential diagnosis of a pancreatic mass. Currently, the paucity of cases published makes it impossible to predict the behavior and prognosis of these tumors or to advocate an optimal therapy.

Background: In recent years, a significant decline in the number of medical school graduates who choose general surgery as a career has been noted in Israel. The aim of this study is to characterize the factors that deter Israeli medical students from choosing general surgery. Previous studies in the United States identified lifestyle and financial issues as the most important factors., Methods: A web-based survey was distributed to graduating medical students throughout Israel. The survey covered different factors and aspects affecting career choice, requiring participants to rate their choices with a 1-5 score., Results: In all, 218 surveys were completed; 72 (33%) students considered general surgery before the surgical clerkship versus only 48 (22%) students after. Professional interest and satisfaction (4.7) were ranked as the most important factors for choosing a residency, followed by an amiable working atmosphere (4.3). The 2 strongest deterrents from general surgery were doctors' inter-relationships (3.5) and compromised lifestyle (3.3). The decision to avoid surgery can be reversed by improving both lifestyle (3.5) and inter-relationships (3.0), but it is less influenced by a substantial increase in residents' salary., Conclusions: More medical graduates would consider general surgery as a career option if the lifestyle and inter-relationships were perceived as better. An increase in monetary reward did not seem to have a paramount impact among Israeli medical graduates. The surgical clerkship is an important turning point in the students' attitude toward surgery as a career and efforts must be made to improve students' experience significantly during this clerkship., (Copyright © 2010 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Vascular injuries caused by subclavian central venous catheter (CVC) insertion can be associated with major complications. Such injuries differ in clinical presentation as well as optimal management, which ranges from observation only to surgical or endovascular repair. We report an injury to a branch of the internal mammary artery following an attempt to introduce a subclavian CVC, resulting in a massive hemothorax. This very rare injury was diagnosed and treated by angiography and embolization; however, the patient later succumbed to multi-organ failure. Suspicion of such an injury in a similar clinical setting should result in immediate angiography that can be lifesaving. To the best of our knowledge, this is the only report of such an adverse event in an adult., (2010 Elsevier Inc. All rights reserved.)

Background: Fine needle aspiration is the main diagnostic tool used to assess thyroid nodules., Objectives: To correlate FNA cytology results with surgical pathological findings in two teaching medical centers across the Atlantic., Methods: We retrospectively identified 484 patients at Hadassah Hebrew University Medical Center, Jerusalem and Mount Sinai Hospital, New York, by means of both preoperative FNA cytology and a final histopathological report. Results compared FNA diagnosis, histological findings and frozen section results (Mt. Sinai only)., Results: The sensitivity value of FNA at Hadassah was 83.0% compared with 79.1% at Mt. Sinai (NS). Specificity values were 86.6 vs. 98.5% (P < 0.05), negative predictive value 78.7 vs. 77.6% (NS) and positive predictive value 89.7 vs. 98.6% (P < 0.05), respectively. "Follicular lesion" was diagnosed on FNA in 33.1% of the patients at Hadassah and in 21.5% at Mt Sinai (P < 0.005) with a malignancy rate of 42.5 vs. 23.1% (P < 0.05), respectively. Frozen section was used in 190 patients at Mt. Sinai (78.5%) with sensitivity and specificity values of 72.3% and 100%. Frozen section results altered the planned operative course in only 6 patients (2.5%). Follicular carcinoma was diagnosed in 12 patients at Hadassah vs. 2 patients at Mt. Sinai (P < 0.05)., Conclusion: The sensitivity of FNA at the two institutions was comparable. While malignancy on frozen section is highly specific, it should be used selectively for suspicious FNA results. Follicular lesions and the rate of malignancy in such lesions were more common at Hadassah, favoring a more aggressive surgical approach.

Background: Uniform and accurate reporting of surgical complications is the basis for quality control. We developed a computerized system for reporting and grading surgical complications in colorectal surgery. This study was conducted to evaluate this computerized reporting system., Study Design: A retrospective chart review was conducted of all surgical complications in patients who underwent resection of the colon or rectum at our institution between the years 1999 and 2004 (n = 408). All complications were recorded using the computerized reporting system and compared with complications reported in the literature., Results: Elective operations were performed in 75.7% of patients, and 24.3% required emergency operations. Of the 408 patients in the study, 239 (58.6%) had an uneventful recovery without complications. At least 1 complication was recorded in 169 (41.4%) patients. Grades 1 and 2 complications were recorded in 83 (20.3%) and 105 (25.7%) patients, respectively, requiring observation or medical treatment only, and 59 patients (14.5%) had grades 3 to 5 complications. The three leading complications were surgical site infection, intraabdominal abscess, and hemorrhage requiring blood transfusion. The grades 3 to 5 complication rate was within the range described in the literature, and the rate of grades 1 and 2 complications was substantially higher. These grades 1 and 2 complications were associated with a substantially longer hospital stay., Conclusions: This novel complication reporting system was found feasible and proved to have a higher sensitivity for recording minor but meaningful complications that tend to prolong hospital stay.

Context: Lithium-associated hyperparathyroidism (LAH) was first described in 1973 but many issues remain in question regarding the pathophysiology as well as the appropriate management of this condition., Objective: Report of four new cases and review of the literature., Results: We describe two males and two females, treated for more than 10 years with lithium due to bipolar disorder, who developed LAH. All underwent parathyroidectomy. In three cases (75%), pathology revealed multiglandular disease, with hyperplasia or two parathyroid adenomas. We observed a cure status in three (75%) of the operated patients. The fourth patient had a residual disease, but had controlled hypercalcemia under the calcimimetic drug cinacalcet. We also observed the association of LAH with incidental papillary thyroid carcinoma in two patients. Review of the literature identified a higher prevalence of LAH in women than men (four out of one) and a controversy in regard to the prevalence of multiglandular disease. As a result, there is no consensus regarding the preferred surgical procedure. The use of cinacalcet as an effective treatment of LAH was previously described in only five cases., Conclusion: In our view, there are apparently two different mechanisms leading to LAH: exacerbation of a pre-existing state of hyperparathyroidism and multiglandular disease. For uncontrolled hypercalcemia, parathyroidectomy is recommended. The issue of routine four-gland exploration and subtotal parathyroidectomy versus intraoperative PTH-determination-guided excision of enlarged glands is still unresolved. The use of the recently developed calcimimetics may offer an alternative to patients who are not candidates for surgery.

Background: Laparoscopic hernia repair has been gaining acceptance as an alternative to open repair. The aim of this study was to present the experience of a general surgery ward with laparoscopic inguinal hernia repair., Materials and Methods: A retrospective search of all laparoscopic inguinal hernia repairs between January 1999 and December 2003 was obtained. Data, including perioperative course, postoperative complication, and long-term follow-up, was documented., Results: A total of 423 hernias were repaired in 220 patients. Long-term follow-up was performed by questionnaire, clinic visit, or both in 182 of the 220 patients (82.7%). Median follow-up time was 27.5 (range, 4-61) months. Two hundred and three (92.3%) hernias were bilateral. Fifty-seven patients (25.9%) had recurrent hernias. There was no conversion to an open hernia repair. There were 10 recurrences (2.3%). Minor complications (e.g., abdominal wall hematoma, epigastric vessels injury, and urinary retention requiring catheterization) occurred in 17 (7.7%) patients. A bladder injury occurred in 1 patient (0.45%). There was no mortality. Mean postoperative stay was 1.1 days (range, 1-10). Satisfaction with the laparoscopic repair was expressed by using a scoring system of 1 to 5, with 85.2% being very satisfied (score of 4-5) and 8.2% being dissatisfied (score of 1-2)., Conclusions: The laparoscopic herniorrhaphy offers a safe and effective repair with acceptable complication and recurrence rates. Good results with the total extraperitoneal technique can be achieved by general laparoscopists and not only in highly specialized hernia centers. It is especially suited for bilateral repair and for recurrent hernias.

Background: Electrical impedance scanning (EIS) identifies tissue impedance changes associated with malignancy. Methods to distinguish benign from malignant thyroid nodules, particularly in patients with indeterminate cytology are lacking., Purpose: To determine the diagnostic accuracy of EIS in the preoperative evaluation of thyroid nodules., Patients and Methods: From September 2002 to December 2006, 216 patients underwent thyroid fine needle aspiration (FNA) and EIS prethyroidectomy in this prospective cohort study. EIS, either positive or negative for malignancy, was correlated with final histopathology. A focal bright spot over a thyroid nodule correlating with increased conductivity and/or capacitance >25% baseline sternocleidomastoid muscle impedance defined positive EIS. Study endpoints were EIS accuracy, sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV). This study has been registered in the National Institutes of Health's public trials registry at ClinicalTrials.gov. The registration number is NCT00571077., Results: EIS correctly diagnosed 96 of 110 patients with malignant and 75 of 106 patients with benign dominant thyroid nodules: Sn = 87%, Sp = 71%, PPV = 76%, NPV = 84%: overall EIS accuracy = 79%. Pretest cancer probability of 51% (110 of 216) increased to 76% (96 of 127) post-EIS, and preoperative use of EIS would result in a significant reduction (71%, 75 of 106) in number of operations performed for benign nodules. EIS performance was similar for 109 patients with indeterminate FNA: Sn = 83%, Sp = 67%, PPV = 61%, NPV = 87%, accuracy = 73%. Pretest probability of cancer increased from 39% (42 of 109) to 61% (35 of 57) post-EIS. The use of EIS would result in a significant reduction (67%, 45 of 67) in the number of purely diagnostic thyroidectomy for indeterminate FNA., Conclusion: EIS shows promise in differentiating thyroid nodules. Further EIS hardware and software optimization is warranted to improve upon the already favorable negative predictive value in indeterminate thyroid nodules.

Background: This study was conducted to determine survival according to the expression of molecular markers in colorectal cancer (CRC) patients of various ethnic origins., Methods: Resection of primary tumor was conducted on 171 patients with CRC. Corresponding archived paraffin-embedded blocks were retrieved and tissue microarray (TMA) constructed. Immunohistochemical staining of the TMA for p53, p27 and Ki-67 was quantified by two independent pathologists. Survival was analyzed using the Kaplan-Meier product limit method., Results: With a median follow-up of 65 months, 56 patients (32.7%) died of disease. AJCC stage correlated with disease-free (DFS, P < 0.0001) and overall survival (OS, P < 0.0001). IHC staining was positive for Ki-67 in 77.4%, p53 in 55.8% and p27 in 54.2% of patients. Primary tumor marker expression did not correlate with DFS or OS. The 5-year DFS for Ashkenazi Jews was 75%, significantly higher than Sephardic Jews (SJ) 64% and Palestinian Arabs (PA) 38%, P = 0.001., Conclusions: Ethnicity among Ashkenazi and SJ and PA appears to have a significant impact on disease outcome in patients with CRC patients, while primary tumor expression of p53, p27 and Ki-67 was unrelated to disease outcome., ((Copyright) 2008 Wiley-Liss, Inc.)

Intussusception (IS), an invagination of a portion of the intestine into itself, has recently attracted considerable interest after the withdrawal of a rotavirus vaccine because of reports on increased risk of IS shortly after vaccination. The present study was designed to shed further light on the mechanism of IS formation and its prevention. Intussusception was induced in adult mice by intraperitoneal injection of lipopolysaccharide (LPS; 8 mg/kg) from salmonella typhimurium. The presence of IS was confirmed at laparotomy. The serum levels TNF-alpha were measured with ELISA. Six hours after LPS injection, 14.5% of the animals demonstrated IS. A total of 65 animals received rofecoxib (20 mg/kg), a selective COX2 inhibitor, 15-30 min before intraperitoneal injection of LPS, and only two (3%) in this group demonstrated IS 6 h later (P < 0.05 vs. control). We confirmed the well-known increase in serum TNF-alpha levels in response to LPS; however, this increase was not blocked by rofecoxib pretreatment. Notably, there was no correlation between the serum TNF-alpha levels and the development of IS. The results show that the occurrence of IS can be significantly decreased by pretreatment with a selective COX-2 inhibitor.

The submucosal plexus regulates various activities of the gastrointestinal mucosa. As the submucosa in the human colon contains adipose tissue we hypothesized that submucosal neurons might also innervate this tissue. We stained submucosal nerves for the enzyme NADPH-diaphorase, which is a marker for nitric oxide synthase-containing nerves. This resulted in the staining of neurons in submucosal ganglia and numerous nerve fibers throughout the submucosa. These fibers were found to be in close contact with adipocytes, and in many cases fine nerve fibers displaying varicosities were found on the surface of these cells. At least some of these fibers originated from submucosal neurons. In addition, cell bodies of submucosal neurons were in close proximity to adipocytes. It is concluded that submucosal nerves innervate adipose tissue in the submucosa, which is a novel role for these nerves, and might have important functional implications.

Objectives: Soybeans have been shown to have numerous health benefits, but the underlying mechanisms are poorly understood. The aim of this study was to characterize some pharmacologic properties of active substances in aqueous soy extract., Methods: The pharmacologic actions of the extract were tested by measuring mechanical activity of isolated guinea-pig ileum in an organ bath., Results: The ileum contracted in response to soy extract in a concentration-dependent manner. This response was unaffected by the nerve blocker tetrodotoxin (10(-6) M) but was completely inhibited by atropine (10(-9) M), indicating an action via muscarinic receptors on the muscle. In the presence of the M(3) muscarinic antagonist 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide and to a lesser extent in the presence of the M(2) muscarinic antagonist 11-([2-[(diethylamino)methyl]-1-piperidinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one, the response was decreased. When acetylcholine (ACh) esterase inhibitors were added to the medium before the addition of soy extract, the response to the extract was potentiated. Preincubation of the extract with exogenous ACh esterase reduced its activity. The response to choline, ACh, and phosphorylcholine was also tested, and none of these substances accurately replicated the response to soy extract. However, some qualitative similarities were observed between the effect of choline and ACh to that of the extract., Conclusion: These results indicate the presence of an ACh-like substance in soy. Due to the abundance and importance of muscarinic receptors, the presence of a cholinergic substance in soy could have numerous implications. The role of this substance in the beneficial effect of soy on various body systems merits further investigation.

Background: Fine-needle aspiration (FNA) is widely used as a diagnostic tool to assess thyroid nodules. This study correlates FNA cytology results with surgical pathologic findings., Methods: All thyroidectomies performed between 1994 and 2004 were reviewed, identifying 242 patients. Data were obtained for FNA diagnosis, demographics, findings on ultrasound, and histologic findings., Results: Among 89 patients with a carcinoma on FNA, 89% of cases were verified on final histopathology. Of 78 patients with "follicular lesion" on FNA, only 36% of cases were verified to be malignant at surgery. Only 13% of the 75 cases diagnosed as benign, mostly colloid nodules, on FNA were found to have a carcinoma on histopathology., Conclusion: A cytologic diagnosis of papillary carcinoma has a highly predictive of thyroid cancer. When dealing with follicular lesions the predictive value of FNA drops considerably. However, we found a 13% false positive result to occur in FNA declared benign lesions.

Background: The principal role of sentinel lymph node (SLN) sampling and ultrastaging in colon cancer is enhanced staging accuracy. The utility of this technique for patients with colon cancer remains controversial., Purpose: This multicenter randomized trial was conducted to determine if focused assessment of the SLN with step sectioning and immunohistochemistry (IHC) enhances the ability to stage the regional nodal basin over conventional histopathology in patients with resectable colon cancer., Patients and Methods: Between August 2002 and April 2006 we randomly assigned 161 patients with stage I-III colon cancer to standard histopathologic evaluation or SLN mapping (ex vivo, subserosal, peritumoral, 1% isosulfan blue dye) and ultrastaging with pan-cytokeratin IHC in conjunction with standard histopathology. SLN-positive disease was defined as individual tumor cells or cell aggregates identified by hematoxylin and eosin (H&E) and/or IHC. Primary end point was the rate of nodal upstaging., Results: Significant nodal upstaging was identified with SLN ultrastaging (Control vs. SLN: 38.7% vs. 57.3%, P = 0.019). When SLNs with cell aggregates < or =0.2 mm in size were excluded, no statistically significant difference in node-positive rate was apparent between the control and SLN arms (38.7% vs. 39.0%, P = 0.97). However, a 10.7% (6/56) nodal upstaging was identified by evaluation of H&E stained step sections of SLNs among study arm patients who would have otherwise been staged node-negative (N0) by conventional pathologic assessment alone., Conclusion: SLN mapping, step sectioning, and immunohistochemistry (IHC) identifies small volume nodal disease and improves staging in patients with resectable colon cancer. A prospective trial is ongoing to determine the clinical significance of colon cancer micrometastasis in sentinel lymph nodes.

Carbohydrate antigen (CA) 19-9 is produced by adenocarcinomas of the pancreas, stomach, gall bladder, colon, ovary and lung. Serum CA 19-9 is considered the most sensitive marker for pancreatic cancer, being elevated in 75% or more of patients with pancreatic cancer. In all three cases of pancreatic cancer presented, patients died of their disease quite shortly after diagnosis. Preoperative imaging was unsuccessful in exposing the actual advanced state extent of the disease and even during surgery its real extent was underestimated. The only prognostic indicator of the observed rapid disease progression was a very significant elevation of preoperative serum CA 19-9.

Objective: To suggest guidelines for hospital organization during terror-related multiple casualty incidents (MCIs) based on the experience of 6 level I trauma centers., Summary Background Data: Most terror-related MCIs are bombings. The sporadic nature of these events complicates in-hospital preparation., Methods: Data were collected at all level I Trauma centers during/after MCIs for the Israel National Trauma registry. Patients were included if they were admitted or died in hospital following injury in suicide bombings (October 1, 2000 to June 30, 2003), which fulfilled Ministry of Health suggested criteria for MCIs (number of admissions, severity of injury)., Results: Included were 325 casualties from 32 events, 34% of which had an Injury Severity Score >16. A third of the admissions arrived within 10 minutes and 65% within 30 minutes. Forty percent of the patients underwent CT scans directly from the ED. Operative procedures were performed on 60% of patients and 36% were transferred directly from the ED to the OR. Initiation of surgical procedures peaked at 1 to 1.5 hours, mainly multidisciplinary abdominal, thoracic, and vascular surgery. Orthopedic and plastic surgery predominated later. A third of the patients were admitted to ICUs, often (31%) directly from the ED., Conclusions: High staffing demands for ED, OR, and ICU overlap. Anesthesiologists, general, thoracic, and vascular surgeons are in immediate demand. ICU admissions occur simultaneously with ongoing patient arrival to the ED. Most patients operated within the first 2 hours require multidisciplinary surgical teams. Demand for orthopedic and plastic surgery and anesthesiology services continues for >24 hours.

The presence of metastases in lymph nodes is the most powerful prognostic factor in breast cancer patients. Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. The aim of the present study was to develop a multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of minimal residual disease in sentinel nodes of breast cancer patients. RNA was extracted from 30 sentinel lymph nodes (SLN) obtained from 28 patients, three primary breast cancers (positive controls), three lymph nodes from patients with benign diseases, and peripheral blood lymphocytes of 10 healthy volunteers (negative controls). RT-PCR was performed using the following markers; cytokeratin (CK)-19, NY-BR-1 and mammaglobin B. RT-PCR results were compared to enhanced histopathologic examination and immunohistochemistry (IHC). All three positive controls showed strong PCR amplification for all three markers. None of the 13 negative controls was amplified by any of the three markers. Among the 30 SLN analysed, breast cancer metastases were detected in six SLNs by routine histology, in eight by IHC and in 15 by RT-PCR. We conclude that a multimarker RT-PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination. This method may prove to be of value in breast cancer staging and prognosis evaluation.

Meconium ileus equivalent is one of the lesser-known manifestations of cystic fibrosis. It manifests as distant small bowel obstruction caused by meconium-like stool plugs and occurs mostly in adult patients. With the improved overall survival of patients with cystic fibrosis, general surgeons may encounter this condition more often in the future. We treated a 19-year-old woman with cystic fibrosis who presented with complete distal small bowel obstruction. Medical therapy with Gastrografin and N-acetylcysteine failed to resolve the obstruction. At surgery, a meconium-like plug in the distal ileum was manually pushed into the colon with subsequent relief of symptoms. Meconium ileus equivalent should be considered and treated in cystic fibrosis patients presenting with small bowel obstruction.

Background: Electrical impedance scanning (EIS) is a novel imaging technique based on differential electrical conductivity and capacitance of malignant and normal human tissues. The aim of this study was to evaluate the accuracy of EIS in the detection of thyroid malignancies., Methods: Patients with thyroid nodules scheduled for thyroid surgery were eligible for the study. Enrolled patients underwent EIS with a T-Scan 2000ED. Nodule location, size, and type (cystic vs. solid) measured by ultrasound, cytology results, thyroid conductivity, and capacitance calculated by EIS were recorded. EIS results were interpreted as positive or negative for malignancy and compared with final histopathology results. Study end points included EIS accuracy, sensitivity, specificity, negative and positive predictive values, and false-positive and false-negative rates., Results: Sixty-four patients were enrolled onto the study, and all underwent either lobectomy-isthmusectomy (20%) or total thyroidectomy (80%). The mean tumor diameter was 2.64 +/- 14.8 mm. Thyroid cancers were identified by histology in 30 patients (46.9%). There were 11 false-positive and four false-negative cases. The overall diagnostic accuracy of EIS was 76.6% (49 of 64 correct diagnoses). The sensitivity and specificity of EIS were 86.7% (26 of 30 true positive) and 67.6% (23 of 34 true negative), respectively. The corresponding positive and negative predictive values were 70.3% and 85.2%., Conclusions: EIS is a potentially useful imaging modality for differentiating thyroid neoplasms. If these results are confirmed in large-scale trials, EIS may be an important part of the evaluation of thyroid nodules.

Background: The clinical profile of breast cancer may vary among different ethnic groups living in the same country and therefore affect the yield of a breast cancer screening program. The present study attempts to better characterize the breast cancer clinical profile of Arab women compared with Jewish women in the greater Jerusalem area with a future aim of establishing a comprehensive and effective screening program for this population., Methods: Retrospective chart review was conducted and the following covariates were correlated with survival: ethnicity, age at diagnosis, and American Joint Committee on Cancer (TNM) stage at diagnosis., Results: A total of 312 women were operated on for breast cancer between 1994 and 1999; 51% were Ashkenazi Jews (AJ), 26% were Sephardic Jews (SJ), 21% were Palestinian Arabs (PA), and 2% patients did not fit into those ethnic groups. The mean age at diagnosis was 51.5 years for the PA group, 53.4 +/- 1.5 for the SJ group, and 55.9 years for the AJ group (P <0.03 PA versus AJ). The tumor size (mean +/- SEM) was 38.8 +/- 3.7 mm, 31.1 +/- 2.4 mm, and 24.5 +/- 1.6 mm for the PA, SJ, and AJ groups, respectively (P = 0.03 for PA versus SJ and P <0.001 for PA versus AJ). Five-year overall survival was 77 %, 72%, and 58% for the AJ, SJ, and PA groups, respectively (P = 0.02); and 5-year disease-free survival was 72%, 51%, and 50% for the AJ, SJ, and PA groups, respectively (P = 0.03, AJ versus SJ)., Conclusions: Our data demonstrate younger age and larger primary tumor size for the Arab patients compared with the Jewish patients. These findings were associated with lower 5-year survival and disease-free survival of the Arab patients.

Aging is believed to affect the structure and function of the enteric nervous system, but little specific information on this topic is available, particularly in humans. The aim of this study was to investigate the effect of age on the structure of myenteric ganglia in the human colon. We examined myenteric ganglia in colonic specimens obtained from 168 patients aged 10 days to 91 years. Nerves were stained in whole mount preparations using the vital fluorescent dye 4-(4-dimethylaminostyryl)-methylpyridinium iodide (4-Di-2-ASP) and other staining methods. Human myenteric ganglia were classified into three types: normal, those containing empty spaces ('cavities') and those containing large nerve fiber bundles. We found a statistically significant increase with age in the proportion of ganglia with cavities. Conversely, there was a decrease with age in the proportion of normal ganglia. The proportion of fiber-containing ganglia did not change with age. These findings indicate that there is an increase with age in the number of abnormally appearing myenteric ganglia in the human colon, which may contribute to the disturbed colonic motility in the aging population.

Background: Familial dysautonomia (FD) is a hereditary disease of the autonomic and sensory nervous system. A prominent manifestation of FD is gastrointestinal dyscoordination, which contributes to the morbidity and mortality in FD., Aim: As the myenteric plexus is an essential factor in gastrointestinal motility control, we compared its morphology in appendices of FD patients and controls., Methods: Appendices from FD patients (N=19) were obtained during surgery of fundoplication and gastrostomy; normal appendices (N=17) were obtained from patients suspected to suffer from acute appendicitis, in whom, however, the appendix was found to be normal. Specimens were stained histochemically for NADPH diaphorase (NADPH-d) and in a blinded manner examined under a light microscope for seven morphologic parameters: ganglionic density, neuronal density, ganglionic area, number of stained neurons per ganglion, nerve bundle width, ratio between nervous tissue area and total area, and neuronal area., Results: Ganglionic density was 10.13 per mm(2) in controls versus 5.01 per mm(2) in FD (p<0.05). Neuronal density was 70.12 per mm(2) in controls, compared with 22.09 per mm(2) in FD (p<0.01). The other parameters were not different between the two groups., Conclusion: Densities of myenteric ganglia and neurons of FD patients were significantly lower than in controls. This deficiency may contribute to the pathogenesis of FD gastroenteropathy.

Objective: To assess evacuation priorities during terror-related mass casualty incidents (MCIs) and their implications for hospital organization/contingency planning., Summary Background Data: Trauma guidelines recommend evacuation of critically injured patients to Level I trauma centers. The recent MCIs in Israel offered an opportunity to study the impositions placed on a prehospital emergency medical service (EMS) regarding evacuation priorities in these circumstances., Methods: A retrospective analysis of medical evacuations from MCIs (29.9.2000-31.9.2002) performed by the Israeli National EMS rescue teams., Results: Thirty-three MCIs yielded data on 1156 casualties. Only 57% (506) of the 1123 available and mobilized ambulances were needed to provide 612 evacuations. Rescue teams arrived on scene within <5 minutes and evacuated the last urgent casualty within 15-20 minutes. The majority of non-urgent and urgent patients were transported to medical centers close to the event. Less than half of the urgent casualties were evacuated to more distant trauma centers. Independent variables predicting evacuation to a trauma center were its being the hospital closest to the event (OR 249.2, P < 0.001), evacuation within <10 minutes of the event (OR 9.3, P = 0.003), and having an urgent patient on the ambulance (OR 5.6, P < 0.001)., Conclusions: Hospitals nearby terror-induced MCIs play a major role in trauma patient care. Thus, all hospitals should be included in contingency plans for MCIs. Further research into the implications of evacuation of the most severely injured casualties to the nearest hospital while evacuating all other casualties to various hospitals in the area is needed. The challenges posed by terror-induced MCIs require consideration of a paradigm shift in trauma care.

Current knowledge on the morphology and physiology of interstitial cells of Cajal (ICC) is mostly based on animal studies, and information about the function of these cells in humans is scarce. There is ultrastructural evidence that ICC in the myenteric region (ICC-MP) of the small intestine of several species are connected by gap junctions, but these were not observed in the human small intestine. The aim of the present study was to determine whether functional coupling also exists among ICC-MP in the human ileum. We visualized ICC-MP in live tissues using Nomarski optics, and verified their identity by staining for c-Kit. ICC were injected intracellularly with the fluorescent dye Lucifer yellow, which crosses gap junctions. In most cases the labelled cells had oval somata with two primary processes. At normal pH (7.3-7.4) only 20.2% (21/104) of the injected ICC were coupled to other ICC. However, at pH 7.8-7.9 coupling incidence increased to 74.5% (35/47, P < 0.0001). The injected cells were coupled to one to 35 other ICC. Octanol blocked coupling in all cases. Apparently, gap junctions interconnect ICC in the human small intestine. Coupling was enhanced by a small increase in pH, suggesting that it may be under physiological control.

Background: and aims: Aspirin and other non-steroidal anti-inflammatory drugs have been shown to reduce the risk of colorectal cancer (CRC). Animal models have shown that aspirin is also effective in reducing the density of aberrant crypt foci (ACF). The aim of the study was to evaluate the effect of chronic administration of aspirin on the distribution pattern and histological characteristics of ACF in patients with CRC., Methods: Our study compared the distribution patterns and histomorphological characteristics of ACF between a group of CRC patients treated with low dose aspirin (n=59) and a control group without aspirin (n=135). ACF were visualised on methylene blue stained macroscopically normal mucosa, microdissected, and serially cut., Results: ACF were found in 75.8% of mucosal samples from the control group and in 36% of mucosal samples from the aspirin treated group, indicating a 47% decline in prevalence of ACF in colonic samples of patients treated with aspirin. A significant reduction from 92.5% to 40% (p<0.0001) was found in distal large bowel samples containing one or more ACF. Similarly, the aspirin treated group showed a reduction in ACF density of 64% and 82%, respectively, in both proximal and distal parts of the colon, indicating a significant reduction in ACF/cm(2) in distal colon samples (p<0.01). The aspirin treated group displayed a 52% reduction in dysplastic ACF although this difference was not statistically significant., Conclusions: Our study has provided evidence of the effective chemopreventive action of low dose aspirin on ACF in humans.

Still debated are the appropriate techniques for the repair of abdominal wall defects and the methods used to measure their strength. Although tension has been used in many studies to test wound strength, bursting pressure reflects more accurately the pathophysiology of wound dehiscence. The aim of the current study was to evaluate three different techniques for closure of abdominal wall defects using a new and more accurate device for bursting pressure measurements. Full thickness abdominal wall defects measuring 2 cm2 were created in 43 anesthetized rats randomly assigned to three groups: simple primary closure (n = 15), Mayo repair (n = 14), and primary closure reinforced with a mesh (n = 14). Thirty days after surgery, the rats were sacrificed. The abdominal wall was fully excised and placed over a bursting chamber made of a metal cylinder connected to a carbon dioxide source with a control valve and a manometer. Gas was gradually released while the pressure was recorded until bursting occurred. Disruption of all closures occurred at the point where the suture itself penetrated the tissue. The average bursting pressure was 1383 +/- 299 mm Hg for the primary closure group, 1200 +/- 409 mm Hg for the mesh reinforcement group, and 1607 +/- 337 mm Hg for the imbrication repair (Mayo) group (P < 0.03). The data suggests an advantage for the Mayo repair over the other two repairs. The bursting chamber tested is a new and more reliable method to study techniques and conditions influencing the strength of abdominal wall closure.

Despite the widespread use of sentinel lymph node biopsy (SLNBx) in the surgical management of breast cancer patients, several areas remain controversial. The following controversies are reviewed: Learning curves and validation studies. There clearly is a learning curve, and a completion ALND should be done until adequate proficiency is exhibited, both in terms of identification and false-negative rates. Location of injection. Intradermal injection offers superior identification rates compared with peritumoral injection, with comparable false-negative rates. Subareolar injection is as accurate as peritumoral injection. The value of scintigraphy. Routine scintigraphy does not enhance identification or false-negative rates. Mapping agents. Blue dye and radioactive tracer combined to provide a higher identification rate than either used alone.SLNBx in DCIS. In patients with a high risk of microinvasion, such as large tumors, a mass or high-grade DCIS-SLNBx is justified.SLNBx following neoadjuvant chemotherapy. Although there is evidence that SLNBx after neoadjuvant chemotherapy may be accurate, these data should be applied cautiously. Implications of non axillary SLN, especially internal mammary nodes. Data do not support routine resection of internal mammary sentinel lymph nodes outside a clinical trial. Implications of micrometastases in the sentinel lymph node seen only on immunohistochemistry. Since the significance of such metastases is unclear, decisions regarding treatment of these patients should be individualized. The value of completion axillary lymph node dissection. Is being addressed in clinical trials. Until those studies mature, completion ALND should be performed for patients with SLN metastases, but may be abandoned for patients with a negative SLN.