The effect of hepatocyte growth factor on intestinal adaption in an experimental model of short bowel syndrome.

PURPOSE: Nowadays, the standard therapy for patients with short bowel syndrome is parenteral nutrition (PN). Various growth factors have been tested to achieve weaning from prolonged PN administration. We evaluated the effect of hepatocyte growth factor (HGF) on structural intestinal adaptation and cell proliferation in a rat model of SBS. METHODS: Thirty Sprague-Dawley rats were divided into three groups; group A rats (sham) underwent bowel transection, group B rats underwent a 75% bowel resection, and group C rats underwent the same procedure but were treated postoperatively with HGF. Histopathologic parameters of intestinal adaptation were determined, while microarray and rt-PCR analyses of ileal RNA were also performed. RESULTS: Treatment with HGF resulted in significant increase in body weight, while the jejunal and ileal villus height and crypt depth were increased in HGF rats (36%, p < 0.05 and 27%, p < 0.05 respectively). Enterocyte proliferation was also significantly increased in HGF rats (21% p < 0.05). Microarray and quantitative rt-PCR analyses showed that the genes hgfac, rac 1, cdc42, and akt 1 were more than twofold up-regulated after HGF treatment. CONCLUSION: HGF emerges as a growth factor that enhances intestinal adaptation. The future use of HGF may potentially reduce the requirement for PN in SBS patients.

Gallstone Ileus in Octogenarians: Is Cholecystectomy Really Needed?

Gallstone ileus is an uncommon complication of cholelithiasis and occurs when a gallstone migrates through a cholecystoenteric fistula and impacts within the gastrointestinal tract. Surgical intervention remains the treatment of choice, which consists of a full-thickness incision of the visceral wall and removal of the impacted gallstone. In this paper we present the treatment approach of 6 cases of gallstone ileus in octogenarians. In our cohort, intestinal obstruction was resolved through an enterotomy or gastrotomy and lithotomy/stone extraction in every patient. No cholecystectomies were undertaken. Despite the fact that gallstone ileus is diagnosed in small percent of patients suffering from gallstone disease, it accounts for a large proportion of intestine obstruction in patients older than 65 years old. Since accurate diagnosis and timely intervention are vital, providers should be familiar with the diagnostic approach and the treatment of this clinical entity.

Radial Basis Function Artificial Neural Network for the Investigation of Thyroid Cytological Lesions.

OBJECTIVE: This study investigates the potential of an artificial intelligence (AI) methodology, the radial basis function (RBF) artificial neural network (ANN), in the evaluation of thyroid lesions. Study Design. The study was performed on 447 patients who had both cytological and histological evaluation in agreement. Cytological specimens were prepared using liquid-based cytology, and the histological result was based on subsequent surgical samples. Each specimen was digitized; on these images, nuclear morphology features were measured by the use of an image analysis system. The extracted measurements (41,324 nuclei) were separated into two sets: the training set that was used to create the RBF ANN and the test set that was used to evaluate the RBF performance. The system aimed to predict the histological status as benign or malignant. RESULTS: The RBF ANN obtained in the training set has sensitivity 82.5%, specificity 94.6%, and overall accuracy 90.3%, while in the test set, these indices were 81.4%, 90.0%, and 86.9%, respectively. Algorithm was used to classify patients on the basis of the RBF ANN, the overall sensitivity was 95.0%, the specificity was 95.5%, and no statistically significant difference was observed. CONCLUSION: AI techniques and especially ANNs, only in the recent years, have been studied extensively. The proposed approach is promising to avoid misdiagnoses and assists the everyday practice of the cytopathology. The major drawback in this approach is the automation of a procedure to accurately detect and measure cell nuclei from the digitized images.

Low expression of miR-20b-5p indicates favorable prognosis in laryngeal squamous cell carcinoma, especially in patients with non-infiltrated regional lymph nodes.

PURPOSE: Tumor recurrence and distant metastasis are very common in laryngeal squamous cell carcinoma (LSCC). In this study, we examined the potential prognostic value of microRNA-20b-5p (miR-20b-5p), a component of the tumor-related miR-106a/363 cluster. MATERIALS AND METHODS: Total RNA was purified from 105 tissue specimens resected from patients having undergone surgical treatment for primary LSCC. After in vitro polyadenylation and reverse transcription, a sensitive real-time quantitative polymerase chain reaction (qPCR) methodology was applied for the relative quantification of miR-20b-5p levels. Then, we proceeded with biostatistical analysis, seeking to assess the prognostic value of miR-20b-5p expression in LSCC. RESULTS: miR-20b-5p positivity constitutes a predictor of inferior DFS and OS in LSCC (P < 0.001 and P = 0.002, respectively). The significant prognostic value of miR-20b-5p expression status seems to be independent of tumor size, histological grade, and TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis showed also that miR-20b-5p expression status can stratify LSCC patients with non-infiltrated regional lymph nodes (N0) into two subgroups with distinct prognosis (P = 0.004 and P = 0.004, respectively). CONCLUSIONS: The miR-20b-5p expression status is a promising molecular tissue biomarker in LSCC, with an independent prognostic value, and thus merits further validation in larger cohorts of patients.

The impact of preoperative sarcopenia on postoperative complications following esophagectomy for esophageal neoplasia: a systematic review and meta-analysis.

Esophageal cancer is characterized by profound changes in body composition due to dysphagia and generalized cachexia. Sarcopenia or muscle wasting is a component of cachexia associated with poor postoperative performance status. The skeletal muscle index (SMI) calculated by computed tomography scans at the level of the third lumbar vertebra is an easily quantifiable and reproducible measure of sarcopenia. The aim of this meta-analysis is to investigate the impact of preoperative sarcopenia (low SMI) on postoperative complications after esophagectomy for neoplastic lesions. In this context, a comprehensive literature search was undertaken to identify studies reporting short-term postoperative outcomes in relation to their preoperative SMI values. Cumulative risk ratios (RR) and risk differences (RD) and their respective 95% confidence intervals (CIs) were calculated using a random-effect model. A total of 11 studies incorporating 1,979 total patients (964 patients with sarcopeniaversus 1,015 without sarcopenia) were included in the final analysis. The results demonstrated a significant increase in overall morbidity (RR 1.16, 95% CI 1.01-1.33), respiratory complications (RR 1.64, 95% CI 1.21-2.22) and anastomotic leaks (RR 1.39, 95% CI 1.10-1.76) in patients with sarcopenia. No statistically significant difference was noted in overall mortality (RD 0, 95% CI -0.02-0.02) or Clavien-Dindo grade III or greater complications (RR 1.17, 95% CI 0.96-1.42). The above results demonstrate the validity of the SMI as a predictive factor for post-esophagectomy complications. Although the risk associated with sarcopenia is not prohibitive for surgery, patients with low SMI require closer vigilance during their postoperative course due to the increased propensity for respiratory and anastomotic complications.

Small bowel perforation with multiple intestinal metastases from lung carcinoma: A case report.

The present report describes the case of an 81-year-old woman who underwent an emergency explorative laparotomy due to small bowel perforation. Diffuse feculent peritonitis due to perforation of the jejunum was identified. In addition, six distinct tumors of the jejunum in close proximity to the perforation site, as well as two more lesions caudally at the ileum, were identified. A separate stenotic tumor was identified at the sigmoid colon, causing moderate dilatation of the whole intestine. An enterectomy, including the perforation site and the proximal six tumors, was performed, followed by limited enterectomies for the distal two tumors and side-to-side anastomoses of the small intestine. All resected tumors were identified at histology as metastatic from lung carcinoma. Postoperatively, the patient remained in a severe septic condition and succumbed the following day. Metastatic lesions from lung carcinoma in the small bowel wall are a rare finding predisposing to bowel perforation. When an acute condition coexists with multiple intestinal metastases, the mortality rate is high despite prompt surgical intervention.

Metastatic squamous cell carcinoma to the pancreas: Report of an extremely rare case.

Secondary pancreatic lesions are very uncommon. Resection of these metastatic lesions with a curative intent has been reported in selected patients; however, the survival benefit from these procedures has yet to be clearly determined. A 78-year-old male patient presented to our department with obstructive jaundice. Three years prior to presentation the patient had undergone right pneumonectomy, due to stage IIA, low-grade squamous cell lung carcinoma. After resection, the patient received adjuvant chemotherapy, with no evidence of local or systemic recurrence over the following 3 years. Abdominal computer tomography on admission revealed a 3-cm lesion located at the head of the pancreas, causing biliary obstruction. Endoscopic ultrasound biopsy revealed malignant cells, suspicious for squamous cell carcinoma. Due to the limited extent of the metastatic disease and in view of the patient's good condition, surgical resection was proposed and the patient successfully underwent pancreaticoduodenectomy. Histological examination of the resected specimen confirmed a squamous cell carcinoma, with an immunochemical profile similar to that of the primary lung tumor. Therefore, pancreatic resection with curative intent may be feasible in selected patients with secondary metastatic tumors. However, further studies are required in order to determine the benefit of these major procedures in terms of survival outcomes.

Ten-year survival outcomes of patients with potentially resectable gastric cancer: impact of clinicopathologic and treatment-related risk factors.

BACKGROUND: Despite therapeutic advancements, gastric cancer (GC) remains a leading cause of death worldwide. METHODS: This retrospective cohort study statistically analyzed the clinicopathologic characteristics, treatments and outcomes of patients with potentially resectable GC managed at our institution between 2006 and 2010. The STROBE checklist was applied. RESULTS: Preoperative assessment of 164 GC patients (male: female ratio 1.87, median age 65 years) assigned 132 (80.5%) to total (56; 42.4%) or subtotal (76; 57.6%) gastrectomy. Resection margins were microscopically tumor-free (R0) in 100 (75.8%), microscopically infiltrated (R1) in 25 (18.9%) and macroscopically infiltrated (R2) in 7 (5.3%) patients. Nodal plane dissection was D0 in 34 (25.8%), D1 in 62 (47.0%) and D2 in 36 (27.3%) patients. Early GC was diagnosed in 19 patients (14.4%). Fluorouracil-based chemotherapy was administered in 69.7% and chemoradiation in 18.2% of patients. The 5- and 10-year survival rates of patients with R0 resection were 74% and 65.4%, respectively. The 2-year survival rates for R1 and R2 resection were 28.9% and 0% respectively. The 5- and 10-year survival rates according to nodal plane dissection were 55.6% and 41.4% for D2, and 53.2% and 49.7% for D1, respectively. On multivariate analysis, T4, N3 and R1/R2 remained independent negative prognostic factors for overall survival. Microscopic or macroscopic infiltration of surgical margins was the worst adverse prognostic factor for survival. CONCLUSION: These results are equivalent to those from centers of excellence and indicate the urgent need for improvements in the field, particularly in the development of predictive models to guide personalized therapy.

Reversal of Novel Anticoagulants in Emergent Surgery and Trauma: A Comprehensive Review and Proposed Management Algorithm.

Non-vitamin K oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used for thromboembolism prevention. Contrary to older anticoagulants, such as coumadin, when antidotes existed and were broadly used in cases of emergent surgery and bleeding, antidotes for NOACs have not been developed until recently. Moreover, the monitoring of NOAC's anticoagulant effect varies across different hospital settings and the absence of a single test that can accurately predict the degree of anticoagulation achieved increases the uncertainty. These uncertainties often result in management dilemmas for clinicians when patients who are on NOACs need a reversal of anticoagulation. Until recently, available antidotes for NOACs included only prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII and the less optimal fresh frozen plasma (FFP). Recently though, novel antidotes for NOACs have been developed, including idarucizumab, which is a monoclonal antibody fragment that binds dabigatran, and andexanet alfa, a modified decoy form of the activated factor X (FXa) that binds FXa inhibitors and AT III. Another option, ciraparantag, which is a small molecule that binds to heparin, thrombin inhibitors and FXa inhibitors, is still in phase I development. In this review, we summarize the current evidence and present the available bypassing and novel reversal agents. Finally, we propose an algorithm for the management of patients who take NOACs and present to the emergency department with either trauma and active bleeding or need for emergent surgery.

A huge asymptomatic pheochromocytoma.

Due to their evolution in the retroperitoneal space, pheochromocytomas may grow significantly in size and remain asymptomatic for a long period of time. Normal values of urine catecholamine levels must not preclude the diagnosis of these endocrine lesions.

De Garengeot's Hernia: Report of a Rare Surgical Emergency and Review of the Literature.

This is a report of a case who was admitted and operated on for a strangulated femoral hernia. The hernia sac contained a gangrenous appendix, which was excised and the hernia was repaired with sutures without complication. De Garengeot's hernia, although very rare, should be included in the differential diagnosis of cases with strangulated hernia and should receive the optimal treatment.

A short review of primary aldosteronism in a question and answer fashion.

OBJECTIVES: The aim of this study was to present up to date information concerning the diagnosis and treatment of primary aldosteronism (PA). PA is the most common cause of endocrine hypertension. It has been reported up to 24% of selective referred hypertensive patients. METHODS: We did a search in Pub-Med and Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists, adrenalectomy, and surgery. We also did cross-referencing search with the above terms. We had divided our study into five sections: Introduction, Diagnosis, Genetics, Treatment, and Conclusions. We present our results in a question and answer fashion in order to make reading more interesting. RESULTS: PA should be searched in all high-risk populations. The gold standard for diagnosis PA is the plasma aldosterone/plasma renin ratio (ARR). If this test is positive, then we proceed with one of the four confirmatory tests. If positive, then we proceed with a localizing technique like adrenal vein sampling (AVS) and CT scan. If the lesion is unilateral, after proper preoperative preparation, we proceed, in adrenalectomy. If the lesion is bilateral or the patient refuses or is not fit for surgery, we treat them with mineralocorticoid receptor antagonists, usually spironolactone. CONCLUSIONS: Primary aldosteronism is the most common and a treatable case of secondary hypertension. Only patients with unilateral adrenal diseases are eligible for surgery, while patients with bilateral and non-surgically correctable PA are usually treated by mineralocorticoid receptor antagonist (MRA). Thus, the distinction between unilateral and bilateral aldosterone hypersecretion is crucial.

Laparoscopic splenectomy: Current concepts.

Since early 1990's, when it was inaugurally introduced, laparoscopic splenectomy has been performed with excellent results in terms of intraoperative and postoperative complications. Nowadays laparoscopic splenectomy is the approach of choice for both benign and malignant diseases of the spleen. However some contraindications still apply. The evolution of the technology has allowed though, cases which were considered to be absolute contraindications for performing a minimal invasive procedure to be treated with modified laparoscopic approaches. Moreover, the introduction of advanced laparoscopic tools for ligation resulted in less intraoperative complications. Today, laparoscopic splenectomy is considered safe, with better outcomes in comparison to open splenectomy, and the increased experience of surgeons allows operative times comparable to those of an open splenectomy. In this review we discuss the indications and the contraindications of laparoscopic splenectomy. Moreover we analyze the standard and modified surgical approaches, and we evaluate the short-term and long-term outcomes.

Advents in the Diagnosis and Management of Ischemic Colitis.

BACKGROUND: Ischemic colitis (IC) is a common type of ischemic insult, resulting from decreased arterial blood flow to the colon. This disease can be caused from either atherosclerotic occlusive vascular disease or non-occlusive disease. The aim of this study is to present the diagnostic methodology and management of this severe disease based on current literature. METHODS: A literature search has been done including articles referring to modern diagnosis and management of IC. RESULTS: IC is usually a transient disease, but it can also cause gangrene of the colon, requiring emergency surgical exploration. Diagnosis is troublesome and is based on imaging examinations, mainly computerized tomography, which in association with colonoscopy can delineate the distribution pattern and severity of disease. CONCLUSION: The majority of patients with mild disease have usually complete clinical recovery within a short period. The severe forms of the disease carry high morbidity and mortality rates and prompt surgical intervention is the only way to improve the associated severe prognosis.

Neuroendocrine Tumors of the Esophagus: State of the Art in Diagnostic and Therapeutic Management.

INTRODUCTION: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms composed of cells containing dense-core neuroendocrine secretory granules in their cytoplasm. NETs of the esophagus are exceedingly uncommon, with a parallel absence of data published on clinical features, prognosis, and proposed treatment strategies. METHODS: As relevant classification is not well-established, knowledge acquired in NETs of lung and gastrointestinal sites usually guides esophageal NET management. Associated subtypes are divided based upon shared neuroendocrine features into small and large cell NET, typical and atypical carcinoid. RESULTS: Common presenting symptoms include dysphagia, abdominal discomfort, weight loss, melena, and on occasion, signs of carcinoid syndrome. Endoscopic findings describe a polypoid, nodular elevated lesion with an overlying surface depicted as mostly smooth and glistening. Disease metastasis is assessed using anatomical imaging, including computed tomography (CT), endoscopic ultrasonography (EUS), and positron emission tomography (PET)-CT. Prognosis is influenced by the extent of lymph node metastasis and potential lymphovascular invasion. Furthermore, proliferative activity, estimated using mitotic count or Ki-67 immunostaining, has been suggested as a significant prognostic parameter. CONCLUSION: Therapeutic approach depends on clinical staging. Nevertheless, currently, a specific treatment algorithm for esophageal NETs has not been elucidated. Endoscopic resection has been proposed in NETs less than 1 cm in size with absence of regional lymph node metastasis, while surgical excision combined with adjuvant chemotherapy remains the treatment of choice.

Erythropoietin and sildenafil protect against ischemia/reperfusion injury following testicular torsion in adult rats.

Testicular torsion/detorsion causes severe tissue damage due to ischemia/reperfusion injury. The present study investigated the protective effect of erythropoietin and sildenafil against ischemia/reperfusion injury following unilateral testicular torsion/detorsion in adult rats. A total of 28 adult male rats were included, and were divided into the following groups: Group A (n=5), sham operated; groups B (n=5), C (n=5), D (n=5) and E (n=8), undergoing right testis torsion and detorsion after 90 min. Group B received no drug treatment. Rats in the groups C and D received low-dose (1,000 IU/kg) or high-dose (3,000 IU/kg) erythropoietin, while those in group E received sildenafil (0.7 mg/kg), through intraperitoneal injection after 60 min of torsion. The right testis was extracted 24 h after detorsion, and the tissue was subjected to histopathological examination and immunohistochemical assessment of cleaved caspase-3 expression. Histological alterations and the quality of spermatogenesis were scored according to the Cosentino and the Johnsen scoring systems, respectively. The results demonstrated normal testicular architecture in group A, while the other groups showed ischemic cellular damages, with the worst scores observed in group B. Groups D and E presented better scores compared with group C. Regarding the quality of spermatogenesis, the best scores were observed in group A, and the worst in group B. Groups C, D and E presented similar results, which were improved in comparison to group B, however, not compared to group A. Furthermore, cleaved caspase-3 levels were lower in groups A, D and E, with equal results observed. Group C had higher levels of cleaved caspase-3 compared with these groups, but lower than group B, which presented the highest cleaved caspase-3 levels. In conclusion, erythropoietin and sildenafil protect testis from ischemia/reperfusion injury by decreasing cellular damage and attenuating apoptosis.

A giant squamous cell carcinoma of the skin of the thoracic wall: a case report and review of the literature.

BACKGROUND: We report a case of a 48-year-old white woman who presented with a huge cutaneous protruding tumor of the thoracic wall below her left breast. CASE PRESENTATION: The lesion was excised with clear margins from the adjacent skin, and subcutaneous tissue was left to heal with second intention. A histological examination of the surgical specimen revealed a well-differentiated infiltrative cutaneous squamous cell carcinoma. Our patient neglected to attend our Oncological Department to receive chemotherapy. Today, 12 months after surgery, she is alive and without evidence of disease recurrence. CONCLUSIONS: Cutaneous squamous cell carcinoma can reach a huge size if left untreated. Surgery is the primary mode of treatment, followed by chemotherapy if applicable.

Early Diagnosis and Surgical Treatment for Necrotizing Fasciitis: A Multicenter Study.

BACKGROUND: Necrotizing fasciitis (NF) is a group of relatively rare infections, usually caused by two or more pathogens. It affects the skin and subcutaneous tissues of lower and upper limbs, perineal area (Fournier's gangrene), and the abdominal wall. Early diagnosis and aggressive surgical management are of high significance for the management of this potentially lethal disease. METHODS: We conducted a retrospective study in patients who presented, during the last decade, at four University Surgical Departments in the area of Athens, Greece, with an admission diagnosis of NF. Demographic, clinical, and laboratory data were gathered, and the preoperative and surgical treatment, as well as the postoperative treatment was analyzed for these patients. RESULTS: A total of 62 patients were included in the study. The mean age of patients was 63.7 (47 male patients). Advanced age (over 65 years) (P < 0.01) and female sex (P = 0.04) correlated significantly with mortality. Perineum was the mostly infected site (46.8%), followed by the lower limbs (35.5%), the upper limbs, and the axillary region (8.1%). Diabetes mellitus was the most common coexisting disease (40.3%), followed by hypertension (25.8%) and obesity (17.7%). The most common symptom was local pain and tenderness (90.3%). Septic shock occurred in eight patients (12.9%) and strongly correlated with mortality (P < 0.01). Laboratory data were used to calculate the LRINEC score of every patient retrospectively; 26 patients (41.9%) had LRINEC score under 6, 20 patients (32.3%) had LRINEC score 6-8, and 16 patients (25.8%) had LRINEC score >9. Surgical debridement was performed in all patients (mean number of repeated debridement 4.8), and in 16 cases (25.8%) the infected limb was amputated. The mean length of hospital stay was 19.7 days, and the overall mortality rate of our series was 17.7%. CONCLUSION: Diagnosis of NF requires high suspect among clinicians, as its clinical image is non-specific. Laboratory tests can depict the severity of the disease; therefore, they must be carefully evaluated. Urgent surgical debridement is the mainstay of treatment in all patients; the need of repetitive surgical debridement is undisputed.

Cytopathologic diagnosis of fine needle aspiration biopsies of thyroid nodules.

Fine-needle aspiration (FNA) cytology is an important diagnostic tool in patients with thyroid lesions. Several systems have been proposed for the cyropathologic diagnosis of the thyroid nodules. However cases with indeterminate cytological findings still remain a matter of debate. In this review we analyze all literature regarding Thyroid Cytopathology Reporting systems trying to identify the most suitable methodology to use in clinical practice for the preoperative diagnosis of thyroid nodules. A review of the English literature was conducted, and data were analyzed and summarized and integrated from the authors' perspective. The main purpose of thyroid FNA is to identify patients with higher risk for malignancy, and to prevent unnecessary surgeries for benign conditions. The Bethesda System for Reporting Thyroid Cytopathology is the most widely used system for the diagnosis of thyroid FNA specimens. This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases. In conclusion, patients who require repeated FNAs for indeterminate diagnoses will be resolved by repeat FNA in a percentage of 72%-80%.