Prevention of Entero-Atmospheric Fistula: The Initial Closure of the Abdomen.

BACKGROUND AND AIMS: The "Open Abdomen" technique for difficult conditions such as trauma, necrotizing pancreatitis, severe peritonitis, reoperations and transplantations have become a very useful way to save patients. The more severe complication of this method are the enteroatmospheric fistulae with a frequency of 5-75% and a mortality up to 42%. So any effort to prevent these is very essential. The aim of this paper is to present methods of the initial (temporary) closure of the abdomen for the prevention of this catastrophe, when early approximation of the abdominal wall is not feasible. METHODS AND MATERIALS: We present two representative case reports and we describe the use of full thickness or split skin grafts as first step for abdominal closure. RESULTS AND CONCLUSIONS: The outcome of our patients by using tissues for temporary abdominal closure seems to have fewer problems than other methods with synthetic materials. We think that this is a reasonable option for the cases where we cannot achieve approximation of the abdominal wall edges in the early days of an open abdomen.

Parecoxib's effects on anastomotic and abdominal wound healing: a randomized Controlled trial.

BACKGROUND: Current evidence regarding the effects of selective cyclooxygenase inhibitors on gastrointestinal anastomoses is controversial. An experimental randomized control study was conducted in our institution to histopathologically evaluate the consequences of parecoxib, on intestinal and abdominal wound healing. METHODS: Twenty-four adult Wistar rats underwent laparotomy, ascending colon transection, and hand-sewn anastomosis. They were randomized to receive either parecoxib (0.5 mg/kg twice daily) or 0.9% normal saline by intraperitoneal injection postoperatively. Animals were euthanatized either on the third or the seventh postoperative day. Semiquantitative methods were used to evaluate both intestinal and abdominal wounds for inflammatory cell composition, angiogenesis, fibroblasts, granular tissue, collagen deposition, epithelization, and presence of necrosis, exudate, and abscess formation. Results are presented as (parecoxib: median [IQR] versus control: median [IQR], P-value). RESULTS: No macroscopic anastomotic leakage or wound dehiscence was observed. Intestinal anastomoses in the parecoxib group, showed significantly decreased epithelization (2 [1] versus 3 [1], [P = 0.004]) and collagen deposition (2 [0] versus 3 [1], [P = 0.041]). No difference was observed in angiogenesis (3 [1] versus 2.5 [1], [P = 0.158]). Abdominal wall specimens appeared to demonstrate decreased epithelization (2 [2] versus 4 [0.5], [P = 0.0004]) in the treatment group. No difference between the two groups was identified regarding collagen deposition (2.5 [1] versus 2 [0.5], [P = 0.280]) and angiogenesis (2.5 [1] versus 2 [1], [P = 0.633]). Necrosis was significantly more present in the parecoxib group in both specimen types, (3.5 [1] versus 2.5 [1], [P = 0.017]) and (3 [1] versus 1 [0.5], [P < 0.0001]). CONCLUSIONS: The present study shows that despite the absence of clinical adverse effects, parecoxib can impair anastomotic and abdominal wound healing on a histopathological level.

Effect of Increased Intra-abdominal Pressure on Liver Histology and Hemodynamics: An Experimental Study.

BACKGROUND: While reduction of portal venous (PV) blood flow has been described in animal models of intra-abdominal hypertension, reports on compensatory changes in hepatic arterial (HA) flow, known as the hepatic arterial buffer response are controversial. MATERIALS AND METHODS: Pneumoperitoneum with helium was induced in 13 piglets. Hemodynamic measurements and pathological assessment were conducted at baseline and during the three subsequent phases: Phase A: 45 minutes with a stable intra-abdominal pressure of 25 mmHg; phase B: 45 minutes with a stable intra-abdominal pressure of 40 mmHg; and phase C during which the abdomen was re-explored and reperfusion of the liver was allowed to take place. RESULTS: Phase B pressure was significantly greater than phase A pressure in both the PV and the inferior vena cava, demonstrating a positive association between escalating intra-abdominal hypertension and the pressure in these two vessels (all p<0.001). In contrast, HA pressure was comparable between baseline and phase A, while it tended to decrease in phase B. Regarding histology, the most notable abnormality was the presence of inflammatory infiltrates and hepatocyte necrosis. CONCLUSION: Helium-insufflation increased PV pressure with a partial compensatory decrease of HA pressure. Nonetheless, findings consistent with hepatic ischemia were observed on pathology.

Contrast-Enhanced Color Doppler Ultrasonography for Preoperative Evaluation of Sentinel Lymph Node in Breast Cancer Patients.

BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard of care for breast cancer patients with non-palpable axillary lymph nodes. We evaluated the usefulness of contrast-enhanced ultrasonography in preoperative detection of malignant SLNs. METHODS: 50 patients with breast cancer (median age: 60 years) underwent a color power Doppler ultrasonography with intravenous contrast (Sonovue®) preoperatively, and findings suggestive of metastatic disease to the SLN were documented. The final histopathological report and the radiological preoperative record were compared. Finally, the sensitivity, specificity and diagnostic accuracy of this evolving diagnostic modality were calculated. RESULTS: Contrast-enhanced ultrasound scan identified a negative SLN in the axilla of 27 patients and final histopathology was negative for 30 cases in total, so negative predictive value was calculated as 90% and positive predictive value was 75%. Overall sensitivity was 83.33% and specificity was 84.38%. Moreover, the ability of contrast-enhanced ultrasound to differentiate between SLN status was only statistically significantly correlated with the actual final histopathological report (p < 0.001), while successful ultrasound prediction was not correlated with any factor. CONCLUSIONS: SLN status can be evaluated preoperatively using contrast-enhanced color Doppler ultrasonography with high accuracy.

Attenuation of Oxidative Stress by Ischemic Preconditioning in an Experimental Model of Intraabdominal Hypertension.

PURPOSE: Increased intra-abdominal pressure, as used in laparoscopic surgery or seen in intraabdominal hypertension (IAH), is associated with tissue ischemia and oxidative stress. Ischemic preconditioning (IP) is a method successfully used in liver and transplant surgery, in order to attenuate the detrimental effects of ischemia and reperfusion. In this experimental study, we tested the ability of IP to modify oxidative stress induced by extremely high intraabdominal pressures. METHODS: Twenty-five female pigs were studied and divided in three groups: a control group, a pneumoperitoneum group (with pressure of 30 mmHg), and an ischemic preconditioning group (initially subjected to preconditioning with pressure of 25 mmHg for 15 min and desufflation for 15 min and then to pneumoperitoneum as in pneumoperitoneum group). Blood samples were obtained at identical time intervals in the three groups. Total oxidative capacity, total antioxidative capacity and total nitric oxide (NO), nitrite and nitrate concentrations were measured and compared between groups. RESULTS: IP increased total antioxidative capacity (p = .045) and protective mediators like nitrite (p = .022). It was also associated with a trend toward lower levels of total oxidative capacity at the end of the abdominal desufflation period but statistical significance was not met. CONCLUSIONS: IP attenuated oxidative stress induced by IAH, mainly by increasing antioxidative capacity and the levels of protective mediators. The fact that IP was effective, even when used at extremely high levels of intraabdominal pressure, reinforces the interest on this method but further studies are needed to clarify its mechanism of action and potential clinical applications.

Merkel cell carcinoma of unknown primary site; case presentation and review of the literature.

Merkel cell carcinoma (MCC) is a rare skin malignancy associated with sun exposure and considered as a Neuroendocrine Tumor due to its characteristic histologic features. However there is increasing number of reports of Unknown Primary MCC's (UPMCC). Although initially UPMCC was considered a variant of known primary MCC, there is growing evidence that it could represent a different clinical entity. We present the case of a 60 year-old male patient who was referred to our department for surgical management of lymph node disease for UPMCC. The patient had undergone excisional biopsy of an inguinal lump, which was found to be an infiltrated lymph node by MCC. The patient underwent full imaging staging including a PET/CT, which failed to identify a primary site, and revealed only intra-abdominal lymph node disease. The patient underwent extended retroperitoneal and inguinal lymph node dissection and remains free of recurrence 16 months postoperatively.

Association of FokI and PvuII polymorphisms with breast cancer staging and survival among Caucasian women: a prospective study.

PURPOSE: Both vitamin D and estrogens play an important role in breast cell growth and differentiation. Therefore, we hypothesized that FokI polymorphism in the Vitamin D Receptor (VDR) gene, as well as PvuII polymorphism in the Estrogen Receptor (ESR) gene might be associated with progression of breast cancer. The aim of this study was to prospectively examine the association of these polymorphisms with histopathological features and prognosis among women with histologically proven breast cancer. METHODS: Patient characteristics, tumor histopathology, and genotyping of one VDR polymorphism variant (FokI) and one ER polymorphism variant (PvuII) were recorded. Patients were also routinely followed up. RESULTS: There was a significant difference regarding nodal stage (p<0.001) between the different genotypes of FokI polymorphisms (FF, Ff, ff), even though a trend was also detected in the frequency between ductal and lobular type, as well as tumor size (p=0.077). When further analysis was performed regarding patients whose polymorphism included the f allele, we found statistically significant differences in tumor size (p<0.001), nodal stage (p=0.03), tumor grade (p=0.04) and lymphovascular invasion (p<0.001), while no differences in nodal status, distant metastases and tumor stage were noticed. No significant associations were found between any of the PvuII polymorphism variants and tumor histopathology and stage. No statistical significance was proven between FokI polymorphism's variants or f allele and overall or progression-free survival. Statistically significant associations between overall and progression- free survival and PvuII polymorphism's variants was demonstrated (p<0.001). CONCLUSION: The f allele was associated with the presence of lymphovascular invasion and poorly differentiated tumors, whereas the PP genotype was associated with increased overall and progression-free survival, suggesting that this variant is related to a more favorable prognosis.

Bilateral obturator pyomyositis with visceral involvement in an immunocompetent adult patient treated without surgery.

BACKGROUND: Primary pyomyositis is a rare bacterial infection that affects large muscle groups mainly in immunocompromised patients. Treatment options include antibiotic treatment with surgical or radiologic interventions. CASE: A 22-year-old immunocompetent athlete was diagnosed with bilateral obturator muscle pyomyositis involving pelvic floor muscles and the urinary bladder after muscle injury during training. Intravenous antibiotic treatment was administered, resulting in eradication of the infection. CONCLUSION: This is the first case of bilateral obturator pyomyositis with coexisting involvement of pelvic floor muscles (levator ani) and viscera (urinary bladder) treated exclusively and with success by the administration of appropriate antibiotic therapy. A non-operative approach may could be attempted for the avoidance of postoperative morbidity and complications, especially when early clinical suspicion and diagnostic work-up lead to early diagnosis.

Multifocal retroperitoneal sarcoma.

Introduction. Retroperitoneal sarcomas comprise a small proportion of all soft tissue sarcomas, and multiple factors influence their clinical behavior. Histopathological type and grade as well as complete surgical resection especially on the first operative attempt are well recognized as the main prognostic factors. Multifocality is another prognostic factor, which compromises therapy and finally makes prognosis worse due to multiple adverse implications. Case Presentation. A rare case of a 65-year-old male patient suffering from a multifocal retroperitoneal liposarcoma successfully treated in our hospital is presented herein. Discussion. Also, general considerations for these tumors are discussed, and especially multifocality is underlined as an ominous sign of retroperitoneal sarcomas behavior. Despite multifocality, once again complete surgical excision remains the mainstay of treatment of these patients, as long as further systemic and local therapies do not provide durable results.

A Rare Coexistence of Retroperitoneal Pararenal Castleman's Disease with Focal Nodular Hyperplasia.

Castleman's disease is a distinct form of lymph node hyperplasia divided into a solitary and a multicentric type. The solitary type occurs most commonly in the mediastinum and is usually asymptomatic. We present a patient with Castleman's disease of the hyaline-vascular solitary type located in the retroperitoneum. The patient was a 38-year-old male, who presented to our hospital with fever. The imaging workup revealed a retroperitoneal mass, measuring 4 × 6 cm, located lateral to the aorta, inferior to the left renal artery and vein, and posterior to the left testicular vein. At workup, a solid hepatic lesion, 3 cm in diameter, located in the left lobe of the liver, segment IV, was also identified. Both lesions were surgically excised. The retroperitoneal tumor had the features of angiofollicular hyperplasia (Castleman's disease), hyaline-vascular type, whereas a diagnosis of focal nodular hyperplasia was made for the hepatic lesion. The patient is well at fourty months followup postoperatively. Surgical excision is the treatment of choice for unifocal Castleman's disease.

Neuroendocrine differentiation in embryonal type hepatoblastoma.

Hepatoblastoma, a malignant tumor which arises occasionally in older children but very rarely in adults, exhibits divergent differentiation with embryonal cells, fetal hepatocytes and immature elements. This report describes an embryonal type hepatoblastoma with neuroendocrine differentiation in a 16-year-old patient, which was diagnosed postoperatively. Clinical and radiologic work-up failed to reveal a primary gastrointestinal malignancy and no primary lesions were detected in any other organ. This feature of hepatoblastoma is considered to be a multidirectional differentiation of the small epithelial or stem cells of the liver. At 2-year follow up, the patient remains symptom-free, with normal laboratory and diagnostic imaging studies, and no recurrent or metastatic disease identified.

Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance.

MicroRNAs are a class of non-coding molecules found to regulate a variety of cellular functions in health and disease. Dysregulation of microRNAs is involved in liver disease, especially hepatocarcinogenesis. Since primary hepatic malignancies are typically characterized by late diagnosis, frequent recurrence, and poor response to adjuvant therapy, there is a need for the discovery of novel biomarkers in order to achieve earlier diagnosis, predict tumor aggressiveness and response to adjuvant therapy. The purpose of this study is to evaluate the expression of certain microRNAs (miR-21, -31, -122, -145, -146a, - 200c, -221, -222 and -223) in patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as to assess their prognostic significance. Micro-RNA expression was assessed by reverse transcription and real-time PCR (RT-PCR). Clinicopathological data and survival rates were retrieved and analyzed. According to our results, miR-21, miR-31, miR-122, miR-221, miR-222 were significantly up-regulated in HCC tissues, whereas miR-145, miR-146a, miR-200c, and miR-223 were found to be down-regulated. Concerning ICC samples, miR-21, miR-31, and miR-223 were found to be over-expressed, whereas miR-122, miR-145, miR-200c, miR-221, and miR-222 were down-regulated. Additionally, expression of miR-21, miR-31, miR-122, and miR-221 in HCC correlated with cirrhosis, while miR-21 and miR-221 associated with tumor stage and poor prognosis. In ICC tissues, miR-21, miR-31, and miR-223 were found to be over-expressed, but no correlation with clinicopathological features was found.

Expression of microRNAs in patients with pancreatic cancer and its prognostic significance.

OBJECTIVES: Investigation of expression profile of well-established microRNAs in pancreatic adenocarcinoma, and its correlation with clinicopathological factors. METHODS: Eighty-eight samples of ductal pancreatic adenocarcinoma and 98 control samples were analyzed by real-time polymerase chain reaction for miR-21, miR-31, miR-122, miR-145, miR-146a, miR-155, miR-210, and miR-222 expressions. The results were normalized and then statistically analyzed using nonparametric statistical tests. RESULTS: According to our results, miR-21, miR-155, miR-210, miR-221, and miR-222, were overexpressed in diseased tissues than in the control samples, whereas miR-31, miR-122, miR-145, and miR-146a were underexpressed. Additionally, the expressions of miR-21 and miR-155 were associated with tumor stage and poor prognosis. CONCLUSIONS: The tumorigenic role of miR-21 and miR-155 was confirmed, whereas down-regulation of miR-31, miR-145, and miR-146a, in dispute with current literature, renders necessary the revision of use of microRNAs as biological markers.

Successful treatment with the mTOR inhibitor everolimus in a patient with perivascular epithelioid cell tumor.

Perivascular epithelioid cell tumor (PEComa) is an extremely rare neoplasm that appears to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites. Malignant PEComas exist but are very rare. These tumors represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. Metastatic PEComa is a rare form of sarcoma for which no effective therapy has been described previously and that has a uniformly fatal outcome. Although there is no known effective therapy, the molecular pathophysiology of aberrant mTOR signaling provides a scientific rationale to target this pathway therapeutically. The difficulty in determining optimal therapy, owing to the sparse literature available, led us to present this case. On this basis, we report a case of metastatic retroperitoneal PEComa treated with an oral mTOR inhibitor, with everolimus achieving significant clinical response.

The effect of warm liver ischaemia & reperfusion injury on circulating plasma lipid levels & lipolytic enzyme activity in rat & the impact of ischaemic preconditioning.

BACKGROUND & OBJECTIVES: Ischaemia/reperfusion (I/R) associated with major liver surgery compromises liver function. Ischaemic preconditioning (IPC) may be effective in minimizing hepatic I/R injury. This study aimed to investigate the impact of liver ischaemic manipulations on lipid metabolism in rat during the process of liver recovery after liver surgery. METHODS: Sixty three male Wistar rats were assigned to three groups: the sham group, the I/R group which underwent warm ischaemia and reperfusion (I/R), and the IPC group. The animals were subdivided in 3 groups [1 st , 3 rd and 7 th postoperative day (PO)]. Hepatic lipase (HL) and total lipase (TL) activity and the levels of aspartate and alanine transaminases (AST, ALT), triglycerides, HDL and cholesterol were measured in plasma. RESULTS: There was no significant difference in the activity of HL and TL between the groups. Significant higher levels of HDL (P<0.0001) were observed in the IPC group when compared to the other groups on the 3 rd PO day. Triglycerides (P<0.0001) and HDL (P=0.003) in the IPC group were higher than the sham group on the 7 th PO day while HDL was also higher in the I/R group. Significantly higher cholesterol levels were found in the I/R and IPC groups on the 7 th PO day, which were not observed in the sham group. There was a similar curve for triglycerides in the sham and IPC groups while there were significantly higher levels of triglycerides on day 7 for the I/R group. The levels of HDL in the IPC group were higher on the 3 rd and 7 th PO day, compared to day 1. INTERPRETATION & CONCLUSION: Warm ischaemia and I/R injury do not seem to affect lipolytic enzyme activity after the 1 st PO day despite the effects on plasma lipids. IPC seems to prevent accumulation of triglycerides and cholesterol in plasma.

The impact of ischemic preconditioning on hemodynamic, biochemical and inflammatory alterations induced by intra-abdominal hypertension: an experimental study in a porcine model.

PURPOSE: Intra-abdominal hypertension (IAH) has several pathophysiologic implications on human organs and systems. The aim of this experimental study was to investigate whether ischemic preconditioning (IP), namely the application of IAH for a small period of time prior to establish pneumoperitoneum, can attenuate the hemodynamic, biochemical and inflammatory alterations observed during IAH. METHODS: Twenty-four pigs were divided into three groups: group A (control group), group B (pneumoperitoneum of 30 mmHg) and group C (ischemic preconditioning, consisting of pneumoperitoneum of 25 mmHg for 15 min and subsequent pneumoperitoneum of 30 mmHg). Hemodynamic (central venous pressure, cardiac index, mean arterial pressure, heart rate, stroke volume index, systemic vascular resistance index, global end-diastolic index, intrathoracic blood index and extravascular lung water index), biochemical (serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), urea and creatinine) and inflammatory (tumour necrosis factor-α, interleukin (IL)-6, IL-10 and C-reactive protein) parameters were measured. RESULTS: (a) Hemodynamics: The increase of central venous pressure monitoring and heart rate and the decrease of cardiac index, mean arterial pressure, stroke volume index, global end-diastolic volume index and intrathoracic blood volume index with the establishment of pneumoperitoneum were attenuated by IP. Systemic vascular resistance index and extravascular lung water were not affected. (b) Urea significantly increased with the pneumoperitoneum. IP, however, attenuated this effect. Οther biochemical parameters (SGOT, SGPT, ALP, γ-GT and creatinine) had a similar upward trend during IAH, which was reversed with IP. (c) Inflammatory parameters: CRP was increased with pneumoperitoneum, an effect that was attenuated with the application of IP. Νo significant differences were observed for interleukins. CONCLUSIONS: Ischemic preconditioning seems to attenuate the pathophysiologic alterations of several hemodynamic, biochemical and inflammatory parameters observed during IAH.

Effect of Acute Surgical Stress on Serum Ghrelin Levels.

BACKGROUND: Ghrelin is an appetite hormone that influences the gastrointestinal function and regulates energy metabolism. Growing evidence also suggests that this hormone plays a central role in immune modulation. Each surgical operation is followed by a series of inflammatory and metabolic changes that constitute the stress response. The aim of our study is to evaluate the effect of stress during different types of abdominal surgery in ghrelin serum levels. METHODS: An overall of 25 patients were prospectively allocated in two groups based on the type of surgical operation. Group A (n = 10) patients were scheduled to undergo cholecystectomy, whereas Group B (n = 15) patients underwent colectomy. Serum ghrelin concentrations were evaluated in each patient preoperatively, after the induction of general anesthesia and tracheal intubation, one and five hours after the beginning of surgery and the morning of the first and second postoperative day. RESULTS: In both groups serum ghrelin concentrations reached their peak level at 24 hr (Group A: 8.4 ± 3.4 ng/mL; Group B: 7.4 ± 1.8 ng/mL) and these values were significantly higher than those in the preoperative period (Group A: 5.0 ±1.5 ng/mL; Group B: 4.8 ± 0.6 ng/mL) (P < 0.05). Forty eight hours after surgery the levels of ghrelin returned to their preoperative status. Patients' gender, age, ASA score and type of surgical procedure did not influence the serum ghrelin levels. CONCLUSIONS: Serum ghrelin concentration appears to elevate in response to surgical stress. Future studies are needed to improve comprehension of the mechanisms underlying responses of this hormone to acute surgical stress and to evaluate their possible clinical implications.

A review on the role of microRNA in biology, diagnosis, and treatment of pancreatic adenocarcinoma.

OBJECTIVES: MicroRNAs are molecules implicated in RNA-RNA interaction, playing a role in cell proliferation and differentiation, as well as in carcinogenesis. Knowledge on their biological features is necessary to understand their role in phenotypic characteristics of pancreatic adenocarcinoma. METHODS: Review of current literature concerning mechanisms of action, studying methods, implementations, and preclinical trials on pancreatic adenocarcinoma. RESULTS: More than 20 microRNAs have been identified, being involved in pancreatic adenocarcinoma biology, affecting tumor growth, metastatic potential, and chemosensitivity. Combinations of microRNAs can be used to differentiate between pancreatic adenocarcinoma and other pancreatic pathologies, as well as to assess prognosis. Manipulations of microRNAs can decrease the rate of growth or reinstall chemosensitivity to certain chemotherapeutic agents. CONCLUSIONS: The field of microRNAs promises novel diagnostic and therapeutic tools in the management of pancreatic adenocarcinoma.