Ischemic postconditioning decreases iNOS gene expression but ischemic preconditioning ameliorates histological injury in a swine model of extended liver resection.

BACKGROUND: Both pre- and postconditioning have been shown to protect the liver parenchyma from ischemia/reperfusion (I/R) injury during hepatectomy by altering the production of NO. However, to date there is no study to compare their effect on the inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) gene expression, who are the main modulators in the pathway of NO during the acute phase of I/R injury. METHODS: We designed a prospective experimental cohort comprising of three groups (sham group-SG, preconditioning-PrG and postconditioning group-PoG) and consisting of 10 animals per group. All animals underwent extended hepatectomy (70%) under prolonged warm ischemia either after preconditioning or followed by postconditioning or without any protective maneuver (SG). Following reperfusion blood samples and liver biopsies were obtained at the start of reperfusion (0 hours), at 6 and 12 hours post reperfusion. iNOS and eNOS gene expression was assessed on liver tissue by polymerase chain reaction (PCR); in addition, the extent of hepatocellular injury was histologically assessed. RESULTS: At the beginning of reperfusion iNOS expression was significantly reduced in the PoG in comparison to the SG (Kruskal-Wallis test, P=0.012; Mann-Whitney U test, P<0.0005 Bonferroni correction) and continued to remain at low levels until 6 hours post reperfusion (Kruskal-Wallis test, P=0.01; Mann-Whitney U test, P<0.0005-Bonferroni correction) This difference was eliminated by 12 hours. No significant differences were found in the expression of eNOS between groups and within time measurements. Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) were found increased at the start of reperfusion; their levels continued to increase by 6 hours in all groups, however only in the PoG the increase attended statistical significance at 12 hours after reperfusion. ALT levels presented only minor alterations during the course of reperfusion. The PrG was found to have more intense hepatocellular injury at the start of reperfusion than the PoG however, that appeared to gradually settle by 12 hours in contrast to PoG where the hepatocellular injury continued to deteriorate. CONCLUSIONS: PoG appeared to decrease iNOS overexpression more effectively than PrG in comparison to animals who have undergone no protective maneuver (SG). However, PrG was more effective than PoG in ameliorating the hepatocellular injury observed at 12 hours after the ischemic insult.

Imaging and Cytopathological Criteria Indicating Malignancy in Mucin-Producing Pancreatic Neoplasms: A Series of 68 Histopathologically Confirmed Cases.

OBJECTIVES: This study aims to evaluate the performance of clinical, imaging, and cytopathological criteria in the identification of high-grade dysplasia/carcinoma (HGD/Ca) in pancreatic mucin-producing cystic neoplasms. METHODS: Sixty-eight consecutive, histopathologically confirmed mucin-producing cystic neoplasms, evaluated by endoscopic ultrasound-guided fine-needle aspiration, were enrolled; specifically, 39 branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), 21 main duct IPMNs, and 8 mucinous cystic neoplasms. The associations between HGD/Ca in histopathology and findings of endoscopic ultrasound and cytology, demographic, lifestyle, and clinical parameters were evaluated, separately in IPMNs and mucinous cystic neoplasms. RESULTS: Age 65 years or more was associated with HGD/Ca in IPMNs. In BD-IPMNs, cyst diameter 3 cm or greater (sensitivity, 68.8%; specificity, 65.2%), a mural nodule (sensitivity, 56.3%; specificity, 78.3%), main pancreatic duct diameter 5 to 9 mm (sensitivity, 50.0%; specificity, 87.0%), and suspicious cytology (sensitivity, 81.3%; specificity, 100%) signaled the presence of HGD/Ca. Similarly, in main duct IPMNs, suspicious cytology predicted HGD/Ca with high sensitivity (88.9%) and excellent specificity (100%). Regarding cytopathological criteria, in BD-IPMNs, HGD/Ca was associated with a high nuclear/cytoplasmic ratio, background necrosis, presence of papillary structures, hypochromatic nuclei, hyperchromatic nuclei, and major nuclear membrane irregularities (thickening and/or indentations). CONCLUSIONS: Clinical, imaging, and cytopathological criteria are useful in the identification of HGD/Ca in IPMNs.

Imprint cytology versus frozen section analysis for intraoperative assessment of sentinel lymph node in breast cancer.

INTRODUCTION: Sentinel lymph node (SLN) biopsy is the gold standard for surgical staging of the axilla in breast cancer (BC). Frozen section (FS) remains the most popular means of intraoperative SLN diagnosis. Imprint cytology (IC) has also been suggested as a less expensive and equally accurate alternative to FS. The aim of our study was to perform a direct comparison between IC and FS on the same SLNs of BC cases operated in a single center by the same surgical team. MATERIALS AND METHODS: Into this prospective study we enrolled 60 consecutive patients with histologically proven T1-T3 BC and clinically negative axilla. Sentinel nodes were detected using a standard protocol. The SLN(s) was always assessed by IC as well as FS analysis and immunohistochemistry. Nevertheless, all intraoperative decisions were based on FS analysis. RESULTS: During the study period 60 patients with invasive BC were registered, with 80 SLNs harvested. Mean number of SLN(s) identified for each patient was 1.33. The sensitivity and specificity were 90% and 100%, respectively, for IC, and 80% and 100% for FS. Relevant positive/negative predictive values were 100%/98% for IC and 100%/96.15%, respectively, for FS. Overall accuracy was 98% for IC and 97% for FS. Therefore, statistically significant difference between the two methods in the detection of positive nodes was not elucidated (p=1.000). CONCLUSIONS: IC appeared to be marginally more sensitive than FS in detecting SLN metastatic activity. Overall accuracy was 98.75%. With regard to the primary lesion characteristics, we conclude that initial lesion size and lymphovascular invasion play a pivotal role in metastatic involvement of the SLN with the dimensions of metastasis bearing no correlation with tumor size. Therefore, IC appears to be a sensitive and accurate method for the intraoperative assessment of SLN in BC patients, but further studies are required to confirm this interesting data.

Biliary Mucinous Cystic Neoplasm of the Liver with Ovarian Stroma and Elevated Serum and Cystic Fluid Cancer Antigen 19-9 Levels.

Biliary mucinous cystic neoplasms of the liver are rare cystic tumors comprising less than 5% of the liver cystic neoplasms. These tumors demonstrate a female predominance and entail a risk of malignant transformation. We present a 56-year-old female patient with a multiloculated liver cystic lesion measuring 22 cm who underwent a cystectomy with en bloc resection of the liver segments II, III, and cholecystectomy. Serum cancer antigen 19.9 was 4,122.00 U/ml, supporting the diagnosis of a biliary cystic tumor. The cytology of the cystic fluid was negative for malignancy and intracystic fluid cancer antigen 19.9 level was measured over 12,000.00 U/l. The patient is free of recurrence at one-year follow up. Although a rare entity, the biliary mucinous cystic neoplasms should be considered in the differential diagnosis in the patients with liver cystic tumors. The appropriate management with complete surgical resection with negative margins is recommended given the risk of recurrence and malignant transformation.

The Effect of Perioperative Ischemia and Reperfusion on Multiorgan Dysfunction following Abdominal Aortic Aneurysm Repair.

Abdominal aortic aneurysms (AAAs) are relatively common and are potentially life-threatening medical problems. The aim of this review is to provide an overview of the effect of I/R injury on multiorgan failure following AAA repair. The PubMed, CINAHL, EMBASE, Medline, Cochrane Review, and Scopus databases were comprehensively searched for articles concerning the pathophysiology of I/R and its systemic effects. Cross-referencing was performed using the bibliographies from the articles obtained. Articles retrieved were restricted to those published in English. One of the most prominent characteristics of AAA open repair is the double physiological phenomenon of ischemia-reperfusion (I/R) that happens either at the time of clamping or following the aortic clamp removal. Ischemia-reperfusion injury causes significant pathophysiological disturbances to distant organs, increasing the possibility for postoperative multiorgan failure. Although tissue injury is mediated by diverse mechanisms, microvascular dysfunction seems to be the final outcome of I/R.

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.

First case of lacosamide-induced psychosis.

Lacosamide (LCM) is a newer antiepileptic drug with a favorable safety profile used in partial epilepsy as adjunctive therapy. The most common side effects include dizziness, headache, confusion, diplopia, nausea, nasopharyngitis, and vomiting. Although sporadic cases of drug-induced psychosis have been reported for some antiepileptic drugs, this was not the case for LCM. We describe the first case of LCM-induced psychosis in a patient with drug-resistant partial epilepsy during the first week of treatment initiation, stressing the importance of clinicians remaining alert for abnormal behavioral symptoms.

Unusual presentation of Mönckeberg's sclerosis in the thyroid vessels of three female patients.

Histopathological findings of Mönckeberg's sclerosis in the thyroid vessels of three female patients are described. Two of the patients presented with papillary carcinoma and the third presented with two cystic adenomatous nodules. Lesions of chronic lymphocytic thyroiditis were observed in two of the cases. The presence of Mönckeberg's sclerosis is an indication for further examination of patients' vascular systems because of the high risk for cardiovascular events.

Intrapancreatic accessory spleen issues: diagnostic and therapeutic challenges.

CONTEXT: Intrapancreatic accessory spleen is an exceptionally rare entity, commonly mistaken for a pancreatic neoplasm. Preoperative diagnosis based on radiologic imaging features is difficult. Aspiration cytology may be misleading due to poor sampling. CASE REPORT: We report a very rare case of an intrapancreatic accessory spleen which radiologically and cytologically mimicked a neuroendocrine pancreatic tumor. CONCLUSION: Modern imaging techniques will probably lead to an increasing number of intrapancreatic accessory spleens being discovered, posing significant diagnostic and therapeutic challenges.

Abnormal uterine bleeding as a presentation of metastatic breast disease in a patient with advanced breast cancer.

BACKGROUND: Extragenital carcinomas secondarily involving the uterus are very rare and they usually occur as a manifestation of widespread disease. When the metastases involve the endometrium in a diffuse, permeative pattern, sparing the glands, they may cause problems in the diagnosis. CASE: A case of metastatic carcinoma to the endometrium with a decidua-like pattern is reported. The patient had a history of breast carcinoma and presented with vaginal bleeding. The pathologic findings in the uterine curettings raised the differential diagnosis between metastatic breast carcinoma and non-neoplastic stromal lesions. The presence of nuclear atypia and mitotic activity along with the appropriate immunohistochemical findings revealed the neoplastic nature of the endometrial lesion and confirmed its origin from the breast. CONCLUSION: Unusual uterine bleeding in a patient with breast cancer should alert the gynecologist to the possibility of metastatic breast disease. Furthermore, the metastasis to the uterus and to other organs of the genital tract can be considered as a preterminal event.

Sutureless pancreatojejunal anastomosis using an absorbable sealant: evaluation in a pig model.

BACKGROUND: Leakage from pancreatojejunal anastomosis continues to be a major source of morbidity in pancreatic surgery. In the present study, we test the hypothesis that a safe, sutureless pancreatojejunal anastomosis can be constructed using a synthetic surgical sealant. MATERIALS AND METHODS: Ten pigs weighing 20 to 25 kg underwent distal pancreatectomy and anastomosis of the pancreatic remnant with a jejunal limb with the use of an absorbable surgical sealant. Integrity of the anastomosis was checked on the 10th postoperative d by means of an autopsy study and histological examination. RESULTS: One animal died on the 3rd postoperative d of peritonitis. The remaining 9 animals had an uneventful postoperative course. Gross and microscopic pathological examination revealed intact pancreatojejunal anastomosis in all surviving animals. CONCLUSIONS: Following distal pancreatectomy in pigs, pancreatojejunal anastomoses with the use of sealant are technically feasible. During a 10-d observation period, the sealant appeared to prevent anastomotic dehiscence and allow normal anastomotic healing.

Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure.

Oxidative mechanisms have been implicated in the pathogenesis of brain edema in acute liver failure (ALF). The aim of this study was to test the hypothesis that inhibition of iron-catalyzed oxidative reactions through iron chelation using deferoxamine could attenuate brain edema in a swine model of ischemic ALF. Following ALF induction (end-to-side portacaval anastomosis and ligation of the hepatoduodenal ligament), 14 animals were randomized to a study group that received an intravenous infusion of 150 mg/kg deferoxamine (group DF; n = 7) or a control group (group C; n = 7). Six sham-operated animals were also assigned to a deferoxamine-treated group (n = 3) or a control group (n = 3). Hemodynamic, neurological, and hematological parameters were monitored postoperatively. All sham animals maintained normal hemodynamics and intracranial pressure. At 18 hours, group DF animals had higher mean arterial pressure (mean +/- standard deviation: 98.0 +/- 15.9 versus 69.9 +/- 15.8 mmHg, P < 0.004), lower intracranial pressure (18.1 +/- 8.6 versus 32.7 +/- 13.4 mmHg, P < 0.032), and higher cerebral perfusion pressure (76.4 +/- 16.4 versus 37.1 +/- 25.6 mmHg, P < 0.006) in comparison with group C. Similar differences were recorded up to the 24th postoperative hour, leading to a significant difference in animal survival (88% in group DF versus 17% in group C, P < 0.001). Furthermore, group DF exhibited an attenuated increase of serum malondialdehyde from the baseline (16% versus 74%, P < 0.05) and lower brain malondialdehyde concentrations (3.7 +/- 1.3 versus 5.7 +/- 2.0 microM/mg of protein, P < 0.05) in comparison with controls. In conclusion, deferoxamine delayed the development of intracranial hypertension and improved survival in pigs with ischemic ALF.

Clinicopathologic features of two rare cases of mesenchymal metastatic tumors in the pancreas: review of the literature.

OBJECTIVES: A clinicopathologic presentation of 2 unusual cases of metastatic mesenchymal neoplasms in the pancreas. METHODS: The first case concerns a 26-year-old man with a history of intracranial mesenchymal chondrosarcoma (since the age of 17), 2 left lung operations, and 3 right thigh operations. Distal pancreatectomy and splenectomy was performed because of suspicious mass in the pancreas. The second case concerns a 66-year-old woman with a history of uterus leiomyosarcoma (10 years ago) with left axillary and right femoral metastases. She underwent distal pancreatectomy and splenectomy because of suspicious mass measuring 4 x 4 cm, in the pancreatic body. RESULTS: In the first case, the pathological examination revealed a tumor measuring 3.8 x 3.5 cm and histologically compatible with mesenchymal chondrosarcoma, developing in a vessel lumen and invading into the pancreatic parenchyma. In the second case, the pathological examination showed metastatic leiomyosarcoma of high-grade malignancy. The incidence of metastatic pancreatic tumors has been reported to be only 1.6% to 3%. Most of these tumors were of epithelial origin, and the most common sites of the primary lesions were the lung, kidney, and gastrointestinal tract. CONCLUSIONS: The cases of metastatic uterus leiomyosarcoma and the metastatic intracranial chondrosarcoma are, to our knowledge, the first to be described.

Juvenile granulosa cell tumor associated with pregnancy: Report of a case and review of the literature.

BACKGROUND: Juvenile granulosa cell tumors account for about 5% of all granulosa cell tumors and are diagnosed in nearly 80% of cases during the first two decades of life. Only 10% of granulosa cell tumors present during pregnancy. The incidence of ovarian malignancies during pregnancy varies from 0.05 to 0.07 per 1000 pregnancies. CASE: A 31-year-old pregnant woman was admitted to our university hospital due to an adnexal mass, 9.5 cm in diameter, which was detected at 34 weeks of gestation. At 37 + 5 weeks of gestation, a cesarean section with right salpingo-oophorectomy and removal of the tumor was performed. Histopathological findings, including immunohistochemical study, led to the diagnosis of juvenile granulosa cell tumor (JGCT). CONCLUSION: The histological features and the differential diagnosis of the JGCT are discussed. The optimal management of such adnexal masses during pregnancy is also discussed. A JGCT that is confined to the ovary appears to have an excellent prognosis and can be treated by unilateral salpingo-oophorectomy.

Sharp liver transection versus clamp crushing technique in liver resections: a prospective study.

BACKGROUND: Parenchymal liver transection constitutes an important phase of liver resection. Serious intraoperative bleeding, together with injuries to vital structures of the liver remnant, can occur during this stage. A method of sharp liver parenchymal transection with scalpel is compared in a prospective randomized manner with the widely used clamp crushing technique. METHODS: Patients scheduled for hepatectomy under selective hepatic vascular exclusion (N = 82) were allocated randomly to either the sharp transection group (n = 41) or the clamp crushing group (n = 41). Warm ischemic time, blood loss and transfusions, postoperative morbidity and mortality, and tumor-free margins were recorded in both groups and analyzed. RESULTS: When the sharp transection group was compared with the clamp crushing group, the two groups were similar in warm ischemic time (median 36 vs 34 minutes), total operative time (median 205 vs 211 minutes), intraoperative blood loss (median 500 vs 460 mL), blood transfusion requirements (median value 0 in both groups), and overall complication rate (44% vs 39%). However, sharp transection yielded better tumor-free margins compared with the clamp crushing technique (12 +/- 1.4 mm vs 8 +/- 1.5 mm, mean +/- SD, P < .05). CONCLUSION: Sharp liver parenchymal transection with a scalpel is equally safe in terms of blood loss and mortality compared with the clamp crushing method. Although it is a technically demanding method, requiring selective hepatic vascular occlusion, it may be recommended when the tumor-free margins are anticipated to be narrow.