Surgical Treatment of Catamenial Chest Pain: Excision of diaphragmatic endometriosis during robot-assisted laparoscopic surgery.

Background: 10% of women of reproductive age are affected by endometriosis, and diaphragmatic endometriosis represents 1-1.5% of these cases. Diaphragmatic endometriotic lesions often require surgical treatment. Objective: This video aims to demonstrate the appearance of diaphragmatic endometriosis and describe our experience with robot-assisted laparoscopic excision of full thickness diaphragmatic endometriosis. Materials and Methods: The patient was a 37-year-old female with the complaint of cyclical right shoulder pain (for 1 year). She previously had caesarean section scar and umbilical endometriosis excision procedures. The magnetic resonance imaging (MRI) of the abdomen highlighted three endometriotic nodules, one of which was described as full thickness on the right hemi-diaphragm. The patient underwent a robot-assisted laparoscopic endometriosis surgery as a joint procedure between the gynaecology and general surgery teams. The falciform ligament was completely divided to obtain full views of the endometriotic lesions on the diaphragm. Superficial diaphragmatic lesions were first excised. The larger deep nodule, which was described on the MRI, was then excised with the full thickness of diaphragm. Pleural cavity was entered intentionally to achieve complete excision of the nodule. Laparoscopic assessment of the right lower pleural cavity through this opening did not show any endometriotic lesions. After the excision, the diaphragm was repaired with a barbed suture. Negative pressure suction of the pleural cavity was performed at the end of this repair instead of using a chest tube. Results: The patient was discharged on the 3rd day with no complications encountered. Histopathological examination confirmed endometriosis. The patient was asymptomatic three months after surgery. Conclusion: Robotic-assisted surgery is an easy and safe choice especially in such challenging dual compartment surgeries by providing a 3D view that abolishes sensory loss and increases depth perception, providing better manoeuvrability with tremor absence.

Brentuximab vedotin for relapsed or refractory Hodgkin lymphoma: experience in Turkey.

Current treatment modalities can cure up to 70-80 % of patients with classical Hodgkin lymphoma. Approximately, 20-30 % of patients require further treatment options. Brentuximab vedotin has been approved for the treatment of relapsed and refractory Hodgkin lymphoma. In the present study, we report the experience with brentuximab vedotin as single agent in 58 patients with relapsed or refractory Hodgkin lymphoma. The objective response rate was 63.5 % with 13 complete responders (26.5 %) among 49 patients evaluated at the early phase of treatment (2-5 cycles). Upon treatment prolongation (≥6 cycles), 37 patients achieved a final objective response rate of 32.4 % with 21.6 % of complete and 10.8 % of partial response. Overall survival at 12 months was 70.6 %, and progression-free survival at 12 months was 32.8 %. Median overall survival could not be reached and median progression-free survival was 7 months. While the median duration of response was 9 months in the whole cohort, it was 11.5 months in the complete responders. Complete response rates in patients treated with >3 chemotherapy regimens before brentuximab vedotin were significantly lower (p = 0.016). Fourteen patients were subsequently transplanted. In conclusion, brentuximab vedotin provided a bridge to transplantation in approximately one quarter of the patients. The declining response rates during the course of treatment suggest that transplantation should be implemented early during brentuximab vedotin treatment.

Effects of the Pringle manoeuvre on the healing of left colonic anastomoses in rats.

BACKGROUND: Whether to perform colorectal cancer and liver metastasis resections simultaneously or in separate procedures is controversial. The aim of the present study was to investigate the effect of the Pringle manoeuvre on the healing of left-sided colonic anastomoses in rats. METHODS: Sixteen rats were randomly separated into two groups. In Groups 1 and 2, 1 cm of descending colon was resected and a primary anastomosis was performed. In Group 2, an intermittent pedicle clamp (the Pringle manoeuvre) was performed. On postoperative day 5, laparotomy was performed and the bursting pressures of all colon anastomoses were determined. Tissues were sampled for assay of hydroxyproline levels. Cultures of intraperitoneal swabs were also performed. RESULTS: Clostridium was twice as abundant in the Pringle manoeuvre group as in the control group (p < 0.05). Anastomosis-bursting pressures and tissue hydroxyproline levels were significantly lower in the Pringle manoeuvre group than in the control group (p < 0.05). CONCLUSIONS: The Pringle manoeuvre may compromise the viability of colonic anastomoses.

Hypoxia-related molecules HIF-1α, CA9, and osteopontin : predictors of survival in patients with high-grade glioma.

PURPOSE: A high expression of hypoxia-inducible factor-1 alpha (HIF)-1α, carbonic anhydrase 9 (CA9), and osteopontin appears to be a strong prognostic indicator in many malignancies; however, their role is unclear in high-grade gliomas. PATIENTS AND METHODS: HIF-1α, CA9, and osteopontin levels in tissue specimens of 92 patients with high-grade glioma were evaluated by immunohistochemistry. RESULTS: Patients with a high expression of cytoplasmic and nuclear HIF-1α, CA9, and osteopontin had significantly shorter overall survival. The expression results of these markers were combined to form a hypoxic profile, and high hypoxic scores (expression of two or three markers) were significantly correlated to poorer overall survival. In multivariate analysis, high hypoxic score-1 (cytoplasmic HIF-1α, CA9, and osteopontin) was the only independent negative prognostic factor for survival (p = 0.028). CONCLUSION: Our results showed that a combination of hypoxic markers is more robust than a single marker for predicting survival in high-grade glioma. It may be necessary to utilize the hypoxic score in selecting patients for targeted therapy in the future.

High expression of nuclear survivin and Aurora B predicts poor overall survival in patients with head and neck squamous cell cancer.

BACKGROUND AND PURPOSE: Survivin is one of the apoptosis inhibitor proteins. Together with Aurora B, it also plays a role in regulating several aspects of mitosis. High expression of these markers is correlated with malignant behavior of various cancers and resistance to therapy. Our aim was to evaluate the prognostic role of these markers in head and neck cancers. PATIENTS AND METHODS: We evaluated the expression of Aurora B and survivin in tissue specimens of 58 patients with head and neck squamous cell carcinoma using immunohistochemistry. RESULTS: Patients who showed high expression of cytoplasmic and nuclear survivin and Aurora B had significantly shorter overall survival (p = 0.036, p < 0.000, p = 0.032, respectively). In multivariate analysis, high expression of nuclear survivin was the only independent negative prognostic factor (p = 0.024). Moreover, it was found that high co-expression of nuclear survivin and Aurora B had a negative effect on survival in univariate (p < 0.000) and multivariate (p < 0.000) analyses. CONCLUSION: The negative prognostic values of high expression of Aurora B and high co-expression of nuclear survivin and Aurora B on survival were shown. These findings suggest that co-expression of nuclear survivin and Aurora B can be useful diagnostic markers and therapeutic targets for head and neck squamous cell carcinoma. However, further studies with a larger number of patients in a more homogeneous disease group are needed to confirm the conclusion.

The age- and gender-dependent effects of desflurane and sevoflurane on rat liver.

OBJECTIVE: This study aimed to investigate the age- and gender-dependent effects of desflurane and sevoflurane on the liver. MATERIAL AND METHOD: Upon the approval of ethics committee, 84 rats were divided into four groups as 21 young male, 21 young female, 21 old male, and 21 old female rats. Then, each group was further divided into three groups as desflurane, sevoflurane, and control groups. Maintaining the minimum alveolar concentration of 1, desflurane at 6vol% and sevoflurane at 2vol% in 6Lmin(-1) 100% O2 were administered for 2h in a transparent plastic container of 40cmx40cmx70cm. Each liver preparation was evaluated for hydropic degeneration, nuclear polymorphism, portal neutrophile infiltration, portal lymphocyte infiltration, and focal necrosis, and each preparation was assigned injury points of 0-3; thus, the number of histopathologically injured cases, total injury scores of each preparation, and the mean injury scores of each group were determined. RESULTS: Desflurane and sevoflurane did not significantly increase hepatic injury in the young male rats, while both agents caused significantly more hepatic injury in the young female rats. In the old rats, both desflurane and sevoflurane inflicted more hepatic injury on both genders. In addition, desflurane caused more hepatic injury in the old female rats than in the young female or the old male rats. CONCLUSION: Hepatic injury associated with desflurane and sevoflurane was mild to moderate, suggesting that both agents can be safely used in routine anaesthesia procedures.

The role of liver biopsy in the workup of liver dysfunction late after SCT: is the role of iron overload underestimated?

Abnormalities in liver function tests are common in hematopoietic SCT (HSCT) recipients. We retrospectively investigated the role of liver biopsy in determining the cause of elevated liver enzymes and its impact on the management of patients in the post-HSCT setting. A total of 24 consecutive liver biopsies were obtained from 20 patients from September 2003 to December 2007. A definite histopathologic diagnosis was obtained in 91.7% of the biopsies. Iron overload (IO) was found in 75% and GVHD in 54.2% of the patients. The initial clinical diagnosis of GVHD was confirmed in 56.5% and refuted in 43.5% of the allogeneic HSCT recipients. The median number of post transplant transfusions, percent transferrin saturation and ferritin levels were found to be higher in patients who had histologically proven hepatic IO (p1=0.007, p2=0.003 and p3=0.009, respectively). Regression analysis showed a significant correlation between serum ferritin levels and histological grade of iron in the hepatocytes. Our data suggest that hepatic IO is a frequent finding in the post-HSCT setting, which contributes to hepatic dysfunction and it should be considered in the differential diagnosis, particularly in patients with high serum ferritin levels.

Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma.

The aim of this study was to compare vascular endothelial growth factor (VEGF), CD 34, and endoglin expressions as markers of angiogenesis in proliferative endometrium (PE), endometrial hyperplasia (EH), and endometrial carcinoma (EC) and to find the possible impact of angiogenesis on malign transformation. Formalin-fixed, paraffin-embedded tissues from 12 patients with PE, 23 patients with simple EH and complex EH with atypia, and 31 patients with EC were included. A semiquantitative scoring system was used to assess the intensity and degree of staining of VEGF. Microvessel density (MVD) was assessed with endoglin and anti-CD 34 in most vascular areas. VEGF expression was significantly higher in EC and EH than PE, but there was no difference between EC and EH. According to CD 34 staining, there were no differences in MVD between groups. However, mean MVD counts assessed by endoglin were significantly higher in EC than PE and EH. Although VEGF expression in EC was significantly higher, it did not correlate with other measures of angiogenesis. MVD using endoglin seemed to reflect neoplastic angiogenesis better than CD 34.

Effects of vitamin E treatment on peroxisome proliferator-activated receptor-alpha expression and insulin resistance in patients with non-alcoholic steatohepatitis: results of a pilot study.

BACKGROUND: Insulin resistance (IR) is commonly associated with non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) may also play a role in the pathogenesis of NASH. A pivotal role in NASH pathogenesis depends on the hypothesis of increased oxidative stress. The aim of our study was to evaluate the effects of supplemental oral vitamin E, a potent antioxidant, on liver functions, PPAR-alpha expression and IR in patients with NASH. METHODS: Nine patients with biopsy-proven NASH were given oral vitamin E 800 mg daily for 24 weeks. Liver functions, lipid parameters, IR index with homeostatic metabolic assessment and liver histology and PPAR-alpha staining index in biopsy specimens were detected before and after the treatment. RESULTS: Seven patients (78%) had IR initially. After 6 months of therapy in nine patients, fasting insulin improved (P = 0.01), but serum cholesterol, triglyceride, fasting blood glucose levels and body mass index remained unchanged. Aspartate aminotransferase and alanine aminotransferase levels decreased (P = 0.01 and P = 0.01, respectively). IR index with homeostatic metabolic assessment resistance improved (P = 0.01), but PPAR-alpha staining index did not change (P = 0.37). Although the histological grade of steatosis decreased (P = 0.01), necroinflammation and fibrosis remained unchanged. In seven patients with IR, however, necroinflammation and PPAR-alpha staining index were improved (P = 0.04 and P = 0.02). CONCLUSION: Vitamin E treatment, in addition to its previously shown beneficial effect by suppressing oxidative stress, may also achieve improvement by reducing IR and PPAR-alpha expression in NASH.

Evaluation of the effect of transplant-related factors and tissue injury on donor-derived hepatocyte and gastrointestinal epithelial cell repopulation following hematopoietic cell transplantation.

The aim of this study was to detect donor-derived hepatocytes and gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic hematopoietic cell transplants, and to assess the effect of tissue injury on the extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were reviewed. Double labeling by immunohistochemistry and fluorescence in situ hybridization was performed. Eighty-nine percent of sex-mismatched samples with histologic evidence of injury demonstrated the presence of donor-derived hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the hepatocytes and gastrointestinal epithelial cells in samples obtained from female recipients with female donors showed a Y chromosome signal. The proportion of donor-derived hepatocyte and gastrointestinal epithelial cells in samples with severe graft-versus-host disease was greater than that of samples with mild/moderate graft-versus-host disease (P = 0.09). No relationship between the source of stem cells and the population rate was detected (P > 0.05). We conclude that some recipient hepatocytes and gastrointestinal tract epithelial cells are replaced by donor-derived cells during tissue injury. The severity of tissue injury seems to influence on the extent of this repopulation.

Fibrinogen storage disease without hypofibrinogenemia associated with estrogen therapy.

BACKGROUND: Cytoplasmic inclusion bodies within hepatocytes may have different etiologies, including the Endoplasmic Reticulum Storage Diseases (ERSDs). ERSD is a pathological condition characterized by abnormal accumulation of proteins destined for secretion in the endoplasmic reticulum of hepatocytes; it may be congenital (primary) or acquired (secondary). Fibrinogen storage disease is a form of ERSD. CASE PRESENTATION: We present a case of fibrinogen storage disease secondary to estrogen replacement therapy. Its causal relationship to the drug is shown by histological, immunohistochemical and ultrastructural studies of paired liver biopsies obtained during and after the drug therapy. CONCLUSION: The liver biopsies of patients with idiopathic liver enzyme abnormalities should be carefully evaluated for cytoplasmic inclusion bodies and, although rare, fibrinogen deposits.

Ameloblastic carcinoma containing melanocyte and melanin pigment in the mandible: a case report and review of the literature.

A case of ameloblastic carcinoma containing melanocyte and melanin in a 66-year-old male with swelling and an ulcerating firm mass in the left submandibular region is presented. The diagnosis was confirmed by biopsy. The current histopathological diagnosis and management are discussed.

The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage--a light and electron microscopic study.

The results regarding taurine pretreatment on CCl(4)-induced hepatic injury are controversial. To assess the therapeutic efficacy of taurine on rat liver injury, hepatic malondialdehyde, glutathione, and hydroxyproline levels together with morphologic alterations in the liver following CCl(4) administration were investigated. The rats were divided into three groups. Taurine-treated animals received 15 ml/kg/day of a 5% taurine solution by a gastric tube for 5 days before administering CCl(4) (2 ml/kg, intraperitoneally, in a single dose). CCl(4)-treated rats received the same amount of saline solution. Control animals received no treatment. The increase of hepatic malondialdehyde formation in the CCl(4)-treated group was partially prevented by taurine pretreatment, but taurine had no significant effect on the glutathione and hydroxyproline content in the CCl(4)-treated rats. Taurine pretreatment induced a marked beneficial effect regarding the prevention of hepatocellular necrosis and atrophy as demonstrated morphologically. In conclusion, these results suggest that taurine pretreatment might not significantly change the biochemical parameters, but prevents the morphologic damage caused by CCl(4) in the early stages.

Effect of mechanical vs dilute ethanol epithelial removal on keratocyte apoptosis and polymorphonuclear leukocyte migration.

PURPOSE: To investigate keratocyte apoptosis and polymorphonuclear (PMN) cell infiltration to the corneal stroma after mechanical epithelial scraping and chemical de-epithelialization with 18% ethanol solution. METHODS: Twelve New Zealand Albino rabbits (24 eyes) were randomly divided into three groups. Group A was the control group with no epithelial removal. Group B underwent a 7.5-mm mechanical epithelial removal with a blunt spatula. Group C underwent 7.5-mm chemical de-epithelialization with 18% ethanol-balanced salt solution. Corneas were stained with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay after 24 h. Only nuclear staining in keratocytes was counted. Polymorphonuclear (PMN) leukocyte densities were also assessed by light microscopy. RESULTS: Mechanical de-epithelialization (group B) and chemical de-epithelialization with 18% ethanol (group C) showed no difference in keratocyte apoptosis compared with the control group. There was also no difference between groups B and C. Group B showed no difference in PMN leukocyte counts compared with the control group. But the number of PMN leukocytes observed in group C was significantly higher than those encountered in the corneas of the control group (P < 0.05) and group B (P < 0.05). CONCLUSIONS: Dilute alcohol induces more PMN cell infiltration when compared with mechanical de-epithelialization although there is no difference in the apoptosis rates.

Keratocyte apoptosis and corneal antioxidant enzyme activities after refractive corneal surgery.

PURPOSE: Refractive corneal surgery induces keratocyte apoptosis and generates reactive oxygen radicals (ROS) in the cornea. The purpose of the present study is to evaluate the correlation between keratocyte apoptosis and corneal antioxidant enzyme activities after different refractive surgical procedures in rabbits. METHODS: Rabbits were divided into six groups. All groups were compared with the control group (Group 1), after epithelial scraping (Group 2), epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK: Group 3), transepithelial PRK (Group 4), creation of a corneal flap with microkeratome (Group 5) and laser-assisted in situ keratomileusis (LASIK, Group 6). Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy were used to detect apoptosis in rabbit eyes. Glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities of the corneal tissues were measured with spectrophotometric methods. RESULTS: Corneal Gpx and SOD activities decreased significantly in all groups when compared with the control group (P<0.05) and groups 2, 3 and 6 showed a significantly higher amount of keratocyte apoptosis (P<0.05). Not only a negative correlation was observed between corneal SOD activity and keratocyte apoptosis (cc: -0.3648) but Gpx activity also showed negative correlation with keratocyte apoptosis (cc: -0.3587). CONCLUSION: The present study illustrates the negative correlation between keratocyte apoptosis and corneal antioxidant enzyme activities. This finding suggests that ROS may be partly responsible for keratocyte apoptosis after refractive surgery.

Bcl-2 and LMP1 expression in nasopharyngeal carcinomas.

In vitro studies of B-cells immortalized by Epstein-Barr Virus (EBV) have shown that B-cell leukemia/lymphoma-2 (bcl-2) protein expression is upregulated by the EBV-latency-associated antigen, latent membrane protein 1 (LMP1). The same phenomenon has also been observed in epithelial cells in vitro. However, such correlation between these 2 markers has not been shown in nasopharyngeal carcinoma (NPC), in which EBV infection is a well-known etiologic factor. This retrospective study examined 35 cases of undifferentiated NPC to answer the question of whether LMP1 and/or bcl-2 presence can be used as biomarkers at treatment response, as well as to see the relationship between bcl-2 and LMP in NPC. Of the 35 patients, 26 (74.3%) were bcl-2, and 10 (28.6%) were LMP1-positive. Although a significant correlation was observed between bcl-2 and LMP1 staining (P =.003), it appeared that bcl-2 expression could be independent of LMP1. Statistical analysis showed that cervical lymph node metastasis (P =.04) and cranial nerve involvement (P =.03) are the only variables that significantly affect patient survival. At this time, bcl-2 and LMP1 presence are not significant indicators of outcome; however, although they are not directly related to survival, expression of both bcl-2 and LMP1 was strongly correlated with cervical lymph node metastasis, which is a potent predictor of patient survival.

Association between the severity of heart failure and the susceptibility of myocytes to apoptosis in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Bcl-2 proto-oncogene, an inhibitor of apoptosis and Bax proto-oncogene, an inducer of apoptosis play critical roles in the molecular circuit controlling apoptosis in cardiac muscle. The ratio of Bax to Bcl-2 proto-oncogene determines survival or death after an apoptotic stimulus. We speculated that susceptibility of myocytes to apoptosis determined as the Bax/Bcl-2 ratio might vary with the severity of heart failure. METHODS AND RESULTS: We studied immunohistochemically 108 endomyocardial biopsy specimens from 30 patients with idiopathic dilated cardiomyopathy (mild heart failure, n=14; moderate or severe heart failure, n=16) with the use of Bcl-2 and Bax monoclonal antibodies. The expression of each protein was determined semiquantitatively as the fraction of myocytes labeled with specific monoclonal antibodies using a digital morphometric analysis system. Patients with mild heart failure showed significantly increased Bax/Bcl-2 ratio than the patients with advanced heart failure (1.59+/-1.26 vs. 0.34+/-0.43, P=0.002). The expression of Bcl-2 was found to be independent of the severity of heart failure whereas the expression of Bax was significantly higher in patients with mild heart failure compared to the patients with moderate or severe heart failure (52.1+/-29.3 vs. 21.6+/-22.4%, P=0.005). Additionally, Bax/Bac-2 ratio was inversely correlated with the mitral E-interventricular septum distance, left ventricular end-systolic and end-diastolic diameter. CONCLUSION: The susceptibility of myocytes to apoptosis is significantly increased in the early phase of heart failure but it decreases with worsening of the disease due to depressed expression of Bax onco-protein. Increased myocyte susceptibility to apoptosis may have a role in the transition from mild heart failure to severe in patients with idiopathic dilated cardiomyopathy.

Effects of topical vitamin E on keratocyte apoptosis after traditional photorefractive keratectomy.

PURPOSE: To evaluate the keratocyte apoptosis and effects of topical vitamin E on keratocyte apoptosis after photorefractive surgery. METHODS: Rabbits were divided into 7 groups, and all groups were compared with controls after epithelial scraping, epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK), transepithelial PRK, production of a corneal flap with microkeratome and laser-assisted in situ keratomileusis (LASIK). The effects of topical Vitamin E treatment were investigated in the traditional PRK group. The terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy have been used to detect apoptosis in rabbit cornea. RESULTS: Transepithelial PRK induced minimal keratocyte apoptosis, less than in all other refractive surgical procedures. The greatest amount of keratocyte apoptosis was observed after traditional PRK (p = 0.001), therefore we tested the effects of topical vitamin E in this group. The number of apoptotic keratocytes significantly reduced after vitamin E therapy (p < 0.005). CONCLUSION: Keratocytes undergo apoptosis after refractive surgery in response to mechanical epithelial removal, preparing of corneal flap and excimer laser stromal photoablation. The topical application of vitamin E immediately after surgery can prevent keratocyte apoptosis, and this result suggests that free radicals may be partly responsible for keratocyte apoptosis after excimer laser keratectomy.