Expression of phosphorylated Akt, mTOR and MAPK in type I endometrial carcinoma: clinical significance.

BACKGROUND/AIM: The Akt/mTOR and MAPK pathways are frequently activated in various tumor types but data on endometrial carcinoma are limited. The aim of the present study was to investigate the clinical significance of the expression of phosphorylated MAPK, Akt and mTOR (p-MAPK, p-Akt, p-mTOR) in type I endometrial carcinoma. MATERIALS AND METHODS: The study comprised of 103 formalin-fixed paraffin-embedded (FFPE) type I endometrial carcino ma cases, retrospectively retrieved and assessed by immuno histochemistry for p-MAPK, p-Akt and p-mTOR expression. The expression of these proteins was also studied in non-neoplastic endometrial tissue adjacent to the tumor. RESULTS: The expression patterns of these molecules differed between malignant and non-tumorous tissue specimens. The immuno reactivity for p-Akt was exclusively detected in the neoplastic tissues. Expression levels of p-MAPK were higher in tumors compared to non-neoplastic endometrium (p<0.001), while p-mTOR was found to be over-expressed in non-neo plastic endometrium compared to carcinomas (p=0.001). Expression of p-Akt was correlated with p-MAPK protein levels (p=0.022, r=0.229). On the other hand, no association was found with clinicopathological parameters and with disease-free (DFS) or overall survival (OS) of the patients. CONCLUSION: Our findings support the de-regulation of the PI3K/Akt/mTOR and MAPK signaling pathways in type I endometrial carcinomas suggesting involvement of these pivotal pathways in endometrial carcinogenesis.

Solitary cecal diverticulitis: an unusual cause of acute right iliac fossa pain-a case report and review of the literature.

Solitary cecal diverticulitis is a rare cause of acute abdominal pain in the Western world. Its clinical presentation, in most cases, mimics acute appendicitis. A 38-year-old Caucasian man presented with acute abdomen and clinical signs of acute appendicitis. Laparotomy was performed and revealed an inflammatory, solitary diverticulum of the cecum. A typical appendectomy was performed and a catheter was inserted for draining percutaneously the inflamed diverticulum of the cecum. The patient had an uneventful recovery and was discharged on the 4th postoperative day. This frequently misdiagnosed condition, in most cases, is being suspected and identified intraoperatively as acute appendicitis. The aim of this study is to review the available different surgical management options and to present an alternative therapeutic approach that may be valuable under specific circumstances.

An immunohistochemical analysis of sex-steroid receptors, tumor suppressor gene p53 and Ki-67 in the normal and neoplastic uterine cervix squamous epithelium.

INTRODUCTION: Malignant transformation of sex-steroid dependent tissues is associated with the loss of expression of sex steroid receptors as well as of the tumor suppression gene p53. The aim of this study is to evaluate the expression of sex-steroid receptors, p53 and Ki-67 in specimens from pre-malignant and malignant cervical epithelial lesions throughout the menstrual cycle. MATERIAL AND METHODS: Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissue sections of normal squamous cervical epithelium, cervical intraepithelial neoplasia and invasive squamous cervical carcinoma, specimens utilizing antibodies against estrogen receptors, progesterone receptors, p53 protein and Ki-67 antigen. RESULTS: In the samples taken from the normal cervical tissue, basal cells were usually estrogen receptor-positive, progesterone receptor-negative, p53-negative and Ki-67-negative throughout the menstrual cycle. In contrast, para-basal cells were estrogen receptor-positive and progesterone receptor-negative in the follicular phase, but estrogen receptor-negative and progesterone receptor-positive and Ki-67 positive in the luteal phase. In cervical precancerous and cancer tissue samples (cervical intraepithelial neoplasia and squamous cervical carcinoma), the expression of estrogen receptors decreased. 31.15% of cervical intraepithelial neoplasia and 11.5% of squamous cervical carcinoma were positive for estrogen receptors. However, the expression of progesterone receptors increased. 29.5% of cervical intraepithelial neoplasia and 49.2% of squamous cervical carcinoma were positive for progesterone receptors. Positive staining for p53 was observed in 15 (24.59%) cases of cervical intraepithelial neoplasia and in 39 (64%) of squamous cervical carcinoma. The expression Ki-67 index in squamous cervical carcinoma cases (47.60%) was significantly higher than of cervical intraepithelial neoplasia cases (30.2%) (p = 0.041). CONCLUSION: The findings of this study suggest that tumor cervical cells evade normal growth control by sex steroid hormones while synchronously abnormal regulatory mechanisms acquire control of the cell cycle.

Necrotizing fasciitis complicating pregnancy: a case report and literature review.

Necrotizing fasciitis is a rare, life-threatening surgical infection in pregnancy with high rates of morbidity and mortality. A 15-year-old primigravid woman, at 28 weeks of gestation with no significant previous medical history, was admitted to our hospital complaining of severe left lower extremity pain and high fever the last 72 hours. During clinical examination, she had a swollen, erythematous and tender to palpation inflamed skin over the medial aspect of the upper thigh without any evidence of injury. Incision drainage was performed immediately and she received broad spectrum antibiotics. During initial laboratory examinations, diabetes mellitus was diagnosed. There was no clinical improvement over the following days. Magnetic resonance imaging (MRI) revealed subcutaneous tissue inflammation and edema of infected tissues confirming the disease entity. Multidisciplinary therapy with immediate aggressive surgical debridement of necrotic tissues, multiple antibiotics, and intensive care monitoring was performed successfully. The patient's postoperative course was uncomplicated and skin defect was closed with split thickness skin grafting. Our case emphasized the potential immunosuppressive role of pregnancy state in conjunction with diabetes mellitus in the development of severe necrotizing soft tissue infections.

The prognostic role of preoperative serum CA 125 levels in patients with endometrial carcinoma.

PURPOSE: Previous studies have shown that elevated preoperative serum CA 125 levels strongly correlate with various clinical and pathological variables and prognosis of patients with endometrial carcinoma (EC). The aim of the present study was to evaluate the clinical significance of preoperative serum CA 125 levels in patients with EC. METHODS: A retrospective study of all EC patients treated at our institution between 1995 and 2010 with available follow-up was conducted. The preoperative serum level of CA 125 was measured in 99 patients and evaluated in relation to various clinical and pathological variables and outcome. We used the cut-off level of 20 U/ml for CA 125 on chi-square test for categorical variables. Survival analysis was performed with the use of Kaplan Meier method, the log rank test and Cox proportional hazards regression analysis. RESULTS: In the early stages of disease the mean values of CA 125 were 35 U/ml (SD±70) for stages IA-IB and 21 U/ml (SD±29) for stage IC (Mann-Whitney test for continuous variables). In advanced stages of disease (III-IV), the values of preoperative serum CA 125 levels were statistically increased, with mean value 54 U/ml (SD±44), in comparison to stages IA-IB (p=0.02) and IC (p=0.007). According to the multivariate analysis, elevated preoperative serum CA 125 level (p=0.043) and histological tumor type (p=0.004) were independent prognostic factors for disease free survival (DFS) and overall survival (OS) of patients with EC. CONCLUSION: The current study suggests that measurement of preoperative serum CA 125 is a useful clinical tool in the prognosis of patients with EC.

Spontaneous uterine rupture in a primigravid woman in the early third trimester attributed to adenomyosis: a case report and review of the literature.

We report a rare case of spontaneous uterine rupture of an unscarred uterus caused by adenomyosis in the early third trimester. A 33-year-old primigravid woman was referred to our department because of severe acute abdominal pain and signs and symptoms of hemorrhagic shock. Ultrasound exanimation performed at admission revealed a living, intrauterine fetus of 28 weeks gestational age with reduced amniotic fluid and presence of free peritoneal fluid. The fetal heart rate was non-reassuring with variable decelerations and severe fetal bradycardia. Emergency cesarean section revealed massive hemoperitoneum and complete rupture in the uterine fundus. Subtotal peripartum hysterectomy with conservation of adnexae was performed. Histological examination revealed adenomyosis at the site of uterine rupture.

A case of severe ADAMTS13 deficiency presenting as thrombotic thrombocytopenic purpura in pregnancy.

INTRODUCTION: Thrombotic thrombocytopenic purpura is a rare life-threatening disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. It is caused by the absent or severe deficiency of the von Willebrand Factor-cleaving protease named ADAMTS13. Pregnancy is a well recognized factor precipitating the appearance of the disease both in women that had reduced levels of ADAMTS13 activity prior to gestation and in those with other inherited or acquired thrombophilic syndromes. CASE REPORT: We report a 25-year old woman with severe ADAMTS13 deficiency presented early in her 1st pregnancy and relapsed in two subsequent gestations. This presentation is uncommon for thrombotic thrombocytopenic purpura is associated with pregnancy (ADAMTS13 deficiency < 5%, without an inhibitor). In the first pregnancy she started with daily plasma exchange 1.5 x volume, corticosteroids and IV immunoglobulin and finally entered remission after 23 sessions and termination of pregnancy. In the second pregnancy she did not receive prophylactic treatment and relapsed in the 3rd trimester. Prophylactic treatment during the third pregnancy with plasma infusions proved also ineffective to prevent relapse. DISCUSSION: Many issues regarding treatment and prevention of thrombotic thrombocytopenic purpura relapses in subsequent pregnancies are unclear. Proposed guidelines recommend that the same treatment should be performed on pregnant and non pregnant patients without modification of plasma replacement dose according to ADAMTS13 levels. In addition, many authors suggest that pregnant patients with history of thrombotic thrombocytopenic purpura and severe deficiency of ADAMTS13 levels should received prophylactic treatment for prevention of relapses in the subsequent pregnancies. CONCLUSION: Severe ADAMTS 13 deficiency may present as thrombotic thrombocytopenic purpura of pregnancy. Pregnant women with thrombotic thrombocytopenic purpura and especially with severe deficiency of ADAMTS13 levels require specific consideration regarding treatment and prophylaxis in subsequent pregnancies.

The expression of omental 11ß-HSD1 is not increased in severely obese women with metabolic syndrome.

OBJECTIVE: Plasma cortisol in obese subjects does not differ from that in normoweight subjects. Extra-adrenal cortisol production by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) can result in local hypercortisolemia. The aim of the present study was to examine the role of visceral hypercortisolemia in the development of metabolic syndrome in severe obesity. METHODS: Eight lean women during hysterectomy (controls) and 19 severely obese women during bariatric surgery were studied, 8 without metabolic syndrome (OM- group) and 11 with it (OM+ group). Biopsies of omental and subcutaneous fat were performed in the severely obese women during surgery, but only omental biopsies in the controls. Expression of 11ß-HSD1, glucocorticoid receptor α (GRα) and glucocorticoid receptor ß (GRß) was evaluated using real-time PCR. RESULTS: Omental 11ß-HSD1 expression was different between groups (one-way ANOVA, p < 0.01). Post-hoc analysis revealed that mean omental 11ß-HSD1 mRNA levels were higher in the OM- group compared to controls, whereas they were similar when comparing the OM+ group with lean controls. Expression of 11ß-HSD1 in subcutaneous fat was not different between OM+ and OM- groups. GRα expression in omental fat did not differ among groups or between omental and subcutaneous fat in severely obese patients. An expression of GRß was not detected. CONCLUSION: Contrary to our original hypothesis, omental 11ß-HSD1 expression is not increased in the OM+ group.

Intraabdominal desmoplastic small round cell tumor: Report of a case and literature review.

INTRODUCTION: Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. Due to our limited knowledge of the pathologic and clinical nature of this disease, there is no clear consensus regarding the optimal therapeutic procedures for treating this neoplasm. A high degree of care and improvements in diagnostic capabilities are required in order to identify this entity and avoid misdiagnosis. CASE PRESENTATION: We report a new case of a 29-year-old male who proceeded to our Emergency Department complaining about non-specific abdominal pain. Physical examination revealed no abnormalities except for a palpable mass in the lower abdomen and a diffuse abdominal pain. Computed Tomography scan showed enlarged paraortic and mesenteric lymphadenopathy, thickness of the small bowel wall and dispersed masses intraperitoneally. He underwent an exploratory laparotomy and the resultant biopsy revealed desmoplastic small round cell tumor. DISCUSSION: Diagnosis of desmoplastic small round cell tumor can easily be missed because it presents with few early warning symptoms and signs, while the routine blood tests are within normal limits. CONCLUSION: A high degree of suspicion, a thorough physical examination, a full imaging check and an aggressive therapeutic approach are required in order to identify this disease and fight for a better quality of life for these patients. In addition we make a review of the literature in an effort to clarify the epidemiological, clinical and pathological aspects of this entity.

Therapeutic options for the management of the cardiorenal syndrome.

Patients with heart failure often present with impaired renal function, which is a predictor of poor outcome. The cardiorenal syndrome is the worsening of renal function, which is accelerated by worsening of heart failure or acute decompensated heart failure. Although it is a frequent clinical entity due to the improved survival of heart failure patients, still its pathophysiology is not well understood, and thus its therapeutic approach remains controversial and sometimes ineffective. Established therapeutic strategies, such as diuretics and inotropes, are often associated with resistance and limited clinical success. That leads to an increasing concern about novel options, such as the use of vasopressin antagonists, adenosine A1 receptor antagonists, and renal-protective dopamine. Initial clinical trials have shown quite encouraging results in some heart failure subpopulations but have failed to demonstrate a clear beneficial role of these agents. On the other hand, ultrafiltration appears to be a more promising therapeutic procedure that will improve volume regulation, while preserving renal and cardiac function. Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of the cardiorenal syndrome remains quite empirical.