Srdjan Dikic

An immunological insight into premature ovarian failure (POF).

Premature ovarian failure (POF), a serious life-changing condition that affects young women, remains an enigma and the researchers challenge. The term POF generally describes a syndrome of gonadal failure before the age of 40, characterized by amenorrhea, sex steroid deficiency and elevated levels of gonadotropins. Infertility and psychological stress are common consequences of this entity the prevalence of which is 0.9-3%. The known cause of this condition includes: genetic aberrations, autoimmune ovarian damage, iatrogenic and environmental factors, although in majority of cases the underlying cause is not identified. For many women in whom the cause of ovarian failure is unknown, autoimmunity may be the pathogenic mechanism. There is currently evidence that some cases of POF are due to faulty recognition of self in the ovary by the immune system, possibly provoked by genetic or environmental factors initiating such immune response. Numerous evidence, including association with multiple autoimmune endocrine disorders, clinical reversibility, transitory estrogen deficiency, histological and immunological features and the demonstration of circulating ovarian antibodies in serum samples from women with POF, have suggested its immunological origin. We discuss the possible role of such an autoimmune process as a cause or consequence of POF including treatment strategies in POF patients.

The role of transvaginal colour Doppler sonography in evaluation of abnormal uterine bleeding

IntroductionTreatment of abnormal uterine bleeding understands a prompt diagnostic procedure, for the sake of defining the etiological factor of disease. The abnormal uterine bleeding is more common in the perimenopausal than in the postmenopausal women, and it is more frequent sign of an endometrial proliferative or hyperplastic changes. Fewer percentages of women with unexpected and/or acyclic and prolonged bleeding have endometrial cancer.Materials and methodsSeventy-one (71) patients with abnormal uterine bleeding, older than 40xa0years, of which 10 were in post-menopause, have been tested. Prior to explorative curettage and histopathological analysis, ultrasonographic and hemodynamic studies, at the uterine blood vessels level (uterine artery bilaterally) had been performed by transvaginal colour Doppler method.ResultsHistopathological results indicated four types of represented changes, on the basis of how the patients were divided into the groups: I, proliferative endometrium—20 patients; II, endometrial adenocarcinoma—23 patients; III, various forms of endometrial hyperplasia—26 patients, IV, atrophic endometrium—2 patients. Significant statistical difference in the endometrial thickness was established between groups I and II, and endometrial cancer was not found in less than 8xa0mm thick endometrium. By analysing hemodynamic parameters, significantly lower PI values were obtained in the group of patients with pathologically altered endometrium, compared to other groups.ConclusionTransvaginal colour Doppler has significant role in the diagnostic process for evaluation of abnormal uterine bleeding in perimenopausal and postmenopausal women. Doppler sonography can help in differentiating physiological from malignant endometrial changes and in deciding on the most efficient therapeutical regime.

Melatonin: a "Higgs boson" in human reproduction.

Abstract As the Higgs boson could be a key to unlocking mysteries regarding our Universe, melatonin, a somewhat mysterious substance secreted by the pineal gland primarily at night, might be a crucial factor in regulating numerous processes in human reproduction. Melatonin is a powerful antioxidant which has an essential role in controlling several physiological reactions, as well as biological rhythms throughout human reproductive life. Melatonin, which is referred to as a hormone, but also as an autocoid, a chronobiotic, a hypnotic, an immunomodulator and a biological modifier, plays a crucial part in establishing homeostatic, neurohumoral balance and circadian rhythm in the body through synergic actions with other hormones and neuropeptides. This paper aims to analyze the effects of melatonin on the reproductive function, as well as to shed light on immunological and oncostatic properties of one of the most powerful hormones.

Early Dumping Syndrome and Reflux Esophagitis Prevention with Pouch Reconstruction

BACKGROUNDnTotal gastrectomy causes numerous disorders, such as reflux esophagitis, dumping syndrome, malabsorption, and malnutrition. To minimize the consequences, different variants of reconstruction are performed. The aim of our study is the comparison of two reconstructive methods: the standard Roux-en-Y and a new modality of pouch interposition, preduodenal-pouch interposition. This study aims to investigate the advantage of bile reflux prevention and to reduce symptoms of dumping syndrome after 3- and 6-mo follow-up.nnnMATERIALS AND METHODSnA total of 60 patients were divided in two groups: (A) 30 patients with Roux-en-Y reconstruction, and (B) 30 patients with the preduodenal-pouch (PDP) type of reconstruction. Endoscopic examination and endoluminal jejunal limb pressure measurements were performed. Scintigraphic measurements of half-emptying time were performed to evaluate meal elimination in the context of reflux esophagitis and early dumping syndrome. The Japan Society of Gastrointestinal Surgery has provided guidelines with which to classify the symptoms of early dumping syndrome. Patients were followed up for periods of 3 and 6 mo after the surgery.nnnRESULTSnOur study groups did not differ with regard to the level of reflux esophagitis (P = 0.688). Average values of pressure at 10 and 15 cm below the esophago-jejunal junction were significantly lower in the PDP group (P < 0.001). Elimination of the test meal between two groups was not significant (P = 0.222). Evaluation of early dumping syndrome symptoms revealed a significant reduction among PDP patients after 3 and 6 mo.nnnCONCLUSIONnOur study showed significant superiority of the new pouch reconstruction over the standard Roux-en-Y approach in the treatment of early dumping syndrome.

Allogeneic blood transfusion in patients in Dukes B stage of colorectal cancer

The aim of this study is to evaluate influence of allogeneic blood transfusion on prognosis in patients in Dukes B stage of colorectal cancer. All patients with colorectal cancer who were admitted at our Department of Surgery between January 2000 and December 2004 were analyzed. One hundred fifty-one patients who fulfilled inclusion criteria were enrolled in further evaluation. B stage according to Dukes classification and curative resection were inclusion criteria. Exclusion criteria were polyposis syndromes, nonpolyposis syndromes, inflammatory bowel disease, autoimmune disease and previous blood transfusion. Patients were divided into two groups: Group 1 received ≤3 units of allogeneic blood transfusion and group 2 received >3 units of allogeneic blood transfusion. “Cutoff” value of 3 units of blood was defined according to our results and literature data. Follow-up was 5xa0year. There was no statistical difference between these groups in local recurrence (χ2xa0=xa00.009, Pxa0>xa00.05) and distant metastasis (χ2xa0xa0=xa00.44, Pxa0>xa00.05). Also, the Kaplan–Meier survival curves were calculated, and long-rank test did not show a survival difference between these two groups (log rankxa0=xa00.075, Pxa0>xa00.05). Postoperative complications are significantly more frequent in Group 2 (χ2xa0=xa04.67, Pxa0<xa00.05). Multivariate logistic regression analysis confirmed that intraoperative blood transfusion more than three units had independent influence on local recurrence. Postoperative transfusion more than 3 units was statistically independent prognostic factor for metastasis and mortality. Overall transfusion less than 3 units of allogeneic blood does not influence the outcome of patients in Dukes B stage of colorectal cancer.

Relation between body mass and postmenopausal symptoms in surgically castrated women.

IntroductionPost-menopause androgens are the essential precursors for estrogen synthesis through their conversion in peripheral tissues. The main postmenopausal estrogen is estrone, which is also peripherally converted into estradiol. Concentrations of these two estrogens are directly proportional in circulation. We wanted to establish whether there is a direct correlation between body mass and postmenopausal symptoms in surgically castrated women.Materials and methodsWe analyzed 30 patients with artificially induced menopause, 3–12xa0months after the operation (hysterectomy and bilateral adnexectomy). Prior to being put on hormone substitution therapy the following was obtained from the patients: Body Mass Index—BMI (kg/m2), measurement of estradiol (E2) by RIA method, and 12 subjective symptoms analyzed according to intensity and frequency. The relationship between BMI, E2 level and subjective symptoms were assessed.ResultsBy analyzing the correlation coefficient it was shown that there was statistically significant causal-consequential connection between the E2 level and BMI (R2=0.1647, p<0.05). There is no strong correlation between BMI and symptoms (R2=0.004, p<0.05). However, E2 level correlated with subjective symptoms (R2=0.2123, p<0.05).ConclusionsEstrogen production in postmenopause is dependent on the substrate availability, and thus with adiposity. Therefore, we were surprised by the lack of correlation between BMI and symptoms. This suggests that estrogen metabolism and biological effects are not primarily affected by BMI, and that expression of postmenopausal symptoms does not depend only on estrogen level.

Surgery indeed has an important role in long-term outcome in patients with pancreatic head cancer.

We read with interest the article by Petermann et al. [1] in the August 2013 issue of World Journal of Surgery. First of all, we would like to congratulate the authors for their very interesting article. In this retrospective study 101 pancreatic head resections due to pancreatic ductal adenocarcinoma were analyzed. The authors wanted to assess the impact of postoperative complications, stratified by severity, on long-term survival of patients after pancreatic head resection for ductal adenocarcinoma. However, we have several concerns about their conclusions. First, the authors concluded that surgery is not associated with severe postoperative complications. Surgery is the cornestone in the treatment of pancreatic cancer. Pancreaticoduodenectomy (PD) is the standard surgical treatment of pancreas head cancer. Using an optimal pancreatic reconstruction technique is thought to be a major prophylactic measure to minimize the risk of PD-related complications. Also, there are many possibilities of type of reconstruction as well as many possibilities for pancreaticojejunostomies (PJA): (1) layer with or without telescope, (2) layer, end-to-end, end-to-side, ‘‘duct to mucosa,’’ ‘‘Blumgart‘s’’ anastomosis, etc. [2]. Further, we don’t agree with authors’ conclusion that surgery is not associated with severe postoperative complications. They did not mention what kind of reconstructions were performed In accordance with this we could state following facts. Delayed gastric emptying (DGE) occurs dominantly after pylorus-preserving pancreaticoduodenectomy (PPPD) and remains a leading cause of PPPD postoperative complications. Delayed gastric emptying was probably exacerbated by some intra-abdominal complications, such as an anastomotic leak or an abscess. Problems could also be caused by the surgical procedure itself, namely injury to the nerve of Latarjet. In one study the incidence of DGE was significantly reduced in the pyloric ring resection group compared to controls, without an increase in dumping syndrome [3]. Most pancreatic fistulas (PF) can be managed nonoperatively, but a significant number of grade C PF do require reoperative surgical intervention. Risk factors for pancreatic fistula are well recognized and include a soft pancreatic parenchyma, small main pancreatic duct caliber, and a distal pancreatic resection (vs PD) [4]. Type of anastomosis is also very important regarding this problem. For example, there is a statistically significant decrease in fistula rate in the invagination group—PJA with invagination compared to other types of anastomoses [5]. Patients with postoperative hemorrhage often have underlying complications such as pancreatic fistula that require urgent surgical treatment. Pancreatic enzymes in combination with infection can cause erosion of the gastroduodenal artery or splenic artery stump, resulting in significant bleeding requiring immediate treatment. D. Zdravkovic (&) D. Bilanovic T. Randjelovic S. Dikic Surgery, Faculty of Medicine, University of Belgrade, Belgrade, Serbia e-mail: drdarkozdravkovic@gmail.com

Nutritional Insight into Preduodenal Pouch Reconstruction One Year after Total Gastrectomy

BACKGROUNDnVarious types of reconstructions have been developed to improve the quality of life of patients following total gastrectomy. In addition, to ensure larger food-intake reservoirs and extend meal transit times, different types of pouch reconstructions have been developed and described. Our opinion is that the most important factor in providing better physiologic regulation of ingested food is restoration of the duodenal passage and enlargement of the gastric substituent.nnnMATERIALS AND METHODSnIn the present study, we compared standard a Roux-en-Y reconstruction and a preduodenal pouch (PDP) reconstruction. We evaluated the quality of life (QoL) for 60 patients during the first postoperative year, comparing serum albumin, protein, hemoglobin, iron, body weight, body mass index, and QoL. QoL was defined according to Korenagas score scale, which has 14 questions, for better understanding of subjective patient perceptions of digestive function.nnnRESULTSnOur study population did not differ in iron and hemoglobin levels at a 1-y follow-up. The difference between total serum albumin level was significant in all observed patients in the follow-up period in favor of the PDP reconstruction group (P = 0.001). The PDP reconstruction group also had a significantly higher serum protein level after 12 mo. The higher score difference between the two groups generally confirm the improved QoL in the PDP group (P = 0.001).nnnCONCLUSIONnThe most important aspects of improved QoL after gastrectomy due to gastric carcinoma are maintenance of the duodenal transit and the addition of a pouch. Jejunal preduodenal pouches provide a better QoL than Roux-en-Y reconstruction. Our study results suggest preduodenal pouch reconstruction should be used as the method of choice.

Obstructive jaundice and cholangitis caused by an arterial ring of the proper hepatic artery around the common bile duct

Summary Background Many different benign and malignant diseases can cause obstruction of the extrahepatic biliary duct. One of the more serious complications of biliary obstruction is cholangitis leading to emergency decompression. Anatomic variations are frequent in this region; however, it has rarely been reported that the extrahepatic bile duct is compressed by the arterial vessels. Case Report We present the case of a 68-year-old woman who was admitted through the emergency department of our hospital with jaundice, abdominal pain and fever. Biochemical analyses of liver function showed increased value of AST (113 IU/L) and AST (128 IU/L). Total bilirubin was 5.88 mg/dl, conjugated bilirubin was 3.00 mg/dl, and alkaline phosphatase was 393 IU/L. We performed abdominal ultrasound (US), magnetic resonance cholangiopancreatography (MRCP), and computed tomography (CT) imaging. Multislice CT angiography showed that the arterial ring of the common hepatic artery around the common bile duct (CBD) originated from the superior mesenteric artery. Cholecystectomy and intraoperative cholangiography were performed, as well as decompression and lavage of the biliary tree. Escherichia coli was identified from bile. Dissection of the hepatoduodenal ligament confirmed that the proper hepatic artery made a vascular ring around the CBD. Finally, a T tube was placed into the CBD. During 5 years of follow-up the patient has been without recurrent episodes of jaundice. In such cases dissection of the proper hepatic artery from the common hepatic duct is the treatment of choice. Conclusions If there are signs of cholangitis decompression and lavage of the biliary tree with “T”, drainage should be performed. Vascular malformations should be considered as a possible cause of extrahepatic biliary obstruction. CT angiography may be helpful in identifying these malformations.

Breast cancer and its impact in male transsexuals

IntroductionLesbian, gay, and bisexuals have unique healthcare needs. Breast cancer is leading cancer in women, worldwide, accounting for 25% of all cases. Annual incidence rates increased significantly in all countries and age groups. The occurrence of breast cancer is rare in transgender population. As they have very limited access to medical care, it is much less likely to pursue breast cancer screening than in other individuals not identified as transgender.Review of the cases from literatureUp to date, only 13 cases of the breast cancer transsexuals (female to male) have been reported in six published papers worldwide. Histological examination of the breast tumor in female-to-male transgender showed progesterone/estrogen-positive invasive ductal carcinoma.DiscussionGender identity describes a person’s inherent sense of being a woman, man, or of neither gender, whereas sexual orientation refers to how people identify their physical and emotional attraction to others. Gender reassignment surgery, as series of complex surgical genital and non-genital procedures, is recognized as the most effective treatment for patients with gender dysphoria. The two main principles of hormone therapy for transgender patients are to reduce endogenous hormone levels and their associated sex characteristics and replace them with hormones of the preferred sex. Breast cancer infrequently occurs in transgender patients. Even breast core biopsies can be difficult for interpreting after changes in breast tissue in female-to-male transsexuals following gender reassignment.ConclusionReviewing the literature, so many different data concerning probability of breast cancer in sexual minority can be found. Breast cancer screening program should be offered to all transgender individuals according to national guidelines. Very important is to take into consideration a transgender person’s natal and surgical anatomy, unique clinical concerns for depression and anxiety, risk of suicide together with risk factors including experiences of harassment or physical or sexual violence, low education level, and unemployment. Understanding the need for mammography in these often marginalized groups is very important in addressing breast cancer disparities despite differences in insurance coverage in some countries and greater concern for the cancer of the breast in residual breast tissue. The best screening rule, ever, for breast cancer in male transsexuals and other similar population should be, besides surgical history and hormonal status, “Screen Now, Screen Regularly and Screen What You Have.”