Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta.

Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p < 0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocking key protective signaling routes abrogated the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-ß1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-ß1 as an attractive target for manipulation in this context.

The Role of E3, E4 Ubiquitin Ligase (UBE4B) in Human Pathologies.

The genome is exposed daily to many deleterious factors. Ubiquitination is a mechanism that regulates several crucial cellular functions, allowing cells to react upon various stimuli in order to preserve their homeostasis. Ubiquitin ligases act as specific regulators and actively participate among others in the DNA damage response (DDR) network. UBE4B is a newly identified member of E3 ubiquitin ligases that appears to be overexpressed in several human neoplasms. The aim of this review is to provide insights into the role of UBE4B ubiquitin ligase in DDR and its association with p53 expression, shedding light particularly on the molecular mechanisms of carcinogenesis.

Klatskin tumors and "Klatskin-mimicking lesions": our 22-year experience

Background and study purpose: Hilar cholangiocarcinoma, also known as Altemeier-Klatskin tumor, is a rare malignancy that arises in the confluence of the hepatic ducts of the porta hepatis. The prognosis is rather poor. Several lesions mimic these tumors and lead to a misdiagnosis, resulting in radical hepatic resections. These lesions are known as Klatskin-mimicking lesions. We present our experience with the diagnosis and treatment of pathological lesions that can mimic a perihilar cholangiocarcinoma and establish an algorithm of treatment Methods: For the current retrospective study, a prospectively established bile-duct tumor database was analyzed by selecting patients with a preoperative diagnosis of perihilar cholangiocarcinoma. Results: In the last 22 years (from January 1, 1996, to December 31, 2017), 73 patients who were referred to our tertiary center with a primary diagnosis of a Klatskin tumor were treated. All patients underwent a thorough evaluation before deciding upon the treatment. However, only 58 cases had a confirmed preoperative diagnosis of hilar cholangiocarcinoma in the final histopathological examination. The final diagnosis in 15 patients differed from the primary cause for referral and the lesions were regarded as Klatskin-mimicking lesions. Conclusions: Clinicians should always highly suspect Klatskin-mimicking lesions when they evaluate a patient for a possible hilar cholangiocarcinoma in order to avoid a misdiagnosis and propose a proper treatment

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Klatskin tumors and "Klatskin-mimicking lesions": our 22-year experience.

Background and study purpose: Hilar cholangiocarcinoma, also known as Altemeier-Klatskin tumor, is a rare malignancy that arises in the confluence of the hepatic ducts of the porta hepatis. The prognosis is rather poor. Several lesions mimic these tumors and lead to a misdiagnosis, resulting in radical hepatic resections. These lesions are known as Klatskin-mimicking lesions. We present our experience with the diagnosis and treatment of pathological lesions that can mimic a perihilar cholangiocarcinoma and establish an algorithm of treatment Methods: For the current retrospective study, a prospectively established bile-duct tumor database was analyzed by selecting patients with a preoperative diagnosis of perihilar cholangiocarcinoma. Results: In the last 22 years (from January 1, 1996, to December 31, 2017), 73 patients who were referred to our tertiary center with a primary diagnosis of a Klatskin tumor were treated. All patients underwent a thorough evaluation before deciding upon the treatment. However, only 58 cases had a confirmed preoperative diagnosis of hilar cholangiocarcinoma in the final histopathological examination. The final diagnosis in 15 patients differed from the primary cause for referral and the lesions were regarded as Klatskin-mimicking lesions. Conclusions: Clinicians should always highly suspect Klatskin-mimicking lesions when they evaluate a patient for a possible hilar cholangiocarcinoma in order to avoid a misdiagnosis and propose a proper treatment.

Making IVF more effective through the evolution of prediction models: is prognosis the missing piece of the puzzle?

Assisted reproductive technology has evolved tremendously since the emergence of in vitro fertilization (IVF). In the course of the recent decade, there have been significant efforts in order to minimize multiple gestations, while improving percentages of singleton pregnancies and offering individualized services in IVF, in line with the trend of personalized medicine. Patients as well as clinicians and the entire IVF team benefit majorly from 'knowing what to expect' from an IVF cycle. Hereby, the question that has emerged is to what extent prognosis could facilitate toward the achievement of the above goal. In the current review, we present prediction models based on patients' characteristics and IVF data, as well as models based on embryo morphology and biomarkers during culture shaping a complication free and cost-effective personalized treatment. The starting point for the implementation of prediction models was initiated by the aspiration of moving toward optimal practice. Thus, prediction models could serve as useful tools that could safely set the expectations involved during this journey guiding and making IVF treatment more effective. The aim and scope of this review is to thoroughly present the evolution and contribution of prediction models toward an efficient IVF treatment. ABBREVIATIONS: IVF: In vitro fertilization; ART: assisted reproduction techniques; BMI: body mass index; OHSS: ovarian hyperstimulation syndrome; eSET: elective single embryo transfer; ESHRE: European Society of Human Reproduction and Embryology; mtDNA: mitochondrial DNA; nDNA: nuclear DNA; ICSI: intracytoplasmic sperm injection; MBR: multiple birth rates; LBR: live birth rates; SART: Society for Assisted Reproductive Technology Clinic Outcome Reporting System; AFC: antral follicle count; GnRH: gonadotrophin releasing hormone; FSH: follicle stimulating hormone; LH: luteinizing hormone; AMH: anti-Müllerian hormone; DHEA: dehydroepiandrosterone; PCOS: polycystic ovarian syndrome; NPCOS: non-polycystic ovarian syndrome; CE: cost-effectiveness; CC: clomiphene citrate; ORT: ovarian reserve test; EU: embryo-uterus; DET: double embryo transfer; CES: Cumulative Embryo Score; GES: Graduated Embryo Score; CSS: Combined Scoring System; MSEQ: Mean Score of Embryo Quality; IMC: integrated morphology cleavage; EFNB2: ephrin-B2; CAMK1D: calcium/calmodulin-dependent protein kinase 1D; GSTA4: glutathione S-transferase alpha 4; GSR: glutathione reductase; PGR: progesterone receptor; AMHR2: anti-Müllerian hormone receptor 2; LIF: leukemia inhibitory factor; sHLA-G: soluble human leukocyte antigen G.

Are computational applications the "crystal ball" in the IVF laboratory? The evolution from mathematics to artificial intelligence.

Mathematics rules the world of science. Innovative technologies based on mathematics have paved the way for implementation of novel strategies in assisted reproduction. Ascertaining efficient embryo selection in order to secure optimal pregnancy rates remains the focus of the in vitro fertilization scientific community and the strongest driver behind innovative approaches. This scoping review aims to describe and analyze complex models based on mathematics for embryo selection, devices, and software most widely employed in the IVF laboratory and algorithms in the service of the cutting-edge technology of artificial intelligence. Despite their promising nature, the practicing embryologist is the one ultimately responsible for the success of the IVF laboratory and thus the one to approve embracing pioneering technologies in routine practice. Applied mathematics and computational biology have already provided significant insight into the selection of the most competent preimplantation embryo. This review describes the leap of evolution from basic mathematics to bioinformatics and investigates the possibility that computational applications may be the means to foretell a promising future for the IVF clinical practice.

A 20-year single center experience in the surgical treatment of colorectal liver metastasis.

PURPOSE: To present our experience in the treatment of patients with liver metastases from colorectal cancer. METHODS: The surgical and histopathological records of our department dating from 1st January 1997 to 31 December 2016 were examined, searching for patients who have undergone surgical treatment of colorectal liver metastasis. RESULTS: A total of 90 patients with colorectal liver metastases were treated in the last 20 years in our department. Their mean age was 65.28 years and 54 (60%) were male. The primary tumor was in the colon in 71 patients (78.9%) and in 19 (21.1%) patients in the rectum. Thirty-six (40%) patients presented with synchronous metastatic liver disease, from which 27 were subjected to simultaneous resection, 2 underwent a liver-first approach and 7 were subjected to resection of primary tumor first. Regarding the number of metastases 67 (74.4%) patients had single metastasis, 12 (13.3%) had 2 lesions, 4 (4.4%) had 3 lesions and 7 (7.8%) had 4-8 lesions. In-hospital and 30-day mortality was 3.85%. Median survival was 41 months. CONCLUSION: Surgical resection is the treatment of choice for the management of liver metastasis from colorectal cancer and can be safely performed. Follow up of patients with colorectal cancer is imperative as metachronous metastasis presents in a significant percentage of patients with negative locoregional lymph nodes of the primary tumor. The order of resection doesn't seem to alter outcome in synchronous metastasis. Recurrence is common and re-resection if feasible is the only chance of cure.

Effects of albumin/glutaraldehyde glue on healing of colonic anastomosis in rats.

AIM: To evaluate the effect of local surgical adhesive glue (albumin/glutaraldehyde-Bioglue) on the healing of colonic anastomoses in rats. METHODS: Forty Albino-Wistar male rats were randomly divided into two groups, with two subgroups of ten animals each. In the control group, an end-to-end colonic anastomosis was performed after segmental resection. In the Bioglue group, the anastomosis was protected with extraluminar application of adhesive glue containing albumin and glutaraldehyde. Half of the rats were sacrificed on the fourth and the rest on the eighth postoperative day. Anastomoses were resected and macroscopically examined. Bursting pressures were calculated and histological features were graded. Other parameters of healing, such as hydroxyproline and collagenase concentrations, were evaluated. The experimental data were summarized and computed from the results of a one-way ANOVA. Fisher's exact test was applied to compare percentages. RESULTS: Bursting pressures, adhesion formation, inflammatory cell infiltration, and collagen deposition were significantly higher on the fourth postoperative day in the albumin/glutaraldehyde group than in the control group. Furthermore, albumin/glutaraldehyde significantly increased adhesion formation, inflammatory cell infiltration, neoangiogenesis, and collagen deposition on the eighth postoperative day. There was no difference in fibroblast activity or hydroxyproline and collagenase concentrations. CONCLUSION: Albumin/glutaraldehyde, when applied on colonic anastomoses, promotes their healing in rats. Therefore, the application of protective local agents in colonic anastomoses leads to better outcomes.

Cecal diverticulitis is a challenging diagnosis: a report of 3 cases.

BACKGROUND: Cecal diverticulitis is an uncommon cause of acute abdominal pain and presents clinically similar to acute appendicitis. There are many perspectives concerning the management of this condition, ranging from different types of surgical resections to conservative treatment with antibiotics. CASE REPORT: We present 3 cases of cecal diverticulitis. One of the patients was treated conservatively with intravenous antibiotics and the other 2 were treated with surgical resection. CONCLUSIONS: Conservative treatment with intravenous antibiotics can be used in uncomplicated cecal diverticulitis. Complicated cecal diverticulitis is managed surgically and the type of resection depends mainly on the extent of inflammation.

Open-access technique and "critical view of safety" as the safest way to perform laparoscopic cholecystectomy.

BACKGROUND: The 2 main challenges of laparoscopic cholecystectomy are primary peritoneal access and safe identification, ligation, and division of the cystic duct and cystic artery. PATIENTS AND METHODS: This is a 13-year period retrospective study from January 2000 to December 2012. All the operations were performed by 1 surgeon and all the data were collected from the hospitals archive. A total of 929 laparoscopic cholecystectomies were performed for symptomatic cholelithiasis. The first author was involved in all the operations either by performing or assisting in them. The open access (OA) technique was used in all cases for the creation of pneumoperitoneum. After establishing the pneumoperitoneum, the "critical view of safety" (CVS) technique was used to ligate and divide the cystic duct and cystic artery. When the OA was not possible or CVS was not feasible, the operation was converted to open. RESULTS: Successful establishment of pneumoperitoneum with OA was possible in 911 of 929 (98.06%) patients and CVS was achieved in 873 patients (95.82%). In 18 patients the operation was converted to open because of dense adhesions not permitting the establishment of the pneumoperitoneum. No intraoperative or postoperative complications occurred in these patients. No bile duct injury occurred in this series. Postoperative complications were recorded in 19 patients (2.04%). Five patients had bleeding from port sites, 12 patients had wound infection at the umbilical incision, and 2 patients developed subhepatic collections, which were drained percutaneously under computed tomographic guidance. CONCLUSIONS: In this series of laparoscopic cholecystectomies, we used the "open access" technique to create pneumoperitoneum and we obtained the "critical view of safety" for the identification of the cystic duct. Our results show that this approach is the safest way to perform and teach laparoscopic cholecystectomy.

Successful treatment of recurrent cholangitis by constructing a hepaticojejunostomy with long Roux-en-Y limb in a long-term surviving patient after a Whipple procedure for pancreatic adenocarcinoma.

PATIENT: Female, 74. FINAL DIAGNOSIS: Recurrent cholangitis. SYMPTOMS: -. MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: Gastroenterology and Hepatology. OBJECTIVE: Unusual clinical course. BACKGROUND: Cholangitis may result from biliary obstruction (e.g., biliary or anastomotic stenosis, or foreign bodies) or occur in the presence of normal biliary drainage. Although reflux of intestinal contents into the biliary tree after hepaticojejunostomy appears to be a rare complication, it is important to emphasize that there are few available surgical therapeutic techniques. CASE REPORT: A 74-year-old woman presented to our hospital after 17 years of episodes of cholangitis. The patient had undergone a pancreatoduodenectomy (Whipple procedure) 18 years earlier due to pancreatic adenocarcinoma. The reconstruction was achieved through the sequential placement of pancreatic, biliary, and retrocolic gastric anastomosis into the same jejunal loop. The postoperative course was uneventful and the patient received adjuvant chemotherapy. Approximately 6 months after the initial operation, the patient started having episodes of cholangitis. Over the next 17 years she experienced several febrile episodes presumed to be secondary to cholangitis. A computing tomography (CT) scan of the abdomen revealed intrahepatic bile ducts partially filled with orally administered contrast material (Gastrografin). Magnetic resonance cholangiopancreatography (MRCP) showed dilatation of the left intrahepatic bile ducts. A percutaneous transhepatic cholangiography showed that the bilioenteric anastomosis was normal, without stenosis. Based on these findings, a diagnosis of a short loop between the hepaticojejunostomy and the gastrojejunostomy permitting the reflux of intestinal juice into the biliary tree was made. During the re-operation, a new hepaticojejunal anastomosis in a 100-cm long Roux-en-Y loop was performed to prevent the reflux of the intestinal fluid into the biliary tree. The patient was discharged on postoperative day 10. One year after the second procedure, the patient enjoys good health and has been free of fever and abdominal pain and has not received any antibiotic therapy. CONCLUSIONS: Lengthening the efferent Roux-en-Y limb should be considered as a therapeutic option when treating a patient with recurrent episodes of cholangitis after hepaticojejunostomy.

Laparoscopic enucleation of a giant submucosal esophageal lipoma. Case report and literature review.

Patient: Female, 40 Final Diagnosis: Esophageal lipoma Symptoms: - Medication: - Clinical Procedure: Laparoscopic enucleation Specialty: Surgery Objective: Rare disease. BACKGROUND: Benign tumors of the esophagus are very rare, constituting only 0.5% to 0.8% of all esophageal neoplasms. Approximately 60% of benign esophageal neoplasms are leiomyomas, 20% are cysts, 5% are polyps, and less than 1% are lipomas. CASE REPORT: A 40-year-old woman was referred to our department with dysphagia that had progressively worsened during the previous 2 years. Physical examination on admission produced normal findings. Upper gastrointestinal endoscopy revealed a submucosal space-occupying mass in the posterior wall of the lower esophagus, with normal mucosa. The mass was yellowish and soft. A computed tomography (CT) of the chest revealed a submucosal esophageal lesion in the posterior wall, with luminal narrowing of the distal esophagus. Thus, a submucosal tumor was identified in this region and esophageal submucosal lipoma was considered the most likely diagnosis. A laparoscopic operation was performed. The tumor was completely enucleated, and measured 10×7×2.5 cm. The pathology showed lipoma. The postoperative course was uneventful, and the patient was discharged 4 days after the operation. CONCLUSIONS: Benign tumors of the esophagus are very rare. Laparoscopic transhiatal enucleation of lower esophageal lipomas and other benign tumors is a safe and effective operation.

Measurement of PSA density by 3 imaging modalities and its correlation with the PSA density of radical prostatectomy specimen.

OBJECTIVE: To evaluate the difference between the PSA density (PSAD) calculated with 3 imaging modalities and the PSAD of the radical prostatectomy specimen. MATERIALS AND METHODS: The PSAD of 60 men with clinically localized prostate cancer was calculated with transabdominal ultrasound (TAUS), transrectal ultrasound (TRUS), and computed tomography (CT) before radical retropubic prostatectomy, and was compared with the PSAD of the surgical specimen using the paired t-test. The relationship of the real prostate volume and the difference between the PSAD calculated with the 3 imaging modalities and that of the PSAD of the specimen was analyzed using Pearson's correlation coefficient. Finally, the sensitivity of PSAD calculated with the examined imaging modalities and the specimen was also studied. RESULTS: The mean difference between the PSAD calculated by each one of the 3 imaging modalities and the PSAD of the specimen was -0.01 ng/ml/cm(3) (P = 0.28) for TAUS, 0.01 ng/ml/cm(3) (P = 0.37) for TRUS, and -0.03 ng/ml/cm(3) (P = 0.001) for CT. This difference has not been shown to depend on the real prostate volume according to Pearson's correlation coefficient, which was 0.056 (P = 0.673) for TAUS, -0.014 (P = 0.917) for TRUS, and 0.184 (P = 0.159) for CT. The sensitivity of PSAD calculated with TAUS, TRUS, and CT was 58.3%, 65%, and 45%, respectively, while that of the specimen was 70%. CONCLUSIONS: Although PSAD showed a moderate sensitivity, TRUS and TAUS are the imaging modalities that calculate it closer to the real PSAD of the specimen.

Malignant transformation of ovarian mature cystic teratoma in a postmenopausal woman presented as acute abdomen.

Malignant transformation of mature cystic teratomas is uncommon but present in clinical practice. Especially in postmenopausal women, the clinical manifestation of a mature teratoma with undiagnosed malignant transformation as acute abdomen is extremely rare. In these cases, total hysterectomy with bilateral salpingo-oophorectomy is the treatment choice since the chance of malignancy is high. The prognosis is good if the cyst is not ruptured, is completely excised and the cancer does not extend beyond the capsule. In any other case, the prognosis is unfavorable since recurrence is common and the tumor is chemoresistant.

Prostate cancer with metastasis to the omentum and massive ascites: a rare manifestation of a common disease.

BACKGROUND: The most common sites of metastasis in prostate cancer include bone and regional lymph nodes followed by lung, liver, and brain. Peritoneal metastasis without skeletal involvement is extremely rare. CASE REPORT: We present herein a patient with hormone refractory prostate cancer with peritoneal metastasis accompanied by ascites but without bone metastasis. The patient initially experienced an excellent response to docetaxel-based chemotherapy. CONCLUSIONS: Prostate cancer can present with distant metastasis in unexpected sites. The lack of skeletal involvement does not exclude the possibility of distant metastases. The presence of ascites may indicate peritoneal disease which could be responsive to current standard chemotherapy.

Successful term pregnancy after treatment of a cesarean scar ectopic gestation by endoscopic technique and conservative therapy.

OBJECTIVE: To describe a case of cesarean scar pregnancy treated successfully by endoscopic technique and medical therapy. DESIGN: Case report. SETTING: State general hospital in a major city. PATIENT(S): A 32-year-old woman with two cesarean sections and a recent curettage presented with ectopic cesarean scar pregnancy. INTERVENTION(S): Transvaginal ultrasound and hysteroscopy were used for diagnosis, and conservative therapy with methotrexate and hysteroscopy to treat the patient. MAIN OUTCOME MEASURE(S): Modified hysteroscopic technique and outcome. RESULT(S): Sonography and hysteroscopy revealed the presence of a gestational sac in the lower segment of the uterus in a patient with a cesarean section scar. She was successfully treated with systemic methotrexate and aspiration of the sac and local methotrexate injection under endoscopic control. CONCLUSION(S): Endoscopic intervention combined with medical treatment can result in a good therapeutic outcome with preservation of fertility in early ectopic cesarean scar pregnancy.

Prognostic and predictive factors in patients with androgen-independent prostate cancer treated with docetaxel and estramustine: a single institution experience.

OBJECTIVES: To investigate potential prognostic and predictive factors in patients with androgen-independent prostate cancer (AIPC) treated with docetaxel chemotherapy. METHODS: This analysis included 94 consecutive AIPC patients who were treated between March 2001 and May 2006 with biweekly docetaxel 45 mg/m(2) (day 2) and estramustine 140 mg three dimes daily (days 1-3). RESULTS: Prostate-specific antigen (PSA) responses were observed in 45 of 84 evaluable patients (53%), whereas objective responses were observed in 16 of 40 patients with measurable disease (40%). Median survival (OS) was 16.2 mo (95% confidence interval [CI], 12.9-19.4) and median time to PSA progression (TTP) 5.0 mo (95%CI, 3.6-7.1). OS was independently associated with pain score baseline PSA and weight loss. Patients with only extraosseous disease had higher PSA response rate (87% vs. 49%, p=0.014) and superior TTP compared with patients with bone metastases with or without extraosseous disease (7.3 vs. 4.3 vs. 4 mo, p=0.002). Concurrent bone and extraosseous metastases were associated with worse prognosis compared with each site alone (median OS: 12.3 vs.19 vs.18.3 mo, p=0.007). CONCLUSIONS: Among patients with AIPC treated with biweekly docetaxel and estramustine, baseline PSA >100, existence of pain, weight loss, and simultaneous extraosseous and bone disease were associated with worse prognosis. Extraosseous metastases seem to be more sensitive than bone disease to this chemotherapy.

Two cycles of etoposide/cisplatin cured all patients with stage I testicular seminoma: risk-adapted protocol of the Hellenic Cooperative Oncology Group.

OBJECTIVES: Adjuvant carboplatin is used as adjuvant therapy in Stage I testicular seminoma. Although cure is the rule, relapses still occur, especially in high-risk populations. We report the results of a risk-adapted strategy by the Hellenic Cooperative Oncology Group. METHODS: From 1996 to 2003, 64 patients with Stage I seminoma and one of two risk factors (maximal tumor diameter greater than 4 cm and/or age younger than 34 years) were prospectively included in a protocol of adjuvant chemotherapy. Treatment consisted of two 3-week courses of etoposide 120 mg/m2 and cisplatin 40 mg/m2 for three consecutive days with granulocyte colony-stimulating factor support. RESULTS: Of the 64 patients, 43 (67%) were younger than 34 years and 55 (86%) had a tumor diameter greater than 4 cm. Neutropenia and nausea and vomiting were the most frequent grade 3 or 4 toxicities (16.5% and 9.5%, respectively), apart from alopecia. After a median follow-up of 60 months (range 7 to 118), no disease relapses have occurred. A metachronous testicular carcinoma has been reported. One patient died of causes unrelated to his disease. CONCLUSIONS: The results of our study have shown that two cycles of etoposide and cisplatin is an effective and safe form of adjuvant therapy for Stage I testicular seminoma. Risk factors can be used to identify patients who could benefit from etoposide and cisplatin treatment.

An overview of stress urinary incontinence treatment in women.

Stress urinary incontinence (SUI) is common in women, but it is under-reported and under-treated. We review here the management of SUI in women. Pelvic floor muscle training treats SUI in the majority of female patients, whereas anti-SUI devices are not widely accepted. Duloxetine has been approved for treating SUI. Suburethral slings have revolutionized the surgical management of SUI with durable efficacy, in contrast with injectable bulking agents.