Laparoscopic versus robotic major hepatectomy: a systematic review and meta-analysis.

BACKGROUND: The implementation of the laparoscopic and robotic approaches for major hepatectomy (LMH and RMH) was slower than that for minor hepatectomy, but has significantly increased over the past years. The role or advantages of RMH remains controversial, and we aimed to compare the peri-/postoperative outcomes of LMH versus RMH. METHODS: A systematic literature review was conducted using the MEDLINE and Cochrane Library databases according to the PRISMA guidelines (end-of-search date: March 16th, 2020). Only comparative studies (LMH vs. RMH) reporting on outcomes of interest were included. Meta-analysis was performed using the random-effects model when substantial heterogeneity was encountered; otherwise, the fixed-effects model was implemented. Quality of evidence assessment was performed using the Newcastle-Ottawa Scale. RESULTS: Seven retrospective cohort studies comparing LMH (n = 300) versus RMH (n = 225) were identified. No significant difference was observed between LMH and RMH regarding overall complications [odds ratio (OR) 1.42, 95% confidence interval (CI) 0.90-2.23; p = 0.13], severe complications (Clavien-Dindo grade ≥ 3) [risk difference (RD) 0.01, 95% CI - 0.03 to 0.05; p = 0.72], and overall mortality (RD 0.00, 95% CI - 0.02 to 0.03; p = 0.73). The two approaches were also equivalent regarding conversion to open hepatectomy (RD 0.03, 95% CI - 0.01 to 0.08; p = 0.15), margin-positive resection (OR 1.34, 95% CI 0.51-3.52; p = 0.55), and transfusion rate (RD - 0.03, 95% CI - 0.16 to 0.11; p = 0.67). No significant difference was observed for LMH versus RMH regarding blood loss [standardized mean difference (SMD) 0.27, 95% CI - 0.24 to 0.77; p = 0.30), operative time (SMD - 0.08, 95% CI - 0.51 to 0.34; p = 0.70), and length of stay (SMD 0.13, 95% CI - 0.58 to 0.84; p = 0.72). CONCLUSION: LMH and RMH have equivalent peri-/postoperative outcomes when performed in select patients and high-volume centers.

Presentation and surgical management of xanthogranulomatous cholecystitis.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a rare benign chronic inflammatory disease of the gallbladder that often presents as cholecystitis and most of the times requires surgical management. In addition, distinguishing XGC from gallbladder cancer preoperatively is still a challenge. The aim of the present systematic review was to outline the clinical presentation and surgical approach of XGC. DATA SOURCES: The present systematic review was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases from inception until June 2020. RESULTS: The laparoscopic cholecystectomy rate (34%) was almost equal to the open cholecystectomy rate (47%) for XGC. An important conversion rate (35%) was observed as well. The XGC cases treated by surgery were associated with low mortality (0.3%), limited intraoperative blood loss (58-270 mL), low complication rates (2%-6%), along with extended operative time (82.6-120 minutes for laparoscopic and 59.6-240 minutes for open cholecystectomy) and hospital stay (3-9 days after laparoscopic and 8.3-18 days after open cholecystectomy). Intraoperative findings during cholecystectomies for XGC included empyema or Mirizzi syndrome. In addition, complex surgical procedures, like wedge hepatic resections and bile duct excision were required during operations for XGC. CONCLUSIONS: XGC seemed to be a rare, benign inflammatory disease that presents similar features as gallbladder cancer. The mortality and complication rates of XGC were low, despite the complex surgical procedures that might be required in some cases.

Minimally Invasive Surgery vs Device Closure for Atrial Septal Defects: A Systematic Review and Meta-analysis.

Device closure is the first-line treatment for most atrial septal defects (ASDs). Minimally invasive cardiac surgery (MICS) has been found safe and effective for ASD closure with comparable mortality/morbidity and superior cosmetic results compared to conventional median sternotomy. Our goal was to compare percutaneous versus MICS of ASDs. A systematic review was performed using PubMed and the Cochrane Library (end-of-search date on May 22, 2019). Meta-analyses were conducted using fixed and random effects models. In the present systematic review, we analyzed six studies including 1577 patients with ASDs who underwent either MICS (n = 642) or device closure (n = 935). Treatment efficacy was significantly higher in the MICS (99.8%; 95% CI 98.9-99.9) compared to the device closure group (97.3%; 95% CI 95.6-98.2), (OR 0.1; 95% CI 0.02-0.6). Surgical patients experienced significantly more complications (16.2%; 95% CI 13.0-19.9) compared to those that were treated with a percutaneous approach (7.1%; 95% CI 5.0-9.8), (OR 2.0; 95% CI 1.2-3.2). Surgery was associated with significantly longer length of hospital stay (5.6 ± 1.7 days) compared to device closure (1.3 ± 1.4 days), (OR 4.8; 95% CI 1.1-20.5). Residual shunts were more common with the transcatheter (3.9%; 95% CI 2.7-5.5) compared to the surgical approach (0.95%; 95% CI 0.3-2.4), (OR 0.1; 95% CI 0.06-0.5). There was no difference between the two techniques in terms of major bleeding, hematoma formation, transfusion requirements, cardiac tamponade, new-onset atrial fibrillation, permanent pacemaker placement, and reoperation rates. MICS for ASD is a safe procedure and compares favorably to transcatheter closure. Despite longer hospitalization requirements, the MICS approach is feasible irrespective of ASD anatomy and may lead to a more effective and durable repair.

Association between endometriosis and gynecological cancers: a critical review of the literature.

BACKGROUND: Endometriosis is one of the most common benign gynecological diseases with an occurrence approximately 10% in reproductive age. Endometriosis has been proposed as a possible precursor of certain ovarian carcinomas such as clear cell and endometrioid ovarian carcinomas. In addition to this pathogenic link, the association with other gynecological tumors and breast cancer has been studied on an epidemiological basis in several studies. OBJECTIVE: The aim of this review was to critically present the recent published evidence on the association of endometriosis with gynecological cancer, and with a special emphasis on ovarian cancer. MATERIALS AND METHODS: A search for eligible studies was conducted in three electronic databases, MEDLINE, EMBASE and CINAHL, for original research in humans published in any language. RESULTS: The present review includes studies examining the association between endometriosis and different types of gynecological cancer (i.e., 25 studies on ovarian cancer, 8 studies on breast cancer, 8 studies on endometrial cancer and 2 studies on cervical cancer). CONCLUSION: The present literature supports the pre-existing evidence suggesting an association between ovarian cancer and endometriosis and specifically its two histologic subtypes (endometrioid and ovarian clear cell cancer). The most recent population-based epidemiological studies cannot provide a clear association between endometriosis and endometrial, cervical or breast cancer.

Stem Cell Therapy for Congenital Heart Disease: A Systematic Review.

BACKGROUND: Congenital heart disease (CHD) constitutes the most prevalent and heterogeneous group of congenital anomalies. Although surgery remains the gold standard treatment modality, stem cell therapy has been gaining ground as a complimentary or alternative treatment option in certain types of CHD. The aim of this study was to present the existing published evidence and ongoing research efforts on the implementation of stem cell-based therapeutic strategies in CHD. METHODS: A systematic review was conducted by searching Medline, ClinicalTrials.gov, and the Cochrane library, along with reference lists of the included studies through April 23, 2017. RESULTS: Nineteen studies were included in this review (8 preclinical, 6 clinical, and 5 ongoing trials). Various routes of cardiac stem cell delivery have been reported, including intracoronary, intramyocardial, intravenous, and epicardial. Depending on their origin and level of differentiation at which they are harvested, stem cells may exhibit different properties. Preclinical studies have mostly focused on modeling right ventricle dysfunction or failure and pulmonary artery hypertension by using pressure or volume overload in vitro or in vivo. Only a limited number of clinical trials on patients with CHD exist, and these primarily focus on hypoplastic left heart syndrome. Cell-based tissue engineering has recently been introduced, and research currently is focusing on developing cell-seeded grafts and patches that could potentially grow in parallel with whole body growth once implanted in the heart. CONCLUSIONS: It seems that stem cell delivery to the diseased heart as an adjunct to surgical palliation may provide some benefits over surgery alone in terms of cardiac function, somatic growth, and quality of life. Despite encouraging preliminary results, stem cell therapies for patients with CHD should only be considered in the setting of well-designed clinical trials. More wet laboratory research experience is needed, and translation of promising findings to large clinical studies is warranted to clearly define the efficacy and safety profile of this alternative and potentially groundbreaking therapeutic approach.

Predictors of surveillance mammography outcomes in women with a personal history of breast cancer.

PURPOSE: To identify predictors of poor mammography surveillance outcomes based on clinico-pathologic features. METHODS: This study was HIPAA compliant and IRB approved. We performed an electronic medical record review for a cohort of women with American Joint Committee on Cancer (AJCC) Stage I or II invasive breast cancer treated with breast conservation therapy who developed subsequent in-breast treatment recurrence (IBTR) or contralateral breast cancer (CBC). Poor surveillance outcome was defined as second breast cancer not detected by surveillance mammography, including interval cancers (diagnosed within 365 days of surveillance mammogram with negative results) and clinically detected cancers (diagnosed without a surveillance mammogram in the preceding 365 days). Univariate and multivariate logistic regression were performed to identify predictors of poor mammography surveillance outcome, including patient and primary tumor characteristics, breast density, mode of primary tumor detection, and time to second cancer diagnosis. RESULTS: 164 women met inclusion criteria (65 with IBTR, 99 with CBC); 124 had screen-detected second cancers. On univariate analysis, poor surveillance outcome (n = 40) was associated with age at primary cancer diagnosis < 50 years (p < 0.0001), AJCC stage II primary cancers (p = 0.007), and heterogeneously or extremely dense breasts (p = 0.04). On multivariate analysis, age < 50 years at primary breast cancer diagnosis remained a significant predictor of poor surveillance outcome (p = 0.001). CONCLUSION: Women younger than age 50 at primary breast cancer diagnosis are at risk of poor surveillance mammography outcomes, and may be appropriate candidates for more intensive clinical and imaging surveillance.

Antibiotics exposure and risk of inflammatory bowel disease: a systematic review.

AIM: The aim of this study was to critically assess all available evidence suggesting an association between antibiotic exposure and new onset of inflammatory bowel disease (IBD). MATERIALS AND METHODS: This systematic review was conducted according to the PRISMA statement and eligible studies were identified through search of PubMed, Embase and the Cochrane Library. Data on patient demographics, antibiotic exposure and confounding factors were analyzed. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of eligible studies. RESULTS: A total of 15 observational studies (10 case control and five cohort) including 8748 patients diagnosed with IBD were systematically reviewed. Antibiotic exposure was mostly associated with Crohn's disease but not with ulcerative colitis. In particular, penicillin's, cephalosporins, metronidazole and fluoroquinolones were most commonly associated with the onset of Crohn's disease. The impact of tetracycline-family antibiotics on the pathogenesis of IBD was not clear. CONCLUSION: There may be an association between antibiotic exposure and the development of IBD; especially Crohn's disease. Even though, clinicians should be cautious when prescribing certain antibiotic regimens to patients with a strong family history of IBD, it should be emphasized that available data are not granular enough to reach any definitive conclusions.

Mortality after endovascular treatment of infrarenal abdominal aortic aneurysms - the newer the better?

Although endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) presents a delicate alternative treatment for abdominal aortic aneurysms (AAA) with lower perioperative mortality, its long-term efficacy remains a matter of concern. The purpose of this study was to evaluate the currently reported mortality evidence after EVAR and to examine the possible effect of aneurysm status and the study period on mortality rates. The PubMed and Cochrane bibliographical databases were thoroughly searched for studies reporting on more than 1 000 patients with non-ruptured or ruptured infrarenal AAA, treated with EVAR from August 1991 to September 2016. A total of 10 910 titles/abstracts were retrieved and 121 studies were deemed relevant. Twenty-six studies met the inclusion criteria and reported on 354 500 patients with a mean age of 74.6 years. Almost all of the studies referred to elective EVAR and the mean aneurysm size was 5.58 cm. The most common early complication for elective EVAR was perioperative bleeding (1.9 %), whereas hospital-acquired pneumonia was a major concern in urgent EVAR (28.5 %). Conversion rate to open surgery was 1.2 %. The 30-day all-cause mortality rate was 4.84 % (1.7 % for non- ruptured aneurysms, 33.8 % for ruptured aneurysms).The overall all-cause late mortality in a mean follow-up period of 23.8 months was 19.1 %. The aneurysm-related late mortality rate was 3.4 %. With respect to the time period of patient enrollment, studies reporting on patients recruited before 2006 were found to face more secondary complications and higher late mortality rates than patients enrolled after 2005.The endovascular treatment of large and anatomically suitable infrarenal AAA in selected patients remains a safe alternative to open repair. Our findings demonstrate that newer studies show better long-term outcomes than the older ones, proposing a possible improvement of EVAR techniques and perioperative care and providing encouraging evidence for a wider application of EVAR.

Intestinal alkaline phosphatase decreases intraperitoneal adhesion formation.

BACKGROUND: Damage to the peritoneum initiates an inflammatory response leading to the formation of adhesions, which subsequently cause significant morbidity in some patients. Intestinal alkaline phosphatase (IAP) is a gut enzyme capable of detoxifying various inflammatory mediators such as lipopolysaccharide, lipoteichoic acid, CpG DNA, and adenosine triphosphate. In this study, we aimed to examine the anti-inflammatory effects of IAP on postoperative adhesions in mice. METHODS: C57BL/6 mice were subjected to a midline laparotomy and then six musculoperitoneal buttons (MPBs) were created by pinching and ligating the peritoneum and underlying muscle. The buttons were half-excised and E-cauterized, and then cecal abrasion was performed. Five hundred microliters of vehicle with IAP 5000 U or vehicle alone were applied over the peritoneal cavity. In some experiments, the mice were euthanized on the first and second postoperative day (POD), and cytokines analysis was done on the MPB, peritoneal tissue, and peritoneal fluid. In separate experiments, the mice were sacrificed on the 21st POD, and adhesion to each button was scored based on type and tenacity. RESULTS: IAP group mice had significantly lower adhesion scores compared with controls (21.5 ± 1.7 versus 13.2 ± 1.3; P = 0.0014, n = 15). MPB from IAP group mice had significantly lower interleukin-1ß and tumor necrosis factor-α protein level compared to control mice (105.66 ± 4.5 versus 69.8 ± 4.8 versus pg/mg, P = 0.0001; 45.25 ± 2.8 pg/mg versus 24.88 ± 4.1 pg/mg; P = 0.0007, n = 10). IAP treatment significantly decreased interleukin-1ß and tumor necrosis factor-α mRNA expression in MPB in the first POD (1.14 ± 0.25 versus 0.33 ± 0.07; P = 0.0068; 1.33 ± 0.31 versus 0.33 ± 0.08; P = 0.0064, n = 10). CONCLUSIONS: Application of IAP during laparotomy could represent a novel approach to prevent postoperative adhesions.

Emerging treatments for ulcerative colitis: a systematic review.

OBJECTIVES: Various investigational medicinal products have been developed for ulcerative colitis (UC). Our aim was to systematically evaluate novel pharmacological therapeutic agents for the treatment of UC. MATERIAL AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed. A search of the medical literature was conducted in the MEDLINE database for original research papers published between 01 January 2010 and 31 October 2014. RESULTS: Twenty one studies, including 11,524 adults were analyzed. Thirteen different novel therapeutic drug options were identified. Vedolizumab and golimumab were superior to placebo as induction and maintenance therapy. Tofacitinib showed dose related efficacy for induction therapy. Etrolizumab showed higher clinical remission rates compared to placebo. Phosphatidylcholine led to an improved clinical activity index. HMPL-004 may become a mesalamine alternative for mild to moderate UC. PF00547,659 was well tolerated. Statins were not beneficial for acute exacerbations of UC. Abatacept, rituximab and visilizumab did not lead to improved outcomes compared to placebo. Higher concentration of BMS 936557 was associated with improved efficacy compared to placebo. Basiliximab did not enhance corticosteroid efficacy. CONCLUSIONS: Patients with UC might achieve clinical response or remission by utilizing some of these agents with a favorable side effect profile. Further studies are needed to evaluate their short- and long-term efficacy and safety.

Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in Mice.

BACKGROUND AND AIMS: Bacterially derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease. METHODS: Mice underwent acute binge or chronic ethanol exposure to induce alcoholic liver injury and steatosis ± IAP supplementation. Liver tissue was assessed for biochemical, inflammatory, and histopathological changes. An ex vivo co-culture system was used to examine the effects of alcohol and IAP treatment in regard to the activation of hepatic stellate cells and their role in the development of alcoholic liver disease. RESULTS: Pretreatment with IAP resulted in significantly lower serum alanine aminotransferase compared to the ethanol alone group in the acute binge model. IAP treatment attenuated the development of alcohol-induced fatty liver, lowered hepatic pro-inflammatory cytokine and serum LPS levels, and prevented alcohol-induced gut barrier dysfunction. Finally, IAP ameliorated the activation of hepatic stellate cells and prevented their lipogenic effect on hepatocytes. CONCLUSIONS: IAP treatment protected mice from alcohol-induced hepatotoxicity and steatosis. Oral IAP supplementation could represent a novel therapy to prevent alcoholic-related liver disease in humans.

Blood Versus Crystalloid Cardioplegia in Pediatric Cardiac Surgery: A Systematic Review and Meta-analysis.

The benefit of blood cardioplegia (BCP) compared to crystalloid cardioplegia (CCP) is still debatable. Our aim was to systematically review and synthesize all available evidence on the use of BCP and CCP to assess if any modality provides superior outcomes in pediatric cardiac surgery. A systematic literature search of the PubMed and Cochrane databases was performed with respect to the PRISMA statement (end-of-search date: January 30th, 2017). We extracted data on study design, demographics, cardioplegia regimens, and perioperative outcomes as well as relevant biochemical markers, namely cardiac troponin I (cTnI), lactate, and ATP levels at baseline, after reperfusion and postoperatively at 1, 4, 12, and 24 h as applicable. Data were appropriately pooled using random and mixed effects models. Our systematic review includes 56 studies reporting on a total of 7711 pediatric patients. A meta-analysis of the 10 eligible studies directly comparing BCP (n = 416) to CCP (n = 281) was also performed. There was no significant difference between the two groups with regard to cTnI and Lac at any measured time point, ATP levels after reperfusion, length of intensive care unit stay (WMD: -0.08, 95% CI -1.52 to 1.36), length of hospital stay (WMD: 0.13, 95% CI -0.85 to 1.12), and 30-day mortality (OR 1.11, 95% CI 0.43-2.88). Only cTnI levels at 4 h postoperatively were significantly lower with BCP (WMD: -1.62, 95% CI -2.07 to -1.18). Based on the available data, neither cardioplegia modality seems to be superior in terms of clinical outcomes, ischemia severity, and overall functional recovery.

Mullerian dysgenesis: a critical review of the literature.

PURPOSE: To present an update of the genetic, clinical, diagnostic, and therapeutic aspects of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. METHODS: Studies were considered eligible if they have evaluated patients with MRKH syndrome. Eligible articles were identified by a search of MEDLINE bibliographical database from 1950 to August 2016. A purely descriptive approach was adopted concerning all outcomes examined by the individual studies. RESULTS: MRKH syndrome is defined as congenital aplasia of the upper vagina and impairment of uterine development in normal 46XX females. Accounting for 1:4500 women, MRKH is the second most common cause of primary amenorrhea following gonadal dysgenesis. Potential association of MRKH syndrome to specific genes has been the focus of recent research. Null-association results of HOXA genes and Wnt5a, Wnt7a, and Wnt9a have been reported, while point mutations of the WNT4 gene point mutations have been associated with an MRKH-like syndrome characterized by Mullerian duct regression and hyperandrogenism. Ultrasound and Magnetic Resonance Imaging (MRI) are the main techniques to establish an accurate diagnosis of the syndrome. Several non-surgical and surgical procedures have been reported for the creation of a functional neovagina; in general, non-surgical treatment should be the first initially pursued. Along with psychological support, recent developments in assisted reproductive technologies of IVF techniques and the availability of gestational surrogacy, as well as the recent breakthrough of successful uterus transplantation, enable women with MRKH syndrome to attain their own genetic child. CONCLUSION(S): MRKH syndrome is a medical modality with important social, legal, and ethical projections that require a multi-disciplinary approach.

Access to health for refugees in Greece: lessons in inequalities.

Eastern Greek islands have been direct passageways of (mainly Syrian) refugees to the European continent over the past year. However, basic medical care has been insufficient. Despite calls for reform, the Greek healthcare system has for many years been costly and dysfunctional, lacking universal equity of access. Thus, mainly volunteers look after the refugee camps in the Greek islands under adverse conditions. Communicable diseases, trauma related injuries and mental health problems are the most common issues facing the refugees. The rapid changes in the epidemiology of multiple conditions that are seen in countries with high immigration rates, like Greece, demand pragmatic solutions. Best available knowledge should be used in delivering health interventions. So far, Greece is failed by international aid, and cross-border policies have not effectively tackled underlying reasons for ill-health in this context, like poverty, conflict and equity of access.

Intestinal alkaline phosphatase prevents metabolic syndrome in mice.

Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.

Adjunct endovascular interventions in carotid body tumors.

OBJECTIVE: Most patients presenting with carotid body tumors (CBTs) seek medical attention when tumors have grown to exceed Shamblin I stage, rendering surgery a challenging undertaking and the associated morbidity a continuing threat to the clinical outcome. This study examined the availability, applicability, and overall clinical efficacy of adjunct endovascular interventions performed alongside CBT surgery and their potential in clinical decision making and clinical practice. METHODS: Studies reporting the feasibility, applicability, and clinical efficacy of adjunct endovascular interventions in the surgical management of CBTs were thoroughly searched using the Medline database from January 1967 to August 2013. RESULTS: There were no randomized studies on the efficacy of endovascular interventions in CBT surgery. Sixty studies met our inclusion criteria, reporting 465 patients (526 CBTs) with a mean age of 39.8 years. The treated CBTs were a mean size of 4.9 cm. Patients treated with surgery with the use of adjunct endovascular interventions had a mean blood loss of 368.4 mL (range, 25-to 2000 mL). There were 57 cranial nerve injuries, of which 28 (49.1%) were permanent. Cerebrovascular accident occurred in nine patients, of which one died. Hospital stay was a mean of 4.4 days (range, 2-17 days). CONCLUSIONS: Preoperative selective endovascular embolization in patients with Shamblin II and Shamblin III CBTs may be beneficial when competently performed by interventional physicians proficient in neurovascular microcatheterization/embolization procedures.

Continuous versus cyclic oral contraceptives for the treatment of endometriosis: a systematic review.

PURPOSE: Recurrence of endometriosis after conservative surgery has been observed in 40-50 % of patients within the first 5 years. A variety of regimens such as combined oral contraceptives, GnRH agonists, danazol, and progestins have been used postoperatively to reduce recurrence rates. Oral contraceptives (oCP) have been used either in a cyclic or in a continuous (no pill-free interval) fashion. The purpose of this article was to summarize the existing evidence on the efficacy and patient compliance for the use of oCP in a continuous versus cyclic fashion following conservative surgery for endometriosis. METHODS: A systematic search of Medline identified four eligible studies. Studies were considered eligible, if they have evaluated oCP therapy, either in a cyclic or continuous regimen, after conservative surgery for endometriosis. Specifically, studies (1) reporting on women with endometriosis who were treated postoperatively with both continuous oCP and cyclic oCP, (2) written in English, (3) with minimum 6 months duration of medical treatment, and (4) with minimum 12 months duration of follow-up were considered eligible for our systematic review. Outcome measures of these eligible studies were tabulated and then analyzed cumulatively. A purely descriptive approach was adopted concerning all variables. RESULTS: Postoperative use of continuous oCP was associated with a reduction in the recurrence rate of dysmenorrhea, delay in the presentation of dysmenorrhea, reduction in nonspecific pelvic pain, and reduction in the recurrence rate for endometrioma. CONCLUSIONS: Use of oCP in a continuous fashion following conservative surgery for endometriosis is more beneficial to cyclic use.

Annual financial impact of well-differentiated thyroid cancer care in the United States.

BACKGROUND: Well-differentiated thyroid cancer (WDTC) is a prevalent disease, which is increasing in incidence faster than any other cancer. Substantial direct medical care costs are related to the diagnosis and treatment of newly diagnosed patients as well as the ongoing surveillance of patients who have a long life expectancy. Prior analyses of the aggregate health care costs attributable to WDTC in the United States have not been reported. METHODS: A stacked cohort cost analysis was performed on the US population from 1985 to 2013 to estimate the number of WDTC survivors in 2013. Incidence rates, and cancer-specific and overall survival were based on Surveillance, Epidemiology, and End Results (SEER) data. Current and projected direct medical care costs attributable to the care of patients with WDTC were then estimated. Health care-related costs and event probabilities were based on Medicare reimbursement schedules and the literature. RESULTS: Estimated overall societal cost of WDTC care in 2013 for all US patients diagnosed after 1985 is $1.6 billion. Diagnosis, surgery, and adjuvant therapy for newly diagnosed patients (41%) constitutes the greatest proportion of costs, followed by surveillance of survivors (37%), and nonoperative death costs attributable to thyroid cancer care (22%). Projected 2030 costs (in 2013 US dollars) based on current incidence trends exceed $3.5 billion. CONCLUSIONS: Health care costs of WDTC are substantial. Unlike other cancers, the majority of the cost is incurred in the initial and continuing phases of care. With the projected increasing incidence, population, and survival trends, costs will continue to escalate.

Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates.

The intestinal microbiota plays a pivotal role in maintaining human health and well-being. Previously, we have shown that mice deficient in the brush-border enzyme intestinal alkaline phosphatase (IAP) suffer from dysbiosis and that oral IAP supplementation normalizes the gut flora. Here we aimed to decipher the molecular mechanism by which IAP promotes bacterial growth. We used an isolated mouse intestinal loop model to directly examine the effect of exogenous IAP on the growth of specific intestinal bacterial species. We studied the effects of various IAP targets on the growth of stool aerobic and anaerobic bacteria as well as on a few specific gut organisms. We determined the effects of ATP and other nucleotides on bacterial growth. Furthermore, we examined the effects of IAP on reversing the inhibitory effects of nucleotides on bacterial growth. We have confirmed that local IAP bioactivity creates a luminal environment that promotes the growth of a wide range of commensal organisms. IAP promotes the growth of stool aerobic and anaerobic bacteria and appears to exert its growth promoting effects by inactivating (dephosphorylating) luminal ATP and other luminal nucleotide triphosphates. We observed that compared with wild-type mice, IAP-knockout mice have more ATP in their luminal contents, and exogenous IAP can reverse the ATP-mediated inhibition of bacterial growth in the isolated intestinal loop. In conclusion, IAP appears to promote the growth of intestinal commensal bacteria by inhibiting the concentration of luminal nucleotide triphosphates.

A novel approach to maintain gut mucosal integrity using an oral enzyme supplement.

OBJECTIVE: To determine the role of intestinal alkaline phosphatase (IAP) in enteral starvation-induced gut barrier dysfunction and to study its therapeutic effect as a supplement to prevent gut-derived sepsis. BACKGROUND: Critically ill patients are at increased risk for systemic sepsis and, in some cases, multiorgan failure leading to death. Years ago, the gut was identified as a major source for this systemic sepsis syndrome. Previously, we have shown that IAP detoxifies bacterial toxins, prevents endotoxemia, and preserves intestinal microbiotal homeostasis. METHODS: WT and IAP-KO mice were used to examine gut barrier function and tight junction protein levels during 48-hour starvation and fed states. Human ileal fluid samples were collected from 20 patients postileostomy and IAP levels were compared between fasted and fed states. To study the effect of IAP supplementation on starvation-induced gut barrier dysfunction, WT mice were fasted for 48 hours +/- IAP supplementation in the drinking water. RESULTS: The loss of IAP expression is associated with decreased expression of intestinal junctional proteins and impaired barrier function. For the first time, we demonstrate that IAP expression is also decreased in humans who are deprived of enteral feeding. Finally, our data demonstrate that IAP supplementation reverses the gut barrier dysfunction and tight junction protein losses due to a lack of enteral feeding. CONCLUSIONS: IAP is a major regulator of gut mucosal permeability and is able to ameliorate starvation-induced gut barrier dysfunction. Enteral IAP supplementation may represent a novel approach to maintain bowel integrity in critically ill patients.