Hemorrhoids: what are the options in 2018?

PURPOSE OF REVIEW: Efforts continue to improve the treatment of patients with symptomatic hemorrhoidal disease by interventions designed to improve efficiency and effectiveness, including by reducing intraoperative and postoperative pain, decreasing operating times, minimizing blood loss and controlling symptoms and recurrence rates. Simultaneously, there are also renewed efforts to minimize the number of patients who will require procedural intervention by focusing on conservative measures that encourage better bowel regulation and habits. The purpose of this brief report is to review the current status of the diagnosis and treatment of patients with hemorrhoidal disease. Overall, new procedures or procedural refinements to existing techniques continue to be introduced with promising short-term outcomes - at least in some instances. In most instances, long-term follow-up or equivalency data are still being accumulated such that a definitive, unequivocal answer to what is truly the best alternative to traditional hemorrhoidectomy remains controversial. One of the challenges is heterogeneity as regards diagnosis, intervention and, especially, outcomes measures such that comparing therapies is too difficult. A recent initiative to standardize metrics has promise. RECENT FINDINGS: Recent studies largely appear to suggest that conservative treatment approaches and managing patient expectations are critically important in which a primary objective should be to minimize the progression to symptomatic disease and complications in patients who are diagnosed with hemorrhoids. The pace of change as regards the development of new or improved surgical techniques appears may be accelerating. SUMMARY: Progress is being made and the knowledge base is being expanded as regards the treatment options for patients with hemorrhoids and expected outcomes. A key initiative to standardize the approaches to diagnosis and treatment about staging, procedural interventions and outcomes will facilitate comparative analytics, if successful.

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation.

Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing Vmax and Km Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF-1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF-1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia.

Structural correlates of the creatine transporter function regulation: the undiscovered country.

Creatine (Cr) and phosphocreatine constitute an energy shuttle that links ATP production in mitochondria to subcellular locations of ATP consumption. Cells in tissues that are reliant on this energy shuttle, such as myocytes and neurons, appear to have very limited ability to synthesize creatine. Therefore, these cells depend on Cr uptake across the cell membrane by a specialized creatine transporter (CrT solute carrier SLC6A8) in order to maintain intracellular creatine levels. Cr supplementation has been shown to have a beneficial effect in numerous in vitro and in vivo models, particularly in cases of oxidative stress, and is also widely used by athletes as a performance enhancement nutraceutical. Intracellular creatine content is maintained within narrow limits. However, the physiological and cellular mechanisms that mediate Cr transport during health and disease (such as cardiac failure) are not understood. In this narrative mini-review, we summarize the last three decades of research on CrT structure, function and regulation.

Removal of Potential Phosphorylation Sites does not Alter Creatine Transporter Response to PKC or Substrate Availability.

BACKGROUND: Creatine, Phosphocreatine, and creatine kinases, constitute an energy shuttle that links ATP production in mitochondria with cellular consumption sites. Myocytes and neurons cannot synthesize creatine and depend on uptake across the cell membrane by a specialized transporter to maintain intracellular creatine levels. Although recent studies have improved our understanding of creatine transport in cardiomyocytes, the structural elements underlying the creatine transporter protein regulation and the relevant intracellular signaling processes are unknown. METHODS: The effects of pharmacological activation of kinases or phosphatases on creatine transport in cardiomyocytes in culture were evaluated. Putative phosphorylation sites in the creatine transporter protein were identified by bioinformatics analyses, and ablated using site-directed mutagenesis. Mutant transporter function and their responses to pharmacological PKC activation or changes in creatine availability in the extracellular environment, were evaluated. RESULTS: PKC activation decreases creatine transport in cardiomyocytes in culture. Elimination of high probability potential phosphorylation sites did not abrogate responses to PKC activation or substrate availability. CONCLUSION: Modulation of creatine transport in cardiomyocytes is a complex process where phosphorylation at predicted sites in the creatine transporter protein does not significantly alter activity. Instead, non-classical structural elements in the creatine transporter and/or interactions with regulatory subunits may modulate its activity.

Creatine supplementation reduces doxorubicin-induced cardiomyocellular injury.

Heart failure is a common complication of doxorubicin (DOX) therapy. Previous studies have shown that DOX adversely impacts cardiac energy metabolism, and the ensuing energy deficiencies antedate clinical manifestations of cardiac toxicity. Brief exposure of cultured cardiomyocytes to DOX significantly decreases creatine transport, which is the cell's sole source of creatine. We present the results of a study performed to determine if physiological creatine supplementation (5 mmol/L) could protect cardiomyocytes in culture from cellular injury resulting from exposure to therapeutic levels of DOX. Creatine supplementation significantly decreased cytotoxicity, apoptosis, and reactive oxygen species production caused by DOX. The protective effect was specific to creatine and depended on its transport into the cell.

Normal cardiac function in mice with supraphysiological cardiac creatine levels.

Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies.

Concomitant vascular reconstruction during pancreatectomy for malignant disease: a propensity score-adjusted, population-based trend analysis involving 10,206 patients.

OBJECTIVE: To assess trends in the frequency of concomitant vascular reconstructions (VRs) from 2000 through 2009 among patients who underwent pancreatectomy, as well as to compare the short-term outcomes between patients who underwent pancreatic resection with and without VR. DESIGN: Single-center series have been conducted to evaluate the short-term and long-term outcomes of VR during pancreatic resection. However, its effectiveness from a population-based perspective is still unknown. Unadjusted, multivariable, and propensity score-adjusted generalized linear models were performed. SETTING: Nationwide Inpatient Sample from 2000 through 2009. PATIENTS: A total of 10,206 patients were involved. MAIN OUTCOME MEASURES: Incidence of VR during pancreatic resection, perioperative in-hospital complications, and length of hospital stay. RESULTS: Overall, 10,206 patients were included in this analysis. Of these, 412 patients (4.0%) underwent VR, with the rate increasing from 0.7% in 2000 to 6.0% in 2009 (P < .001). Patients who underwent pancreatic resection with VR were at a higher risk for intraoperative (propensity score-adjusted odds ratio, 1.94; P = .001) and postoperative (propensity score-adjusted odds ratio, 1.36; P = .008) complications, while the mortality and median length of hospital stay were similar to those of patients without VR. Among the 25% of hospitals with the highest surgical volume, patients who underwent pancreatic surgery with VR had significantly higher rates of postoperative complications and mortality than patients without VR. CONCLUSIONS: The frequency of VR during pancreatic surgery is increasing in the United States. In contrast with most single-center analyses, this population-based study demonstrated that patients who underwent VR during pancreatic surgery had higher rates of adverse postoperative outcomes than their counterparts who underwent pancreatic resection only. Prospective studies incorporating long-term outcomes are warranted to further define which patients benefit from VR.

Racial differences among patients undergoing laparoscopic gastric bypass surgery: a population-based trend analysis from 2002 to 2008.

BACKGROUND: Laparoscopic gastric bypass surgery (LGBS) has become the most widely used bariatric procedure due to its beneficial long-term outcomes for patients with morbid obesity. However, it is unclear whether racial differences in admission for LGBS have changed over time compared to racial differences in all other admissions. We aimed to investigate the trends and differences in the use of LGBS among white, African-American, and Hispanic patients from 2002 to 2008. METHODS: We performed a secondary analysis of data on obese adult patients operated between 2002 and 2008, using the Nationwide Inpatient Sample (NIS) database. The probability of being admitted for LGBS was estimated using logistic regression with race, year, and year by race interaction as predictors, controlling for numerous patient and hospital characteristics. RESULTS: Among 1,704,972 obese hospitalized patients captured through NIS from 2002 to 2008, 2.6 % underwent LGBS (2.8 % Whites, 1.7 % African-Americans, and 2.6 % Hispanics). In adjusted analysis, obese African-American (OR 0.48, p < 0.001) and Hispanic patients (OR 0.59, p < 0.001) were less likely to be admitted for LGBS than white patients in 2002. Race-year interactions showed that the odds of African-Americans undergoing LGBS significantly increased from 2002 to 2008 compared with Whites (annual OR 1.03, p < 0.001) while no such increase was detected for Hispanics (annual OR 1.02, p = 0.11). In 2008, African-American (OR 0.58, p < 0.001) and Hispanic patients (OR 0.65, p < 0.001) still had lower odds than white patients. CONCLUSIONS: This is the first study showing that the difference in the use of LGBS between obese African-American and white patients declined between 2002 and 2008. However, LGBS use still remained significantly lower for both African-American and Hispanic patients in 2008 compared with white patients.

Exposing cardiomyocytes to subclinical concentrations of doxorubicin rapidly reduces their creatine transport.

Doxorubicin is commonly used to treat leukemia, lymphomas, and solid tumors, such as soft tissue sarcomas or breast cancer. A major side effect of doxorubicin therapy is dose-dependent cardiotoxicity. Doxorubicin's effects on cardiac energy metabolism are emerging as key elements mediating its toxicity. We evaluated the effect of doxorubicin on [(14)C]creatine uptake in rat neonatal cardiac myocytes and HL-1 murine cardiac cells expressing the human creatine transporter protein. A significant and irreversible decrease in creatine transport was detected after an incubation with 50-100 nmol/l doxorubicin. These concentrations are well below peak plasma levels (5 µmol/l) and within the ranges (25-250 nmol/l) for steady-state plasma concentrations reported after the administration of 15-90 mg/m(2) doxorubicin for chemotherapy. The decrease in creatine transport was not solely because of increased cell death due to doxorubicin's cytotoxic effects. Kinetic analysis showed that doxorubicin decreased V(max), K(m), and creatine transporter protein content. Cell surface biotinylation experiments confirmed that the amount of creatine transporter protein present at the cell surface was reduced. Cardiomyocytes rely on uptake by a dedicated creatine transporter to meet their intracellular creatine needs. Our findings show that the cardiomyocellular transport capacity for creatine is substantially decreased by doxorubicin administration and suggest that this effect may be an important early event in the pathogenesis of doxorubicin-mediated cardiotoxicity.

Multifactorial analysis of the learning curve for robot-assisted laparoscopic biliopancreatic diversion with duodenal switch.

OBJECTIVE: To assess the impact of surgeon, patient, and case-specific factors on the learning curve of robot-assisted laparoscopic biliopancreatic diversion with duodenal switch (RA-LBPD/DS). BACKGROUND: The BPD/DS has better resolution of diabetes and hypercholesterolemia, and the best long-term weight loss compared to the laparoscopic gastric band or the Roux-en-Y gastric bypass. Despite excellent results, the BPD/DS is least commonly performed because of greater malabsorption, longer operative duration, and higher technical complication rates. A reduction in technical complications and operative duration will enable the BPD/DS to be offered more frequently. METHODS: Consecutive patients (N = 120) undergoing RA-LBPD/DS between October 2000 and August 2008 were analyzed using univariate and multivariate logistic regression to determine the influence of surgeon and patient factors on complications and operative duration. Independent variables were case number, age, gender, body mass index, American Society of Anesthesiologists (ASA) score, difficult anatomy, and need for extensive adhesiolysis. Dependent variables were complications (leaks, bleeding, and conversion) and operative duration. The best-fit model predicted the risk factors for complications, and a risk-adjusted cumulative sum analysis estimated the learning curve. RESULTS: : Operative duration decreased an average of 3 minutes with each successive case (P < 0.001, R² = 0.63) and with patient's female gender. Adhesiolysis, difficult anatomy, liver biopsy, and higher ASA score increased operative duration. The incidence of high blood loss (13.3%), conversion (2.2%), and leaks (5.8%) were experienced by a total of 22 patients (18.3%). There was no mortality. Complications declined after 50 cases and were strongly predicted by increasing surgeon case number. CONCLUSIONS: The learning curve for the RA-LBPD/DS is 50 cases. Risk factors influencing outcomes were identified.

Laparoscopic appendectomy outcomes on the weekend and during the week are no different: a national study of 151,774 patients.

BACKGROUND: The "weekend effect" is defined as increased morbidity and mortality for patients admitted on weekends compared with weekdays. It has been observed for several diseases, including myocardial infarction and renal insufficiency; however, it has not yet been investigated for laparoscopic appendectomy in acute appendicitis-one of the most prevalent surgical diagnoses. METHODS: The present study is based on the Nationwide Inpatient Sample (NIS) from 1999 to 2008. The following outcomes were compared between patients undergoing laparoscopic appendectomy for acute appendicitis admitted on weekdays versus weekends: severity of appendicitis, intraoperative and postoperative complications, conversion rate, in-hospital mortality, and length of hospital stay. Unadjusted and risk-adjusted generalized linear regression analyses were performed. RESULTS: Overall, 151,774 patients were included, mean age was 39.6 years, 52.6% (n = 79,801) were male, and 25.3% (n = 38,317) were admitted on weekends. After risk adjustment, the conversion rate was lower [odds ratio (OR): 0.94, p = 0.004, number needed to harm (NNH): 244], whereas pulmonary complications (OR: 1.12, p = 0.028, NNH: 649) and reoperations (OR: 1.21, p = 0.013, NNH: 1,028) were slightly higher on weekends than on weekdays. Overall postoperative complications (OR: 1.03, p = 0.24), mortality (OR: 1.37, p = 0.075) and length of hospital stay (mean on weekday: 2.00 days, weekends: 2.01 days, p = 0.29) were not statistically different. CONCLUSIONS: The present investigation provides evidence that no clinically significant "weekend effect" for patients undergoing laparoscopic appendectomy exists. Therefore, hospital or staffing policy changes are not justified based on the findings from this large national study.

Adjuvant radiotherapy in the treatment of invasive intraductal papillary mucinous neoplasm of the pancreas: an analysis of the surveillance, epidemiology, and end results registry.

BACKGROUND: Management and outcomes of patients with invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas are not well established. We investigated whether adjuvant radiotherapy (RT) improved cancer-specific survival (CSS) and overall survival (OS) among patients undergoing surgical resection for invasive IPMN. METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was used in this retrospective cohort study. All adult patients with resection of invasive IPMN from 1988 to 2007 were included. CSS and OS were analyzed using Kaplan-Meier curves. Unadjusted and propensity-score-adjusted Cox proportional-hazards modeling were used for subgroup analyses. RESULTS: 972 patients were included. Adjuvant RT was administered to 31.8% (n=309) of patients. There was no difference in overall median CSS or OS in patients who received adjuvant RT (5-year CSS: 26.5 months; 5-year OS: 23.5 months) versus those who did not (CSS: 28.5 months, P=0.17; OS: 23.5 months, P=0.23). Univariate predictors of survival were lymph node (LN) involvement, T4-classified tumors, and poorly differentiated tumor grade (all P<0.05). In the propensity-score-adjusted analysis, adjuvant RT was associated with improved 5-year CSS [hazard ratio (HR): 0.67, P=0.004] and 5-year OS (HR: 0.73, P=0.014) among all patients with LN involvement, though further analysis by T-classification demonstrated no survival differences among patients with T1/T2 disease; patients with T3/T4-classified tumors had improved CSS (HR: 0.71, P=0.022) but no difference in OS (HR: 0.76, P=0.06). CONCLUSION: On propensity-score-adjusted analysis, adjuvant RT was associated with improved survival in selected subsets of patients with invasive IPMN, particularly those with T3/T4 tumors and LN involvement.

Cholecystectomy concomitant with laparoscopic gastric bypass: a trend analysis of the nationwide inpatient sample from 2001 to 2008.

BACKGROUND: Gallstone formation is common in obese patients, particularly during rapid weight loss. Whether a concomitant cholecystectomy should be performed during laparoscopic gastric bypass surgery is still contentious. We aimed to analyze trends in concomitant cholecystectomy and laparoscopic gastric bypass surgery (2001-2008), to identify factors associated with concomitant cholecystectomy, and to compare short-term outcomes after laparoscopic gastric bypass with and without concomitant cholecystectomy. METHODS: We used data from adults undergoing laparoscopic gastric bypass for obesity from the Nationwide Inpatient Sample. The Cochran-Armitage trend test was used to assess changes over time. Unadjusted and risk-adjusted generalized linear models were performed to assess predictors of concomitant cholecystectomy and to assess postoperative short-term outcomes. RESULTS: A total of 70,287 patients were included: mean age was 43.1 years and 81.6% were female. Concomitant cholecystectomy was performed in 6,402 (9.1%) patients. The proportion of patients undergoing concomitant cholecystectomy decreased significantly from 26.3% in 2001 to 3.7% in 2008 (p for trend < 0.001). Patients who underwent concomitant cholecystectomy had higher rates of mortality (unadjusted odds ratios [OR], 2.16; p = 0.012), overall postoperative complications (risk-adjusted OR, 1.59; p = 0.001), and reinterventions (risk-adjusted OR, 3.83; p < 0.001), less frequent routine discharge (risk-adjusted OR, 0.70; p = 0.05), and longer adjusted hospital stay (median difference, 0.4 days; p < 0.001). CONCLUSIONS: Concomitant cholecystectomy and laparoscopic gastric bypass surgery have decreased significantly over the last decade. Given the higher rates of postoperative complications, reinterventions, mortality, as well as longer hospital stay, concomitant cholecystectomy should only be considered in patients with symptomatic gallbladder disease.

Biliopancreatic diversion with duodenal switch.

The biliopancreatic diversion with a duodenal switch (BPD-DS) is a less commonly performed but very effective bariatric procedure that has been in existence for more than 20 years. It is particularly effective for the resolution of diabetes and is associated with the highest weight loss among other bariatric operations. Typically, the BPD-DS is not associated with postgastrectomy symptoms, such as dumping and marginal ulceration. Because of its complexity, it has usually been performed by laparotomy in the past; but, more recently, minimally invasive techniques are being used with acceptable risk.

Bariatric surgery using a network and teleconferencing to serve remote patients in the Veterans Administration Health Care System: feasibility and results.

BACKGROUND: Previously, Midwestern veteran patients had limited bariatric surgery access because they lived long distances from a bariatric surgery center (BSC). The creation and outcomes of a network to increase bariatric surgery access and patient satisfaction with teleconsultation are discussed. METHODS: Several referring Midwestern Veterans Affairs Medical Centers (VAMCs) performed pre- and postoperative management and were linked by teleconferencing and a computerized patient record system to a single BSC. RESULTS: Twenty-eight high-risk patients (older, male) residing an average distance of 324.5 miles from the BSC underwent gastric bypass. Eighty-two percent used teleconferencing for the initial surgical consultation with excellent patient satisfaction saving at least 19,000 miles and 69 travel days. Surgical outcomes were equivalent and follow-up was excellent (96.6%) compared with non-Veterans Affairs patients. CONCLUSIONS: A cooperative network using teleconference and computerized records facilitated bariatric surgery in high-risk, remotely located VA patients with high patient satisfaction and without compromising surgical outcomes.