Efficient microwave synthesis of flurbiprofen derivatives and their enhancement of efficacy in chronic inflammatory pain models and gastro-protective potential in post-operative model.

Present research was designed to synthesize and characterize the flurbiprofen derivatives and to evaluate their analgesic, anti-inflammatory and gastro-protective activities in post-operative and chronic inflammatory pain models. Flurbiprofen derivatives were produced by using three-step processes involving esterification, hydrazide production, and schiff base, each of which modified a different carboxyl group. All the newly synthesized flurbiprofen derivatives (NS5-NS8) were characterized by 1H NMR,13C NMR,19F NMR and HR-ESI-MS, and the post-operative, inflammatory pain and ulcerogenic activities were determined in well-established in-vivo animal models. To evaluate post-operative and inflammatory pain, various doses of compounds [1, 3, 10, and 30 mg/kg (bwt)] were used, while their ulcerogenic potential was assessed at doses of 100 and 150 mg/kg (bwt). The incisional damage linked pain was significantly (p < 0.001) reduced by derivatives at different doses in both the acute and repeated tests with decreased response of phologistic agent-induced inflammation. The stomach histology and biochemical features demonstrate that the synthesized derivatives have no potential to cause ulcerogenicity as compared to aspirin and flurbiprofen. Furthermore, docking shows that the hydrazide moiety of these compounds is crucial in interacting within COX-2 binding site. Therefore, the synthesized compounds exhibit strong analgesic and anti-inflammatory effects and a low risk of causing ulcers. These attributes render them potentially valuable therapeutic agents for the treatment of pathological disorders associated with inflammation and pain.Communicated by Ramaswamy H. Sarma.

Bio-oriented synthesis of ibuprofen derivatives for enhancement efficacy in post-operative and chronic inflammatory pain models.

The discovery of post-operative, chronic inflammatory pain and any gastroulcerogenic potential using well-established animal models in vivo with new structures, high efficiency, broad-spectrum, and low toxicity has been the focus of medicinal chemists. In the present article, we are reporting the design and synthesis of various derivatives of ibuprofen by modifying the carboxyl group of ibuprofen using three steps reactions; esterification under microwave-irradiation in 10 minutes, hydrazide formation, and finally schiff's base reaction. Microwave-assisted esterification reaction can be employed to quickly explore and increase molecular diversity in synthetic chemistry. All of the newly synthesized compounds (NS1-NS4) were characterized by 1H-, 13C-NMR, and HR-ESI-MS spectroscopy and evaluated for post-operative, chronic inflammatory pain and any gastroulcerogenic potential using well-established animal models in vivo. The synthesized compounds at the tested doses of 100 and 150 mg kg-1 significantly attenuated the incisional-injury induced post-operative pain like condition and, also inhibited the phologistic agent induced inflammatory responses in both the acute and chronic testing paradigms. The gastric histological and biochemical parameters exhibited that the synthesized compounds were devoid of any ulcerogenic potential in comparison to aspirin and ibuprofen. These findings concluded that the synthesized ibuprofen derivatives exhibited profound analgesic, anti-inflammatory properties with reduced ulcerogenic potential and might be considered as effective therapeutic agents to treat pathological conditions associated with pain and inflammation.

Formulation and Characterization of Polymeric Cross-Linked Hydrogel Patches for Topical Delivery of Antibiotic for Healing Wound Infections.

Wound healing faces significant challenges in clinical settings. It often contains a series of dynamic and complex physiological healing processes. Instead of creams, ointments and solutions, alternative treatment approaches are needed. The main objective of the study was to formulate bacitracin zinc-loaded topical patches as a new therapeutic agent for potential wound healing. A free radical polymerization technique was optimized for synthesis. Polyethylene glycol-8000 (PEG-8000) was chemically cross-linked with acrylic acid in aqueous medium, using Carbopol 934 as a permeation enhancer and tween 80 as surfactant. Ammonium persulfate and N,N'-Methylenebisacrylamide (MBA) were utilized as initiator and cross-linker. FTIR, DSC, TGA, and SEM were performed, and patches were evaluated for swelling dynamics, sol-gel analysis, in vitro drug release in various media. A Franz diffusion cell was used for the permeation study. Irritation and wound healing with the drug-loaded patches were also studied. The characterization studies confirmed the formation of a cross-linked hydrogel network. The highest swelling and drug release were observed in formulations containing highest Polyethylene glycol-8000 and lowest N,N'-Methylenebisacrylamide concentrations. The pH-sensitive behavior of patches was also confirmed as more swelling, drug release and drug permeation across skin were observed at pH 7.4. Fabricated patches showed no sign of irritation or erythema as evaluated by the Draize scale. Faster wound healing was also observed with fabricated patches compared to marketed formulations. Therefore, such a polymeric network can be a promising technology for speeding up wound healing and minor skin injuries through enhanced drug deposition.

Preparation of Spilanthes acmella based emulgel: Antimicrobial study and evaluation.

SSTIs (Skin and soft tissue infections) are the most commonly occurring infections among all age groups. This study aimed to create an herbal emulgel for the treatment of bacterial skin infections as many bacteria have developed strong resistance against antibiotics. Spilanthe acmella plant extract contains spilanthol which has strong anti-bacterial properties. Methanolic S. acmella extract-based emulgels being promising drug delivery systems have been evaluated for various parameters like physical characteristics, viscosity, pH, spreading coefficient, Bioadhesive strength determination, Extrudability, antioxidant and antibacterial activity. 200µg/100µl exhibited the highest antioxidative activity 60.01±0.28% radical scavenging activity. MIC values of pure extract found in the range of 0.83±0.21 to 1.66±0.41µg/100µl, MBC values found in the range of 1.66±0.41 to 3.33±0.83µg/100µl for all strains of bacteria. Statistically significant antibacterial activity of all extract containing emulgels was observed against S. aureus, P. aeruginosa, E. coli p-value = 0.00, while maximum antibacterial effect all formulations have produaced zone of inhibitions against E. Coli p-value = 0.00. The current study thus suggests the use of S. acmella extract-based emulgel for the treatment of bacterial skin infections caused by S. aureus, P. aeruginosa and E. coli.

Upgrading to cardiac resynchronisation therapy: Concordance of real-world experience with clinical guidelines.

OBJECTIVE: Revision to cardiac resynchronisation therapy (CRT) in patients with existing pacemakers with worsening heart failure (HF) can improve symptoms and cardiac function. We identify factors that predict improvement in left ventricular ejection fraction (LVEF) within a year of CRT revision. METHODS: We performed a retrospective study of 146 consecutive patients (16% female, mean age 73 ± 11 years, mean LVEF 27 ± 8%) undergoing revision to CRT (January 2012 to May 2018) in a single tertiary centre. LVEF was measured pre-revision and 3, 6 and 12 months post-upgrade. RESULTS: At 6 months, 68% of patients demonstrated improvement in LVEF (mean ΔLVEF + 6.7% ± 9.6). Compared to patients in atrial fibrillation (AF), patients with sinus rhythm had a greater improvement in LVEF at 6 months (sinus 8.4 ± 10.3% vs. AF 4.2 ± 8.0%, p = 0.02). Compared to ischaemic cardiomyopathy (ICM), patients with non-ischaemic cardiomyopathy (NICM) had a greater improvement in LVEF at 6 months (NICM 8.4 ± 9.8% vs ICM 4.8 ± 9.2%, p = 0.05). Patients with RV pacing ≥40% at baseline had a greater improvement in LVEF at 6 months (≥40% RV pacing 9.3 ± 10.2 vs. < 40% RV pacing 4.0 ± 7.4%, p = 0.01). All improvements were sustained over 12 months post-revision. There was no significant difference between genders, years between initial implant and revision, or previous device type. CONCLUSIONS: Our real-world experience supports current guidelines on CRT revision. NICM, ≥40% RV pacing and sinus rhythm are the main predictors of improvement in LVEF in patients who underwent CRT revision.

The indications and safety of prolonged temporary pacing using active-fixation leads and externalized pulse generator.

BACKGROUND: Temporary cardiac pacing, conventionally achieved using a passive transvenous pacing wire, can be life-saving for unstable arrhythmias. However, they run the risk of complications, the longer they remain in-situ. Externalized prolonged temporary pacing (EPTP), using active-fixation lead and an externalized pulse generator; may be an alternative for transient pacing indications, concurrent illness or sepsis that precludes permanent pacing. METHODS: Sixty-seven patients (mean age 69 ± 14 years; 82% male) underwent EPTP between November 2011 and April 2019. EPTP was performed in a sterile facility, under fluoroscopy, using active-fixation leads anchored to the right ventricle septum. Externalized lead was connected to a re-sterilized pulse generator and secured to anterior chest wall with transparent dressings. EPTP indications and patient outcomes were evaluated. RESULTS: Pacing indications were high-grade atrio-ventricular (AV) block (73.2%), sinus arrest (14.9%), overdrive suppression of VT (5.9%) and pause-dependent VT (4.5%). Reasons for ETPT rather than permanent pacing included: sepsis (38.8%), CIED-related infection (8.9%), transient pacing indication (25%), to allow further investigations prior to decision on CIED type (22%), and over-drive arrhythmia suppression (6%). Sixty three percent patients were severely ill in an ICU. Mean duration of pacing was 16 ± 12 days. Sixty seven percent patients subsequently received a CIED and had no evidence of device-related infection at 1-year post-implant. There were three non-fatal complications during EPTP while no deaths were attributed to EPTP. CONCLUSION: EPTP is a safe and useful method of prolonged temporary pacing for patients who require chronotropic support, but in whom immediate permanent pacemaker implantation is contraindicated.

Outcome of hepatitis C patients in a community with predominant genotype 3 with standard-of-care treatment before and after advent of direct-acting antivirals: A retrospective-cum-prospective study.

BACKGROUND AND OBJECTIVE: Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are mainly caused by hepatitis C infection. It is a worldwide predominant pathogen and is one of the main causes of healthcare problem in Asia. In the last few decades, there has been a considerable change in the treatment regimen for hepatitis C virus. The objective of this research was to relate the treatment response with sustained viral response in various therapies which have been the standard of care from time to time. MATERIALS AND METHODS: This hospital-based, retrospective-cum-prospective research span over a period of 2 years; we enrolled hepatitis C patients who attended the Department of Gastroenterology and Hepatology, Government Medical College, Srinagar, since June 2015 till May 2017. Subsequently, the database was prepared, containing all the relevant information about these patients. CONCLUSIONS: (i) In retrospective group: The overall efficacy (sustained viral response at 24 weeks [SVR-24]) of pegylated interferon a2a and ribavirin regimen was 90.96%. (ii) In prospective group: The efficacy (SVR) of different regimens was found to be as: sofosbuvir + ribavirin + daclatasvir (SVR-24, 83.33%); sofosbuvir + ribavirin (SVR-12, 94.57%); and sofosbuvir + daclatasvir (SVR-12, 98.00%).

Real-world treatment switching to sacubitril/valsartan in patients with heart failure with reduced ejection fraction: A cohort study.

BACKGROUND: Sacubitril/valsartan is an effective treatment for heart failure with reduced ejection fraction (HFrEF) based on clinical trial data. However, little is known about its use or impact in real-world practice. The aim of this study was to describe our routine clinical experience of switching otherwise optimally treated patients with HFrEF to sacubitril/valsartan with respect to patient outcomes such as quality of life (QoL) and echocardiographic variables. METHODS AND RESULTS: From June 2017 to May 2019, 80 consecutive stable patients with HFrEF on established and maximally tolerated guideline-directed HF therapies were initiated on sacubitril/valsartan with bimonthly uptitration. Clinical assessment, biochemistry, echocardiography and QoL were compared pretreatment and post-treatment switching. We were able to successfully switch 89% of patients from renin-angiotensin axis inhibitors to sacubitril/valsartan (71 of 80 patients). After 3 months of switch therapy, we observed clinically significant and incremental improvements in blood pressure (systolic blood pressure 123 vs 112 mm Hg, p<0.001; diastolic blood pressure 72 vs 68 mm Hg, p=0.004), New York Heart Association functional classification score (2.3 vs 1.9, p<0.001), Minnesota Living with Heart Failure Questionnaire score (46 vs 38, p=0.016), left ventricular ejection fraction (26% vs 33%, p<0.001) and left ventricular end systolic diameter (5.2 vs 4.9 cm, p=0.013) compared with baseline. There were no significant changes in renal function or serum potassium. CONCLUSION: This study provides real-world clinical practice data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan. The data provide evidence beyond that observed in clinical trial settings of the potential benefits of sacubitril/valsartan when used as part of a multidisciplinary heart failure programme.

Evaluation of iron deficiency anaemia for gastrointestinal causes in patients without GI symptoms in high prevalent GI malignancy zones.

BACKGROUND AND STUDY AIMS: Gastric cancer is highly prevalent in Kashmir, as are lower gastrointestinal (LGI) malignancies. Colonic cancer, gastric cancer, and coeliac disease are the most important gastrointestinal (GI) causes of iron deficiency anaemia (IDA) worldwide. Approximately 9% of patients with IDA present with a suspicious lesion in the GI tract upon examination. However, the absence of GI symptoms and a possible lesion accounting for blood loss in IDA have not been studied in this zone with a high prevalence of GI malignancy. We aimed to examine IDA patients without GI symptoms to determine the most plausible cause of their blood loss. PATIENTS AND METHODS: A total of 100 patients with IDA and 250 control subjects without IDA and referred for gastrointestinal endoscopy were enrolled in a cross-sectional, comparative study. Patients presenting with a significant lesion proportionate to their anaemia in the upper GI tract were not examined further, if no further strong indications were present. RESULTS: Twenty-nine patients (29%) were found to have malignancy: 13 with gastric cancer and 16 with colonic malignancies. Other apparent causes of GI blood loss included peptic ulcer disease in 10 (10%) patients, haemorrhoids in 22 (25%), polyps in eight (three in the upper GI tract and five in the LGI tract), gastric erosions in eight (8%), and angiodysplasia, diverticulitis, and trichuriasis in two (2%) each. CONCLUSION: In light of the high incidence of GI malignancies in this patient group, a low threshold for GI screening as well as mass screening for IDA is needed.

Role of the VDR Bsm I and Apa I polymorphisms in the risk of colorectal cancer in Kashmir.

OBJECTIVE: A case-control study aiming to evaluate the relationship between Bsm I and Apa I restriction fragment gene polymorphisms and colorectal cancer (CRC) was carried out in Kashmir, including a total of 368 subjects (180 cases and 188 controls). METHODS: DNA samples extracted from the blood of the subjects were analyzed for 3' untranslated region (3' UTR) Apa I and Bsm I polymorphisms using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). RESULTS: A statistically significant 2.7-fold increased risk was observed in individuals found homozygous for the presence of the 'b' allele, in comparison to subjects homozygous for the 'B' allele (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.49-4.86 (Bsm I)), and a statistically insignificant 2-fold increased risk was found among individuals with the 'aa' genotype, as compared to subjects with the 'AA' genotype (OR 2.017, 95% CI 0.86-4.7). Our study also yielded statistically significant results when the Apa I polymorphism was stratified by age (≤ 50 years) and dwelling area (rural area), and the Bsm I polymorphism by gender (male gender), suggesting a possible role of Apa I and Bsm I polymorphisms in the etiology of CRC in Kashmir. CONCLUSION: We conclude that Apa I and Bsm I single-nucleotide polymorphisms (SNPs) in the vitamin D receptor gene (VDR) might be associated with susceptibility to CRC among Kashmiris.

Association of a VDR gene polymorphism with risk of colorectal cancer in Kashmir.

Roles of the vitamin D receptor in etiology of cancers, including colorectal cancer, have been repeatedly stressed in different parts of the world. A case control study aimed to evaluate the relationship between the two was therefore initiated in Kashmir, known both for its increasing incidence of gastrointestinal cancers and deficiency of micro-nutrients especially vitamin D. The study included a total of 617 subjects (312 colorectal cancer cases and 305 controls), with sampling carried out over a period of 5 years. DNA samples from the blood of the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a 1.3 fold increased risk among individuals homozygous for f variants as compared to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our study also showed statistically significant results when dwelling and tumor location characteristics were stratified with Fok I polymorphism, all of which suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir.

Once daily controlled release matrix tablet of Prochlorperazine maleate: influence of Ethocel® and/or Methocel® on in vitro drug release and bioavailability.

CONTEXT: Controlled release (CR) matrix tablet of Prochlorperazine maleate was developed to improve its patient compliance. METHODS: Tablet formulations F1, F2 and F3 based on different concentrations of Methocel(®) K100 LV-CR Premium, were compacted by direct compression method while tablet formulations F4, F5 and F6, based on distinct blends of Methocel(®) K100 LV-CR Premium and Ethocel(®) Standard 7FP Premium, were compressed by flow-bound dry granulation-slugging method. The prepared powder mixtures, granules and tablets were evaluated for their physicochemical performance. Bioequivalence study of the optimized test tablet versus reference-conventional Stemitil(®) tablet was conducted on rabbits, using HPLC-UV system at λ(max) 254 nm. RESULTS: The test tablet, containing 28% Methocel(®) and 58% Ethocel(®) (F6) exhibited desired zero order kinetics for 24 h and was found stable at accelerated storage conditions for 6 months. In vitro drug release rate decreased as the Ethocel(®) content in the blend was increased, perhaps due to slower penetrability of water. Hydrodynamic conditions and hardness of tablets could not affect drug release kinetics. The tablet displayed significantly (p < 0.05) optimized peak drug concentration-C(max) (45 ± 3.42 vs. 64.5 ± 4.03), extended half life-t(1/2) (16.071 ± 3.97 vs. 5.257 ± 1.314 h) and bioequivalence to the reference tablet taken three times a day (1409 ± 15 ng·h/mL vs. 1346 ± 23 ng h/mL). The tablet showed strong Level A correlation (R(2) = 0.8458) between drug absorbed in vivo and drug released in vitro. CONCLUSIONS: The developed tablet may be adopted by pharmaceutical industry to improve patient compliance of the Prochlorperazine maleate.

Physicochemical characterization of artemether solid dispersions with hydrophilic carriers by freeze dried and melt methods.

Solid dispersions of artemether (ARM), a poorly soluble drug, were prepared using polyvinylpyrrolidone (PVPK25, MW 25000) and polyethyleneglycol (PEG4000, MW 4000) as excipients. These dispersions were studied by physical mixture, freeze-drying, and melting methods. They were characterized by X-ray diffraction pattern, fourier transform infrared spectrophotometry, differential scanning calorimetery, and dissolution studies. X-ray diffraction pattern revealed the complete crystalline nature of artemether, whereas physical mixtures, melt mixtures (MM), and freeze-dried solid dispersions (FDSD) of ARM-PVP and ARM-PEG showed reduced peak intensities with increased PVP/PEG content. PEG showed lower decreases in intensity than PVP preparations. Differential scanning calorimetery also confirmed this finding by showing either a small or absent endotherm. Red shifts in O-H stretching vibrations of ARM were higher in the MM of ARM-PVP than its FDSD as exhibited by fourier transform infrared spectrophotometry. The carbonyl peak of PEG was blue shifted in MM and FDSD, whereas the C=O peak of PVP was red shifted in FDSD and MM, indicating different H-bonding by PEG and PVP with ARM. The rate of dissolution (phosphate buffer at pH 4.5) was improved up to 4-fold in MM and FDSD compared to artemether, and up to 50% compared to physical mixtures. The preparation of solid dispersions influenced the rate of dissolution at various drug-carrier ratios, i.e., the dissolution order of 1:1-1:4 ratio was MM > FDSD; FDSD > MM at 1:6-1:8 ratios of both ARM-PVP and ARM-PEG; and FDSD of ARM-PEG > FDSD of ARM-PVP > MM of ARM-PEG > MM of ARM-PVP at a 1:10 ratio.

Correlation of hepatic venous pressure gradient with variceal bleeding, size of esophageal varices, etiology, ascites and degree of liver dysfunction in cirrhosis of liver.

An elevated hepatic venous pressure gradient (HVPG) has been associated with risk of variceal bleeding, and outcome and survival after variceal bleeding. In this pilot study, we measured HVPG in 40 patients with liver cirrhosis and studied its relationship with etiology of liver disease, esophageal variceal size, history of variceal bleeding or ascites, biochemical liver tests and Child-Pugh class. There was no procedurerelated complication. The mean (SD) HVPG was similar in patients who had history of variceal bleeding as compared to those who did not (15.4 [2.8] mmHg vs. 13.9 [2.7] mmHg, p=0.1); HVPG had no significant association with etiology of cirrhosis (p=0.4). HVPG levels were significantly higher in patients with larger esophageal varices (grade III/IV vs. I/II: 15.2 [2.7] mmHg vs.13.1 [2.8] mmHg, p=0.04), poorer Child-Pugh class (B or C versus A), and presence of ascites (p=0.04). Thus, HVPG correlated with variceal size, Child-Pugh class, and presence of ascites, but not with variceal bleeding status.

Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial.

BACKGROUND AND AIM: Following successful endoscopic therapy in patients with peptic ulcer bleeding, rebleeding occurs in 20% of patients. Rebleeding remains the most important determinant of poor prognosis. We investigated whether or not administration of pantoprazole infusion would improve the outcome in ulcer bleeding following successful endoscopic therapy. METHODS: In this double-blind, placebo-controlled, prospective trial, patients who had gastric or duodenal ulcers with active bleeding or non-bleeding visible vessel received combined endoscopy therapy with injection of epinephrine and heater probe application. Patients who achieved hemostasis were randomly assigned to receive pantoprazole (80 mg intravenous bolus followed by an infusion at a rate of 8 mg per hour) or placebo for 72 h. The primary end-point was the rate of rebleeding. RESULTS: Rebleeding was lower in the pantoprazole group (8 of 102 patients, 7.8%) than in the placebo group (20 of 101 patients, 19.8%; P = 0.01). Patients in the pantoprazole group required significantly fewer transfusions (1 +/- 2.5 vs 2 +/- 3.3; P = 0.003) and days of hospitalization (5.6 +/- 5.3 vs 7.7 +/- 7.3; P = 0.0003). Rescue therapies were needed more frequently in the placebo group (7.8% vs 19.8%; P = 0.01). Three (2.9%) patients in the pantoprazole group and eight (7.9%) in the placebo group required surgery to control their bleeding (P = 0.12). Two patients in the pantoprazole group and four in the placebo group died (P = 0.45). CONCLUSION: In patients with bleeding peptic ulcers, the use of high dose pantoprazole infusion following successful endoscopic therapy is effective in reducing rebleeding, transfusion requirements and hospital stay.

Endoscopic ligation vs. sclerotherapy in adults with extrahepatic portal venous obstruction: a prospective randomized study.

BACKGROUND: Endoscopic sclerotherapy is a well-established treatment for bleeding esophageal varices, although it has a substantial complication rate. A prospective randomized trial was conducted to determine whether endoscopic variceal ligation is safer and more effective than sclerotherapy in adults with bleeding esophageal varices because of extrahepatic portal venous obstruction. METHODS: Thirty-six patients underwent sclerotherapy and 37 had band ligation. RESULTS: Ligation and sclerotherapy were equally effective for achieving variceal eradication (94.6% vs. 91.7%, respectively; p=0.67). However, ligation achieved eradication with fewer endoscopic sessions (3.7 [1.2] vs. 7.7 [3.3]; p <0.0001) and within a shorter time interval (50.1 [17.7] days vs. 99 [54.8] days; p <0.0001). In the ligation group, recurrent bleeding was less frequent (2.7% vs. 19.4%; p=0.028; however, Bonferroni correction for multiple testing removes this significance) and the rate of major complications was lower (2.7% vs. 22.2%; p=0.014). Total cost per patient was significantly higher in the sclerotherapy vs. the ligation group ($216.6 [71.8] vs. $182.6 [63.4]; p=0.035). During the follow-up period after variceal eradication, no significant differences were found between the sclerotherapy and the ligation groups with respect to recurrent bleeding (3% vs. 2.9%; p=1.0), esophageal variceal recurrence (9.1% vs. 11.4%; p=1.0), and formation of new gastric varices (9.1% vs. 14.3%; p=0.51). CONCLUSIONS: Variceal band ligation is superior to sclerotherapy, because it is less costly and achieves variceal eradication more quickly, with lower relative frequencies of recurrent variceal bleeding and complications.

Endoscopic management of early postoperative biliary ascariasis in patients with biliary tract surgery.

Bile leak and residual stones are well known complications of biliary tract surgery. In endemic areas of ascariasis, invasion of the biliary tract by roundworms during the early postoperative period is an infrequent but serious complication. The present study describes the endoscopic management of postoperative biliary ascariasis in 19 consecutive patients. There were 5 men and 14 women with a mean age of 33.3 +/- 6.3 years. All patients had undergone cholecystectomy, with choledocholithotomy and placement of a T-tube in 13 (68.4%) patients. Eight (42.1%) patients including two with T-tubes were acutely sick at referral. Altogether, 16 (84.2%) patients had widened papillae due to previous endoscopic sphincterotomy (3 patients) or recent dilatation of the sphincter of Oddi by Bake's dilators (13 patients). All patients with a T-tube in situ had undergone unsuccessful attempts to remove the worms by flushing saline through the T-tube. Endoscopic retrograde cholangiopancreatography was performed 4 to 16 days after biliary tract surgery and revealed roundworms in the common bile duct in 10 patients, in the hepatic ducts in 2, or in both ducts in 7. Three patients had coexisting biliary leakage: from the cystic duct stump in two and from a T-tube track in one. Endoscopic treatment consisted of extracting the worms from the biliary tree and placing stents in those with coexisting leakage. Endoscopic success was defined as complete worm extraction and resolution of biliary leakage and was achieved in all patients. Complications occurred in one (5.3%) patient. We concluded that endoscopic management is an effective, safe approach for extracting ascarids from the biliary tree during the early postoperative period. It reduces the hospital stay, avoids T-tube-related complications, and permits a postoperative complication to be treated using a nonsurgical method.

Fifteen-year follow up of endoscopic injection sclerotherapy in children with extrahepatic portal venous obstruction.

BACKGROUND AND AIM: Endoscopic sclerotherapy has emerged as an effective treatment for bleeding esophageal varices both in adults and children but the long-term outcome is poorly defined in children. The authors report a 15-year follow up of sclerotherapy in children with extrahepatic portal venous obstruction. METHODS: Between June 1982 and February 1992, 69 children with bleeding esophageal varices underwent sclerotherapy; variceal eradication was achieved in 63 (91.3%) patients, with procedure-related morbidity of 28.9% and mortality of 1.4%. Fifty-nine patients with variceal eradication were followed for between 10.4 and 20.1 years (mean, 15.1 +/- 3.1 years). RESULTS: After a median period of 3 years (range, 1.2-12.8 years), seven (11.9%) patients presented with recurrent bleeding (esophageal varices, four; gastric varices, two; and duodenal ulcer, one). Recurrent bleeding occurred in six of seven (85.7%) patients within the first 4 years of initial variceal eradication. Esophageal varices recurred in eight (13.6%) patients. Five of the seven patients with recurrent bleeding and all eight with recurrent varices were effectively treated with further sclerotherapy. Two patients with gastric variceal bleeding unresponsive to sclerotherapy underwent shunt surgery. Elective surgery was required in eight additional patients for reasons other than recurrent varices or bleeding. CONCLUSIONS: The authors conclude that (i) sclerotherapy is the ideal, safe and effective treatment for bleeding esophageal varices, that it prevented bleeding in 88.1% patients after variceal eradication and hence, should be included in primary management strategies; (ii) follow-up endoscopy should be performed on a yearly basis for the first 4 years after variceal eradication; and (iii) surgery is required as a complementary technique for patients with uncontrolled bleeding, painful splenomegaly, growth retardation and symptomatic portal biliopathy.