Surgical repair of endoscopy-induced colonic perforations: a case-matched study of short-term morbidity and mortality.

BACKGROUND: Our aim was to describe the clinical outcomes of surgical interventions performed for the management of colonoscopy-related perforations and to compare these outcomes with those of matched colorectal surgeries performed in elective and emergency settings. METHODS: We included patients with endoscopic colonic perforation who underwent surgical intervention from the 2014-2017 National Surgery Quality Improvement Program participant use data colorectal targeted procedure file. The primary outcome in this study was short term surgical morbidity and mortality. Patients (group 1) were matched with 1:2 ratio to control patients undergoing same surgical interventions for other indications on an elective (group 2) or emergency basis (group 3). Bivariate analysis was conducted to compare categorical variables between the three groups, and multivariate logistic regression was used to evaluate the association between the surgical indication and 30-day postoperative outcomes. RESULTS: A total of 590 patients were included. The average age of the patients was 66.5±13.6 with female gender predominance (381, 64.6%) The majority of patients underwent open colectomy (365, 61.9%) while the rest had suturing (140, 23.7%) and laparoscopic colectomy (85, 14.4%). Overall mortality occurred in 4.1% and no statistically significant difference in mortality was found between the three techniques (P=0.468). Composite morbidity occurred in 163 patients (27.6%). It was significantly lower in laparoscopic colectomy (14.1%) compared to 30.2% and 29.4% in open colectomy and suturing approaches (P=0.014). Patients undergoing colectomy for iatrogenic colonic perforation had less mortality, infection rates and sepsis, as well as bleeding episodes compared to those who had colectomy on an emergent basis. Outcomes were comparable between the former group and patients undergoing elective colectomy for other indications. CONCLUSIONS: Surgical management of colonoscopy related perforations is safe and effective with outcomes that are similar to that of patients undergoing elective colectomy.

A rare case of bilateral para-rectal hydatid disease: A case report.

INTRODUCTION: Cystic hydatidosis is a parasitic infection caused by the organism Echinococcus Granulosus that is well known to be endemic in the Mediterranean region, eastern Europe and South America and usually presents as hydatid disease of the liver but may affect other organs. The disease occurs when humans become the accidental host through ingestion of the eggs from contaminated food. CASE PRESENTATION: We present a case of Hydatid disease presenting as hives refractory to medical therapy over 4 years duration which was revealed to be caused by para-rectal hydatid cysts. Patient received Albendazole for a duration of 2.5 months and then underwent laparoscopic resection of the para-rectal cysts. CLINICAL DISCUSSION: Pelvic Hydatidosis is a very rare condition accounting for 0.7 % of all cases reported. In most cases, it is coexistent with cysts present elsewhere in the body, namely the liver, which is the case in the presented patient. Imaging is used as a modality to establish the diagnosis of cystic hydatidosis namely Ultrasound (US), Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI). The incidental finding of the hydatid cysts in this patient demonstrated the efficiency of a CT scan as a tool for detection and subsequently diagnosis of the disease in the pelvis. Surgery is the treatment of choice for cysts with daughter vesicles that are not candidates for percutaneous drainage, large liver hydatid cysts of more than 10 cm in diameter, cysts with a risk of rupture in case of trauma, and extrahepatic disease such as the lung, bone, brain, kidneys or pelvis. CONCLUSION: This article reports the rare occurrence of para-rectal hydatid disease which is only described in few case reports in the literature and provides an overview on diagnosis, and management of the disease.

Management of Radiation Proctitis.

Radiation proctitis is radiation-induced rectal mucositis, occurring as a result of radiation therapy for various pelvic malignancies. The management of radiation proctitis is challenging as guidelines are not currently available, and studies of the various treatment modalities are limited. There are various medical, endoscopic, and surgical measures for treating chronic radiation proctitis. Medical options such as anti-inflammatory agents, antioxidants, formalin application, and hyperbaric oxygen may improve bleeding related to chronic radiation proctitis. Endoscopic measures such as argon plasma coagulation are effective and safe. Surgery is considered for refractory or severe cases. A review and discussion of the different treatment modalities is presented.

Radiation proctopathy.

Radiation therapy is a widely utilized treatment modality for pelvic malignancies, including prostate cancer, rectal cancer, and cervical cancer. Given its fixed position in the pelvis, the rectum is at a high risk for injury secondary to ionizing radiation. Despite advances made in radiation science, up to 75% of the patients will suffer from acute radiation proctitis and up to 20% may experience chronic symptoms. Symptoms can be variable and include diarrhea, bleeding, incontinence, and fistulization. A multitude of treatment options exist. This article summarizes the latest knowledge relating to radiation proctopathy focusing on the vast array of treatment options.

Catastrophic bleeding from a marginal ulcer after gastric bypass.

Marginal ulceration at the gastrojejunal anastomosis is a common complication following Roux-Y gastric bypass (RYGB). Hemodynamically significant hemorrhagic marginal ulcers are usually treated either endoscopically or surgically. We describe a unique case of life-threatening hemorrhagic marginal ulcer eroding into the main splenic artery. This condition was initially managed with angiographic embolization, followed by surgical intervention.

Complications of transanal endoscopic microsurgery are rare and minor: a single institution's analysis and comparison to existing data.

BACKGROUND: Transanal endoscopic microsurgery, a minimally invasive procedure for treatment of early-stage rectal cancer, carcinoid tumors, and adenomas, is shown to be a safe procedure with very low perioperative morbidity. OBJECTIVE: We aimed to compare the outcomes of transanal endoscopic microsurgery at a large volume tertiary care center with the existing literature. DESIGN: We retrospectively reviewed a prospectively collected database of 325 transanal endoscopic microsurgery procedures and looked for risk factors associated with complications. Indications for transanal endoscopic microsurgery included rectal adenocarcinomas, adenomas, and carcinoids. SETTING: Procedures were performed by a single surgeon at a large-volume tertiary care center. PATIENTS: Patients were enrolled over a 20-year period, and data were collected on demographics, perioperative details, tumor characteristics, and complications. INTERVENTIONS: Transanal endoscopic microsurgery was performed on all 325 patients. MAIN OUTCOME MEASURES: Main outcome measures were urinary retention, late bleeding requiring intervention, dehiscence, peritoneal cavity entry, conversion to abdominal approach, fecal soiling, and rectovaginal fistula. RESULTS: Intraoperative bleeding was associated with larger tumor size, whereas postoperative bleeding requiring intervention was not associated with any factors studied. Peritoneal cavity entry and urinary retention were more likely if the tumor was in either the anterior or lateral position in the rectum. The peritoneal cavity was entered in 9 patients, and conversion to abdominal approach occurred in 1 patient. Intraoperative bleeding, by surgeon's choice, and urinary retention, by patient's choice, were associated with a greater likelihood of admission to the inpatient ward. Fecal soiling was not reported by patients and not recorded. LIMITATIONS: This study was limited because it was a retrospective analysis CONCLUSIONS: Transanal endoscopic microsurgery is an extremely safe procedure, offering very low perioperative morbidity. The overall morbidity found in our study was 10.5%, on par with published data for large series of 21%, 7.7%, and 14.9%. In contrast, complications from radical resection are reported at 18% to 55%.

Zinc salts provide a novel, prolonged and rapid inhibition of gastric acid secretion.

OBJECTIVES: The overproduction of acid and the associated illnesses linked to hypersecretion have a lifetime prevalence of 25-35% in the United States. Although a variety of pharmaceutical agents have been used to reduce the production of acid, alarming new evidence questions the long-term efficacy and safety of the agents. These issues coupled with the delayed onset of action and the return of symptoms in over 60% of the patients is less than satisfactory. The purpose of this study was to determine whether administration of a zinc salt could lead to a rapid and sustained increase in gastric pH in both animals and in humans and provide a new rapid acid suppression therapy. METHODS: Intracellular pH was measured with 2',7'-bis-(2-carboxyethyl)-5-and-6-carboxy-fluorescein in both human and rat gastric glands following an acid load±a secretagogue. In a separate series of studies, whole stomach acid secretion was monitored in rats. A final study used healthy human volunteers while monitoring with a gastric pH measurement received placebo, zinc salt, or a zinc salt and proton pump inhibitor (PPI). RESULTS: We demonstrate that exposure to ZnCl(2) immediately abolished secretagogue-induced acid secretion in isolated human and rat gastric glands, and in intact rat stomachs. Chronic low-dose zinc exposure effectively inhibited acid secretion in whole stomachs and isolated glands. In a randomized cross-over study in 12 volunteers, exposure to a single dose of ZnCl(2) raised intragastric pH for over 3 h, including a fast onset of effect. CONCLUSIONS: Our findings demonstrate that zinc offers a novel rapid and prolonged therapy to inhibit gastric acid secretion in human and rat models.

Ethanol inhibits gastric acid secretion in rats through increased AMP-kinase activity.

The effects of ethanol on gastric acid secretion remain controversial. The present study examines the effect of low-dose (2%) short term (15-20 min) ethanol exposure on gastric acid secretion via a potential interaction with AMP-activated protein kinase (AMPK). Real-time fluorescence digital imaging was used to provide functional evidence for the interaction of ethanol and AMPK in modulating secretagogue-induced acid secretion. Individual rat gastric glands were loaded with the pH-sensitive dye BCECF and the secretagogues carbachol (200 microM) or histamine (200 microM) were added to induce secretion. Rates of pH recovery were calculated as DeltapH(i)/Deltat. In one series of experiments, secretagogue-induced acid secretion was inhibited by 2% ethanol, or the AMPK activator AICAR monophosphate (AICAR) (20 mM). In a separate series, 2% ethanol was added in combination with compound C (20 microM), an AMPK inhibitor, to prevent activation of AMPK. 2% ethanol significantly suppressed stimulated acid secretion. In order to confirm modulation of AMPK activity by ethanol, the specific AMPK inhibitor compound C was used, which reversed the inhibitory effects of ethanol on stimulated acid secretion. This study demonstrates that low dose ethanol (2%) inhibits secretagogue-dependent acid secretion by activation of the AMPK pathway in rat gastric parietal cells.

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion.

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to be a metabolic energy regulator in various cells. Activation is a direct result of rising AMP concentration coupled with falling adenosine triphosphate (ATP). AMPK activation during metabolic stress consequently reduces cellular ATP consumption. The gastric parietal cell has a large abundance of mitochondria per cell volume due to the numerous energy-dependent transporters and channels responsible for acid secretion. We identified AMPK in the parietal cell as a metabolic energy regulator that can switch acid secretion off as cellular ATP levels fall. AMPK presence in murine gastric glands was evaluated by immunofluorescent localization. We used a digital imaging system to monitor acid secretion as observed by proton efflux from parietal cells in hand-dissected gastric glands loaded with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein. Individual murine gastric glands were exposed to histamine, pentagastrin, or carbachol. AMPK was pharmacologically activated with 5-aminoimidazole-4-carboxamide-1-beta-D: -riboside (AICAR) monophosphate or inhibited with 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine (compound C) or ATP. Acid secretion was evaluated under these conditions as the rate of intracellular pH recovery. In addition, whole-stomach pH measurements were performed. Immunofluorescent localization confirmed the presence of AMPK in gastric mucosa. Exposure to AICAR monophosphate significantly reduced secretagogue-induced acid secretion; addition of compound C or ATP restored acid secretion. Our results indicate that secretagogue-induced acid secretion could be significantly reduced with AMPK activation and restored with its deactivation. We therefore propose the AMPK as a cellular metabolic off switch for gastric acid secretion.

The paradox of the pouch: prompt emptying predicts improved weight loss after laparoscopic Roux-Y gastric bypass.

INTRODUCTION: The utility of routine upper gastrointestinal (UGI) evaluations after laparoscopic Roux-Y gastric bypass (LRYGB) has yet to be determined, primarily being used to rule out a gastrojejunal leak. Additional information can be assessed with these studies, including the rate of contrast emptying from the pouch; some patients show no or very slow emptying while others show a faster rate of emptying. No or slow emptying is likely due to anastomotic edema and/or a small initial stomal diameter. The aim of this study is to ascertain whether initial pouch emptying (or lack thereof) predicts postoperative weight loss. METHODS: Between August 2002 and July 2006, 405 LRYGB were performed by a single surgeon using a linear stapler technique. Patient demographics were entered into a longitudinal, prospective database. All patients had an UGI study on postoperative day 1. At 1-year follow-up, 304 patients were available for analysis. The patients were divided into two groups: group A, 188 patients with normal gastric emptying, and group B, 116 patients with very slow or no emptying of contrast. Analysis of covariance (ANCOVA) was used to compare weight loss between the two groups. The following covariates were considered in all analyses: age, sex, length of stay, and operative time. RESULTS: There was a statistically significant difference in weight loss between the two gastric emptying groups adjusting for age, sex, and operative time (p=0.007). Subjects with prompt gastric emptying (group A) showed more weight loss (50.6 kg versus 47.3 kg) and greater body mass index (BMI) loss (mean loss of 18.1 versus mean loss of 16.6 kg/m(2)) when compared with group B patients with slow or no emptying of the gastric pouch. CONCLUSIONS: Many factors (psychosocial, behavioral, hormonal, and anatomical) influence weight loss after LRYGB. Although we are uncertain of the mechanism, patients with normal initial pouch emptying tend to lose more weight than patients who initially exhibit slow or no emptying of the gastric pouch.

Extraction of a large self-amputated colonic lipoma: A case report.

Despite being the most common benign tumor of nonepithelial origin in the colon, colonic lipomas are nonetheless considered a rare occurrence. The minority of patients presenting with symptomatic colonic lipoma are generally treated with resection. We report a case of a symptomatic patient who, on presentation, was found to have a partially obstructing, self-amputated colonic mass on colonoscopy, requiring endoscopic fragmentation to extrude what was later histologically diagnosed to be a lipoma.

PI3 kinase dependent stimulation of gastric acid secretion by dexamethasone.

Excessive gastric acid secretion plays an important role in the pathogenesis of peptic ulcers. Dexamethasone, a widely used drug, is known to stimulate gastric acid secretion and increase the incidence of peptic ulcers. However little is known about the mechanism of the dexamethasone's effect on parietal cells. The present study was performed to investigate the contribution of the phosphatidylinositol-3-kinase (PI3 kinase) to dexamethasone induced stimulation of gastric acid secretion. In vivo pretreatment with dexamethasone injections (150 microg/100g for 3 days) or in vitro exposure to (10 microM for > 20 minutes) significantly increased acid secretion in isolated gastric glands approximately 2-3 fold. The dexamethasone induced stimulation of gastric acid secretion was concentration dependent and significantly blunted by the H+/K2+ ATPase inhibitor omeprazole (200 microM), the PI3 kinase inhibitor Wortmannin (500 nM), the protein kinase inhibitor staurosporine (2.5 microM) and the Cl(-) channel blocker NPPB (100 microM); but not by the H(2) antagonist cimetidine (100 microM). In conclusion, it was observed that dexamethasone's effect on proton extrusion requires the activity of a PI3 kinase pathway, an apical Cl(-) channel and the H2+/K2+ ATPase.

Characteristics of rat downregulated in adenoma (rDRA) expressed in HEK 293 cells.

Studies with apical membrane vesicles have shown that two distinct and separate anion exchange processes are present in rat distal colon, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive CL(-)-HCO(3)(-) exchange, and DIDS-resistant Cl(-)-OH(-) exchange. These studies proposed that anion exchanger (AE)-1 isoform encodes the former as both apical membrane DIDS-sensitive CL(-)-HCO(3)(-) exchange, and AE1 specific mRNA are present only in surface cells and are downregulated in Na-depleted rats, whereas downregulated in adenoma (DRA) encodes the latter as both DIDS-resistant Cl(-)-OH(-) exchange, and DRA-specific proteins are present in apical membranes of both surface and crypt cells and are not altered in Na(+)-depleted rats. Studies were, therefore, initiated to identify the function of rat DRA (rDRA) in vitro. rDRA cDNA isolated from rat distal colon encodes a 757-amino-acid protein which has 96 and 81% homology with mDRA and hDRA, respectively. rDRA-specific mRNA expression was detectable only in specific segments of the digestive tract (duodenum, ileum, cecum, proximal colon, and distal colon) but not in the stomach, jejunum, or in the kidney, brain, heart, and lung. HEK 293 cells stably transfected with rDRA exhibited DIDS-insensitive and intracellular acid pH (pH(i) 6.5)-sensitive Cl uptake that: (1) was significantly stimulated by outward Cl(-), HCO(3)(-), isobutyrate, and possibly OH(-) gradients; (2) was saturated as a function of increasing extracellular Cl concentrations with an apparent K (m) for Cl of 2.9 +/- 0.3 mM; and (3) was inhibited competitively by extracellular oxalate but not by SO(4)(2-). A high rate of DIDS-insensitive Cl influx at pH 6.5 was also present under physiological Cl(-) concentration. Our observations that rDRA mediates DIDS-insensitive, acid pH-dependent Cl(-) uptake are consistent with prior observations that rDRA does not mediate DIDS-sensitive Cl(-)-HCO(3)(-) exchange in rat distal colon. We speculate that, in addition to mediating pH-sensitive Cl(-) uptake, rDRA may function as a modifier of other anion transport proteins.

DeltaF508 mutation results in impaired gastric acid secretion.

The cystic fibrosis transmembrane conductance regulator (CFTR) is recognized as a multifunctional protein that is involved in Cl(-) secretion, as well as acting as a regulatory protein. In order for acid secretion to take place a complex interaction of transport proteins and channels must occur at the apical pole of the parietal cell. Included in this process is at least one K(+) and Cl(-) channel, allowing for both recycling of K(+) for the H,K-ATPase, and Cl(-) secretion, necessary for the generation of concentrated HCl in the gastric gland lumen. We have previously shown that an ATP-sensitive potassium channel (K(ATP)) is expressed in parietal cells. In the present study we measured secretagogue-induced acid secretion from wild-type and DeltaF508-deficient mice in isolated gastric glands and whole stomach preparations. Secretagogue-induced acid secretion in wild-type mouse gastric glands could be significantly reduced with either glibenclamide or the specific inhibitor CFTR-inh172. In DeltaF508-deficient mice, however, histamine-induced acid secretion was significantly less than in wild-type mice. Furthermore, immunofluorescent localization of sulfonylurea 1 and 2 failed to show expression of a sulfonylurea receptor in the parietal cell, thus further implicating CFTR as the ATP-binding cassette transporter associated with the K(ATP) channels. These results demonstrate a regulatory role for the CFTR protein in normal gastric acid secretion.

A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence.

AIMS: To study the efficacy of rifaximin, a nonabsorbable antibiotic, in relieving chronic functional symptoms of bloating and flatulence. METHODS: Randomized double-blind placebo-controlled trial consisting of three 10-day phases: baseline (phase 1), treatment with rifaximin 400 mg b.i.d. or placebo (phase 2), and post-treatment period (phase 3). Primary efficacy variable was subjective global symptom relief at the end of each phase. A symptom score was calculated from a symptom diary. Lactulose H2-breath test (LHBT) was performed at baseline and end of study. RESULTS: One hundred and twenty-four patients were enrolled (63 rifaximin and 61 placebo). Baseline characteristics were comparable and none had an abnormal baseline LHBT. Rome II criteria were met in 58.7% and 54.1%, respectively. At the end of phase 2, there was a significant difference in global symptom relief with rifaximin versus placebo (41.3% vs 22.9%, p = 0.03). This improvement was maintained at the end of phase 3 (28.6% vs 11.5%, p = 0.02). Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group (p < 0.05). Among patients with IBS, a favorable response to rifaximin was noted (40.5% vs 18.2%; p = 0.04) persisting by the end of phase 3 (27% vs 9.1%; p = 0.05). H2-breath excretion dropped significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores (p = 0.01). No adverse events were reported. CONCLUSIONS: Rifaximin is a safe and effective treatment for abdominal bloating and flatulence, including in IBS patients. Symptom improvement correlates with reduction in H2-breath excretion. Future trials are needed to examine the efficacy of long-term or cyclic rifaximin in functional colonic disorders.