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Cancers Jan 2022Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At...
INTRODUCTION
Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer. We hypothesized that the rate of signet ring cell cancer in asymptomatic patients with CDH1 mutations may be higher than anticipated and that the surgery could be conducted with acceptable short-term and long-term complications suggesting that the quality of life with the surgery is acceptable.
METHODS
We prospectively studied the role of total gastrectomy in symptomatic and asymptomatic patients with CDH1 mutations. A total of 43 patients with mutations of the CDH1 gene were studied prospectively, including 8 with symptoms and 35 without symptoms. Total gastrectomy was recommended to each. Quality of life was assessed in patients who underwent prophylactic gastrectomy. Proportions are compared with Fisher's exact test.
RESULTS
In total, 13 (30%) asymptomatic patients declined surgery. Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 asymptomatic patients (14%) had endoscopically proven signet ring cell cancer preoperatively, while 21 of 22 (95%) had it on final pathology ( = 0.05). Each asymptomatic patient was T1, N0, while seven out of eight symptomatic patients had T3-T4 tumors and six had positive lymph nodes. None had operative complications or operative death. The median follow-up was 7 years. Five (63%) symptomatic patients died, while only one (95%) prophylactic patient died of a non-gastric cancer- or surgery-related issue ( = 0.05). A total of 15 prophylactic patients had long-term follow-up. Each had significant weight loss (mean 23%) but all had a normal body mass index. In total, 40% had bile reflux gastritis controlled with sucralfate. Each returned to work and, if given the choice, said that they would undergo the surgery again.
CONCLUSIONS
Total gastrectomy is indicated for patients who have an inherented CDH1 mutation. Endoscopic screening is not reliable for diagnosing signet ring cell stomach cancer. If patients wait for symptoms, they will have a more advanced disease and significantly reduced survival. Operative complications of prophylactic gastrectomy are minimal, and long-term quality of life is acceptable.
PubMed: 35158993
DOI: 10.3390/cancers14030728 -
Arquivos Brasileiros de Cirurgia... 2022Oxidative stress is one of the main mechanisms associated with the rupture of the defense mechanisms of the colonic epithelial barrier; it reduces the tissue content of...
AIM
Oxidative stress is one of the main mechanisms associated with the rupture of the defense mechanisms of the colonic epithelial barrier; it reduces the tissue content of the claudin-3 and occludin proteins, which are the main constituents of intercellular tight junctions. Sucralfate (SCF) has antioxidant activity and has been used to treat different forms of colitis. This study aimed to measure the tissue claudin-3 and occludin content of the colon mucosa without fecal transit, subjected to intervention with SCF.
METHODS
Thirty-six rats were subjected to left colon colostomy and distal mucous fistula. They were divided into two groups according to euthanasia that was performed 2 or 4 weeks after the intervention. Each group was divided into three subgroups according to the enema applied daily: saline alone, SCF at 1 g/kg/day, or SCF at 2 g/kg/day. Colitis was diagnosed by the histological analysis adopting the previous validate scale. The tissue expression of both proteins was identified by immunohistochemical technique. The content of proteins was quantified by computer-assisted image analysis.
RESULTS
The inflammatory score was high in colonic segments without fecal transit, and enemas with SCF reduced the inflammatory score in these segments, mainly in those animals submitted to intervention with SCF in greater concentration and for a longer period of intervention. There was an increase in tissue content of claudin-3 and occludin, related to SCF concentration. The tissue content of both proteins was not related to the intervention time.
CONCLUSION
Enemas with SCF reduced the inflammation and increased the tissue content of claudin-3 and occludin in colonic mucosa without fecal stream.
Topics: Animals; Colitis; Enema; Rats; Rats, Wistar; Sucralfate
PubMed: 35107492
DOI: 10.1590/0102-672020210002e1630 -
Pharmaceuticals (Basel, Switzerland) Dec 2021(L.) Lam., Convolvulaceae is widely distributed in Asian areas from tropical to warm-temperature regions. Their tubers are known for their antioxidant, anti-bacterial,...
(L.) Lam., Convolvulaceae is widely distributed in Asian areas from tropical to warm-temperature regions. Their tubers are known for their antioxidant, anti-bacterial, anti-diabetic, wound healing, anti-inflammatory, and anti-ulcer activities. The preventive and therapeutic effects of orange-fleshed sweet potato on gastric ulcers have not been investigated. In this study, the carotenoid extract (CE) of orange-fleshed sweet potato was found to protect against gastric ulcers induced by HCl/ethanol in mice. The anti-inflammatory and antioxidant activities of the carotenoid pigment extract were also evaluated as possible evidence of their protective effects. Administration of CE reduced gastric ulcers. Oral administration of CE (100 mg/kg) protected against gastric ulcers by 78.1%, similar to the positive control, sucralfate (77.5%). CE showed potent reducing power and decreased nitric oxide production in a mouse macrophage cell line, RAW 264.7, in a concentration-dependent manner. The production of the inflammatory cytokine interleukin-6 and prostaglandin E was also reduced by CE in a dose-dependent manner. The high carotenoid content of orange-fleshed sweet potato could play a role in its protective effect against gastric ulcers. This result suggests the possibility of developing functional products using this nutrient-fortified material.
PubMed: 34959718
DOI: 10.3390/ph14121320 -
Medicina (Kaunas, Lithuania) Nov 2021: Drug-induced esophageal ulcer is caused by focal drug stimulation. It may occur in adults and children. Limited research is available in pediatric patients with...
: Drug-induced esophageal ulcer is caused by focal drug stimulation. It may occur in adults and children. Limited research is available in pediatric patients with drug-induced esophageal ulcer; therefore, we designed this study to determine the characteristics of this disease in this population. : Thirty-two pediatric patients diagnosed with drug-induced esophageal ulcers from a hospital database of upper gastrointestinal tract endoscopies were included. After treatment, patients were followed for 2 months after upper gastrointestinal endoscopy. : Female patients were predominant (56.2%/43.8%). The mean age of patients was 15.6 years (median, 16 years; interquartile range, 2 years). Doxycycline was administered in most cases (56.3%); other drugs were dicloxacillin, amoxicillin, clindamycin, L-arginine, and nonsteroidal anti-inflammatory drugs. Doxycycline was associated with kissing ulcers. Esophageal ulcers induced by nonsteroidal anti-inflammatory drugs were more often associated with gastric or duodenal ulcers. The most common location was the middle-third of the esophagus (78.1%). Patients were treated with proton pump inhibitors, sucralfate, or H2-blockers. The mean duration for which symptoms lasted was 9.2 days. No esophageal stricture was found in 24 patients who were followed for 2 months after upper gastrointestinal endoscopy. : The authors suggest informing patients to take medicine with enough water (approximately 100 mL) and enough time (15-30 min) before recumbency, especially high-risk drugs, such as doxycycline or nonsteroidal anti-inflammatory drugs.
Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Doxycycline; Female; Hospitals; Humans; Male; Peptic Ulcer; Taiwan
PubMed: 34946231
DOI: 10.3390/medicina57121286 -
Frontline Gastroenterology 2021A total of 30 000 people are treated with pelvic radiotherapy annually in the UK. Rectal bleeding is common following pelvic radiotherapy and one of the main causes is...
Endoscopically delivered Purastat for the treatment of severe haemorrhagic radiation proctopathy: a service evaluation of a new endoscopic treatment for a challenging condition.
BACKGROUND
A total of 30 000 people are treated with pelvic radiotherapy annually in the UK. Rectal bleeding is common following pelvic radiotherapy and one of the main causes is radiation proctopathy (RP). Six per cent develop severe bleeding from RP, leading to anaemia requiring iron +/- blood transfusion. There are very few safe, effective, evidence-based treatments. Purastat is a haemostatic agent licensed for gastrointestinal bleeding. It is a self-assembling peptide that forms a molecular mesh in contact with blood, thereby sealing blood vessels. There are numerous studies showing its efficacy and safety in various surgical/endoscopic settings. This service evaluation reports the first experience of the use of Purastat in RP.
METHODS
Consecutive patients attending pelvic radiation disease clinic with severe refractory RP were offered treatment with Purastat. This was defined as rectal bleeding into the pan±anaemia with no response to rectal sucralfate. Purastat was applied endoscopically at four weekly intervals up to three times, with more as required. Bleeding severity, endoscopic grade and haemoglobin were recorded.
RESULTS
Twenty-one patients were treated (18 men, median age 76 years) with a median of three treatments. Ten were on antithrombotics, 1 had thrombocytopenia and 13 had anaemia at baseline. Median episodes of bleeding reduced from 4.5 (0-27) to 2 (0-16) in the 7 days prior to the first and third treatment, respectively. Endoscopic grade was improved. Mean haemoglobin increased from 116.0 to 122.7. There were no complications.
CONCLUSION
Even in this cohort of severe refractory RP, there was an improvement in bleeding and endoscopic grade with Purastat. A randomised controlled trial is planned.
PubMed: 34925747
DOI: 10.1136/flgastro-2020-101735 -
ACS Applied Materials & Interfaces Dec 2021Excess nutrient uptake is one of the main factors of complications related to metabolism disorders. Therefore, efforts have emerged to modulate nutrient transport in the...
Excess nutrient uptake is one of the main factors of complications related to metabolism disorders. Therefore, efforts have emerged to modulate nutrient transport in the intestine. However, current approaches are mainly invasive interventions with various side effects. Here, a pH-responsive hydrogel is formulated by acidifying the hydroxide compounds within sucralfate to allow electrostatic interactions between pectin and aluminum ions. The pH responsiveness relies on the alternation of cations and hydroxide species, providing reversible shifting from a hydrogel to a complex coacervate system. It acts as a transient physical barrier coating to inhibit intestinal absorption and changes the viscosity and barrier function in different parts of the gastrointestinal tract, showing enhanced mucoadhesive properties. The therapeutic hydrogel remarkably lowers the immediate blood glucose response by modulating nutrient contact with bowel mucosa, suggesting potential in treating diabetes. In addition, it significantly reduces weight gain, fat accumulation, and hepatic lipid deposition in rodent models. This study provides a novel strategy for fabricating pH-responsive hydrogels, which may serve as a competent candidate for metabolism disorder management.
Topics: Adhesives; Animals; Drug Delivery Systems; Glucose Metabolism Disorders; Glucose Tolerance Test; Hydrogels; Hydrogen-Ion Concentration; Hydroxides; Materials Testing; Mice; Molecular Structure; Optical Imaging; Pectins; Sucralfate
PubMed: 34871495
DOI: 10.1021/acsami.1c17706 -
Acta Cirurgica Brasileira 2021To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis.
PURPOSE
To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis.
METHODS
Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis.
RESULTS
Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate.
CONCLUSIONS
Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.
Topics: Animals; Cadherins; Catenins; Enema; Intestinal Mucosa; Male; Oxidative Stress; Rats; Rats, Wistar; Sucralfate
PubMed: 34852133
DOI: 10.1590/ACB361007 -
Journal of Veterinary Internal Medicine Jan 2022Esophagostomy tubes (E-tubes) are widely utilized for extended nutritional support in dogs and cats. Problems associated with their use include the unwieldy excess...
BACKGROUND
Esophagostomy tubes (E-tubes) are widely utilized for extended nutritional support in dogs and cats. Problems associated with their use include the unwieldy excess (10-20 cm) of external tubing, constant need for neck wraps and necessity for skin sutures, suture tract infection, and tube loss if sutures fail.
OBJECTIVES
To evaluate 2 different, low profile (LP) "button" products intended for use in people as enteral (jejunostomy [J] and gastrojejunostomy [G-J]) feeding tubes for suitability as LP E-tubes in dogs and cats.
ANIMALS
A young giant breed dog that required extended (>6 months) nutritional and fluid support during recovery from severe neurological illness with protracted adipsia, anorexia, and dysphagia.
METHODS
Prospective evaluation of 2 commercially available LP feeding devices after placement of a standard E-tube. An LP J-tube and an LP G-J tube were assessed in consecutive 4-week trials, for tube retention, patient comfort, stoma health, and functionality.
RESULTS
Both products performed extremely and equally well as LP E-tubes in this clinical patient, enhancing patient freedom and comfort by eliminating external tubing, skin sutures, and bandaging. The dual port G-J tube allows medication delivery (eg, sucralfate) to the entire esophagus, but for safety alone (ie, to avoid aspiration), the single port J-tube appears the best device for client-owned patients.
CONCLUSIONS AND CLINICAL IMPORTANCE
The LP enteral feeding tubes from the human medical field can be successfully used as LP E-tubes in dogs and cats, offering superior patient comfort, with no obvious detriment to the patient and main drawback of higher cost.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Enteral Nutrition; Esophagostomy; Esophagus; Humans
PubMed: 34786762
DOI: 10.1111/jvim.16313 -
Diseases of the Esophagus : Official... May 2022Esophageal adenocarcinoma (EAC) is an aggressive cancer, associated with reflux esophagitis and intestinal metaplasia (IM). One underlying biological mechanism, which...
INTRODUCTION
Esophageal adenocarcinoma (EAC) is an aggressive cancer, associated with reflux esophagitis and intestinal metaplasia (IM). One underlying biological mechanism, which possibly drives the development of EAC, is the dysregulated expression of Bone Morphogenetic Proteins (BMPs).
AIM
To investigate if local delivery of Noggin, a BMP antagonist, reduced EAC.
METHODS
After obtaining proof of principal on local delivery of a Noggin/Sucralfate substance, a randomized controlled trial to test the effects of Noggin on EAC development was performed in a surgical rat model. In the model, an esophago-jejunostomy leads to development of reflux-esophagitis, IM and eventually EAC. Rats were treated by Noggin/Sucralfate or Sucralfate alone. Treatment was administered from 26 to 29 weeks after the operation.
RESULTS
Of the 112 operated rats, 52 survived beyond 26 weeks. Finally, 25 rats treated with Noggin/Sucralfate and 21 with Sucralfate, were evaluated. At the end, 39 (85%) of the animals had IM while 28 (61%) developed cancer. There were significantly more cancers in the Noggin/Sucralfate arm (50%) versus the Sucralfate group (73%) (Chi square, P < 0.05). Most cancers were mucous producing T3 adenocarcinomas. There were no significant differences in the amount of IM, size or grade of the cancers, or expression of columnar and squamous markers between the two groups.
CONCLUSION
In this study, we demonstrated that inhibition of BMPs by Noggin reduced development of EAC in a surgical esophagitis-IM-EAC rat model. In future, effective targeting of the BMP pathway with selective BMP-inhibitors could become an important asset to improve EAC patient outcome.
Topics: Adenocarcinoma; Animals; Barrett Esophagus; Bone Morphogenetic Proteins; Esophageal Neoplasms; Esophagitis, Peptic; Humans; Metaplasia; Random Allocation; Rats; Sucralfate
PubMed: 34718471
DOI: 10.1093/dote/doab072 -
Case Reports in Gastroenterology 2021We commonly see patients presenting with either portal hypertensive gastropathy (PHG) or radiation gastritis. Radiation-induced hemorrhagic gastritis is an unusual...
We commonly see patients presenting with either portal hypertensive gastropathy (PHG) or radiation gastritis. Radiation-induced hemorrhagic gastritis is an unusual lethal complication postradiation. Patients with preexisting PHG have very friable mucosa that can easily bleed after radiation for cancer treatment. There is an increased risk of bleeding with both entities present together. Our aim is to focus on treatment and possible prevention of gastrointestinal bleeding in patients with preexisting PHG undergoing radiation therapy for newly diagnosed cancer. Several therapies like prednisolone, argon plasma coagulation, laser coagulation have been proposed. There are no set guidelines for treatment. In these patients, if radiation therapy is indicated either for hepatic or gastrointestinal malignancy, it is suggested to premedicate with proton pump inhibitors or sucralfate. We describe a case of 73-year-old female who presented with upper gastrointestinal bleeding. She had liver cirrhosis secondary to nonalcoholic fatty liver disease and diagnosed with pancreatic cancer, for which she received chemoradiation. She was found to have both radiation gastritis and PHG with diffuse erythematous, edematous, congested mucosa with diffuse oozing blood in the antrum making it very challenging to treat.
PubMed: 34616249
DOI: 10.1159/000516569