Recent advances, novel targets and treatments for cholelithiasis; a narrative review.

Cholelithiasis is a common and frequent condition all over the world with a high prevalence rate in western countries. Individuals with cholesterol gallstone disease experience intense gastrointestinal symptoms and have a high risk of developing comorbidities like cholecystitis, Gall bladder (GB) cancer and pancreatitis. Multiple risk factors associated with cholesterol gallstones include but not limited to genetics, dietary habits, lifestyle changes, comorbid conditions and various drugs. These factors may lead to alteration in bile, cholesterol & phospholipids homeostasis in the GB, intestine and hepatocytes culminating in cholesterol gallstones formation. Surgical (cholecystectomy) and non-surgical (oral dissolution therapy) treatments are available for the disease, albeit with certain complications and high treatment cost. Thus, there is a need for interventions, complementary or alternative therapies for the treatment and prevention of cholesterol gallstones. Currently available drug therapies used for cholesterol gallstones include statins and ezetimibe. Many patients consider traditional herbal practitioners due to their promise of non-invasive and pain free management of gall stones. This present a positive shift towards generally acceptable safety and cost effectiveness of herbal treatment warranting extensive research for alternative or complementary choice such as herbal plants as an emerging area for their potential therapeutic effects. This review discusses current strategies, latest trends available in the disease pathogenesis, drug development for novel targets, risk management, newer anti-lithogenic drugs and herbal plants that target the different aspects of the disease.

Megacystis microcolon intestinal hypoperistalsis syndrome: late sequelae and possible pathogenesis.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is characterized by hypoperistalsis in the presence of ganglion cells, malrotation, microcolon, bladder distension, and female predilection. We draw attention to the long-term management of a patient with MMIHS and propose a pathogenetic mechanism to account for this syndrome. We propose that the initial event in the pathogenesis of MMIHS is an intramural inflammatory process that affects the gastrointestinal and urinary tracts. This leads to extensive fibrosis which destroys the intestinal neural network, producing hypoperistalsis. The same process causes neuromuscular incoordination in the bladder wall, resulting in irregular bladder contractions against a "closed sphincter" leading to bladder distension. The enlarged bladder then interferes with the rotation of the intestine causing malrotation.

Management of pulmonary blastoma in children.

Pulmonary blastoma is a rare neoplasm, accounting for 0.5 per cent of all primary malignant pulmonary tumors. The clinical features, radiologic findings, and management of five children with pulmonary blastoma are described. The female/male ratio was 4:1. Mean age at presentation was 34 months, with a mean duration of symptoms of 1.8 months. Fever and cough were the most common symptoms. Opacification of the right lung field with mediastinal shift to the left was the predominant roentgenologic feature. The tumor involved the right chest in all patients. Thoracotomy was performed in all patients to establish the diagnosis. Two patients underwent complete resection at the initial operation, an incomplete resection was performed in one patient. Delayed complete resection was performed in another patient. All the patients received combination chemotherapy and one patient also received radiotherapy for primary disease. Two patients with histologic and immunohistochemical evidence of striated muscle differentiation were treated as rhabdomyosarcomas. Both these patients have survived for 24 and 67 months after diagnosis. The tumor recurred in three patients. Recurrence was treated with a combination of surgery, chemotherapy, and radiotherapy. Overall disease-free survival rate was 40 per cent. Long-term follow-up and additional patients are required to provide prognostic information.

Growth hormone reverses impaired wound healing in protein-malnourished rats treated with corticosteroids.

Corticosteroid (CS) administration amplifies the inhibitory effect of protein malnutrition (PM) on wound healing. Abdominal surgery in protein malnourished patients receiving corticosteroids (eg, advanced malignancy, transplant recipients) may be complicated by wound dehiscence or anastomotic breakdown. Although preoperative parenteral nutrition can reduce the incidence of these complications, this is not possible in patients requiring urgent surgical intervention. In a previous report we demonstrated that postoperative growth hormone (GH) administration could restore normal wound healing in PM rats. This study evaluates the effect of GH on wound healing in PM rats treated with CS. Forty-eight female Sprague-Dawley rats weighing 180 to 210 g were divided into four groups: (1) normally nourished; (2) PM only; (3) PM + CS; and (4) PM + CS + GH. PM rats (groups 2 to 4) received 5.5% protein chow every other day for 8 weeks. Control rats (group 1) received 23.4% protein chow for the same duration. Group 3 and 4 rats received prednisolone (2 mg/kg, intramuscularly) during the last 3 weeks of PM. All animals underwent precise 5-cm midline celiotomies. Postoperatively, rats in all groups were given 23.4% protein chow. Group 3 and 4 rats continued to receive CS postoperatively. Group 4 rats were given GH (0.5 mg/d, intraperitoneally) postoperatively for 5 days. Wound testing was performed on the 6th postoperative day after removal of the sutures. A balloon inserted into the peritoneal cavity through the vagina was gradually inflated. The pressure at which the wound disrupted was recorded as the wound bursting strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Communicating bronchopulmonary foregut malformations: classification and embryogenesis.

Communicating bronchopulmonary foregut malformations (CBPFMs) are characterized by a fistula between an isolated portion of respiratory tissue (ie, a lung, a lung lobe, or a segment) and esophagus or stomach. We combine our 30-year (1959 to 1989) experience of 6 cases with 51 reported patients to propose a CBPFM classification supported by a proposed embryogenesis theory. Group I (16%): anomaly is associated with esophageal atresia and tracheoesophageal fistula. Group II (33%): one lung originates from the lower esophagus. Group III (46%): an isolated anatomic lung lobe or segment communicates with the esophagus or stomach. Group IV (5%): A portion of the normal bronchial system communicates with the esophagus. The portion of the lung served by the communicating bronchus receives systemic blood supply. The right and left lung sacs curve dorsally to embrace the lower esophagus during normal lung development. At this stage a part of the lung bud joins the esophagus. This segment then breaks away from the main pulmonary anlage to form a CBPFM. CBPFMs should be considered in the workup of infants with respiratory distress and/or recurrent pneumonias. Patients with suspected pulmonary sequestration should undergo contrast studies to exclude a gastrointestinal communication.

Benign testicular tumors in children with congenital adrenal hyperplasia.

The association between testicular tumors/nodules and congenital adrenal hyperplasia (CAH) has been previously reported. From 1960 to 1989, three patients (13 to 18 years old) with long-standing CAH developed testicular masses. Two patients with 21-hydroxylase deficiency were diagnosed in the neonatal period while one other with 11-hydroxylase deficiency was diagnosed at 3 years of age when he presented with sexual precocity. In all three patients, medical compliance was poor. The testicular masses were bilateral in two patients and unilateral in one, measured 1 to 2 cm, and occupied only the upper half of the testicle. Testicular biopsy specimens were obtained after at least 6 months of evidence of compliance with the adrenocorticotrophic hormone (ACTH) suppressive medication and failure of the nodules to regress. On gross examination the masses appeared to be firm yellow brown nodules. Light microscopy showed interlacing strands, cords, and rests of cells resembling interstitial (Leydig) cells but with no Reinke crystalloids. Electronmicroscopy in all patients showed variable amounts of both smooth and rough endoplasmic reticulum, the later with occasional dilated cisternae. Follow-up ranged from 6 months to 6 years. No further surgical treatment has been necessary. There has been no evidence of recurrence, distant metastases, or secondary malignancies during the time of follow-up. These findings suggest that testicular tumors may develop from chronic excessive ACTH stimulation of a putative pluripotential testicular cell, a Leydig cell, or an adrenal cortical rest. Unlike other testicular tumors these do not require orchiectomy as the initial form of therapy.

Malrotation of the intestine in children.

Intestinal malrotation may be complicated by volvulus and intestinal necrosis. One hundred two children (64 male, 38 female) undergoing surgical abdominal exploration from 1977 to 1987 had malrotation. Fifty-two patients were less than 7 days of age, 13 from 8 to 30 days, 26 from 31 to 365 days, and 11 were older than 1 year of age. Of infants, 39 of 65 had 40-week gestations, 18 of 65 had 36- to 39-week gestations, and 8 of 65 had less than 36-week gestations. Chief symptomatology included: bilious emesis (47), intestinal obstruction (19), abdominal pain (11), and bloody stools (7). Seventy patients had congenital anomalies (50 single, 20 multiple). Diagnostic evaluations included 56 upper gastrointestinal series and 27 barium enemas. Each patient underwent correction of malrotation and appendectomy, and correction of congenital anomalies (omphalocele-9, gastroschisis-6, diaphragmatic hernia-7). Complications included short gut (2), sepsis (5), feeding difficulties (2), pneumonia (3), small bowel obstruction (2), and other (15). Nine patients (8.8%) died (trisomy 18-1, trisomy 13-1, intestinal necrosis-3, hepatic failure-1, prematurity-1, other sepsis-2). Two hundred sixteen children with intestinal malrotation have been treated from 1937 to 1987. Mortality rate has improved from 23% to 2.9%.