Hirshsprung's disease; the clinical differentiation and treatment of children with Hirschsprung's disease and pseudo-Hirschsprung's disease

Hirschsprung's disease is marked by constipation from the time of birth, with the development, if uncorrected, of a protuberant abdomen and flared costal margins. The rectal ampulla is empty and the abdomen is filled with fecal masses. Pain is not prominent. Flatus is passed in large amounts. Encopresis does not occur. Barium enema shows the characteristic narrowed distal rectal segment and biopsy of the rectum shows absence of the ganglion cells of the myenteric plexus. Treatment is operative resection of the distal narrow segment and a primary anastomosis.Hirschsprung's disease may be mimicked in children with:1. Psychogenic constipation-pseudo-Hirschsprung's disease. Unlike Hirschsprung's disease, symptoms do not appear at birth, encopresis is common, and the barium enema shows no narrow distal segment.2. Mental retardation and cerebral defect.3. Corrected imperforate anus-on the basis of stenosis, imperfect innervation or poor habit training.4. Cretinism-with severe constipation and intestinal dilatation perhaps the presenting symptoms. Treatment of these four groups of children with severe constipation not due to Hirschsprung's disease is:For Group 1, open discussion with parent and child. Assumption by the physician of full control of the details of treatment, and relegation of parent to the role of the physician's agent in following the prescribed regimen. For Group 2, an enema regimen. Whereas fairly rapid restoration (and then persistence) of normal bowel habit can be expected in Group 1, the basic defects in Group 2 may require indefinite continuation of treatment. For Group 3, regular enema regimen, in the less severe cases-one identical with that used in Group 1, and dilatation of strictures or anoplasty. In Group 4, thyroid hormone therapy relieves the constipation of hypothyroidism and causes reversion of radiographic changes in the colon and rectum.     

Symposium on diarrhea. 3. Investigation of chronic diarrhea.

The practical approach to the investigation of diarrhea must be logical and based on anatomic considerations. The site of the underlying disorder may be determined by the clinical picture, and the logic of investigation will be influenced by the history. Important specific investigation in a case of colonic diarrhea include a careful rectal examination, stool inspection, sigmoidoscopy, rectal biopsy and barium enema study. Colonoscopy has been used, but its role has yet to be defined. In a case of small-bowel steatorrhea or diarrhea quantitative chemical estimation of the daily output of stool fat is useful, and to this investigation is added a small-bowel radiograph series and, if the radiographic findings are abnormal, small-bowel biopsy. Other investigations for small-bowel disease may include the breath test with carbon-14-labelled glycocholic acid, the lactose tolerance test, duodenal aspiration for giardiasis, analysis of serum immunoglobulins and, on occasion, isolation of vasoactive intestinal polypeptide hormone (which may aid the diagnosis of functioning tumours of the pancreas or small bowel). Investigations for pancreatic steatorrhea include abdominal radiography, performance of the secretin test and testing of the response to pancreatic replacement therapy. In some patients it may be useful to use endoscopic retrograde cholangiopancreatography to differentiate pancreatic carcinoma and chronic pancreatitis.     

HIRSCHSPRUNG'S DISEASE—The Clinical Differentiation and Treatment of Children with Hirschsprung's Disease and Pseudo-Hirschsprung's Disease

Hirschsprung''s disease is marked by constipation from the time of birth, with the development, if uncorrected, of a protuberant abdomen and flared costal margins. The rectal ampulla is empty and the abdomen is filled with fecal masses. Pain is not prominent. Flatus is passed in large amounts. Encopresis does not occur. Barium enema shows the characteristic narrowed distal rectal segment and biopsy of the rectum shows absence of the ganglion cells of the myenteric plexus.Treatment is operative resection of the distal narrow segment and a primary anastomosis.Hirschsprung''s disease may be mimicked in children with:1. Psychogenic constipation—pseudo-Hirschsprung''s disease. Unlike Hirschsprung''s disease, symptoms do not appear at birth, encopresis is common, and the barium enema shows no narrow distal segment.2. Mental retardation and cerebral defect.3. Corrected imperforate anus—on the basis of stenosis, imperfect innervation or poor habit training.4. Cretinism—with severe constipation and intestinal dilatation perhaps the presenting symptoms.Treatment of these four groups of children with severe constipation not due to Hirschsprung''s disease is:For Group 1, open discussion with parent and child. Assumption by the physician of full control of the details of treatment, and relegation of parent to the role of the physician''s agent in following the prescribed regimen.For Group 2, an enema regimen. Whereas fairly rapid restoration (and then persistence) of normal bowel habit can be expected in Group 1, the basic defects in Group 2 may require indefinite continuation of treatment.For Group 3, regular enema regimen, in the less severe cases—one identical with that used in Group 1, and dilatation of strictures or anoplasty.In Group 4, thyroid hormone therapy relieves the constipation of hypothyroidism and causes reversion of radiographic changes in the colon and rectum.     

Predictive value of rectal bleeding in screening for rectal and sigmoid polyps.

Overt rectal bleeding is a common symptom of colorectal cancer and polyps but also occurs in apparently healthy people. It is not known how often this represents bleeding from an undiagnosed rectal or sigmoid polyp or cancer. Three hundred and nineteen apparently healthy men aged over 50, selected by random sampling, were interviewed and underwent flexible sigmoidoscopy to at least 30 cm. Polyps of 10 mm or more in diameter were diagnosed in 12, one of whom also had an adenocarcinoma. Rectal bleeding during the previous six months was reported by 48, four of whom were found to have polyps; seven polyps and one cancer were diagnosed among the 271 who reported no rectal bleeding. Rectal bleeding had a specificity of 86%, a sensitivity of 33%, and a positive predictive value of 8% for rectal or sigmoid polyps or cancer. Restricting the analysis to those subjects who regularly inspected their stools did not improve the predictive value. Sigmoidoscopy in apparently healthy subjects with rectal bleeding will not result in the diagnosis of appreciable numbers of rectal and sigmoid polyps or cancers.     

Development of In Situ Gelling and Bio Adhesive 5-Fluorouracil Enema

In this study, a novel 5-Fluorouracil (5-FU) enema with good bio adhesion and temperature sensitivity was developed using in situ gelling technology. The preparation was formulated as a free-flowing liquid before use, while a layer of gel film was quickly formed when administered in the rectum, with a large contact surface area. It also demonstrated good biocompatibility, appropriate gel strength and bio adhesive force with excellent adhesion to rectal mucosa and prolonged action time, allowing more effective drug absorption and diffusion to surrounding tissues. Poloxamer 407 and poloxamer 188 were applied to adjust the gelling temperature. With the addition of carbopol and polycarbophil (bio adhesive substances), the solubility of 5-FU and gel strength increased, the temperature of gelation and the surface area of drug contact on mucous epithelium decreased. Decreased adhesive force between the preparation and the mucous membrane of the rectum was demonstrated with improving carbopol and polycarbophil’s concentration. In vitro release demonstrated that 5-FU in situ gelling enema with different bases had a rapid and almost complete drug release. We used an optimized formulation of P407/P188/polycarbophil/5-FU (17/2.5/0.2/1.0) for animal experiments. The result showed that the drug evenly covered the surface of the rectum and there was no leakage in 6 hours. The in situ gelling enema showed significantly higher rectal tissue levels of 5-FU compared with suppository and intravenous administration, indicating that 5-FU could be well absorbed due to the enlarged releasing area, longer retention time and larger amount of dissolved active ingredients. Systemically, 5-FU levels in the enema group were similar to those in the suppository group and significantly lower than the intravenous group. The enema was not associated with morphological damage to rectal tissue. These results suggest that the bio adhesive and in situ gelling enema could be a more effective rectal delivery system of 5-FU.     

Ischemic Colitis

Twenty cases of ischemic colitis are reviewed; 19 were obtained from autopsy files and the diagnosis in one was made from a surgical specimen. The majority of the patients were elderly with generalized arteriosclerosis. In approximately two-thirds of the patients the ischemic colitis was precipitated by preceding trauma, operation or congestive heart failure. Clinically, ischemic colitis is characterized by abdominal pain, distension and bleeding per rectum. Perforation of large bowel may occur. The lesions tend to be localized around the splenic flexure and junction of the descending and sigmoid colon, and in cases following aortic graft surgery the rectum is involved. Microscopically, there is necrosis, hemorrhage and ulceration. In less severe cases the mucosa only is affected. Cases with perforation show necrosis of all layers. It is considered that ischemic colitis is comparatively frequent and should be distinguished from other inflammatory conditions of the colon.     

Should colonoscopy be the first investigation for colonic disease?

Many patients with suspected colonic disease undergo rigid sigmoidoscopy, barium enema examination, and ultimately total colonoscopy, but the need for preliminary radiology has not been formally assessed. A total of 168 patients requiring large bowel investigation were therefore randomised to undergo either rigid sigmoidoscopy plus double contrast barium enema examination or total colonoscopy. Disease was found in 56 patients, including 14 with a carcinoma, 11 with polyps, and 16 with inflammatory bowel disease, the remainder having diverticular disease alone. Of the 89 patients allocated to double contrast barium enema examination, nine required a subsequent colonoscopy for suspected tumour or polyps, three because of incomplete radiological examination, and 12 for rectal bleeding for which no cause was found at the radiological examination. In 16 patients this yielded further information or altered treatment. Of the 79 patients undergoing total colonoscopy, only six required subsequent radiology.As both procedures were well tolerated with no major complications total colonoscopy may be the preferred initial investigation where facilities allow.     

Needle biopsy in diagnosis of prostatic cancer

Four methods available for the diagnosis of carcinoma of the prostate-digital rectal evaluation, prostatic smear, needle biopsy and open perineal or transurethral biopsy-were studied and correlated.One hundred ten patients with clinical indications of cancer of the prostate were subjected to needle biopsy and open perineal or transurethral biopsy. Seventy of the same patients had prostatic smear examination. Using the open perineal biopsy or the positive transurethral biopsy as the standard, the accuracy of prostatic palpation, prostatic smear and needle biopsy were obtained.A high degree of correlation (74 per cent) was demonstrated between digital rectal evaluation and positive surgical biopsies in both early and late cases. There were 17 false positive clinical diagnoses. The prostatic smear showed an overall correlation of 45 per cent when compared with the results of positive surgical biopsy. The overall accuracy of needle biopsy was 73 per cent. However, in the last 39 cases, including eight in which the carcinomas were of groups A and B (curable), the needle accuracy was 100 per cent. When there is clinical indication of malignant disease of the prostate, needle biopsy of the lesion is warranted and should be done before definitive or palliative treatment is undertaken.     

Colonoscopic polypectomy in children.

Five children presenting with chronic and intermittent rectal bleeding were diagnosed as having colorectal polyps by fibreoptic colonoscopy performed under sedation. Three of the children had had barium-enema films reported on as normal. Eight polyps were seen, of which six were proximal to the sigmoid colon. All were removed endoscopically (one by proctoscopy, one by snare-intussusception) without complication. Colonoscopic polypectomy is a safe and efficient procedure in children, and colonoscopy may be regarded as first-line management in those with rectal bleeding.     

Malignant hyperthermia in plastic surgery

Malignant hyperthermia is a seemingly rare genetic myopathy. Hypermetabolic crisis accompanied by a rise in body temperature to as high as 44 degrees C is its hallmark. Malignant hyperthermia is usually triggered by potent inhalated anesthetics and/or depolarizing muscle relaxants. Because of the extraordinary risk of death in patients who are at risk, plastic surgeons may be reluctant to operate on these patients. Five such patients were referred to the Plastic Surgery Service and the UCLA Malignant Hyperthermia Center for anesthetic and surgical management following plastic surgical procedures aborted for first episodes of malignant hyperthermia. They were anesthetized with nitrous oxide, barbiturates, opiates, tranquilizers, and nondepolarizing muscle relaxants. The patients were not treated prophylactically with dantrolene. Cardiac monitoring, end-tidal pCO2, and rectal temperatures were followed. After completion of their plastic surgical procedures, all five patients had a vastus lateralis muscle biopsy performed and subsequent caffeine/halothane contracture studies completed. The contracture study was positive in all patients studied. No anesthetic or surgical complications were encountered. This study demonstrates that patients at risk of developing malignant hyperthermia crisis can have plastic surgical procedures performed safely while undergoing appropriately selected general anesthesia.     

Surgical Management of Regional Enteritis

The present-day concepts concerning the surgical management of regional enteritis are reviewed and the multitude of problems that may arise in surgical treatment are discussed. The primary treatment of regional enteritis remains medical. Surgical intervention is necessary only for the complications of intractability, obstruction, fistula, abscess formation, anal and rectal complications, massive hemorrhage and perforation. To ensure the best possible results, medical treatment should continue after surgery. A perfect operation for this disease does not exist. Operations for regional enteritis can now be performed with a mortality rate of less than 2%, and although the recurrence rate following surgery averages approximately 30%, the disease is well controlled in the majority of patients with medical and/or surgical treatment.     

Plastic bread-bag clips in the gastrointestinal tract: report of 5 cases and review of the literature

Plastic bread-bag clips have been identified as a cause of local perforation or obstruction at many sites in the gastrointestinal tract. This study is the largest case series yet reported, consisting of 3 cases presenting as small-bowel perforation, 1 case in which the clip was found incidentally in the small bowel at laparotomy during vascular surgery and 1 case in which the clip was found incidentally in the small bowel at autopsy. In all cases there was no radiographic evidence to suggest a foreign body in the gastrointestinal tract. People older than 60 years of age who have either partial or full dentures seem to be particularly at risk for the accidental ingestion of these devices. If accidentally ingested, plastic bread-bag clips represent a significant health hazard. As the population ages, small-bowel perforation secondary to ingestion of such clips may occur with increasing frequency. The authors recommend elimination or redesign of the clips, to prevent their being swallowed and becoming impacted in the small bowel or to allow them to be identified in the gastrointestinal tract by conventional radiography.     

Helicobacter pylori and non-steroidal anti-inflammatory drugs: does infection affect the outcome of NSAID therapy?

1. H. pylori gastritis appears to increase the likelihood of developing dyspeptic symptoms on NSAID therapy. 2. There is preliminary evidence that the histologic severity of H. pylori gastritis may be adversely affected by NSAID therapy, with a consequent increase in the risk of developing a peptic ulcer, possibly with complications. Whether this results from an effect on the inflammatory process or results from a quantitative increase in H. pylori colonization is unknown. In these respects, ASA may differ from other NSAIDs. 3. Ulcers are more likely to develop during the course of NSAID therapy in those infected with H. pylori; eradication of the infection reduces ulcer recurrence in the face of continued NSAID therapy, and it seems likely that this must reduce but not abolish the risk of GI bleeding in those using NSAIDs. Eradication also reduces the damage (and possibly risks) of low-dose aspirin therapy. 4. While H. pylori and NSAID use are independent risk factors for GI bleeding, whether or not they are interactive remains unresolved. 5. The effect of H. pylori infection on the risk of perforation during NSAID therapy, or conversely, the contribution of NSAID therapy to the risk of perforation in H. pylori-infected subjects, is also unclear at the present time. 6. Only large outcome studies of accurately diagnosed patients (with regard to H. pylori gastritis), and with much more specific detail as to the type of NSAID, dose and duration of therapy, employing only well-defined end-points, such as significant hemorrhage, perforation or death, and avoiding all surrogate markers short of these end points can hope to unravel this tangled web.     

Oxidative DNA Damage in the Prostate May Predispose Men to a Higher Risk of Prostate Cancer

DNA damage has been associated with prostate cancer risk. Men who were referred for initial prostate biopsy for elevated prostate-specific antigen or abnormal digital rectal examination are often found with no cancer but have a higher risk of developing prostate cancer than the general population of men in their lifetime. In this study, we investigated whether DNA damage is one of the factors that predispose these men referred for prostate biopsies to a higher risk of prostate cancer. We found significantly elevated levels of 8-oxo-2-deoxyguanosine immunoreactivity in the prostates of the referred men (n = 50) in comparison to the control prostates of men (n = 32) with no indication for referral for prostate biopsy. Twelve of these control men were healthy middle-aged men and 20 of them were older men whose conditions were diagnosed with bladder cancer but with normal serum prostate-specific antigen and digital rectal examination and no evidence of prostate disease. In all the 8-oxo-2-deoxyguanosine-positive prostates, we detected phosphorylation of the ataxia telangiectasia mutated kinase and expression of the immune-stimulatory molecule MIC in the prostate epithelium. These data suggest that: 1) oxidative DNA damage has occurred in the “referred” but pathologically normal prostates, indicating that these prostates may be subjected to genomic instability and eventually neoplastic transformation; 2) in response to DNA damage, two surveillance pathways, represented by ataxia telangiectasia mutated phosphorylation and induction of the NKG2D ligand MIC, were activated to prevent tumorigenesis.     

Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma

ABSTRACT: We report two cases of gastrointestinal perforation (GIP) after radiotherapy in patients receiving tyrosine kinase inhibitor (TKI) for advanced renal cell carcinoma (RCC). Case 1 was a 61-year-old woman with lung metastases after a radical nephrectomy for a right RCC (cT3aN0M0) treated with interferon-alpha (OIF, 5 MIU, three times per week). She developed lytic metastases of the left femur and the left acetabulum. She was treated with palliative radiotherapy to the metastatic portion (3 Gy [MULTIPLICATION SIGN] 10 fractions), and 400 mg sorafenib twice per day plus continuing interferon alpha. She experienced sudden left lower abdominal pain after four weeks of treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. Case 2 was a 48-year-old man with lung, lymph node, and bone metastases after a radical nephrectomy for a right RCC (cT2N0M0), and was treated with 400 mg sorafenib twice per day. He developed lytic bone metastases of the lumbar vertebrae, which was treated with palliative radiotherapy to L2-4 (3 Gy [MULTIPLICATION SIGN] 10 fractions). He experienced sudden abdominal pain after two months of radiation treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. These cases underwent radiotherapy, and therefore this may be related to the radiosensitivity of TKI.     

Retrograde spread of hydrocortisone containing foam given intrarectally in ulcerative colitis.

A method is described of estimating retrograde spread through the colon of a 10% hydrocortisone acetate foam by labelling the foam with technetium-99m sulphur colloid and observing spread after intrarectal administration by serial gamma-camera pictures. The recommended 51 ml dose of foam reached the mid-sigmoid colon in all of the nine patients who had active ulcerative colitis. Furthermore, in seven the foam reached the proximal sigmoid colon. Foam spread less extensively in five patients with quiescent disease than in those with active disease. Increasing the volume of enema to 50 ml did not improve retrograde spread through the colon. These results suggest that 10% hydrocortisone foam may be useful in treating patients with distal ulcerative colitis that is not necessarily limited to the rectum.     

Male mating strategies under predation risk: do females call the shots?

Many authors have reported that, under elevated risk of predation,male guppies (Poecilia reticulata) alter their behavior fromcourtship to forced copulation (gonopodial thrusts not precededby sigmoid displays). This shift is presumed to benefit thebrightly colored male, whose intense courting activity mightotherwise increase his risk of detection and attack by predators.However, there is some evidence that females engaged in reproductiveactivity with males may be even more vulnerable to predatorsthan the males themselves, which suggests an alternative hypothesis:females in high-risk situations are less receptive to male courtship,and this leads males to change their behavior. We tested thishypothesis by providing either males and females separately,or both sexes concurrently, with information about elevatedpredation risk from a cichlid (Crenicichla sp.). We found thatwhen only females were provided with information about increased risk,males performed fewer courtship displays and fewer thrusts.They did not perform more forced copulations in any treatmentgroup. Nonetheless, our results suggest that the female's perceptionof predation risk can be at least as important as the male'sin changing male mating behavior.     

Rectal Swabs for Analysis of the Intestinal Microbiota

The composition of the gut microbiota is associated with various disease states, most notably inflammatory bowel disease, obesity and malnutrition. This underlines that analysis of intestinal microbiota is potentially an interesting target for clinical diagnostics. Currently, the most commonly used sample types are feces and mucosal biopsy specimens. Because sampling method, storage and processing of samples impact microbiota analysis, each sample type has its own limitations. An ideal sample type for use in routine diagnostics should be easy to obtain in a standardized fashion without perturbation of the microbiota. Rectal swabs may satisfy these criteria, but little is known about microbiota analysis on these sample types. In this study we investigated the characteristics and applicability of rectal swabs for gut microbiota profiling in a clinical routine setting in patients presenting with various gastro-intestinal disorders. We found that rectal swabs appeared to be a convenient means of sampling the human gut microbiota. Swabs can be performed on demand, whenever a patient presents; swab-derived microbiota profiles are reproducible, whether they are gathered at home by patients or by medical professionals in an outpatient setting and may be ideally suited for clinical diagnostics and large-scale studies.     

Schistosomiasis mekongi diagnosed by rectal biopsy.

Schistosoma mekongi, a parasite of the dog which is endemic in small foci along the Mikong river, is rarely seen in Europe. A case of schistosomiasis caused by S mekongi was recently seen in France, in a native of Laos who had been living in Thailand. He was admitted for treatment of previous diagnosed tuberculoid leprosy but was found to have hepatosplenomegaly, with a high eosinophil count and high bilirubin concentrations. Serological examination suggested schistosomiasis, but there were no parasites in the urine and the rectal mucosa looked normal on endoscopy. Nevertheless, rectal biopsy showed schistosomal proctitis and many ova of S mekongi. Two courses of praziquantel cleared the ova from his rectal mucosa. Although serological examination using S mansoni antigen suggested schistosomiasis, only biopsy of normal looking rectal mucosa allowed the diagnosis to established.     

Is Repeat Biopsy for Isolated High-Grade Prostatic Intraepithelial Neoplasia Necessary?

Numerous studies have cited the positive predictive value of isolated highgrade prostatic intraepithelial neoplasia (HGPIN) to the detection of cancer. Epidemiological, morphological, and molecular data support the potential for malignant transformation of HGPIN, yet no current method can discriminate which lesions will progress to clinically significant prostate cancer versus more latent lesions. Recent analyses of multiple retrospective studies have found similar rates of cancer detection following either diagnosis of isolated HGPIN or an initial negative biopsy. This may reflect increased use of extended biopsy techniques involving 10 or more cores rather than the true ability of HGPIN to undergo malignant transformation. This article discusses controversies surrounding management of an isolated diagnosis of HGPIN and whether repeat biopsy of HGPIN should be mandatory or selective in the context of other predictive values such as rising prostate-specific antigen or lesion on digital rectal examination.