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Rectal suction biopsy (RSB) is a well-known diagnostic procedure for disorders of bowel motility such as Hirschsprung's disease (HD). However, there are few reports about the optimal method of obtaining rectal tissue. We introduce a new technique using Gruenwald's nasal cutting forceps (NCF). From 1986 to 1999, we performed 130 sets of rectal biopsies in patients suspected of having HD. In group I (1986 to 1994), 68 sets of three-site biopsies (2, 3, and 5 cm above the dentate line) were performed using a conventional blind RSB technique. In group II (1995 to 1999), 62 sets of one-site biopsies (2 cm above the dentate line) were performed using Gruenwald's NCF after anal dilatation during general anesthesia. Hematoxylin-eosin staining and acetylcholinesterase histochemistry were used to examine all specimens. Biopsy specimens in group II (4.39 +/- 1.07 mm(2)) were larger than in group I (1.59 +/- 0.39 mm(2)) ( P < 0.01). In 18 cases (26 %) in group I, normal and HD bowel could not be differentiated because the specimens were too small to detect ganglion cells (i.e., only lamina propria [9 cases] or a small area of submucosa [9 cases] was present). These cases required repeat biopsy. All cases of HD diagnosed in group I (n = 20) were based on the findings of biopsies taken at 2 cm; biopsies from 3 and 5 cm did not provide additional information. There were 2 cases of post-biopsy hemorrhage in group I. In group II, 18 subjects were diagnosed with HD and 39 were confirmed to have normal bowel. There were no complications and repeating the biopsy was unnecessary. Three cases of hypoganglionosis (1 in group I and 2 in group II) were missed because the myenteric plexus abnormalities could not be detected by RSB. Intestinal neuronal dysplasia (IND) was diagnosed in 5 cases (2 in group I by repeat full-thickness biopsy and 3 in group II by rectal biopsy). We conclude that our new technique is advantageous and safe to differentiate between normal bowel, HD, and even IND on the basis of a single biopsy taken 2 cm above the dentate line. The biopsy can be taken under direct vision and is histopathologically accurate.

Abstract: Background: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as “allied disorders of Hirschsprung's disease” and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. Methods: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis‐microcolon‐intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo‐obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese‐ and English‐language articles in PubMed and Ichu‐Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. Results: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full‐thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. Conclusions: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies. [ABSTRACT FROM AUTHOR]

Purpose: Tumor necrosis is one of the indicators of tumor aggressiveness. F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. Methods: This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). Results: In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 ( p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 ( p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 ( p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. Conclusions: FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor. [ABSTRACT FROM AUTHOR]

Purpose: C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. Methods: The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. Results: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor ( N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis ( P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance ( P = NS). Conclusion: MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor. [ABSTRACT FROM AUTHOR]

Conventional acetylcholinesterase (AChE) histochemistry is both time consuming and complicated and requires the mixing of reagents that are toxic to the human body. We developed a rapid technique for performing AChE histochemistry, which has already been published, and now present a kit for performing AChE histochemistry that is a further improvement. Rectal suction biopsy specimens taken from 20 constipated patients and three full thickness biopsy specimens taken from 4 Hirschsprung's disease (HD) patients during pull-through surgery from aganglionic, transitional, and ganglionic bowel segments were tested using our rapid technique and the new kit. Each specimen was incubated for only 6 min. All ganglion cells stained clearly for AchE in just 6 min using both techniques. However, the kit was able to stain AchE positive nerve fibers more clearly and did not detect endogenous peroxidase-containing histiocytes, as did the earlier rapid technique. The kit could also detect AchE positive nerve fibers in the circular and longitudinal muscle layers, unlike the earlier rapid technique. The kit allows AChE histochemistry to be performed rapidly with complete accuracy, without any risk for toxicity. Moreover, the kit provides more focused information on AchE distribution in the bowel itself without any extraneous staining and can be used for diagnosing HD and allied disorders as well as establishing the exact level of innervation for pull-through resection. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We present a new approach to treating selected cases of Hirschsprung disease (HD) where suction rectal biopsy (SRBx) is performed in an operating room, and rapid acetylcholinesterase staining (RAST) is used to identify histopathology within 20 minutes, allowing primary laparoscopy-assisted transanal pull-through (PLTPT) to be commenced “immediately” (n = 7). Materials and Methods: All subjects had an obvious caliber change in the rectum/sigmoid colon on barium enema and were strongly suspected of having HD. Results: Rapid acetylcholinesterase staining clearly demonstrated acetylcholinesterase-positive hypertrophic nerve trunks and absence of ganglion cells in all SRBx specimens, indicating that all 7 patients had HD. All 7 proceeded to uneventful PLTPT. By taking this approach, SRBx results were available extremely quickly, and hospital stay was reduced by 2 to 4 days. Discussion: Our approach enhanced the treatment of selected cases of HD by proceeding immediately to PLTPT after SRBx specimens were examined using RAST. [Copyright &y& Elsevier]

Connective tissue growth factor (CTGF) is a newly described protein that stimulates transforming growth factor-beta1 (TGF-beta1). We evaluated the expression of CTGF mRNA in operative biopsy specimens from biliary atresia (BA) patients and normal controls to assess the role of CTGF in BA. Liver biopsy specimens were taken from BA patients at the time of portoenterostomy (n=22) and compared with specimens taken from normal controls (n=6). In situ hybridization was used to stain CTGF mRNA in all specimens. The distribution of collagen type IV (C-IV) was also assessed in the same specimens as an indicator of the severity of fibrosis present at the time of biopsy. Results were analyzed to determine whether there was any correlation between CTGF and C-IV and outcome. Of the 22 postoperative BA patients, eventual outcome was good in 17 (group I), and five (group II) subsequently required liver transplantation. Control specimens (n=6) had no apparent CTGF mRNA expression, and median C-IV positive immunoreactivity was 1.23+/-0.25%. CTGF mRNA was weakly expressed in hepatic stellate cells (HSC) and hepatocytes in specimens from group I, and median C-IV-positive immunoreactivity was 3.18+/-0.86%. However, in specimens from group II, there was increased CTGF mRNA in HSC and hepatocytes. Median C-IV-positive immunoreactivity was 6.31+/-0.96%. There was a significant correlation between CTGF mRNA intensity and the amount of C-IV, which implies that CTGF expression reflects prognosis. This study provides the first evidence that CTGF is strongly expressed in BA, in particular in HSC and hepatocytes, suggesting that they may be a source of CTGF. The strong correlation with C-IV indicates that CTGF plays a major role in the pathogenesis of progressive fibrosis in BA. [ABSTRACT FROM AUTHOR]

Background. Hypoganglionosis (HP) is characterized histologically by a decreased number of ganglion cells in intestinal myenteric plexuses and functionally by severely impaired gut motility. The purpose of the present study was to investigate the neuromuscular junction (NMJ) in small- and large-intestine biopsy specimens from patients with HP. Methods. Fresh frozen sections of small and large intestine from three patients with HP and five age/site-matched controls were examined. All specimens were labeled with neural cell adhesion molecule (NCAM) antibodies and synaptophysin (SY) antibodies to delineate the NMJ. Results. Normal small- and large-intestine specimens had a moderate number of NCAM-positive NMJ in association with nerve fibers in the lamina propria, muscularis mucosa, and many NCAM-positive NMJ in association with nerve fibers in the circular and longitudinal muscle layers. In HP, there was lack of expression of NCAM-positive NMJ in association with nerve fibers in the lamina propria, muscularis mucosa, and circular and longitudinal muscle layers in both small- and large-intestine specimens, and a marked increase in NCAM expression in the muscularis mucosa and the inner border of the circular muscle layer that was only seen in HP specimens. SY-positive synaptic vesicles were observed throughout the gut in all normal specimens, but there was a lack of SY expression in HP specimens. Expression of NCAM and SY in ganglion cells was the same in all specimens. Conclusion. These findings suggest there is a complicated abnormality of the NMJ in HP that may prove to contribute to the disturbances in gut motility seen in this condition. [ABSTRACT FROM AUTHOR]

To describe manifestations of acetylcholinesterase (AchE) activity in the bowel of patients presenting with refractory constipation and correlate them with outcome, rectal biopsy specimens (RBS) from 165 patients who presented with refractory constipation between 1988 and 1999 were examined. Age at biopsy ranged from 4 days to 17 years; 45 subjects were excluded because they satisfied diagnostic criteria for Hirschsprung's disease, intestinal neuronal dysplasia, or hypoganglionosis. Thirty-five autopsy subjects were used as controls. All RBS were compared and AchE activity was assessed in the lamina propria (LP), muscularis mucosae (MM), and around the submucosal vessels (V). Variations in AchE distribution were classified as grade I (no AchE-positive nerve fibers in the LP or MM), grade II (some positive fibers in the LP or MM), grade III (moderate positive fibers in the LP or MM), grade IV (many positive fibers in the LP, MM, or V), or grade V (fibrillar, foamy, or amorphous staining for AchE). All grade I (11/120) and V (12/120) subjects achieved normal bowel control with laxatives alone and all grade II subjects (58/120) did with laxatives and enemas. Grade III subjects (34/120) required addition of cisapride. All grade IV subjects (5/120) were unresponsive to conservative management and 4/5 were found to have a megarectum, which was treated surgically. AchE distribution correlated well with eventual outcome and requirement for surgery. AchE distribution could also be used to classify bowel motility disorders, and we suggest the term AchE-positive disease be used to describe them. [ABSTRACT FROM AUTHOR]

We report a case of persistent obstruction after laparoscopy-assisted transanal endorectal pullthrough for Hirschsprung's disease in a 4-week-old boy with biopsy-proven HD. Before pull-through, the posterior rectal cuff was split along its entire length cranially, starting from the dentate line. Initial recovery was uneventful; however, signs of obstruction developed 3 weeks postoperatively. Reoperation through a posterior sagittal approach confirmed a residual rectal cuff surrounding the neo-rectum circumferentially. The dorsal side of the residual rectal cuff was removed completely. At follow-up 5 years later, he defecates 2 to 4 times a day with occasional staining. We hypothesize that the persistent postoperative obstruction was caused by a long residual rectal cuff that spontaneously reapproximated and/or became folded during pull-through. Therefore, a shorter cuff with near-total posterior excision should be strongly considered during laparoscopy-assisted transanal endorectal pull-through for Hirschsprung's disease. [ABSTRACT FROM AUTHOR]