Histological characteristics of eosinophilic myenteric ganglionitis: an under-recognised cause of chronic intestinal pseudo-obstruction.

Eosinophilic myenteric ganglionitis (EMG) is characterised by eosinophilic infiltration of the myenteric plexus. EMG has been rarely reported as a cause of chronic intestinal pseudo-obstruction (CIPO), and its histopathological features are not fully elucidated. We analysed seven patients with CIPO. Three of them were diagnosed with EMG and four patients were categorised as non-EMG. Clinicopathological features were similar in both groups. These features included subtle to mild lymphocytic infiltration at the myenteric ganglia/muscularis propria, loss of myenteric ganglions and interstitial cells of Cajal (ICC), and no significant findings in the mucosa. The exceptions were moderate to severe degree of eosinophilic infiltration at the myenteric ganglia/muscularis propria in EMG. Functional gastrointestinal obstruction may be associated with inflammatory cell infiltration at the myenteric ganglia/muscularis propria, leading to subsequent hypoganglionosis and deficiency of ICC in EMG. Pathologists and clinicians should be aware of this distinction during differential diagnosis of patients with CIPO.

Isolation of high-purity myenteric plexus from adult human and mouse gastrointestinal tract.

The enteric nervous system (ENS) orchestrates a broad range of important gastrointestinal functions such as intestinal motility and gastric secretion. The ENS can be affected by environmental factors, diet and disease. Changes due to these alterations are often hard to evaluate in detail when whole gut samples are used. Analyses based on pure ENS tissue can more effectively reflect the ongoing changes during pathological processes. Here, we present an optimized approach for the isolation of pure myenteric plexus (MP) from adult mouse and human. To do so, muscle tissue was individually digested with a purified collagenase. After incubation and a gentle mechanical disruption step, MP networks could be collected with anatomical integrity. These tissues could be stored and used either for immediate genomic, proteomic or in vitro approaches, and enteric neurospheres could be generated and differentiated. In a pilot experiment, the influence of bacterial lipopolysaccharide on human MP was analyzed using 2-dimensional gel electrophoresis. The method also allows investigation of factors that are secreted by myenteric tissue in vitro. The isolation of pure MP in large amounts allows new analytical approaches that can provide a new perspective in evaluating changes of the ENS in experimental models, human disease and aging.

Histological findings in resected bowel of motility-disordered patients.

Gastrointestinal (GI) motility disorders are prevalent conditions associated with pain and bowel dysfunction. Some motility-disordered patients with intractable symptoms have undergone bowel resection aimed at palliating their symptoms. Our objective was to describe a population of motility-disordered patients with histopathological abnormalities identified in full-thickness surgical biopsies. A retrospective cohort study using prospectively collected clinical data and pathology reports was conducted. All adult patients referred to a tertiary motility clinic from 1996 to 2011 who had bowel resection for motility disorder were consecutively sampled. Fisher's exact test was used. Ninety-seven patients were referred for motility disorder during this time and pathology reports were available for 62 patients (63.9%). Hypertrophy or hyperplasia of the myenteric plexus was reported in 13 patients (21.0%). These patients were predominantly females with constipation-dominant symptoms. They were more likely to have objective evidence of colonic inertia (P = 0.01) than patients without myenteric plexus hypertrophy/hyperplasia. Consistent histopathologic abnormalities of myenteric plexus hypertrophy/hyperplasia were described in 21 per cent of patients with refractory GI motility disorders referred for surgical management. Our findings contrast with the hypoganglionosis reported in the slow transit constipation literature. Future studies are needed to systematically investigate these novel histologic findings through a follow-up immunohistochemical study of stored bowel specimens.

Does different approach during pancreatoduodenectomy influence intestinal migrating myoelectrical complex recovery? Study in experimental pig model.

It is said that leaving intact the functional motor unit of the pylorus leads to better gastric emptying and reduces postoperative upper gut motility disturbances. However, despite obvious different surgical approach, both major pancreatoduodenectomies lead to substantial myoelectrical dysfunctions. The latter are not efficiently recognized. We compared Whipple and Longmire-Traverso procedures in terms of electromyography patterns of the upper jejunum musculature and the density of Cajal cells network. Twelve male weaned pigs underwent surgery first to implant bipolar electrodes and telemetry transmitters for continuous electromyography recordings and then, after 1 week recovery, to create Whipple (n=6) and Longmire-Traverso (n=6) pancreatoduodenectomies. The first myoelectric activity was already registered 1-2 hours after both operations. Time to first regular patterns of migrating myoelectrical complex activity was significantly longer in the Whipple than in the Longmire-Traverso group (68.2±12.9 versus 27.8±51 hours, p=0.002). However, the restored patterns were substantially disturbed in both groups. Namely, after Longmire-Traverso operation, migrating myoelectrical complex cycles were very often and significantly shorter versus control ones, with reverse migration in the area of anastomosis while after Whipple procedure migrating myoelectrical complex cycles were less frequent and of short duration, significantly shorter in comparison even with Longmire-Traverso group. Cajal cells network in the vicinity of anastomosis, and distally from it, presented greater destruction after the Whipple operation. In conclusion, the advantage of one of two major pancreatoduodenectomies in terms of myoelectrical activity correctness in upper gut has not been proved in the study.

The human ileocaecal junction: anatomical evidence of a sphincter.

PURPOSE: The human ileocaecal junction (ICJ) is a major transition zone regulating intestinal transit. Historically, it has often been considered a valve rather than a sphincter. The microscopic anatomy of this junction was studied searching for evidence of an anatomical sphincter and neuromuscular specialisation. METHODS: Ileocaecal specimens were obtained from ten cadavers and five surgical donors (7 male, mean age 81 years, age range 68-94) and examined by histology and immunohistochemistry. Quantitative analyses of muscle thickness and submucosal vascularity were performed together with immunohistochemical studies of innervation and the distribution of interstitial cells of Cajal. RESULTS: The thickness of the muscular layer in both the ileum and the colon increased significantly over a distance of 1 cm leading up to the base of the ileal papilla where it reached a maximum (4.19 ± 2.0 mm) before gradually tapering towards the tip of the papilla. Submucosal vascularity in the ileal papilla was not increased compared to the adjacent ileum or caecum/colon. Neuronal density was less in the caecum and ileal papilla compared to the terminal ileum (P < 0.05). Interstitial cells of Cajal were identified within the myenteric plexus of the ICJ but their density was similar to the adjacent bowel. CONCLUSIONS: A localised muscle thickening at the base of the ileal papilla is consistent with an intrinsic anatomical sphincter. There was no evidence that the ICJ has increased submucosal vascularity or a greater density of innervation compared to the adjacent bowel. The term ileocaecal valve is misleading and should be replaced by ileocaecal junction.

Chronic effect of vagotomy in the morphometry of the myenteric plexus of rats' duodenum / Efeito crônico da vagotomia sobre a morfometria do plexo mioentérico do duodeno de ratos

BACKGROUND: The gastrointestinal disorders have been associated with morphological alterations in the myenteric nervous plexus. AIM: To evaluate, through morphometric studies, the chronic effects of the subdiaphragmatic trunk vagotomy on the nervous plexus. METHODS: Fifteen male exemplars of Wistar Rattus novergicus weighing about 150g, distributed into three groups, have been used: control (n=5), Sham (n=5) and vagotomized (n=5). The animals were sacrificed after 30 and 90 days post surgery. Fragments of duodenum were fixed in Bouin solution, embedded into paraffin and stained with HE and PAS. Morphometric analysis was performed by a Carl Zeiss KM 450 image system. The following aspects were observed: the density of nervous cells per linear micrometer (µm) (ND); the area of perikarya (µm²) (NA); the number of satellite cells per µm (SCD); and the number of satellite cells per neuron (SC/N). The averages were compared with the help of "software" program Sigma Plus through two way - ANOVA and Tuckey post-test. RESULTS: Denervation increased SC/N (p<0,05) and NA (p<0,05), in a time-dependent denervation way (p<0,05). However ND and SCD, decreased, which significantly with the animal's age (p<0,001). CONCLUSION: Vagotomy altered the myenteric plexus morphology in a time-dependent way.

RACIONAL: As disfunções gastrintestinais têm sido associadas à alterações morfológicas no plexo nervoso mioentérico. OBJETIVO: Avaliar através do estudo morfométrico, os efeitos crônicos da vagotomia troncular subdiafragmática sobre esse plexo nervoso. MÉTODOS: Foram utilizados 15 exemplares machos de Rattus novergicus da variedade Wistar, com cerca de 150 g, distribuídos nos grupos controle (n=5), Sham (n=5) e vagotomizados (n=5). Os animais foram sacrificados depois de 30 e 90 dias após as operações. Em seguida, fragmentos do duodeno foram fixados em solução de Bouin, incluídos em parafina e corados por HE e PAS. A análise morfométrica foi realizada por meio do sistema de análise de imagem Carl Zeiss KM 450. Foram observados: a densidade de células nervosas por micrômetro linear (µm); a área dos pericários (µm²); o número de células satélites por µm; e o número de células satélites por neurônio. As médias foram comparadas com o auxílio do programa de "software" Sigma Plus através do Two way - ANOVA e do pós-teste de Tukey. RESULTADOS: A desnervação aumentou o número de células satélites por neurônios (p<0,05) e a área média dos pericários (p<0,05), de maneira dependente do tempo de desnervação (p<0,05), mas diminuiu significativamente a densidade de neurônios (p<0,05) e de células satélites (p<0,05) em função da idade (p<0,001). CONCLUSÃO: A vagotomia alterou a morfologia do plexo mioentérico de maneira dependente do tempo.

Mucosal stimulation activates secretomotor neurons via long myenteric pathways in guinea pig ileum.

This study examined whether mucosal stimulation activates long secretomotor neural reflexes and, if so, how they are organized. The submucosa of in vitro full thickness guinea pig ileal preparations was exposed in the distal portion and intracellular recordings were obtained from electrophysiologically identified secretomotor neurons. Axons in the intact mucosa of the oral segment were stimulated by a large bipolar stimulating electrode. In control preparations, a single stimulus pulse evoked a fast excitatory postsynaptic potential (EPSP) in 86% of neurons located 0.7-1.0 cm anal to the stimulus site. A stimulus train evoked multiple fast EPSPs, but slow EPSPs were not observed. To examine whether mucosal stimulation specifically activated mucosal sensory nerve terminals, the mucosa/submucosa was severed from the underlying layers and repositioned. In these preparations, fast EPSPs could not be elicited in 89% of cells. Superfusion with phorbol dibutyrate enhanced excitability of sensory neurons and pressure-pulse application of serotonin to the mucosa increased the fast EPSPs evoked by mucosal stimulation, providing further evidence that sensory neurons were involved. To determine whether these reflexes projected through the myenteric plexus, this plexus was surgically lesioned between the stimulus site and the impaled neuron. No fast EPSPs were recorded in these preparations following mucosal stimulation whereas lesioning the submucosal plexus had no effect. These results demonstrate that mucosal stimulation triggers a long myenteric pathway that activates submucosal secretomotor neurons. This pathway projects in parallel with motor and vasodilator reflexes, and this common pathway may enable coordination of intestinal secretion, blood flow, and motility.

Roux-en-Y or 'uncut' Roux procedure? Relation of intestinal migrating motor complex recovery to the preservation of the network of interstitial cells of Cajal in pigs.

We designed a conscious pig model to investigate myoelectric activity and the number of interstitial cells of Cajal (ICC) in the proximal jejunum following the Roux-en-Y and 'uncut' Roux procedures in relation to clinical outcomes. Twelve male Polish White pigs (8 weeks old, 10-13 kg) underwent surgery under general anaesthesia first to implant bipolar electrodes and telemetry transmitters for continuous electromyography recordings and then, after 1 week recovery, to create Roux-en-Y (n = 6) and 'uncut' Roux loops (n = 6). Upper gut tissue specimens were studied for the expression of c-kit staining procedure to quantitatively identify the presence of interstitial cells of Cajal. The intestinal migrating motor complex was restored within 10.5 and 37 h in 'uncut' Roux and Roux-en-Y pigs, respectively (P < 0.05). During 2 weeks, the 'uncut' Roux piglets increased their body weight by 18.0%, whereas the Roux-en-Y piglets increased their body weight by only 7.3% (P < or = 0.05). Two weeks after surgery, the number of ICC located in the region of Auerbach's plexus was higher and adhesions in the abdominal cavity lower in the 'uncut' Roux group. In conclusion, in the pig model, preservation of smooth muscle and ICC network continuity in the proximal jejunum may play an important role in early postsurgical recovery.

[Dose "extended" surgery for pancreatic head adenocarcinoma have survival impact?].

Adenocarcinoma of the pancreas is the most difficult to treat, and the prognosis, even if curative resection is possible, is dismal. Improving survival in this intractable disease is a challenging issue. Most Japanese surgeons have stressed that resection with extended lymphadenectomy and autonomic nerve dissection (extended surgery) can offer a better chance of long-term survival. On the other hand, surgeons in Western countries are skeptical about extended surgery and have preferred resection without extended lymphadenectomy (standard surgery). Two randomized controlled trials (RCTs) on "standard vs. extended surgery for pancreatic head adenocarcinoma" were reported in 1998 from Italy and in 2002 from USA. Those two RCTs demonstrated that extended surgery did not improve patient survival; however, they had little impact on Japanese surgeons because the extended surgery used in those RCTs were not "true" extended surgery. Thereafter, one RCT was conducted in Japan in which extensive lymphadenectomy including paraaortic node and complete resection of autonomic nerves around the common hepatic and the superior mesenteric arteries were performed in extended surgery. Unexpectedly, the results showed that the survival rates were similar between extended and standard surgeries, compatible with the results of the Western RCTs. We should therefore conclude that extended surgery does not improve survival for patients with pancreas head adenocarcinoma.

[Standard surgery as part of the multidisciplinary treatment for pancreatic cancer].

Standardization of surgical procedure for pancreatic cancer has been recognized to be necessary and important these days. Recent studies appear to exhibit efficacy of the adjuvant chemoradiation therapy before or after pancreatic surgery. In this study, we examined the standard surgery as part of the multidisciplinary treatment for pancreatic cancer. Invasive ductal carcinoma of the pancreas was resected in 121 patients in our institution from 1992 through 2005. We stopped performing an extended lymphadenectomy with pancreatectomy in 2003, but the survival rates were not significantly different between the cases before and after 2003. We usually resect half of the nerve plexus around the superior mesenteric artery (SMA) as a standard procedure. When we achieved the microscopically curative resection (R0) even if the plexus around SMA or the portal vein was invaded, there were a few long survivors for more than five years. The R0 resection is the most important factor for prolonged survival. Pancreatectomy including removal of regional lymph nodes (D2) and half of the nerve plexus around SMA and combined resection of the infiltrated portal vein is thought to be a standard surgery from the viewpoint of decrease in morbidity and maintenance of curability.

[Trend in the management of pancreatic adenocarcinoma--Japan vs. US and Europe].

Pancreatic adenocarcinoma remains to have poor prognosis. Most of all patients have locally advanced disease with or without distant disease when diagnosed. Current rationale for the treatment of pancreatic adenocarcinoma in the US and European countries consists of the following formula: (1) accurate staging by improved imaging. (2) a balanced-resection which means not too extensive not too limited. (3) centralized treatment in high-volume center with minimal surgical mortality. (4) surgery alone is not enough for cure and need more radical adjuvant or neoadjuvant therapy. On the other hands, Japanese surgeons had challenged to improve outcome by radical resections but did not show their advantages in terms of survival benefit as shown in recent randomized controlled trials. Now we should look back to surgical role and think 'who can benefit by surgical resection'. The efficacy of "Japanese" radical resection including vascular resection or pancreatic nerve plexus resection should be evaluated, although the devise of novel diagnostic modalities and more effective adjuvant or neoadjuvant therapy are crucial to improve prognosis of this disease.

[Effects of intrinsic denervation of the jejunum after extensive enterectomy in the rat bowel syndrome]. / Efeitos da desnervação intrínseca do jejuno após enterectomia extensa na síndrome do intestino curto em ratos.

PURPOSE: To investigate the effects of intrinsic denervation of the jejunum after the extensive intestinal resection in rats. METHODS: Thirty male Wistar rats were distributed into three groups, depending on the experimental procedure: Group C (control), Group R (resection) and Group D (resection plus denervation). The body weight gain and a histomorphometric study of the jejunal mucosa were performed. RESULTS: The mean body weight of the group D animals showed a higher increase when compared to group R (D=312.2+/-21 g and R=196.7+/-36.2g). The number of jejunum myenteric neurons was smaller in group D (344.8+/-34.8 neurons/mm) when compared to other groups (R=909.0+/-55.5 and C=898.5+/-73.3). A hyperplasia of the jejunum mucosal epithelium was observed in the group D but also in the group R (R=7.3+/-3.9 mm2 and D=10.8+/-4.3 mm2), when compared to group C (C=5.8+/-3.0 mm2). The epithelial cell proliferation of the jejunum was higher in group D animals (48.7%) when compared to the other groups (R=31.9% and C=23.6%). CONCLUSIONS: The denervated animals presented an increase the body weight gain and mucosal cell proliferation responses when compared to the control group. This experimental model may provide new strategies for the surgical treatment of the short bowel syndrome.

Efeitos da desnervação intrínseca do jejuno após enterectomia extensa na síndrome do intestino curto em ratos / Effects of intrinsic denervation of the jejunum after extensive enterectomy in the rat bowel syndrome

OBJETIVO: Investigar em ratos Wistar as respostas adaptativas da mucosa em conseqüência da desnervação intrínseca do jejuno após ressecção intestinal extensa. MÉTODOS: Utilizaram-se 30 ratos distribuídos em três grupos segundo o procedimento realizado: C (controle), R (ressecção intestinal) e D (ressecção intestinal e desnervação intrínseca do jejuno). Posteriormente foi avaliado o ganho de peso e realizado estudos morfométrico da mucosa intestinal. RESULTADOS: Os animais do grupo D apresentaram ganho ponderal consideravelmente maior do que os do grupo R (D=312,2±21g e R=196,7±36,2g). A contagem neuronal mostrou diminuição na população de neurônios mientéricos no grupo D (344,8±34,8 neurônios/mm de jejuno) em relação aos outros grupos (R=909,0±55,5 e C=898,5±73,3). A área do epitélio da mucosa jejunal foi maior no grupo D (10,8±4,3mm²) em comparação aos grupos R (7,3±3,9mm²) e C (5,8±3,0mm²). O índice de proliferação celular epitelial da mucosa foi maior no grupo D (48,7 por cento), em relação aos grupos R (31,9 por cento) e C (23,6 por cento). CONCLUSÕES: O modelo experimental mostrou-se eficaz em melhorar o ganho ponderal dos animais submetidos à ressecção intestinal extensa, provocando intensificação da resposta hiperplásica da mucosa, a qual provavelmente levou a aumento da superfície de absorção de nutrientes. Abrem-se boas perspectivas para novas abordagens cirúrgicas para a síndrome do intestino curto.

Sympathetic denervation-induced changes in G protein expression in enteric neurons of the guinea pig colon.

Chronic sympathetic denervation entails subsensitivity to alpha(2)-adrenoceptor agonists and supersensitivity to kappa- and mu-opioid receptor agonists modulating cholinergic neurons in the guinea pig colon. A possible role for signal transduction G proteins in contributing to development of these sensitivity changes was investigated. Pertussis toxin (PTX), a blocker of the G(i/o)-type family of G proteins significantly reduced the inhibitory effects of UK14,304 (alpha(2)-adrenoceptor agonist), U69593 (kappa-opioid receptor agonist) and DAMGO (mu-opioid receptor agonist) on acetylcholine (ACh) overflow in preparations obtained from normal animals, but not in those obtained from sympathetically denervated animals. In this experimental condition, immunoblot analysis revealed reduced levels of G(alphao), G(alphai2), G(alphai3) and G(beta) in myenteric plexus synaptosomes. On reverse, synaptosomal levels of G(alphai1) and G(alphaz), a PTX-insensitive G-protein, increased after chronic ablation of the sympathetic pathways. These data suggest that changes in the function and expression of inhibitory G proteins coupled to alpha(2)-adrenoceptors, kappa- and mu-opioid receptors occur in the myenteric plexus of the guinea pig colon after chronic sympathetic denervation. The possibility that regulation of G proteins represents one of the biochemical mechanisms at the basis of the changes in sensitivity of enteric cholinergic neurons to alpha(2)-adrenoceptor, kappa- and mu-opioid receptor agonists is discussed.

Congenital interstitial cell of cajal hyperplasia with neuronal intestinal dysplasia.

Interstitial cells of Cajal (ICCs) are intestinal pacemaker cells that initiate peristalsis in the stomach and intestine, and are considered to be precursors of gastrointestinal stromal tumors (GISTs). We report a 2-year-old girl who suffered from scanty stool passage since birth. On barium enema, the distal colon was rigid with narrow lumen, whereas the proximal colon was dilated and atonic. She received right hemicolectomy and ileostomy. Histopathologically, there was continuous proliferation of spindle cells located between the layers of the muscularis propria throughout the right colon. These spindle cells were positive for c-kit and CD34 but negative for myogenic or neurogenic markers, indicating they are ICCs. No germline or somatic mutation of the juxtamembrane domain of c-kit gene was detected. In addition, the changes of the submucosal plexus fulfilled the histologic criteria of neuronal intestinal dysplasia type B. To our knowledge, this is the first reported case of congenital ICC hyperplasia. Further studies of ICC development may contribute to better understanding of the pathogenesis of this congenital malformation and the tumorigenesis of GIST.

Survival of neurons and interstitial cells of Cajal after autotransplantation of myenteric ganglia from small intestine in the lethal spotted mouse.

To avoid mutilating surgery in the treatment of distal aganglionosis, transplantation of autologous nervous elements to the affected intestine would be an attractive option. This treatment modality has emerged as a possible alternative for different brain disorders, mostly using fetal nervous tissue. Our objective was to evaluate whether myenteric ganglia (MG) and interstitial cells of Cajal (ICC) could survive a transplantation procedure and to evaluate possible differences between animals with distal colonic aganglionosis (lethal spotted mice) and their healthy littermates. Autologous transplantation of MG with adherent smooth muscle from small intestine to the subcapsular space of the kidney was performed in mice 3-12 weeks of age. The transplants were evaluated 5 to 9 days postoperatively. The presence of myenteric neurons in the transplants was registered using immunohistochemical detection of different neurotransmitters and markers. For identification of ICC antibodies against c-kit, a cell surface tyrosine-kinase receptor, were used. The transplants showed overall good survival. Neurons containing the general neuronal marker protein gene-related product, the neuronal nitric oxide synthesizing enzyme, and the neuropeptides vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, calcitonin gene-related peptide, galanin, substance P, and neuropeptide Y could be shown throughout the transplants. ICC were consistently seen in the grafted tissue among the smooth muscle cells, particularly in the deep muscular plexus, and within the MG. No obvious differences in ICC or enteric neuronal tissue survival, or in the frequency of the various neuronal populations displayed could be detected between the two groups of animals. These findings support the use of autologous MG for further research on transplantation of enteric ganglia as a possible alternative treatment for colonic aganglionosis.

Effect of selective gastric intrinsic denervation on gastric motility in turkeys.

The effect of selectively denervating portions of the myenteric plexus on gastroduodenal (GD) motility was examined in domestic turkeys (Meleagris gallopavo). The neural network beneath the lateral or medial side of the isthmus between the glandular stomach and the muscular stomach was denervated by application of 1% benzalkonium chloride (BC). Image intensification radiology (IIR) was performed postsurgically on the research subjects to observe GD contractions and to analyze aberrations. Two trials were performed. The first employed temporal controls by checking GD motility in all treated birds before and after BC had taken effect. The second trial controlled for the trauma associated with the surgical procedure by applying 0.9% saline solution in lieu of BC in four turkeys. The normal GD contractions sequence as confirmed by these controls was thin muscle contraction, duodenal contraction and outflow, thick muscle contraction, and, finally, glandular stomach contraction. Ablation of the nerves beneath the medial or lateral side of the isthmus resulted in the same abnormality in GD motility, namely a lack of thick muscle contractions. These results indicate that the entire myenteric plexus associated with the isthmus must remain intact for proper GD motility to take place. Furthermore, it can be inferred that initiation and regulation of the thick muscle pair acts via nerves encircling the isthmus. Secondary regulatory mechanisms controlling GD motility may exist and should be tested through future investigation.

Changes in colonic motility in dogs after a resection of the inferior mesenteric ganglion and plexus.

In a curative resection for advanced sigmoid or rectal cancer, an extensive dissection of the regional lymph nodes is generally required. This often necessitates the removal of the autonomic nerves around the inferior mesenteric artery. The present study was done in an attempt to clarify the influence of a neurectomy around the inferior mesenteric ganglion and plexus on the motility of the colon. In eight dogs, we resected the ganglion and plexus around the inferior mesenteric artery, together with an implantation of strain gauge force transducers in various parts of the colon, and 7-10 days later, colonic motility was examined. The percentage of contractile states and contractile forces increased at both the distal colon in fasting dogs, as well as at the middle colon in the late postprandial period. At the distal colon, contractile forces were noted in the early and late postprandial periods. These contractile abnormalities at the middle and distal colon may thus explain the frequent bowel movements or diarrhea often observed after extensive surgery in patients with sigmoid or rectal cancer.

Morphological changes in the myenteric plexus of rat ileum after transection and end-to-end anastomosis.

Surgical interruption of the gastrointestinal tract is widely used for investigating the structure of the enteric nervous system and in the treatment of certain pathological conditions of the gastrointestinal tract. The effects of transection and end-to-end anastomosis and myotomy on nerve cells of the myenteric plexus were studied by light and electron microscopy, 1, 2 and 6 wk postsurgically. During the 1st wk, degeneration of some nerve cells was indicated by the dilation of the endoplasmic reticulum and dispersion of Nissl substance. The degenerative process (an early electron-dense lamellar degeneration and a late floccular degeneration) was accompanied by some regenerative changes during the recovery period. Quantitative light microscopic analysis demonstrated a significant decrease in the number of neurons located 1 and 5 mm from operation sites in the intestine.

Intestinal neuronal dysplasia as a cause of surgical failure in Hirschsprung's disease: a new modality for surgical management.

Two hundred fifteen cases of Hirschsprung's disease (HD) had follow-up after definitive surgical treatment, which had been performed between September 1983 and August 1994. Of these, 20 (9.3%) had recurrence of obstructive symptoms that was unresponsive to conservative treatment. Nine cases were improved by posterior anorectal myectomy (PARM). The other 11 patients, who did not have improvement after PARM, had a re-pull-through. Reoperation consisted of excision of the descending and left transverse colon with pull-through of the right colon, regardless of the histology of the colon. The blood supply was based on the ileocolic vessels, with or without division of the right colic artery. To provide a smooth course for these blood vessels, without kinking, and to obtain adequate length of the right colon with less dissection, the entire bowel was derotated clockwise. Re-pull-through was then performed from the left side of the abdomen. The excised bowel from both operations was examined, using H&E staining, for possible evidence of intestinal neuronal dysplasia (IND) or acquired aganglionosis. All had ganglion cells in the remaining colon and at the distal limit of the pull-through. Histological signs of IND were present in all patients in the previously pulled-through colon. Apart from one mentally retarded child, all had satisfactory bowel movement in a 10 to 54-month follow-up period. IND should be considered a cause of surgical failure in HD. Subtotal colectomy and pull-through of the right colon after clockwise derotation of the entire bowel appears to be effective when symptoms persist after conservative therapy or PARM.