Bruno Salerni

The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation

Background: Idiopathic slow transit constipation is one of the most severe and often intractable forms of constipation. As motor abnormalities are thought to play an important pathogenetic role, studies have been performed on the colonic neuroenteric system, which rules the motor aspects of the viscus. Aims: We hypothesised that important neuropathological abnormalities of the large bowel are present, that these are not confined to the interstitial cells of Cajal and ganglion cells, and that the previously described reduction of enteric neurones, if confirmed, might be related to an increase in programmed cell death (apoptosis). Patients and methods: Surgical specimens from 26 severely constipated patients were assessed by conventional and immunohistochemical methods. Specific staining for enteric neurones, glial cells, interstitial cells of Cajal, and fibroblast-like cells associated with the latter were used. In addition, gangliar cell apoptosis was evaluated by means of indirect and direct techniques. Data from patients were compared with those obtained in 10 controls. Results: Severely constipated patients displayed a significant decrease in enteric gangliar cells, glial cells, and interstitial cells of Cajal. Fibroblast-like cells associated with the latter did not differ significantly between patients and controls. Patients had significantly more apoptotic enteric neurones than controls. Conclusion: Severely constipated patients have important neuroenteric abnormalities, not confined to gangliar cells and interstitial cells of Cajal. The reduction of enteric neurones may in part be due to increased apoptotic phenomena.

Enteric nervous system abnormalities in inflammatory bowel diseases

Abstract  Various studies have described abnormalities of the enteric nervous system (ENS) in tissue samples from patients with chronic idiopathic inflammatory bowel diseases (IBD). The distribution of density of the different cell types of the ENS was however not studied in a systematic way. The aim of this study was to examine the density of neurons, enteroglial cells and interstitial cells of Cajal (ICC) in the different plexuses of the ENS in samples from patients with Crohn’s disease (CD), ulcerative colitis (UC) and controls. Tissue samples from 16 patients with CD (ileum) and 16 patients with UC obtained in involved and non‐involved areas were studied using immunohistochemistry with antibodies directed against neuron‐specific enolase, S100, C‐Kit and CD3. Sections were analysed blindly by two pathologists and the number of positive cells was counted for each type. Overall, an increase was noted for neuronal cell bodies, enteroglia and ICC in the deep muscular plexus in CD. In uninvolved areas of CD patients, the number of enteroglial cells was decreased. In UC, an increase of ICC in the muscularis propria and enteroglial cells was observed in diseased tissue. The study confirms the presence of abnormalities of the different cells of the ENS in IBD. The presence of lesions in samples from uninvolved areas, such as a reduction of enteroglia, supports a pathogenetic role of the ENS.

Enteric glial cells: new players in gastrointestinal motility?

The enteric glial cells, in addition to being support structures for the enteric nervous system, have many other additional roles, such as modulators for the homeostasis of enteric neurons, cells involved in enteric neurotransmission and antigen-presenting cells. Moreover, in the last years, data have been accumulating that demonstrate a possible active role of these cells in the pathophysiology of gastrointestinal motor activity. Thus, as also shown by recent evidence in both experimental animal models, and in some human diseases, alterations of enteric glial cells might have some role in the development of intestinal motor abnormalities.

Identification of Patients at Low Risk for Thyroidectomy-Related Hypocalcemia by Intraoperative Quick PTH

BackgroundTransient hypoparathyroidism is a frequent and challenging complication following total thyroidectomy. The aim of the study was to identify patients at risk of developing thyroidectomy-related hypocalcemia and symptoms by means of the intraoperative quick parathyroid hormone (PTH) assay.MethodsEighty-one patients undergoing total thyroidectomy were included in the study. Quick PTH levels were measured at induction of anaesthesia and 10 minutes after total thyroidectomy. A sample of 10 patients who underwent unilateral thyroid lobectomy was considered as a control group. The accuracy of intraoperative PTH decline in predicting postoperative hypoparathyroidism was analysed.ResultsAfter total thyroidectomy, 27 patients (33.3%) developed postoperative hypocalcemia. Symptoms were reported by 21 patients (25.9%). The mean percentage decline of intraoperative quick PTH was 81% in hypocalcemic compared with 39% in normocalcemic patients (P < 0.001), and it was 83% in symptomatic compared with 42% in asymptomatic patients (P < 0.001). Mean proportion decline of quick PTH after unilateral lobectomy was 20%, significantly lower than the 53% registered after total thyroidectomy (P = 0.005). Analysis of variation of intraoperative quick PTH with the receiver operator characteristics (ROC) curve showed a 75.7% decline as the cut-off value predicting postoperative hypocalcemia with the highest accuracy (91.4%) (sensitivity: 81.5% specificity: 96.3% positive likelihood ratio: 22; negative likelihood ratio: 0.2). Regarding the prediction of postoperative symptoms, a 79.5% decline was the most accurate (92.6%) cut-off point (sensitivity: 76.2% specificity: 98.3% positive likelihood ratio: 46; negative likelihood ratio: 0.2).ConclusionsQuick PTH monitoring during total thyroidectomy is a useful means for identifying low-risk patients for postoperative hypoparathyroidism and candidates for early, safe discharge. Furthermore, it is an objective method complementary to the surgeon’s judgement of the intraoperative function of parathyroid glands, which should be implanted in the event of a 75%–80% decline.

Clinical Appraisal of 99mTechnetium-Sestamibi SPECT/CT Compared to Conventional SPECT in Patients with Primary Hyperparathyroidism and Concomitant Nodular Goiter

BACKGROUND Although 99m Technetium-sestamibi scintigraphy with single-photon emission computed tomography (SPECT) and, recently, hybrid SPECT/computed tomography (CT) have been claimed to be the preoperative methods of choice for parathyroid localization in patients with primary hyperparathyroidism (PHPT) and concomitant nodular goiter (NG), they have never been compared in this setting. We aimed at testing the hypothesis that SPECT/CT may be superior to SPECT for parathyroid localization in patients with PHPT and NG. METHODS Thirty-three patients with PHPT and NG (one or more nodular lesions based on cervical ultrasound) who underwent open parathyroidectomy during 2004-2009 were reviewed. All patients had preoperative 99m Tc-sestamibi planar scintigraphy and SPECT (18 patients) or SPECT/CT (15 patients) after cervical ultrasound. Sensitivity, specificity, and positive predictive value (PPV) (for both correct neck side and quadrant identification) were calculated for the two procedures through comparison with intraoperative findings. In addition, operative times were assessed if the surgery was only for PHPT and not for the six patients who also had thyroidectomy. RESULTS The sensitivity of SPECT/CT for correctly identifying the neck side containing an abnormal parathyroid was 93.7% versus 80% for SPECT (p = 0.21, not significant [ns]). The specificity and PPV for this attribute were 92.9% and 93.7%, respectively, for SPECT/CT versus 87.5% and 88.9%, respectively, for SPECT (p = 0.75 and 0.8, ns). SPECT/CT showed higher sensitivity than SPECT (87.5% vs. 55.6%; p = 0.0001) and higher PPV (87.5% vs. 62.5%; p = 0.0022) for correctly identifying the neck quadrant affected by PHPT. The specificity for this was 95.5% for SPECT/CT versus 88.5% for SPECT (p = 0.26, ns). Mean operative time was shorter after SPECT/CT than after SPECT (38 vs. 56 minutes; p = 0.034). One of the patients having SPECT/CT had double adenomas, and two had ectopic parathyroid glands, all of which were recognized preoperatively by this technique. Two of the patients having SPECT had double adenomas, and two had ectopic glands, none of which were recognized preoperatively. No patient had persistent or recurrent PHPT. CONCLUSIONS SPECT/CT is superior to SPECT for preoperative imaging of patients with PHPT and NG. We recommend the routine use of SPECT/CT for work-up of all such patients, particularly if minimally invasive parathyroid surgery is planned.

Colonic mast cells in controls and slow transit constipation patients.

Aliment Pharmacol Ther 2011; 34: 92–99

Colonic neuropathological aspects in patients with intractable constipation due to obstructed defecation

One of the most frequent subtypes of constipation is represented by obstructed defecation, and it has recently been reported that these patients may have colonic motor abnormalities in addition to alterations of the anorectal area. However, it is unknown whether these patients display abnormalities of the enteric nervous system, as reported in other groups of constipated subjects. For this reason, we evaluated the neuropathologic aspects of the enteric nervous system in a homogeneous group of patients with obstructed defecation. Colonic specimens from 11 patients (nine women, age range 39–66 years) undergoing surgery for symptoms refractory to any therapeutic measure, including biofeedback training, were obtained and examined by means of conventional histological methods and immunohistochemistry (NSE, S100, c-Kit, formamide-mAb, Bcl-2, CD34, alfa-actin). Analysis of the specimens showed that the enteric neurons were significantly decreased only in the submucosal plexus of patients (P<0.0001 vs controls), whereas the enteric glial cells of constipated patients were reduced in both the myenteric (P=0.018 vs controls) and the submucosal plexus (P=0.004 vs controls). No difference between patients and controls were found concerning c-Kit and CD34 expression, and the number of apoptotic neurons. These findings support the concept that at least a subgroup of patients with obstructed defecation and severe, intractable symptoms display abnormalities of the enteric nervous system, mostly related to the enteric glial cells. These findings might explain some of the pathophysiological abnormalities, and help to better understand this condition.

Is pseudomelanosis coli a marker of colonic neuropathy in severely constipated patients

Aims:  To study relationships between the number of pseudomelanosis coli cells and that of colonic enteric neurons and interstitial cells of Cajal, which are significantly reduced compared with controls in severely constipated patients. Pseudomelanosis coli is frequent in patients using anthraquinone laxatives. It is not known whether the prolonged use of these compounds damages the enteric nervous system in constipated patients.

Prognostic Variables for Cancer-Related Survival in Node-Negative Colorectal Carcinomas

Background/Aim: The efficacy of adjuvant treatment in node-negative colorectal carcinoma is unproven. The purpose of this study was to analyze the prognostic value of routinely detectable clinicopathological variables in order to identify subgroups of node-negative colorectal cancer patients at a high risk of a recurrence. Methods: Seventy-three patients who did not receive radio- or chemotherapy were selected among 112 node-negative colorectal cancer patients who underwent curative resection. Follow-up was a minimum of 5 years or until death. The influence of 17 demographic, clinical, and pathological variables on the 5-year cancer-related survival was assessed using univariate and multivariate analyses. Results: The compliance with follow-up was 99%. The 5-year survival rate was 81%. Univariate analysis showed that T4 lesions (p < 0.001), age >70 years (p = 0.008), lymphatic invasion (p = 0.001), and neural invasion (p = 0.02) were significantly associated with a decreased survival. T4 stage (hazard ratio 12.75, p < 0.001) and age >70 (hazard ratio 3.08, p = 0.04) significantly affected the cancer-related survival on multivariate analysis. Conclusions: Node-negative colorectal cancer patients with T4 carcinoma or those aged over 70 years have a higher risk of recurrences after resection. They should receive adjuvant or neoadjuvant treatment compatible with their performance status.

Preoperative predictors of sternotomy need in mediastinal goiter management

The objective of this study was to identify the preoperative risk factors for patients in need of a sternotomy in the management of mediastinal goiters in order to provide better preoperative planning and patient consent.