Radiomics: a new tool to differentiate adrenocortical adenoma from carcinoma.

BACKGROUND: The main challenge in the management of indeterminate incidentally discovered adrenal tumours is to differentiate benign from malignant lesions. In the absence of clear signs of invasion or metastases, imaging techniques do not always precisely define the nature of the mass. The present pilot study aimed to determine whether radiomics may predict malignancy in adrenocortical tumours. METHODS: CT images in unenhanced, arterial, and venous phases from 19 patients who had undergone resection of adrenocortical tumours and a cohort who had undergone surveillance for at least 5 years for incidentalomas were reviewed. A volume of interest was drawn for each lesion using dedicated software, and, for each phase, first-order (histogram) and second-order (grey-level colour matrix and run-length matrix) radiological features were extracted. Data were revised by an unsupervised machine learning approach using the K-means clustering technique. RESULTS: Of operated patients, nine had non-functional adenoma and 10 carcinoma. There were 11 patients in the surveillance group. Two first-order features in unenhanced CT and one in arterial CT, and 14 second-order parameters in unenhanced and venous CT and 10 second-order features in arterial CT, were able to differentiate adrenocortical carcinoma from adenoma (P < 0.050). After excluding two malignant outliers, the unsupervised machine learning approach correctly predicted malignancy in seven of eight adrenocortical carcinomas in all phases. CONCLUSION: Radiomics with CT texture analysis was able to discriminate malignant from benign adrenocortical tumours, even by an unsupervised machine learning approach, in nearly all patients.

Pelvic floor rehabilitation for defecation disorders.

Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.

INPP4B overexpression and c-KIT downregulation in human achalasia.

BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. METHODS: Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the "edgeR" option of R-Bioconductor. Data were validated by real-time RT-PCR, western blotting and immunohistochemistry. KEY RESULTS: Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P ≤ 10-3 . Nine genes with a P ≤ 10-4 were further validated. CYR61, CTGF, c-KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c-KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho-Akt was significantly reduced in achalasia patients vs controls. CONCLUSIONS & INFERENCES: The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia.

Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation.

BACKGROUND: Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson's disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls. METHODS: Twenty-nine PD/CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts from PD/CC, CC, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors were also assessed. KEY RESULTS: Four subgroups of PD/CC patients were identified: delayed colonic transit plus altered anorectal manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%); and no transit and manometric impairment (9%). There were no differences in the number of neurons/ganglion between PD/CC vs CC or vs controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs controls (P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced in PD/CC vs CC and controls (P<.05). CONCLUSIONS AND INFERENCES: Colonic motor and rectal sensory functions are impaired in most PD/CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory-motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute to PD/CC pathophysiology.

Mild to moderate increase of serum calcitonin levels only in presence of large medullary thyroid cancer deposits.

Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome.

Functional significance of the novel H-RAS gene mutation M72I in a patient with medullary thyroid cancer.

Medullary thyroid cancer (MTC) accounts for around 5-10% of all thyroid cancers. Though usually sporadic, 1 in 4 cases are of genetic origin, with germinal mutations in the RET proto-oncogene in familial forms and somatic mutations both in RET and in the RAS family genes in sporadic ones.This study aimed to characterize a rare H-RAS sequence variant -M72I- in a patient with sporadic MTC, focusing on its functional significance.Mutation analysis was performed for the RET, N-RAS, K-RAS and H-RAS genes by direct sequencing. Western blot analysis was done on 4 thyroid tissues from 1 patient carrying the M72I mutation in H-RAS, 1 with the Q61R mutation in H-RAS, 1 with no RET, H-RAS, K-RAS or N-RAS gene mutations, and 1 normal thyroid, using different antibodies against Erk1/2, phospho-Erk1/2 (Thr202/Tyr204), Akt and phospho-Akt (Ser473). Large-scale molecular dynamics simulations were completed for H-RAS wt and H-RAS M72I.Western blot analysis demonstrated that both MAPK and PI3K/Akt pathways were activated in the MTC patient carrying the M72I variant. In silico results showed conformational changes in H-RAS that could influence its activation by Sos and phosphate binding. Results of molecular dynamics were consistent with Western blot experiments.The M72I mutation may contribute effectively to proliferation and survival signaling throughout the MAPK and PI3K/Akt pathways. This work underscores the importance of studying genetic alterations that may lead to carcinogenesis.

99Tc nanocolloid sentinel node procedure in papillary thyroid carcinoma: our mono-institutional experience on a large series of patients.

The sentinel lymph node was defined as the first lymph node to receive drainage from a primary cancer. The aims of this study were to investigate the efficacy of radiocolloid lymphoscintigraphy and of the hand-held gamma probe procedure for sentinel lymph node biopsy in papillary thyroid carcinoma and to evaluate these results in clinical staging. A total of 99 consecutive papillary thyroid carcinoma patients entered the study. Patients underwent radiocolloid lymphoscintigraphy before surgery. Intra-operative sentinel lymph node localization was performed using a hand-held gamma probe. Patients were observed at follow-up at 2 and 6 months and, thereafter, yearly. Sequential lymphoscintigraphy was able to identify at least one sentinel lymph node in 98/99 cases (99%), using intra-operative hand-held gamma probe, the surgeon was able to detect at least one sentinel lymph node in all cases. Sentinel lymph node metastases were diagnosed in 49%. Overall, 79 patients underwent ablative (131)I therapy. The median value of thyroglobulin in N0 vs. N1 patients was 1 ng/ml vs. 1.9 ng/ml (p = 0.03) and 0.2 ng/ml vs. 1 ng/ml (p = 0.001) before and after (131)I therapy, respectively. The pre-operative lymphoscintigraphy and the intra-operative gamma probe offer significant advantages over the vital dye technique, described in our previous experience. The rate of nodal involvement (49%) is very high considering that no patients had clinically palpable nodes or suspected at echography. (131)I whole body scan and thyroglobulin measurements confirmed sentinel lymph node in papillary thyroid carcinoma as a reliable procedure. In patients classified N0, by sentinel lymph node biopsy, ablative (131)I therapy could be avoided.

Cost-effectiveness of different diagnostic strategies to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough in Italy.

BACKGROUND: Chronic persistent cough is a common and disabling disorder and gastro-oesophageal reflux disease is considered to be the third leading cause, after asthma and postnasal drip. Therefore, patients with unexplained chronic persistent cough usually undergo a stepwise evaluation to establish the existence of a reflux disease. AIM: To identify the most cost-effective diagnostic approach to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough. METHODS: Direct and indirect costs associated with six diagnostic strategies using 24-h oesophageal pH-metry, oesophago-gastroduodenoscopy and the proton pump inhibitors test in different sequences, were evaluated using a decision tree model. If the first test was positive, the diagnostic work-up was stopped, if negative the patient proceeded to the second test, and so on. Clinical data from an observational prospective trial conducted in 51 patients with unexplained chronic persistent cough were used in the economic model. RESULTS: All six strategies had the same clinical effectiveness (78.4%). The diagnostic work-up with the lowest cost was the proton pump inhibitors test followed by pH-metry and then oesophago-gastroduodenoscopy with a total cost of euro 211.08 (direct euro 142.93, indirect euro 68.15). CONCLUSIONS: This study shows that the lowest cost is the strategy where proton pump inhibitors test is performed as first investigation. Implementation of this diagnostic work-up may lead to cost savings in the management of patients with chronic persistent cough.

The role of ultrasound in the differential diagnosis of serous and mucinous cystic tumours of the pancreas.

OBJECTIVE: To evaluate the usefulness of a series of ultrasound parameters in the differential diagnosis between serous and mucinous forms of cystic tumours of the pancreas. SETTING: Retrospective comparative study between the histological analysis of surgical specimens from cystic tumours of the pancreas (4 serous cystadenomas, 6 mucinous cystadenomas and 11 mucinous cystadenocarcinomas) and ultrasound evaluation. METHODS: The ultrasound images of the 21 tumours were analysed by an operator who did not know the result of the histological diagnosis and were divided according to Johnson's criteria (number of cysts > 6 and diameter < 2 cm for serous tumours; number of cysts <6 and diameter >2cm for mucinous tumours) and according to other anatomicopathological parameters such as the presence of septae, endocystic projections, central scar, central calcification and/or in the tumour wall. RESULTS: The ultrasound study gave a correct diagnosis in two out of the four (50%) serous cystic tumours. A central scar and internal calcification was present in one of them. Fifteen (88.2%) of the 17 mucinous tumours were correctly diagnosed; one presented peripheral calcifications and three endocystic projections. CONCLUSION: Ultrasound has a high degree of sensitivity in the differential diagnosis of serous and mucinous cystic tumours of the pancreas if the ultrasound aspects corresponding to the anatomicopathological structure of the neoplasms are correctly evaluated.

Endoscopic ultrasonography in the diagnosis of gastrointestinal amyloid deposits: clinical case report.

A case of systemic amyloidosis of the digestive tract is described here, with particular attention to the endoscopic ultrasonography aspects, characterized by a wide-spread thickening of the stomach and rectum walls, with loss of the normal layer structure of the mucosa and submucosa. Endoscopic ultrasonography, especially in pseudotumoral forms, may contribute to the differential diagnosis from neoplastic lesions, in which the wall thickening appears to be localized and accompanied by parietal infiltration.

DNA analysis with flow cytometry and image cytometry in colorectal polyps.

Ploidy was studied with flow and image cytometry in 51 polyps removed endoscopically from 44 patients. Evaluation was carried out on frozen material in 34 cases and on material fixed in formalin and embedded in paraffin in the remaining 17. Data analysis showed a statistically significant correlation between polyp size and aneuploidy frequency (P > 0.05). No statistically significant correlation was found between aneuploidy frequency and histological type. The linear correlation study did, however, show a correlation tendency between histological type and aneuploidy (R = 0.42211).

Histiocytoid hemangioma with prominent fingernail involvement.

Only 2 cases of histiocytoid hemangioma localized in the nail apparatus have been reported in the literature. We describe here a patient affected by multiple histiocytoid hemangiomas involving the 3rd right digit and fingernail. The pathological features were typical for a diagnosis of histiocytoid hemangioma showing vascular proliferation characterized by enlarged endothelial cells associated with inflammatory cells. Phenotypic characterization of the proliferating cells confirmed their vascular origin.

5-Aminosalicylic acid suppositories in the management of ulcerative colitis.

5-aminosalicylic acid (5-ASA) suppositories have been used in the author's out-patient clinic in Bologna for the treatment of distal ulcerative colitis (UC). One hundred fifty-six patients with mild or moderate attacks of UC were treated using different protocols for controlling active disease. Improvement was observed in 88.5 percent of the therapeutic cycles after one month. A small preliminary maintenance study using only 400-mg suppositories of 5-ASA twice a day for 6 or 12 months showed a remission percentage similar to salicylazosulfapyridine (SASP).

5-Aminosalicylic acid in patients with ulcerative colitis in remission: plasma levels after administration of a new rectal enema.

Plasma levels of total 5-aminosalicylic acid (5-ASA) were determined after a single administration of 2 g and 4 g 5-ASA enemas to 6 patients with ulcerative colitis. The mean plasma levels and AUC values confirmed that the active substance is poorly absorbed by rectal route.