Neuroprotective role of phosphoserine in primary open-angle glaucoma patients.

OBJECTIVE: To evaluate the neuroprotective role of phosphoserine (P-Ser) in primary open-angle glaucoma (POAG) patients and to compare its therapeutic effectiveness to placebo treatment. PATIENTS AND METHODS: Fifty-one patients (24 males and 27 females) between 35 and 61 years (average 46 years ± 3.8 SD) affected by POAG were enrolled in this study. Patients were divided in two groups: group A included 28 subjects that received an oral P-Ser treatment for 12 months; and group B included 23 subjects that received an oral placebo treatment for 12 months. Complete ophthalmological examination, standard automated perimetric examination, analysis of ON fibers via scanning laser polarimetry and glaucoma staging was performed in all patients at enrolment and 1, 3, 6, and 12 months after. Statistical analysis was performed using STATA 14.0 (Collage Station, TX, USA). RESULTS: Mean deviation (MD) and pattern standard deviation (PSD) analysis by means of 30-2 full threshold of the visual fields (VFs), retinal nerve fiber layer (RNFL) thickness by means of GDx, and IOP were considered to evaluate P-Ser therapy effectiveness in both groups. A statistically significant improvement (p<0.05) in VF, RNFL thickness and IOP compared to pre-treatment was found in patients in group A. CONCLUSIONS: Our study shows a significant improvement in several variables in patients with glaucoma treated with P-Ser compared to placebo and suggests a potential neuroprotective effect of P-Ser in treating glaucoma patients in association with the traditional hypotonic topical therapy.

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.

Prevalence and clinical picture of gastroesophageal prolapse in gastroesophageal reflux disease.

The prevalence of gastroesophageal (GE) mucosal prolapse in patients with gastroesophageal reflux disease (GERD) was investigated as well as the clinical profile and treatment outcome of these patients. Of the patients who were referred to our service between 1980 and 2008, those patients who received a complete diagnostic work-up, and were successively treated and followed up at our center with interviews, radiology studies, endoscopy, and, when indicated, esophageal manometry and pH recording were selected. The prevalence of GE prolapse in GERD patients was 13.5% (70/516) (40 males and 30 females with a median age of 48, interquartile range 38-57). All patients had dysphagia and reflux symptoms, and 98% (69/70) had epigastric or retrosternal pain. Belching decreased the intensity or resolved the pain in 70% (49/70) of the cases, gross esophagitis was documented in 90% (63/70) of the cases, and hiatus hernias were observed in 62% (43/70) of the cases. GE prolapse in GERD patients was accompanied by more severe pain (P < 0.05) usually associated with belching, more severe esophagitis, and dysphagia (P < 0.05). A fundoplication was offered to 100% of the patients and was accepted by 56% (39/70) (median follow up 60 months, interquartile range 54-72), which included two Collis-Nissen techniques for true short esophagus. Patients who did not accept surgery were medically treated (median follow up 60 months, interquartile range 21-72). Persistent pain was reported in 98% (30/31) of medical cases, belching was reported in 45% (14/31), and GERD symptoms and esophagitis were reported in 81% (25/31). After surgery, pain was resolved in 98% (38/39) of the operative cases, and 79% (31/39) of them were free of GERD symptoms and esophagitis. GE prolapse has a relatively low prevalence in GERD patients. It is characterized by epigastric or retrosternal pain, and the need to belch to attenuate or resolve the pain. The pain is allegedly a result of the mechanical consequences of prolapse of the gastric mucosa into the esophagus.

Comparison between subjective and objective assessment of the long-term results after the Heller-Dor operation in patients affected by oesophageal achalasia.

INTRODUCTION: Nowadays the subjective assessment of Health-Related Quality of Life after surgery for achalasia is often associated with the instrumental methods in order to evaluate long-term results of therapy. AIMS: To assess the long-term objective and subjective results of the surgical treatment of achalasia and to study the correlation between clinical-instrumental methods and those based on the patient's self-assessment and on Health-Related Quality of Life questionnaires. METHODS: One hundred and twenty-four patients consecutively submitted to trans-abdominal Heller-Dor operation were periodically followed up with clinical examination, endoscopy, barium swallow and manometry. The Health-Related Quality of Life was assessed using the 36 item short form (SF-36) and the Psychological General Well-Being Index questionnaire. The statistical comparison between the results of the self-assessment questionnaires and the long-term clinical-instrumental result was calculated by means of linear regression analysis. RESULTS: Over the years, 123 patients underwent at least one complete clinical-instrumental check-up and filled the self-assessment questionnaires. Mean follow-up was 105 months (range 12-288) with a median of 82.5 months. The result of the surgery was considered satisfactory in 93.5% of the patients, while the reflux oesophagitis observed in 6.5% of the cases was the main cause of failure. Clinical scores for dysphagia and for gastro-oesophageal reflux symptoms were significantly reduced after surgery. The results of the SF-36 and Psychological General Well-Being Index questionnaires were in our population very high and clinical correlation (p<0.05) emerged in physical function, in role physical, in mental health and in vitality domains of SF-36 questionnaire, and in self-control and general health scales of Psychological General Well-Being Index questionnaire. CONCLUSIONS: Health-Related Quality of Life questionnaires can be considered valid aids in evaluating surgical results, but the clinical-instrumental evaluation remains the cardinal point of every long-term assessment in order to diagnose complications, the disease-related conditions of the patient and to acquire reliable data on which scientific discussion can be based.

Review article: indications for anti-reflux surgery in gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GERD) is a complex multifactorial disorder whose treatment is based on knowledge of its pathophysiology, natural history and evolution. Recently the relationship between the severest degrees of cardial incontinence and hiatus hernia has been emphasized, which causes the impairment of the mechanical properties of the gastro-oesophageal barrier and of oesophageal acid clearing. Among different types of hiatus hernia, those characterized by the permanent axial orad migration of the oesophago-gastric (EG) junction (nonreducible hiatus hernia) are correlated with severe GERD. Barium swallow may adequately differentiate hiatal insufficiency, concentric hiatus hernia and short oesophagus which are the steps of migration across or above the diaphragm. When associated with panmural oesophagitis and fibrosis of the oesophageal wall, these conditions may be the cause of recurrence of hiatus hernia and reflux after laparoscopic standard anti-reflux surgical procedures; in the presence of nonreducibility of the EG junction below the diaphragm without tension, dedicated surgical procedures are necessary. It is currently agreed that surgical therapy is indicated for patients affected by severe GERD who are not compliant with long-term medical therapy, require high dosages of drugs and are too young for lifetime medical treatment. While the existence of severe GERD correlated with an irreversible anatomical disorder represents an elective indication for surgery, warrants further investigation. Accurate identification of the functional and anatomical abnormalities underlying GERD is mandatory in order to decide whether medical or surgical therapy should be implemented, and to tailor the surgical technique, laparoscopic or open, to each patient.

[Role of videofluorography in the study of esophageal motility disorders]. / Ruolo della videofluorografia nello studio dei disordini della motilità esofagea.

PURPOSE: To repropose the importance of videofluoroscopy in the study of esophageal motor disorders, comparing the radiologic and manometric results; the manometric results are considered the reference parameters. MATERIAL AND METHODS: From 1996 to 1999, 76 patients (42 males and 34 females), were studied first using manometry and then videofluoroscopy. The patients had symptoms like dysphagia, thoracic pain or both. The manometric study was performed with a perfusional system equipped with 6 tips (4 radial for the study of the esophageal sphincters and 2 placed longitudinally for the study of the esophageal peristalsis). With the patient in a supine position we analysed 5-10 deglutitions with 5 ml water bolus at 20-25 degrees C, administered using a graduated syringe. The radiologic study was performed with a remote-control digital television system, connected to a video recorder. Three 7.5 ml bolues of high density barium suspension (250% weight/volume) were injected orally in the upright position and other three were injected in the prone position following the passage from the oral cavity to the stomach. RESULTS: The comparison of the manometric and videofluoroscopic results suggests that the total sensitivity of the radiological study in the detection of esophageal motor disorders was 92%. In particular dynamic radiologic investigation diagnosed the normal esophageal functionality in 100% of the cases, nonspecific esophageal motility disorders in 89.6%, diffuse esophageal spasm in 100% of the cases, the presence of achalasia in 90%, whereas "nutcraker esophagus" only in 50%. Videofluoroscopy therefore showed high sensitivity in four groups of the five considered. It has some limitations in the diagnosis of initial achalasia, and is not sufficiently sensitive in the diagnosis of "nutcracker esophagus". CONCLUSIONS: Videofluoroscopy is a simple method which presents high sensitivity and specificity in the detection of motility disorders of the esophagus and could therefore be proposed as the first diagnostic method in patients with specific symptoms.

[Pulmonary metastasis of malignant peritoneal mesothelioma. Review of the literature and a case report]. / Metastasi polmonari da mesotelioma maligno peritoneale. Revisione della letteratura in riferimento ad un caso clinico.

The authors describe the clinical case of a 54 year old patient, affected by malignant peritoneal mesothelioma treated by chemotherapy, who subsequently developed a lung lesion, treated by surgical wedge resection. The histologic examination of the surgical specimen, which led to the diagnosis of an intraparenchymal necrotic focus, confirms the favourable result of the adjuvant therapy. A review of the literature showing the rarity of lung metastases from malignant peritoneal mesothelioma is presented.

Unsuspected carcinoma of the gall bladder: case report of trocar-site metastasis following laparoscopic cholecystectomy.

Cancer of the gall bladder is a rare malignant neoplasm with an unfavourable prognosis. Laparoscopic surgery has brought about the emergence of possible neoplastic diffusion along trocar tracts in cases where unrecognized carcinoma of the gall bladder is present. The authors present a case of neoplastic abdominal diffusion discovered 4 months after laparoscopic cholecystectomy in which histologic examination of the surgical specimen revealed the presence of unrecognized carcinoma of the gall bladder.

Bile duct hamartomas: diagnostic problems and treatment.

Biliary hamartomas are rare, benign malformations of the biliary tract, usually discovered at autopsy or erroneously confused with metastasis or other cystic hepatic lesions. For these reasons it is necessary to consider them in the differential diagnosis. The authors describe three cases of biliary hamartoma in which the definitive diagnosis was obtained only with the use of histologic examination which represents the only means available that can draw conclusions about the real nature of this lesion.

Papillary cystic neoplasm of the pancreas: a description of two clinical cases.

Papillary-cystic neoplasm of the pancreas is a rare neoplasm principally effecting women in the 2nd and 3rd decades of life. It is considered a low grade malignancy due to it's favourable prognosis and the rarity of metastatic diffusion. Pre-operative diagnosis is rare due to the similarity with other cystic pancreatic lesions. It is for this reason that definitive diagnosis is made at histologic examination of the surgical specimen and total surgical excision represents the therapy of choice. The authors herein describe 2 cases of papillary-cystic neoplasm of the pancreas, thus bringing the total number of cases reported in the world literature to 294.

[Congenital duplication of the gallbladder. A rare case of a trabecular gallbladder]. / Duplicazione congenita della colecisti. Un raro caso di colecisti trabecolare.

Duplication of the gallbladder is a congenital anomaly of rare preoperative diagnostic finding, which could be present in an asymptomatic or symptomatic form. The authors report a case of double gallbladder, which becomes clinically manifest through repeated biliary colics. The preoperative diagnostic procedures did not reveal the malformation, but only the presence of lithiasis in one of the gallbladders, in the common bile duct and, for an anomalous insertion of the cystic duct, a suspect cancer of the distal choledochus.