Association of quantitative MRI-based radiomic features with prognostic factors and recurrence rate in oropharyngeal squamous cell carcinoma.

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.

Postoperative outcome after oesophagectomy for cancer: Nutritional status is the missing ring in the current prognostic scores.

BACKGROUND: Several prognostic scores were designed in order to estimate the risk of postoperative adverse events. None of them includes a component directly associated to the nutritional status. The aims of the study were the evaluation of performance of risk-adjusted models for early outcomes after oesophagectomy and to develop a score for severe complication prediction with special consideration regarding nutritional status. METHODS: A comparison of POSSUM and Charlson score and their derivates, ASA, Lagarde score and nutritional index (PNI) was performed on 167 patients undergoing oesophagectomy for cancer. A logistic regression model was also estimated to obtain a new prognostic score for severe morbidity prediction. RESULTS: Overall morbidity was 35.3% (59 cases), severe complications (grade III-V of Clavien-Dindo classification) occurred in 20 cases. Discrimination was poor for all the scores. Multivariable analysis identified pulse, connective tissue disease, PNI and potassium as independent predictors of severe morbidity. This model showed good discrimination and calibration. Internal validation using standard bootstrapping techniques confirmed the good performance. CONCLUSIONS: Nutrition could be an independent risk factor for major complications and a nutritional status coefficient could be included in current prognostic scores to improve risk estimation of major postoperative complications after oesophagectomy for cancer.

Shorter myotomy on the gastric site (≤2.5 cm) provides adequate relief of dysphagia in achalasia patients.

The right length of the myotomy on the gastric side for esophageal achalasia is still a debated issue. We aimed to investigate the final outcome after classic myotomy (CM) as compared with a longer myotomy on the gastric side (LM) in two cohorts of achalasia patients. Forty-four achalasia patients who underwent laparoscopic Heller-Dor were considered; patients with a sigmoid-shaped esophagus were excluded. Symptoms were scored using a detailed questionnaire for dysphagia, regurgitation, and chest pain. Barium swallow, endoscopy, and esophageal manometry were performed before and 6 months after the surgical treatment; 24-hour pH-monitoring was also performed 6 months after the procedure. CM was defined as a gastric myotomy length in the range of 1.5-2.0 cm, while LM was 2.5-3 cm in length. The surgical treatment (CM or LM) was adopted in two consecutive cohorts. Treatment failure was defined as a postoperative symptom score >10th percentile of the preoperative score (i.e. >8). Of the 44 patients representing the study population, 20 had CM and 24 had LM. The patients' demographic and clinical parameters (age, sex, symptom score, duration of symptoms, esophageal diameter, and manometric pattern) were similar in the two groups. The median follow up was 24 months (interquartile range 12-39). One patient in each group was classified as a treatment failure. After the treatment, there was a significant decrease in both groups' symptom score, and resting and residual pressure (P < 0.01), with no statistically significant differences between the two groups in terms of postoperative symptom score, resting and residual pressure, or total and abdominal lower esophageal sphincter length and esophageal diameter. Extending the length of the myotomy on the gastric side does not seem to change the final outcome of the laparoscopic Heller-Dor procedure.

Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma-a pilot study.

BACKGROUND: To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. METHODS: We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent computed tomography-based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. RESULTS: All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. CONCLUSIONS: In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

Programmed cell death 4 nuclear loss and miR-21 or activated Akt overexpression in esophageal squamous cell carcinogenesis.

The programmed cell death 4 (PDCD4) tumor suppressor is down-regulated in several malignancies, and the (subcellular) expression of its protein product is modulated by both oncomiR miR-21 and protein kinase B (Akt). PDCD4 and activated Akt (phosphorylated Akt [pAkt]) expression were assessed immunohistochemically in 53 tissue samples obtained from 25 endoscopic esophageal mucosal resections performed for squamous intraepithelial neoplasia (IEN) or squamous intramucosal carcinoma (IM-SSC). In total, 33 IEN (low-grade = 15; high-grade = 15) and 20 IM-SSC specimens were considered; 50 additional tissue samples of histologically proven normal esophageal mucosa were considered as normal controls. To further validate the results achieved, miR-21 expression (as assessed by quantitative real-time polymerase chain reaction and in situ hybridization) was tested in another series of 15 normal esophageal tissue samples, 15 high-grade IEN, and 15 IM-SCCs. Normal suprabasal squamous epithelial layers consistently featured strong PDCD4 nuclear immunostaining, which was significantly lower (P < 0.001) in IEN (both low-and high-grade) and in IM-SSC. Conversely, pAkt and miR-21 expression was significantly up-regulated in the whole spectrum of preneoplastic/neoplastic lesions considered. PDCD4 down-regulation, as assessed by immunohistochemistry, is a reliable biomarker of early-stage squamous cell esophageal neoplasia, providing additional information in the histological assessment of these lesions.

A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone. METHODS: We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR). RESULTS: In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD. CONCLUSIONS: Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.

A new endoscopic technique for suspension of esophageal prosthesis for refractory caustic esophageal strictures.

There is no clear consensus concerning the best endoscopic treatment of benign refractory esophageal strictures due to caustic ingestion. Different procedures are currently used: frequent multiple dilations, retrievable self-expanding stent, nasogastric intubation and surgery. We describe a new technique to fix a suspended esophageal silicone prosthesis to the neck in benign esophageal strictures; this permits us to avoid the frequent risk of migration of the expandable metallic or plastic stents. Under general anesthesia a rigid esophagoscope was placed in the patient's hypopharynx. Using transillumination from the optical device, the patient's neck was pierced with a needle. A n.0 monofilament surgical wire was pushed into the needle, grasped by a standard foreign body forceps through the esophagoscope and pulled out of the mouth (as in percutaneous endoscopic gastrostomy procedure). After tying the proximal end of the silicone prosthesis with the wire, it was placed through the strictures under endoscopic view. This procedure was successfully utilized in four patients suffering from benign refractory esophageal strictures due to caustic ingestion. The prosthesis and its suspension from the neck were well-tolerated until removal (mean duration 4 months). A postoperative transitory myositis was diagnosed in only one patient. One of the most frequent complications of esophageal prostheses in refractory esophageal strictures due to caustic ingestion is distal migration. Different solutions were proposed. For example the suspension of a wire coming from the nose and then fixed behind the ear. This solution is not considered optimal because of patient complaints and moreover the aesthetic aspect is compromised. The procedure we utilized in four patients utilized the setting of a silicone tube hanging from the neck in a way similar to that of endoscopic pharyngostomy. This solution is a valid alternative both for quality of life and for functional results.

Refinement of a transplantation project in the non-human primate by the use of a humane endpoint.

An assessment scheme was developed to establish a humane endpoint in a pig-to-primate renal xenotransplantation project, with a view to minimizing and controlling any pain or suffering conditions in the animals involved while still achieving the scientific objective. In particular, the assessment criteria for identifying the earliest endpoint are described, bearing in mind both the researcher's need to obtain top-quality data and the ethical need to safeguard the animals. The scheme should also be applicable to other experiments involving non-human primates (e.g. allotransplantation, survival after major surgery, pharmacological safety tests) because it considers reproducible general parameters together with aspects specific to each experimental model.

An update on xenotransplantation.

Xenotransplantation is one of the possible avenues currently being explored to address the shortage problem of human organs. With this in mind, this article will briefly review the current situation with respect to the immunological, physiological and biosafety aspects related to the transplantation of pig organs into primates. Acute humoral xenograft rejection (AHXR) currently remains the central immunological obstacle and the development of strategies for both a better control of the elicited anti-pig humoral immune response or the prevention of the onset of coagulation disorders that accompany AHXR are the two primary focuses of research. To date, porcine xenografts have been shown to sustain the life of nonhuman primates for several months. Such preclinical studies have also demonstrated the absence of insurmountable physiological incompatibilities between pig and primate. In addition, reassuring findings regarding biosafety aspects have been generated and pro-active research aimed at the identification of an organ source with a higher safety profile is also underway. These advancements, in conjunction with ongoing research in pig genetic engineering, immunosuppression and tolerance are expected to further extend the survival of porcine xenografts transplanted into primates. However, until further physiological, efficacy and safety data are generated in relevant primate models, clinical xenotransplantation should not be considered.

Pseudoachalasia: not only esophago-gastric cancer.

Pseudoachalasia is a rare clinical entity which has clinical, radiographic and manometric features often indistinguishable from achalasia. A small primary adenocarcinoma arising at the gastroesophageal junction or a tumor of the distal esophagus are the most frequent causes. Rarely, processes other than esophagogastric cancers may lead to the development of pseudoachalasia. We present three cases of pseudoachalasia in which the primary cause of the disease was not an esophagogastric cancer. The causes were a pancreatic carcinoma, a breast cancer and an histiocytosis X. Aspects of these three patients' diagnostic and therapeutic course are discussed in detail.

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer.

This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m(-2), cisplatin 75 mg m(-2) on day 1 and fluorouracil 750 mg m(-2) day(-1) on days 2-5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m(-2) week(-1) for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week(-1)). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2-66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1-12.4), and the 1- and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3-4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified.

Minimally invasive enucleation of esophageal leiomyoma.

BACKGROUND: Leiomyoma accounts for 70% of all benign tumors of the esophagus. Open enucleation via thoracotomy has long been the standard procedure, but thoracoscopic and laparoscopic approaches have recently emerged as interesting alternatives. To date, only case reports or very small series of such techniques have been reported. The authors report their experience over the past decade. METHODS: Between January 1999 and August 2005, 11 patients (6 men and 5 women; median age, 44 years) underwent surgery after presenting with dysphagia, chest pain, or heartburn. The surgical approaches included right video-assisted thoracoscopy (n = 7) for tumors of the middle lower third of the esophagus and laparoscopy (n = 4) for tumors within 4 to 5 cm of the lower esophageal sphincter or located at the gastroesophageal junction (GEJ). Intraoperative endoscopy with air insufflation during enucleation was used to confirm mucosal integrity and safeguard against esophageal perforation. Reapproximation of the muscle layers was performed after tumor enucleation to prevent the development of a pseudodiverticulum. A Nissen or Toupet fundoplication was added for patients undergoing laparoscopic enucleation of the leiomyoma. RESULTS: The median operative time was 150 min. All tumors were benign leiomyomas (median size, 4.5 cm). One leiomyoma located at the gastroesophageal junction required intraoperative mucosal repair with three stitches for an esophageal perforation (preoperative biopsies had been taken). There were no major morbidities, including deaths or postoperative leaks. The median postoperative hospital stay was 6 days. All the patients were free of dysphagia during a median followup period of 27 months. One patient had a small (< 2 cm) asymptomatic pseudodiverticulum at the 6-month follow-up endoscopy. CONCLUSIONS: Video-assisted enucleation of esophageal leiomyoma can be performed effectively and safely with no mortality and low morbidity. Thoracoscopic and laparoscopic techniques for the removal of esophageal leiomyomas may be recommended as the treatment of choice in centers experienced with minimally invasive surgery.

Endoscopic treatment of pseudosarcomatous squamous carcinoma of the esophagus: case report and personal experience.

Spindle cell (or pseudosarcomatous) squamous carcinoma (PSC) is a rare malignant neoplasm of the esophagus, potentially capable of causing lymph node and distant metastases. Indications for surgery are the same as for squamous cell carcinoma (SCC) of the esophagus. The aims of this paper were to report a case of endoscopically treated PSC and to review our experience of surgically-treated patients with PSC in order to identify patients potentially suitable for endoscopic treatment. In our series of 4,460 patients with carcinoma of the esophagus observed between 1980 and 2003, 28 (0.6%) had the histological features of PSC. One had a PSC histologically confirmed (8cm-long polyp with a 3cm-large base) and endoscopically treated for high surgical risk. The patient had a close follow-up with endoscopic biopsies and ultrasonography with no local recurrence at 3 years. The overall survival rate was 22% for PSC and 17% for SCC (P = n.s.); after 5 years, the survival rates were 22% and 13%, respectively (P = n.s.). In our opinion the limited tendency to parietal infiltration and the good chance of disclosure in an early stage with endoscopic ultrasonography, justify non-surgical solutions in patients with a high surgical risk, possibly associated with adjuvant chemo- and radiotherapy since lymph node involvement is reported in 50% of cases. The limited number of patients with PSC involved in the present series prevent any significant statistical comparisons between the different groups, but the survival rates were roughly the same in the nonsurgical curative therapy as in the curative resection group, while the chances of survival were significantly lower in patients given palliative surgery and or non-curative treatments (P < 0.05).

Single-band mucosectomy for granular cell tumor of the esophagus: safe and easy technique.

BACKGROUND: Mucosectomy involves resection of a digestive wall fragment that frequently removes a part or even all of the submucosal mass. The single-band mucosectomy technique was used to remove a granular cell tumor (GCT) of the esophagus. Only 3% of GCTs, which are relatively uncommon neoplasms, arise in the esophagus. Ultrasonography has allowed for more frequent recognition and better definition of this disease. Until recently, surgical resection of the esophagus has been the only treatment alternative to endoscopic surveillance. Endoscopic techniques such as mucosal resection (EMR), laser, and argon plasma have been proposed as safe and effective alternatives to surgery. However, to date, only a few reports of these endoscopic techniques have been published. This study aimed to evaluate the safety and feasibility of single-band mucosectomy for removing a GCT of the esophagus. METHODS: Six patients (1 man and 5 women; mean age, 45 years) with a GCT were studied between January 2000 and May 2004. They underwent EMR after endoscopic ultrasonography. RESULTS: The EMR was performed with a diathermic loop after injection of saline solution into the esophageal wall. Only one session was necessary for removal of the tumor from all 6 patients, and no complication was observed. During a mean clinical endoscopic follow-up period of 36 months, no recurrences, scars, or stenoses were observed. CONCLUSIONS: These findings show EMR to be a safe and effective technique that allows complete removal of GCTs. Furthermore, this technique provides tissue for a definitive pathologic diagnosis, which laser and argon plasma do not provide. We recommend EMR as the treatment of choice for GCTs after an accurate ultrasonographic evaluation.

Changing attitude to organ donation and transplantation in university students during the years of medical school in Italy.

UNLABELLED: The shortage of organ donations is a major limiting factor in transplant programs. Since a favorable attitude of health professionals to organ donation can positively influence the decision of families of potential donors, educating physicians early in their careers may become crucial in this setting. The aim of this study was to compare medical student opinions on organ donation and transplantation at different stages in their undergraduate career. METHODS: Medical students were prospectively surveyed in their first and fourth years by an anonymous 10-item questionnaire. RESULTS: The 100 of 195 (51.3%) students completed both questionnaires including 29 men, of an overall cohort mean age 23.7 (range, 22-32 years). 91% of the students had attended classical or scientific high school and 83% were Catholic. Their attitude to transplantation remained strongly positive (96% vs 92%, fourth vs first year). 96% of the fourth year students would accept an human donor organ or an artificial organ (vs 95% of first year) and 91% would accept an animal organ (vs 84%). The students showed a positive attitude to organ donation (96% vs 91%, fourth vs first year). Most of them were prepared to donate their organs after death (88% vs 87%). 63% of the fourth year students signed a donor card. In conclusion, medical student attitudes to organ donation and transplantation are highly positive, but do not improve during the first 3 years of Medical School. An educational program is therefore needed.

The laparoscopic Heller-Dor operation remains an effective treatment for esophageal achalasia at a minimum 6-year follow-up.

BACKGROUND: The aim of this study was to investigate the long-term clinical outcome of the laparoscopic Heller Dor procedure for esophageal achalasia. METHODS: A total of 71 consecutive patients with a minimum 6 year follow-up were evaluated. These patients were seen at 1 and 6 months after the operation (at which time barium swallow, endoscopy, manometry, and pH monitoring were performed), and annually thereafter. A dedicated symptom score, that combined severity and frequency of symptoms was used. RESULTS: The median symptom score decreased from 22 (range, 9-29) preoperatively to 4 (range, 0-16) at last follow-up, (p < 0.01). During the follow-up period, 13 patients suffered symptom recurrence; seven of them (54%) had already been diagnosed at the 1-year follow-up. All of these patients were treated with complementary pneumatic dilations. Overall, at a minimum of 6- years after the operation, 81.7% of the patients were satisfied with the treatment and were able to eat normally. CONCLUSIONS: The long-term outcome of laparoscopic surgical treatment of esophageal achalasia is only slightly affected by the length of the follow-up and most of the symptomatic failures occur in the early period after the operation.

Pancreatic cancer cells invasiveness is mainly affected by interleukin-1beta not by transforming growth factor-beta1.

BACKGROUND: We investigated in vitro whether IL-1beta and TGF-beta1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion. MATERIALS AND METHODS: Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1beta and TGF-beta1 were evaluated using three primary and three metastatic pancreatic cancer cell lines. RESULTS: Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1beta did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-beta1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines. CONCLUSIONS: IL-1beta enhances the invasive capacity of pancreatic cancer cells, whereas TGF-beta1 has paradoxical effects on pancreatic cancer cells; this makes it difficult to interfere with TGF-beta1 signaling in pancreatic cancer treatment.

Botulinum toxin injection versus laparoscopic myotomy for the treatment of esophageal achalasia: economic analysis of a randomized trial.

BACKGROUND: The treatment of esophageal achalasia is still controversial: current therapies are palliative and aim to relieve dysphagia by disrupting or relaxing the lower esophageal sphincter muscle fibers with botulinum toxin. The aim of this study was to compare the clinical and economic results of two such treatments: laparoscopic myotomy and botulinum toxin injection. METHODS: A total of 37 patients with esophageal achalasia were randomly assigned to receive laparoscopic myotomy (20) or two Botox injections 1 month apart (17). All patients were treated at the same hospital and were part of a larger multicenter study. Symptom score, lower esophageal sphincter pressure, and esophageal diameter at barium swallow were compared. The economic analysis was performed considering only the direct costs (cost per treatment and cost effectiveness, i.e., cost per patient healed). RESULTS: Mortality and morbidity were nil in both groups. The actuarial probability of being asymptomatic at 2 years was 90% for surgery and 34% for Botox (p < 0.05). The initial cost was lower for Botox (1,245 Euros) than for surgery (3,555 Euros), but when cost effectiveness at 2 years was considered, this difference nearly disappeared: Botox 3,364 Euros, surgery 3,950 Euros. CONCLUSION: Botox is still the least costly treatment, but the minimal difference in the longer term does not justify its use, given that surgery is a risk-free, definitive treatment.

Expression of CTLA-4 in nonhuman primate lymphocytes and its use as a potential target for specific immunotoxin-mediated apoptosis: results of in vitro studies.

T-cell-mediated immunoregulation is one of the main mechanisms implicated in induction and maintenance of transplantation tolerance. In this regard, deletion or modulation of xeno/alloantigen-specific T cells, as well as blocking of their interactions with other cell populations, are currently being pursued for tolerance induction in humans as well as nonhuman primates. In order to investigate whether cytotoxic T-lymphocyte antigen-4 (CTLA-4) may represent a suitable target for a T cell depletion approach in nonhuman primate models, we analysed CTLA-4 expression in peripheral blood mononuclear cells (PBMCs) from nonhuman primates and the potential role of two anti-CTLA-4 saporin-conjugated immunotoxins. The analysis was performed in PBMCs from 8 cynomolgus monkeys from Philippines and from Mauritius both at protein level by flow cytometry and at transcriptional level by RT-PCR. In addition, the apoptotic role of the immunotoxins was investigated. The results showed that CTLA-4 was expressed at variable levels depending on the origin of the cynomolgus monkeys and the resting or activated cell condition. CTLA-4 was not expressed on resting Mauritius PBMCs and showed a lower up-regulation upon PMA/PHA activation compared to the Philippines PBMCs that expressed CTLA-4 also before activation. Two CTLA-4 RNA transcripts (672 and 550 bp) were detected with levels variations after cell stimulation. Two anti-CTLA-4 immunotoxins induced in vitro apoptosis of activated PBMCs from both sources of cynomolgus monkeys. This is the first report that documents CTLA-4 expression both at protein and transcriptional level by nonhuman primate PBMCs and provides novel perspectives of xeno/allograft rejection immunotherapy based on CTLA-4 targeting.

[How to prevent saphenous nerve injury. A personal modified technique for the stripping of the long saphenous vein]. / Come prevenire le lesioni del nervo safeno. Una tecnica personale modificata per lo stripping della grande safena.

BACKGROUND: In literature the incidence of paresthesia caused by long stripping (LS) of the saphenous vein (SV) varies widely. Best results have been reported with the invagination technique by Van Der Stricht. However, this technique is associated with a high incidence of vein rupture and incomplete stripping. The aim of this study is to test a personal technique to avoid the SV rupture and to reduce the incidence of saphenous nerve injury. METHODS: Sixty-eight patients underwent LS of the SV from groin to ankle under monolateral spinal anesthesia on a one-day surgery basis using a personal technique combining external and invaginated saphenous stripping. All patients underwent a clinical re-evalutation 1, 3, 6, 12, 24 and 48 months after the operation. RESULTS: No intraoperative complications were recorded. Stripping of the long saphenous vein was complete in all cases without any rupture of the veins. Only one postoperative hematoma of the leg (1.5%) which was naturally reabsorbed, was recorded; four patients (5.9%) had transitory saphenous nerve injury. Permanent saphenous nerve damage was found in only one of 68 patients (1.5%). All the patients were discharged on the day of operation and we did not register any prolonged hospitalization. CONCLUSIONS: The result of our approach was a very low postoperative complication rate (1.5% of permanent neurological damage) without any rupture of the vein.