Vaccination adjuvated against hepatitis B in Spanish National Healthcare System (SNS) workers typed as non-responders to conventional vaccines.

TRIAL DESIGN: An interventional, phase 4, single group assignment, without masking (open label), preventive clinical trial was carried out in health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B. METHODS: 67 health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B, were enrolled in the Clinical Trial. All participants were from 18 years up to 64 years old. INCLUSION CRITERIA: NHS workers -including university students doing their internships in health centres dependent on the National Health System (inclusion of students is regulated and limited by specific instructions on labour prevention in each autonomous community)- classified as non-responders. The criteria defining them as non-responders to the conventional hepatitis B vaccine is anti HBsAb titers < 10 mUI/ml following the application of six doses of conventional vaccine at 20 µg doses (two complete guidelines). The objective of this study was to provide Health workers-staff with an additional protection tool against hepatitis B infection, and to evaluate the efficacy of the adjuvanted vaccine in healthy non-responders to conventional hepatitis B vaccine. The primary outcome was the measurement of antibody antiHBs before the first Fendrix® dose and a month after the administration of each dose. Other outcome was collection of adverse effects during administration and all those that could be related to the vaccine and that occur within 30 days after each dose. In this study, only one group was assigned. There was no randomization or masking. RESULTS: The participants were recruited between April 13, 2018 and October 31, 2019. 67 participants were enrolled in the Clinical Trial and included the analyses. The primary immunisation consists of 4 separate 0.5 ml doses of Fendrix®, administered at the following schedule: 1 month, 2 months and 6 months from the date of the first dose. Once the positivity was reached in any of the doses, the participant finished the study and was not given the following doses. 68.66% (46 out 67) had a positive response to first dose of Fendrix®. 57.14% (12 out 21) had a positive response to second dose of Fendrix®. 22.22% (2 out 9) had a positive response to third dose of Fendrix and 42.96% (3 out 7) had a positive response to last dose of Fendrix®. Overall, 94.02% (64 out 67) of participants had a positive response to Fendrix®. No serious adverse event occurred. CONCLUSIONS: The use of Fendrix®, is a viable vaccine alternative for NHS workers classified as "non-responders". Revaccination of healthy non-responders with Fendrix®, resulted in very high proportions of responders without adverse events. TRIAL REGISTRATION: The trial was registered in the Spanish National Trial Register (REEC), ClinicalTrials.gov and inclusion has been stopped (identifier NCT03410953; EudraCT-number 2016-004991-23). FUNDING: GRS 1360/A/16: Call for aid for the financing of research projects in biomedicine, health management and socio-health care to be developed in the centres of the Regional Health Management of Autonomous Community of Castile-Leon. In addition, this work has been supported by the Spanish Platform for Clinical Research and Clinical Trials, SCReN (Spanish Clinical Research Network), funded by the Subdirectorate General for Research Evaluation and Promotion of the Carlos III Health Institute (ISCIII), through the project PT13/0002/0039 and project PT17/0017/0023 integrated in the State Plan for R&D&I 2013-2016 and co-financed by and the European Regional Development Fund (ERDF).

Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O.

AIM: The present study was specifically designed to assess the major clinical and pathological variables of patients with colorectal peritoneal carcinomatosis in order to investigate whether currently used criteria appropriately select candidates for peritonectomy procedures (cytoreductive surgery) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Preoperative, operative and follow-up data on 146 consecutive patients presenting with peritoneal carcinomatosis of colorectal origin and treated by surgical cytoreduction combined with HIPEC in 5 Italian Hospital and University Centers were prospectively entered in a common database. Univariate and multivariate analyses were used to assess the prognostic value of clinical and pathologic factors. RESULTS: Over a minimum 24-month follow-up, the overall morbidity rate was 27.4% (mortality rate: 2.7%) and was directly related to the extent of surgery. Peritoneal cancer index (PCI), unfavorable peritoneal sites, synchronous or previously resected liver metastasis and the completeness of cytoreduction, all emerged as independent prognostic factors correlated with survival. CONCLUSIONS: Until research provides more effective criteria for selecting patients based upon the biomolecular features of carcinomatosis, patients should be selected according to the existing independent prognostic variables.

Male breast cancer: 6-year experience.

AIM: Breast cancer in men is a very rare neoplasm accounting 1% of all breast cancer with an incidence ratio of 1:100 of men to women and about 1% of all malignancies in men. On the basis of the literature review the authors tried to determine the main characteristics of this rare neoplasm in terms of epidemiology, diagnosis, prognosis, treatment and survival. METHODS: The authors report the experience of the Breast Unit of the San Giovanni Addolorata Hospital in Rome, where 4 cases of male breast cancer were observed and treated over 784 breast cancers. RESULTS: All tumours were ductal carcinomas. The extent of disease was as follows: 3 cases with stage I and 1 case with Stage IIIB; in two cases estrogen and progesterone receptors expression was 100% and in the other two cases it was 20-80%. Median follow up was 57.5 months. At present, after 6-year follow up the three patients with stage I are in good conditions; the patient with stage III died after 27 months with metastatic disease. CONCLUSIONS: Surgical treatment remains the gold standard in male breast cancer. The prognosis for males with breast cancer is similar to female patients on equal terms of stage of disease. Adjuvant therapy is based on retrospective studies of male breast cancer conducted over the past 20 years using the guidelines for breast cancer in women.

[Primary breast lymphoma: case report and review of literature]. / Linfoma primitivo della mammella: descrizione di un caso clinico e revisione della letteratura.

Primary non-Hodgkin's lymphoma of the breast is a rare entity representing 0.04-0.5% of all malignant female breast tumors, less than 1% of all patients with non-Hodgkin lymphoma and approximately 1.7-2.2% of all patients with extranodal non-Hodgkin lymphomas. A 75 years old patient presented with masses in the lateral part of the left breast for 6 weeks. Ultrasound detected 3 masses suggesting fibroadenomas while mammography set the suspicion of breast multicentric carcinoma. Fine needle aspiration cytology of one mass showed low grade lymphoma subsequently confirmed with histopathology which diagnosed extranodal non-Hodgkin lymphoma MALT type CD 20+/CD 79a+/CD 3-/Bcl 2- and index of proliferation Ki 67=30% (stage IE). Primary non-Hodgkin lymphomas of the breast, though rare, should be considered in the differential diagnosis of breast malignancies. At present, a standard treatment doesn't exist yet; low grade lymphomas should be managed with excision biopsy and/or local radiation therapy, while high grade lymphomas should be managed with chemotherapy in association with radiation therapy.

Prognostic value of Goseki histological classification in adenocarcinoma of the cardia.

Various histologic classification systems have been proposed as prognostic factors for gastric cancer. We assessed the prognostic value of Goseki classification as well as the TNM staging system, histological tumour grading, Lauren, WHO, Goseki and Siewert classifications in 100 patients with cardia carcinoma undergoing curative surgery. Two patients were lost at follow-up. The median time of follow-up in the remaining patients was 32.9 months after surgery (range: 0.1-142.1 months). No differences in survival rates were observed according to tumour grading, Lauren or WHO histologic or Siewert topographical classification. No differences were found according to Goseki classes, when considering either the mucin content of the carcinoma (types I and III vs II and IV) or the differentiation grade (types I and II vs III and IV). Multivariate analysis showed that the only lymph node positivity was a significant predictor of survival: 7.2% of patients with, but 41.5% of those without nodal involvement were alive after five years (P=0.0001). In conclusion, we found no prognostic role for Goseki or the traditional histological indexes, while the TNM staging system and particularly lymph node positivity were the main predictors of survival in patients with cardia adenocarcinoma.

[The role of color flow-Doppler ultrasonography in the diagnosis of nodular goiter]. / Ruolo dell'ecocolordoppler nello studio del gozzo nodulare.

Sixtysix patients were submitted to color Doppler ultrasonography, with flowmetric analysis, in the preoperative work up of their thyroid nodules. Three different groups (and two subsets) were so identified, corresponding to the different pathological nodule types: hyperplasia, adenoma, and cancer. The data obtained were then compared to the final pathological results. The color Doppler ultrasonography showed a diagnostic accuracy rate of 87.8%. An evaluation of the peak systolic velocity proved to be very useful in the differential diagnosis between adenomas and cancers. The color Doppler ultrasonography represents a sound method for evaluating thyroid nodules.

[The role of color-Doppler ultrasonography in preoperative study of hyperparathyroidism]. / Ruolo dell'ecocolor-doppler nello studio preoperatorio degli iperparatiroidismi.

The different diagnostic modalities (MIBI scan, ultrasound, CT, MNR) applied in the preoperative study of hyperparathyroidism, have given excellent sensitivity results, only slightly lower than those obtained by surgical exploration performed by experienced surgeons. Yet, their only limitation lies in a lower level of specificity. Other cervical tumours, such as thyroid nodules, lymphoadenopaties, vascular and macular lesions, can in fact be erroneously taken as hyperfunctioning parathyroids. The present paper shows a clinical experience of 27 patients affected by IPT (14 primary IPT, 10 secondary, 3 terziary) who underwent Color-Doppler Ultrasonography and US before surgical exploration. As a result, global sensitivity level reached 81.5%, specificity 100%. In IPT I and III, sensitivity reached 100% while in IPT II it was only 72.2%. In conclusion, Color-Doppler associated with conventional US increases the specificity rate of IPT pre-operative diagnosis.

Distribution of 1,2 DMH-induced colonic aberrant crypt foci after administration of a gastrin receptor antagonist (CR2945), in the murine model.

Our previous experimental data demonstrated that a new gastrin receptor antagonist (CR2945) has a chemopreventive effect on dimethylhydrazine-induced colon cancer in mice. The aim of this study is to test the effect of CR2945 on the appearance and distribution of aberrant crypt foci (ACF), proposed as early "preneoplastic" lesions in colon carcinogenesis, in the murine model. 176 CD1 male mice were randomly divided into 4 groups: group 1, sham group received 2 daily intra-peritoneal injections of saline solution; group 2 received 1 weekly intra-peritoneal injection of DMH 20 mg/kg, for 5 weeks, and 2 daily intra-peritoneal injections of equal volume of NaCl 0.9%; group 3 and 4 received the same weekly dose of DMH and 2 daily injections of CR2945 at the respective doses of 2.5 and 7.5 mg/Kg for 5 weeks. The rodents were sacrified 15, 20, 25, and 38 weeks after receiving the first injection. The number of ACF per area (ACF frequency), their multiplicity (number of crypts per focus), ACF frequency according to each colonic site were recorded. No ACF were found in the sham group. No substantial differences were observed in ACF distribution between the remaining groups. Our hypothesis is that CR2945 does not alter the final number of ACF but might induce a regression of some dysplastic ACF.

A simple ultrasonographic test for preoperative haemodynamic evaluation of varicocele.

According to the haemodynamic classification of varicocele type I is caused by renospermatic reflux due to a proximal nutcracker phenomenon or to valvular insufficiency of the left internal spermatic vein. Type II is due to ileospermatic reflux and type III may be characterized by a combination of I and II refluxes. Although this classification proposed by Coolsaet is precious for decision making, it is seldom used in clinical practice being based on a complex angiographic evaluation which is invasive and exposes the patient (often a teenager or with infertility disturbances) to excessive radiations. The aim of the present study was to work up an original ultrasonographic test for preoperative haemodynamic evaluation of varicocele in order to indicate the most appropriate microsurgical treatment. Sixty-three patients underwent a preoperative clinico-echographic dynamic test which allowed to classify 76.9% of the cases as haemodynamic type I, 10.7% as type II and 12.3% as type III. Microsurgical shunts were performed in all cases and evaluation of recurrences was accurately carried out with ultrasonographic measurement of residual varicosities. In 6% of the cases varicosities were consistently reduced in size and in 94% absence of varicosities was demonstrated. Varicocele increased in size or was unchanged in none of the cases. In conclusion the test hereby described was shown to be simple and easily reproducible. It allowed a haemodynamic and objective classification of varicocele offering a unique opportunity for tailoring to the individual patient the most appropriate treatment. Furthermore, ultrasonographic postoperative follow-up is the most reliable and objective method to control the "true" incidence of post-varicocelectomy recurrences.

Long-term results of microsurgical drainage for idiopathic varicocele.

The long-term results of microsurgical shunts for idiopathic varicocele are reported in the present paper. Sixty-two patients with a total of 65 varicoceles (three were bilateral) were followed up for 1 to 8 years. Pre- and postoperative ultrasonographic evaluation of varicocele size was considered of great importance in order to reduce the bias of subjective clinical diagnosis and to achieve a reliable and objective follow-up. Microsurgical shunts were tailored to the type of reflux: renospermatic (76.9%), iliospermatic (10.8%) or mixed type (12.3%), 94% of patients experienced a complete morphologic disappearance of varicosities, while in 6% of the cases a consistent reduction of size was objectified although varicosities were still detectable at ultrasonographic examination. In patients with severe infertility a significant increase of seminal parameters was observed postoperatively and this improvement showed a higher statistical significance in patients aged < 30 years.

Is intraoperative ultrasonography useful in pancreatic cancer surgery?

Preoperative staging of pancreatic cancer represents a major challenge for a suitable surgical management of the disease. In a consistent number of patients laparotomy is still necessary in order to decide whether the tumor is resectable or not. In the present paper the Authors report their experience with intraoperative ultrasonography (IOU) in evaluating pancreatic cancer resectability. Very important data for intraoperative decision making were obtained in 37.9% of the patients, useful information in 31%, while in 31% IOU may be looked forward to as an important aid in decision making and for a safely guided dissection.

The effect of L-carnitine, administered through intravenous infusion of glucose, on both glucose and insulin levels in healthy subjects.

The goal of the present study was to evaluate the effect of L-carnitine on plasma glucose and insulin levels. Two parallel studies were set-up, of 40 and 20 healthy volunteers, respectively. Each group received 500 cc of 10% glucose or 5% glucose, to which were randomly added 4 g or 2 g of L-carnitine and administered a week apart. Results showed that L-carnitine was able to reduce the increase in glucose plasma levels induced by infusion of the glucose solution. This finding was not dependent on an insulin-dependent mechanism.

[The drug treatment of postoperative pain]. / Trattamento farmacologico del dolore postoperatorio.

The study, conducted on 40 patients with pain resulting from "minor" general surgery, for the purpose of evaluating the efficacy and tolerability of ST-679 (administered in a single oral dose of 1200 mg in 20 patients) and to compare them with those of paracetamol (administered in a single oral dose of 1000 mg in 20 patients), demonstrated that the new drug was active on all recorded parameters and superior to the reference drug. The evaluation of the evolution of pain, performed using the Scott-Huskisson visual analog scale, evidenced that the maximum analgesic efficacy of ST-679 is reached after 1 hour and 15 minutes from assumption and remains unaltered until the final observation (6 hours). The paracetamol registers maximum analgesic efficacy after 30 minutes, but does not remain constant for the entire observation period. All the other parameters evaluated (variation in pain intensity, peak of analgesic activity and total remission of pain) are significantly favorable to ST-679. The tolerability of ST-679 was very good and better than the reference drug.

[The treatment of postoperative pain in obstetrical-gynecologic surgery. A comparative study between ST-679 and paracetamol]. / Trattamento del dolore postoperatorio nella chirurgia ostetrico-ginecologica. Studio comparativo tra ST-679 e paracetamolo.

In double-blind conditions, ST-679 (a single oral 1200 mg dose in 20 patients), or paracetamol (a single oral dose of 1000 mg in 20 patients) was administered to forty patients who presented pain as a result of obstetrical-gynecological surgery. The study proposed to evaluate the analgesic efficacy and tolerability of ST-679, a new non-steroid antiphlogistic drug, as compared to a reference drug amply utilized in clinical practice such as paracetamol. The average estimation of tolerability, with regard to paracetamol, was significantly in favor of ST-679.

[An evaluation of the analgesic activity and tolerance of ST-679 in patients with pain following orthopedic and traumatological interventions]. / Valutazione dell'attività analgesica e della tollerabilità di ST-679 in pazienti con dolore conseguente ad interventi di competenza ortopedica e traumatologica.

The analgesic efficacy and tolerability of ST-679 (administered in a single oral dose of 1200 mg) was evaluated in a double-blind parallel-group study, as compared with paracetamol (administered in a single oral dose of 1000 mg) on 40 patients with pain following orthopedic or traumatological surgery. ST-679 was shown to possess better analgesic qualities with respect to paracetamol, in that the effect establishes itself more quickly and, moreover, both the maximum analgesic activity performed as well as the constant level on which such activity tends to stabilize is greater. No adverse reaction was recorded for either treatment, but ST-679 demonstrated a better tolerability with regard to paracetamol.