Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated malignancies using adenovirus vectors in vitro and in vivo.

The consistent presence of EBV genomes in certain tumor types (in particular, AIDS-related central nervous system lymphomas and nasopharyngeal carcinomas) may allow novel, EBV-based targeting strategies. Tumors contain the latent (transforming) form of EBV infection. However, expression of either of the EBV immediate-early proteins, BZLF1 and BRLF1, is sufficient to induce lytic EBV infection, resulting in death of the host cell. We have constructed replication-deficient adenovirus vectors expressing the BZLF1 or BRLF1 immediate-early genes and examined their utility for killing latently infected lymphoma cells in vitro and in vivo. We show that both the BZLF1 and BRLF1 vectors efficiently induce lytic EBV infection in Jijoye cells (an EBV-positive Burkitt lymphoma cell line). Furthermore, lytic EBV infection converts the antiviral drug, ganciclovir (GCV), into a toxic (phosphorylated) form, which inhibits cellular as well as viral DNA polymerase. When Jijoye cells are infected with the BZLF1 or BRLF1 adenovirus vectors in the presence of GCV, viral reactivation is induced, but virus replication is inhibited (thus preventing the release of infectious EBV particles); yet cells are still efficiently killed. Finally, we demonstrate that the BZLF1 and BRLF1 adenovirus vectors induce lytic EBV infection when they are directly inoculated into Jijoye cell tumors grown in severe combined immunodeficiency mice. These results suggest that induction of lytic EBV infection in tumors, in combination with GCV, may be an effective strategy for treating EBV-associated malignancies.

Surgical management of substernal goitres. When is sternotomy inevitable?

PURPOSE: Aim of this retrospective study is to report personal experience in the surgical management of substernal goitres emphasizing the guidelines for preoperative planning of sternotomy in selected cases. PATIENTS AND METHODS: Medical records of all patients (n=355) submitted to thyroidectomy for struma in our Operative Unit, between 1993-2003, were analysed. A substernal goitre was defined as a goitre having a significant retrosternal extension (>50%) requiring mediastinal dissection. RESULTS: A total of 18 out of 355 patients undergoing thyroidectomy for struma in our Operative Unit had substernal goitres. The most common symptoms, at presentation, were the presence of neck mass and respiratory disorders. Standard cervical incision was adequate to achieve total thyroidectomy in 17 cases while, in one patient with computed tomography images showing the presence of a huge goitre extending below the aortic arch, a sternotomic approach was inevitable to ensure safe removal. No major morbidity or perioperative deaths occurred. One patient with scleroderma experienced bilateral paralysis of laryngeal nerves for two months, with full recovery thereafter. CONCLUSIONS: While removal of the majority of substernal goitres can be achieved by means of cervical incision, this approach is not always safe. In a selected number of cases with an iceberg shaped substernal goiter and with >70% of the volume lying below the thoracic outlet, a sternotomic approach is inevitable. Preoperative diagnostic work-up should, thus, include chest X-ray and computed tomography. Overall results in the present patient population, have been excellent since morbidity has been minimal and mortality absent, and all patients are symptom free.

Controlled trial of acyclovir for chickenpox evaluating time of initiation and duration of therapy and viral resistance.

BACKGROUND: Chickenpox is prevalent in the US despite the availability of an effective vaccine. Acyclovir treatment is limited by concerns about efficacy if given after the first day of rash and by concerns about induction of viral resistance. OBJECTIVE: Evaluate initiation and duration of acyclovir treatment of chickenpox and its effect on viral resistance. STUDY DESIGN: Randomized, placebo-controlled, double blind trial in immunocompetent patients who were stratified by age at enrollment (children, 2 to 11 years; adolescents, > or = 12 to 18 years; adults, > or = 19 years) and duration of rash (< or = 24 h vs. >24 to 48 h). Lesions were staged, counted and cultured; temperatures and symptoms were recorded daily. INTERVENTION: Subjects presenting within 24 h of rash onset (Group A) were randomly assigned to 5 or 7 days of oral acyclovir treatment, 80 mg/kg/day up to a maximum of 3,200 mg/day in four divided doses. Subjects whose rash was >24 to 48 h old were randomized to receive 5 days of acyclovir treatment beginning on the first (Group B1) or second study day (Group B2). Matching placebos were used to ensure that subjects uniformly received 28 doses of study compound. RESULTS: Of the 177 subjects recruited Group A patients who were treated on the first day of rash had the greatest number of significantly shortened event times with 5 days of therapy being equivalent to 7 days. There also were some shorter times to events for Group B1 patients who began therapy on the second day of rash vs. Group B2 patients who started acyclovir on the third. These included: time to maximum lesion formation (adolescents, P = 0.007; children, P = 0.03); 50% healing in adolescents (P = 0.005); and residual facial lesions in adults (P = 0.047). The probability of viral shedding was significantly reduced for Group A subjects vs. Group B1 subjects (P = 0.006). Viruses shed during therapy remained susceptible to acyclovir and retained normal thymidine kinase function. CONCLUSIONS: Immunocompetent children, adolescents and adults with chickenpox displayed a gradation in their clinical responses to acyclovir that correlated with the time from onset of rash to initiation of therapy. Five days of therapy is sufficient because a 7-day course provided no additional benefit. The susceptibility to acyclovir of viruses shed during treatment did not change; however, the effect of therapy on resistance of latent virus was not assessed.

[Constipation following hysterectomy. Retrospective study based on 105 cases]. / Stipsi post isterectomia. Studio retrospettivo su 105 casi.

Constipation after surgery is considered as a subgroup of patients in whom the disorder begins after pelvic surgery. A group of patients (median age 52 years with a range of 34-65 years) who had a hysterectomy underwent a retrospective study with the aid of a questionnaire and clinical records, to evaluate the incidence of constipation before and after the operation. Forty patients were operated on for benign pathology and 65 for malignant pathology. Forty-two patients underwent a Wertheim-Meigs, 39 had laparohysterectomy, 20 had a colpohysterectomy and 4 had a Schauta. The incidence of constipation increased from 25% preoperatively to 38% postoperatively (p < 0.05). There is no difference in the incidence of postoperative constipation among the various operations. Constipation after hysterectomy is associated with urinary disorders. These data confirm previous studies on the effect of hysterectomy on urinary and defaecatory functions and they show how a simple colpohisterectomy can cause constipation.

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.

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.

Photostability of naturally occurring whitening agents in cosmetic microemulsions.

An o/w microemulsion formulated using lecithin and an alkyl glucoside as mild, non-irritant surfactants was proposed as a cosmetic vehicle for arbutin and kojic acid, naturally occurring whitening agents. After assessing the physicochemical stability of the microemulsion in the presence and absence of whitening agents, several perfumed compositions, developed using fragrant molecules of natural or synthetic origin, were introduced, and the olfactory impact of the perfumed microemulsion was evaluated. The photostability to UVB irradiation of both whitening agents was determined in aqueous solutions and in microemulsions, and also in the presence of the perfumed compositions. The stability of arbutin and kojic acid was higher in microemulsions than in aqueous solutions, and only in some cases did the presence of odorous molecules appear to influence it: linalool exerted some protective effect towards kojic acid photodegradation.

[Benign thyroid disease: 20-year experience in surgical therapy]. / Malattia tiroidea benigna: esperienza ventennale di terapia chirurgica.

This retrospective study compares recurrence and postoperative complication rates after isthmo-lobectomy and subtotal thyroidectomy (group I) vs near-total and total thyroidectomy (group II) for benign thyroid disease. Seven hundred and forty-three patients were operated on for thyroid diseases over the period from 1977 to 1998. We considered 202 patients operated on for benign thyroid disease from 1988 to 1998. The follow-up ranged from 1 to 10 years (mean: 3.4 yrs). One hundred and thirty-two patients (65.3%) were operated on for bilateral nodular goitre, 35 (17.3%) for unilateral nodular goitre, 14 (6.9%) for toxic goitre and 21 (10.4%) for thyroiditis. Over the period 1988-1992, 19 patients underwent isthmo-lobectomy and 71 subtotal thyroidectomy (group I). From 1993 to 1998, 39 patients underwent near-total thyroidectomy and 61 total thyroidectomy (group II). The relapse rate was 14.4% in group I, while there were no recurrences in group II (p = 0.000064). Temporary hypocalcaemia was significantly higher (p = 0.000001) in group II (29%) than in group I (2.2%). Within group II, the rate was significantly higher (p = 0.0013) after total thyroidectomy (37.7%) than after near-total thyroidectomy (15.4%). In our experience, near-total and total thyroidectomy are an appropriate approach for preventing recurrence in patients with benign thyroid disease despite the fact that the risk of temporary hypocalcaemia is higher than after less radical surgery. Near-total thyroidectomy and the exercise of all due care in the surgical technique may help to reduce its incidence.

[Tardive cecal metastasis from ovarian cancer: a case report]. / Metastasi colica tardiva da carcinoma ovarico. A proposito di un caso clinico.

Intestinal insolvement is a frequent sequela of metastatic ovarian cancer may be syncronous or following ovaric resection, after several years of disease free condition. The authors herein describe a clinical report of a case of cecal metastatic neoplasm due to ovarian cancer treated with surgical resection 24 years before.

[Severe hypercalcemia due to acute primary hyperparathyroidism: role if parathyroidectomy]. / Ipercalcemia grave da iperparatiroidismo primitivo acuto: ruolo della paratiroidectomia.

Grave hypercalcemia may complicate primary hyperparathyroidism. This clinical condition is potentially life-threatening, if it is untreated. The emergency therapy consist in rehydratation, stimulation of diuresis and somministration of biphosphonates. A urgent surgery is required if conservative therapy is not successful. The Authors herein present a consecutive series of 6 cases with acute hypercalcemic crisis due primary hyperparathyroidism, successful treated with urgent parathyroidectomy after conservative treatment.

[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.

[Lymphangiomatosis of the spleen. Report of a clinical case]. / La linfangiomatosi splenica, a proposito di un caso clinico.

Lymphangiomatosis confined to the spleen is a very are condition. The authors in this article describes one new case and briefly reviews the literature. In this case, after the exclusion of an hydatidosis of the spleen, a total splenectomy was performed. The histologic findings confirmed the lymphangiomatosis of the spleen. The authors emphasize the surgical strategy in splenic lymphangiomyomatosis, infact the total splenectomy is mandatory, because the splenic parenchyma is nearly completely substitute by the cysts. For this reason is preferably, before surgery, to perform the antibateric profilaxis against the OPSI.

[Hypoparathyroidism following total thyroidectomy: prognostic value of intraoperative parathyroid hormone assay]. / Ipoparatiroidismo dopo tiroidectomia totale: utilità prognostica del dosaggio intraoperatorio del paratormone.

Transient and definitive hypoparathyroidism represent a frequent complication after thyroid surgery. Recently some authors proposed the use of intraoperative parathyroid hormone assay for the rapid detection of this complication. In this paper the authors describe the data obtained from 42 total thyroidectomies with intraoperative measurements of parathyroid hormone. When parathormone decrement was over 75% during thyroidectomy, the hypocalcemic symptomatology was found in all cases during postoperative observation. The authors emphasize intraoperative PTH dosage for immediate identification of patients at risk for postoperative hypoparathyroidism. In this cases parathyroid autotransplantation is suggested to prevent postoperative hypoparathyroidism.

Severe hemorrhagic complications in pancreatitis.

Severe bleeding may complicate the course of either acute or chronic pancreatitis, the latter being more frequently involved. Pseudocysts, severe inflammation, regional necrosis and infection may cause major vessel erosion with or without pseudoaneurysm formation which eventually may result in severe bleeding into the gastrointestinal tract, retroperitoneum and peritoneal cavity. The AA report their experience on 8 cases and analyze the data of a comprehensive review of 389 cases of massive bleeding reported in the literature during the last 100 years until December 1993. Mortality rate seems to be related to the etiology of the bleeding along with its localization and the underlying anatomo-pathologic findings. In patients with chronic pancreatitis it is 22% while in patients with acute pancreatitis or chronic pancreatitis with acute exacerbation it is 60.4% and 57.1% respectively. Splenic, gastroduodenal and superior pancreaticoduodenal arteries are the most commonly involved vessels being associated respectively with a mortality rate of 20.5%, 27.9% and 46.1%. Massive haemorrhage complicating infected necrosis or abscesses implies a worse prognosis when compared to severe bleeding associated with pseudocyst with or without pseudoaneurysm. The increasing use of diagnostic and interventional radiology appears to be the way forward to improve survival rates. Awareness of high risk predisposing condition, activism in achieving an early identification of the bleeding sources, and eventually its angiographic control are essential guidelines for successful approach to the most unpredictable complication of pancreatitis. When embolization fails or is followed by recurrence of hemorrhage, definitive surgical procedures should be immediately instituted.

[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.

Colonic lesions in pancreatitis.

Lesions of the colon are generally considered to be uncommon sequelae of pancreatitis. They include: localized paralytic ileus (colon cut-off sign), necrosis, fistulae, stenosis and varices. On the basis of an extensive review of the literature (432 cases), it is suggested indeed that the real incidence is significant. The anatomic relationship of the large bowel to the pancreas is an important factor in the genesis and localization of the lesions. Enzymatic-inflammatory and ischemic processes are involved in the most highly supported theories. Colon cut-off sign is almost always spontaneously reversible and may represent an "alarm" for more serious complications. Massive necrosis develops during the early stage of severe pancreatitis and its mortality rate has been reported to be high. Fistulae are late complications of the disease, associated with a protracted course and probably a consequence of pancreatic suppuration or pseudocysts. Stenoses are the most interesting colonic complications following pancreatitis and caused by either acute obstruction of the colon due to an inflammatory mass or progressive obstruction due to pericolic fibrosis. In this case, the clinical picture may mimic carcinoma.

[Acute biliary pancreatitis. Role of laparoscopy after 30 years of traditional surgery experience]. / Pancreatite acuta biliare. Ruolo della laparoscopia dopo un'esperienza di chirurgia tradizionale di oltre trenta anni.

The authors herein show their own experience in the treatment of acute biliary pancreatitis. Aim of this study is to evaluate the effectiveness and the safety of the "early" laparoscopic approach to the mild to moderate acute biliary pancreatitis. The authors studied sixty cases of laparoscopic cholecystectomy with intraoperative colangiography for acute biliary pancreatitis (M/F 1:1.2; mean age 59.6 yrs, range 29.79). The patients were divided in two groups on the basis of the severity of the pancreatitis, defined through Ranson's score and Balthazar classification. The mortality rate was nil. Intraoperative morbidity rate was 6.6% in the group I (3/45), and 13.3% in the group II (2/15). Postoperative morbidity rate was 6.7% (3/45) in the group I and 40% in the group II (6/15). The authors show an original diagnostic and therapeutic algorithm for the treatment of acute biliary pancreatitis. Early laparoscopic cholecystectomy with I.O.C. is proposed as the gold standard treatment for mild to moderate acute biliary pancreatitis. This approach appears to be effective and safe in their experience. In case of severe acute biliary pancreatitis, further investigations are mandatory to evaluate the role of laparoscopic approach.

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.

An improved technique for temporary diverting ileostomy.

A modification of the Turnbull technique for a temporary diverting ileostomy, which may be also applied to diverting colostomies, is described herein. According to the technical modification described, a totally diverting ileostomy is performed with the help of a Foley catheter secured in the subcutaneous tissue, and pulled upward and to the right like a sling around the efferent loop. This simple modification allows for better protection of distal anastomosis and an optimal diversion of enteric transit. Furthermore, this technique also permits an easier postoperative handling of the stoma, an easier application of the stomal bags and at the same time, it also more efficiently prevents the eventual subcutaneous infiltration with enteric contaminated fluid. In the authors' preliminary experience with ten cases the procedure was shown to offer advantages in reducing local discomfort and also in achieving the objectives of a totally diverting ileostomy.