Transoral robotic surgery of parapharyngeal space tumours: a series of four cases.

Tumours arising from the parapharyngeal space (PPS) represent less than 1% of all head and neck tumours. Salivary gland tumours account for 40-50% of PPS lesions and are located in the pre-styloid parapharyngeal space. Pleomorphic adenomas represent 80-90% of salivary tumours in the PPS. Recently, transoral robotic surgery (TORS) has become common in head and neck surgery as a minimally invasive procedure. Four cases of benign PPS tumour treated with TORS are presented here. Preoperative diagnosis was conducted by fine needle aspiration biopsy and magnetic resonance imaging, and the results were used to plan the correct surgical approach. One case required a change of approach to conventional transoral blunt dissection. Patients required pain control and reported dysphagia symptoms for a period of weeks, but no nasogastric tube was needed at any time. This case series indicates that TORS is a safe surgical procedure for the excision of benign tumours of the PPS in selected cases.

Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial.

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.

Status of level IIb lymph nodes of the neck in squamous cell carcinoma of the oral tongue in patients who underwent modified radical neck dissection and lymph node sentinel biopsy.

Status of lymph nodes of level IIb was examined to identify the incidence of nodal metastasis and the lymphatic drainage in squamous cell carcinoma of the oral tongue in patients undergoing modified radical neck dissection (MRND) and sentinel node biopsy (SNB). Overall, 72 patients were divided into two groups; 38 patients (Group A) of any T and N+ or T3-T4- N0 stage underwent MRND. The surgical specimens were sent to the Pathology Department, divided into specific levels (I, IIa, IIb, III, IV, V) and labelled. The remaining 34 patients (Group B) T1-T2 -N0 stage were submitted to SNB. The histological examination of the specimens of the two groups was performed by staining with haematoxylin and eosin several sections from each node at different levels and then using a molecular marker such as cytokeratin and Epithelial Membrane Antigen (EMA). In Group A: In N0 there were no occult metastases at level IIb; in N+ neck, 8 cases (33.3%) showed metastasis at level IIb (P = 0.04). Metastases at level IIb were observed only in combination with other levels (P = 0.03). In Group B, direct lymphatic drainage was found in 2 patients (5.9%) at level IIb. There were no occult metastases at level IIb. Out of the 54 sentinel nodes harvested, 4 lymph nodes (7.4%) were found to be metastatic; these 4 sentinel nodes were found respectively in 4 patients, 1 at level III, 3 at level II a with an occult metastasis rate of 11.7%. In conclusion, SNB has prospected a new concept of lymphatic drainage that is variable and individual. SNB has demonstrated that direct lymphatic drainage is possible to level II b. In our experience with early cancer of the tongue (T1-T2 NO ), SNB aided with lympho-scintigraphy seems to be a good technique for staging the neck with minimal morbidity.

Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients.

BACKGROUND: Despite advances in cytomegalovirus (CMV) prophylaxis and therapy, some transplant recipients still develop refractory CMV infections. Maribavir (MBV), an investigational benzimidazole antiviral agent, acts by a mechanism different from that of existing anti-CMV drugs. Previous Phase I and II studies have demonstrated a favorable safety profile for MBV, but its utility in treatment of complex CMV syndromes is unknown. METHODS: Between June and December 2008, MBV was released for use under individual emergency investigational new drug applications requested by treating physicians and approved by the US Food and Drug Administration and local institutional review boards. Six patients (5 solid organ transplant recipients and 1 hematopoietic stem cell transplant recipient) who had failed to respond to other therapies and/or had known ganciclovir-resistant CMV were treated with MBV at a starting oral dose of 400 mg twice daily. RESULTS: Patients were treated for a median of 207 days (range, 15-376). Four of 6 patients had no detectable CMV DNAemia within 6 weeks of starting MBV therapy. One patient, who had an initial viral load of 1.8 million copies/mL, developed MBV resistance mutations. One patient, who had low serum levels of MBV, had persistent CMV DNAemia and viruria without developing genotypic or phenotypic resistance to MBV. One patient cleared CMV DNAemia, but died of pneumonia and multiorgan failure. No significant adverse effects attributable to MBV were observed. CONCLUSIONS: MBV deserves further systematic evaluation as treatment for CMV infection that is resistant and/or refractory to standard therapies, but its optimal dose, duration of therapy, and use in combinations versus as a single agent have yet to be determined.

A randomized, double-blind, pharmacokinetic study of oral maribavir with tacrolimus in stable renal transplant recipients.

Maribavir is being developed as a novel agent for the prevention or treatment of cytomegalovirus infections after stem cell and organ transplantation. This was a randomized, double-blind, placebo-controlled study designed to evaluate the potential pharmacokinetic interaction of concomitant administration of maribavir and tacrolimus. Twenty-five adult renal transplant recipients with stable renal function and stable dosing regimens of tacrolimus were randomized (20 maribavir 400 mg p.o. q12 h: 5 placebo). Tacrolimus whole blood concentration profiles were determined before and after 7 days of co-administration with maribavir. When co-administered with maribavir, tacrolimus mean C(max) increased 38%, tacrolimus trough concentrations (12 h post-dose) increased 57% and tacrolimus AUC((0-tau)) increased 51%. Apparent oral clearance of tacrolimus decreased 34% and T(max) was delayed by 0.5 h. There were no serious adverse events and no subject prematurely discontinued treatment. Because of the limited 7-day dosing course, the adverse event profile could not be adequately assessed. However, as seen with other maribavir studies, dysgeusia was common (90% of maribavir subjects and 20% of placebo subjects). In conclusion, co-administration of maribavir 400 mg twice daily increases exposure to tacrolimus. Routine therapeutic drug monitoring of tacrolimus blood concentrations should be included both at initiation and completion of maribavir treatment.

Enteroviral meningitis: natural history and outcome of pleconaril therapy.

Enteroviral meningitis causes appreciable morbidity in adults, including hospitalization, decreased activity, and headache. Limited data define the natural history of disease. No antiviral therapeutic agent has demonstrated improved outcome in controlled clinical trials. Pleconaril, an inhibitor of enterovirus replication, was tested in two placebo-controlled clinical trials. Of 607 randomized patients in a multicenter, double-blind placebo-controlled study of pleconaril (200 mg three times daily versus an identical-appearing placebo), 240 patients were confirmed to have enterovirus infection. The time to headache resolution was evaluated by using Kaplan-Meier survival methodology. A Cox regression model evaluated multivariate factors associated with disease resolution. Resolution of headache in patients with concomitant moderate to severe nausea at baseline occurred at a median of 9.5 days in the absence of therapy and was reduced to 7.0 days for pleconaril recipients (P = 0.009). For a headache score of > 5 alone, treated patients resolved headache significantly more rapidly (P = 0.005). Males resolved headache 50% faster than females. Regardless of randomization group, patients with a baseline headache score of 5 or greater resolved headache 50% more slowly than patients with a baseline headache score of 4. No differences in either clinical or laboratory adverse events were noted. Over 50% of untreated patients had a persistent headache that was greater than 1 week in duration. Pleconaril shortened the course of illness compared to placebo recipients, especially in the early disease course. However, the benefit was achieved only modestly in a subgroup analysis of patients with more severe disease after adjusting for confounding variables.

[Endoscopic excisional biopsy with laser CO2 for the diagnosis and treatment of glottic carcinoma (T1-selected T2)]. / Endoscopic excisional biopsy with laser CO2 for the diagnosis and treatment of glottic carcinoma (T1-selected T2).

UNLABELLED: AIMS AND BACKGROUNDS: In T1-T2a glottic carcinoma before considering which type of treatment is the best option a biopsy is necessary. A peculiar aspect of this type of lesions is the fact that in the same specimen it is possible to find different grade of dysplasia even carcinoma in situ or microinvasive or invasive. An incisional biopsy could mislead the diagnosis. The aim of this study was to report the oncological results of the excisional biopsy for T1-T2a glottic cancer. MATERIALS AND METHODS: From November 1999 to December 2001, 18 patients (13 T1, 5 T2a) with carcinoma of the vocal cord underwent excisional biopsy of the lesion. In the case of negative margins no further treatment was done. The average follow-up was 2 years and 3 months. RESULTS: Local control was achieved in 100% for T1, 80% for T2. Radiotherapy was added in 2 cases. CONCLUSION: In our experience "excisional biopsy" for unadvanced glottic tumors is an ideal surgical technique for a one stage procedure of diagnosis and therapy.

[The stapler in total laryngectomy with closed technique]. / The stapler in total laryngectomy with closed technique.

UNLABELLED: AIMS AND BACKGROUNDS: The use of the stapler in total laryngectomy with closed technique is described by the authors. MATERIALS AND METHODS: From October 1999 to December 2002, 27 total laryngectomy were performed, 15 with a stapler and 5 cases had a primary tracheoesophageal puncture. RESULTS: Only one patient developed a pharyngocutaneous fistula, no other patients experienced post-operative complications. All cases in this study had negative surgical margins. CONCLUSION: The correct indication for the use of the stapler is a tumor that needs a total laryngectomy, but completely endolaryngeal. The technique allows to remove the nso-gastric tube at the end of the first week after the operation, to avoid soiling the surgical field, to reduce the time in theatre. This technique seems to be safe as the traditional suture.

[Treatment of the facial nerve and the neck in malignant parotid gland tumors]. / Il trattamento del nervo facciale e del collo nei tumori maligni della ghiandola parotide.

In the surgery of malignancies of the parotid gland the management of the facial nerve and of the neck is very important. In fact, many authors declared as the surgery of parotid gland can be considered as the surgery of facial nerve and others underlined the role of the neck management in a complete treatment of these neoplasms. The features of 47 cases of parotid gland neoplasms observed at the National Cancer Institut of Naples (Naples, Italy) are reported. In all cases a total parotidectomy was performed with neck dissection in case of neck metastases or electively in selected cases and resection of the facial nerve only in case of macroscopic tumor involvement. Radiotherapy was administrated in case of involvement of the facial nerve, and/or of the skin and/or of multiple neck metastases. The results of our experience emphasize as the neoplasms of the parotid gland can be treated sparing the facial nerve when it is clearly not involved without making worse prognosis; on the other side planing a neck dissection should be mandatory in case of high degree malignancies, and/or of tumors larger than T2, and/or of involvement of the facial nerve, and/or of the skin and/or cervical lymph nodes.

Prognostic value of sentinel node in oral cancer.

AIMS AND BACKGROUND: In stage I oral squamous cell carcinoma, clinical examination and imaging techniques are unable to identify 60-90% of patients at risk of micrometastasis, while the sentinel node biopsy technique allows to avoid the morbidity of elective neck dissection in patients not actually affected by micrometastases. MATERIALS AND METHODS: Forty-one T1-T2N0 patients underwent lymphoscintigraphy after peritumoral injection of human albumin labeled with 99Tc. Focal areas of radiotracer uptake were marked on the skin preoperatively. The sentinel lymph node (SLN) was identified by the combined use of blue dye and gamma probe and subsequently removed. Complete neck dissection was then performed in all patients and the histological findings were compared with those of SLN biopsy. RESULTS: The SLN was identified in 95% of the patients; in four cases (10%) two SLNs were isolated. In 18% of our patients the SLNs were located outside the expected drainage area. When the histology of the negative SLNs was compared with the pathological status of the neck dissection specimens no false negatives were found. Five SLNs in four patients contained micrometastases and were the only positive lymph nodes. CONCLUSIONS: SLN biopsy can be a valuable staging technique in T2 and T2 oral cancer with uninvolved neck in patients whose lymphatic drainage of the neck has not been altered by previous surgery or radiotherapy. It provides reliable detection of micrometastasis, indicating which level(s) should be removed ipsilaterally or contralaterally, and allows the surgeon to accurately plan neck dissection, taking into consideration the pattern of lymphatic drainage of each individual patient. In this way unnecessary neck dissection and its morphofunctional sequelae can be avoided in a considerable number of patients.

Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection.

The purpose of this investigation was to prospectively characterize acute hepatitis C virus (HCV) infections and to evaluate the hypothesis that the outcome is affected by identifiable clinical or viral factors. One hundred forty-two people with a history of illicit drug use who were HCV antibody-negative in 1988 were followed semiannually through 1996. HCV seroconversion (second generation enzyme immunoassay and recombinant immunoblot assay) was recognized in 43 (30%) of the participants, who were followed up for a median of 72 months. HCV RNA was detected and quantified by polymerase chain reaction in a median of 10 specimens per participant and showed two distinct patterns of viremia: viral clearance was noted in 6 (14%) of the participants, and viral persistence was observed in 37 (86%) of the participants. Subjects with viral clearance were more likely to be white (P =.004), have jaundice (P =.03), and have lower peak viral titer (P =.003). However, the outcome for a given person could not be predicted by clinical features, RNA level, or HCV subtype (as ascertained by analysis of core-E1 complementary DNA sequence). No acute infections were recognized by health care providers. At the time of seroconversion, HCV RNA was detectable in 81% of participants, and recombinant immunoblot assay (RIBA) was positive in 85% of participants. We conclude that approximately 85% of people with acute hepatitis C develop persistent viremia. However, acute infections are uncommonly recognized clinically, underscoring the importance of screening individuals at risk. Long-term follow-up, but no single laboratory test, is necessary to ascertain the outcome and in some cases make the diagnosis of acute HCV infection.

Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as a decoy.

We hypothesized that hepatitis C virus (HCV) persistence is related to the sequence variability of putative envelope genes. This hypothesis was tested by characterizing quasispecies in specimens collected every six months from a cohort of acutely HCV-infected subjects (mean duration of specimen collection, 72 months after seroconversion). We evaluated 5 individuals who spontaneously cleared viremia and 10 individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, the first PCR-positive sample was examined by using a previously described method that combines heteroduplex analysis and analysis of single-stranded conformational polymorphisms. The ratio of nonsynonymous to synonymous substitutions (dN/dS) within each sample was evaluated as an indicator of relative selective pressure. Amino acid sequences were analyzed for signature patterns, glycosylation signals, and charge. Quasispecies complexity was higher and E1 dN/dS ratios (selective pressure) were lower in those with persistent viremia; the association with persistence was strengthened by the presence of a combination of both characteristics. In contrast, a trend toward higher HVR1 dN/dS ratios was detected among those with persistent viremia. We did not detect any such association for factors that may affect complexity such as serum HCV RNA concentration. HVR1 had a lower positive charge in subjects with persistent viremia, although no consistent motifs were detected. Our data suggest that HCV persistence is associated with a complex quasispecies and immune response to HVR1.

Hallux rigidus: resección artroplástica metatarsofalángica

La función normal de la primera articulación metatarsofalángica depende no sólo de aspectos inherentes a la propia articulación, sino también de la movilidad sesamoidea y de la capacidad del primer metatarsiano para la flexión plantar. Microtraumatismos agudos o crónicos pueden dañar la superficie articular cuando la flexión plantar del primer metatarsiano se encuentra limitada por un metatarsiano hipermóvil o un metatarsiano de excesiva longitud o un metatarsus primus elevatus. Clasificamos a los hallux rigidus según Regnauld y consideramos las conductas terapéuticas en los distintos estadios, analizando en particular nuestra experiencia con la técnica de Valente Valenti o artrectomía en bisagra, que venimos efectuando desde hace más de 10 años. Analizamos resultados y complicaciones

Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. Women and Infants Transmission Study.

Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually infected with HIV-1 and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.

Hallux rigidus: resección artroplástica metatarsofalángica

La función normal de la primera articulación metatarsofalángica depende no sólo de aspectos inherentes a la propia articulación, sino también de la movilidad sesamoidea y de la capacidad del primer metatarsiano para la flexión plantar. Microtraumatismos agudos o crónicos pueden dañar la superficie articular cuando la flexión plantar del primer metatarsiano se encuentra limitada por un metatarsiano hipermóvil o un metatarsiano de excesiva longitud o un metatarsus primus elevatus. Clasificamos a los hallux rigidus según Regnauld y consideramos las conductas terapéuticas en los distintos estadios, analizando en particular nuestra experiencia con la técnica de Valente Valenti o artrectomía en bisagra, que venimos efectuando desde hace más de 10 años. Analizamos resultados y complicaciones

Incidence and risk factors for hepatitis C among injection drug users in Baltimore, Maryland.

Between 1988 and 1996, the incidence of and risk factors for hepatitis C virus (HCV) infection were studied in a cohort of injection drug users in Baltimore, Maryland. By second-generation antibody testing of stored serum samples, 142 participants were found to be susceptible to HCV at the time they entered the study. After a median follow-up of 6.5 years, 43 participants (30.3%) developed antibodies to HCV (anti-HCV). The overall incidence was 6.4 cases per 100 person-years, but a substantial decline in the annual incidence rate was observed after the first 2 years (1988 to 1990, 13.4/100 person-years; 1991 to 1996, 2.3/100 person-years [P = 0.0001 for trend]). Participants who acknowledged active drug use, especially those who acknowledged frequent use and sharing of drug paraphernalia, were at increased risk of HCV infection. However, high-risk sexual practices were not associated with HCV seroconversion. Efforts to reduce HCV infection must be focused on curbing drug use and especially on the sharing of needles and drug paraphernalia.

Hepatitis A among homosexual men and injection drug users: more evidence for vaccination.

As agencies develop guidelines for administering the newly developed hepatitis A virus (HAV) vaccine, information is needed regarding the occurrence of HAV infection in groups putatively at risk for the infection. We tested serum samples from 300 injection drug users (IDUs), 300 homosexual males, and 300 blood donors for the presence of total antibody to HAV (anti-HAV). Anti-HAV was detected in 66% of IDUs, 32% of homosexual males, and 14% of blood donors. Anti-HAV was not significantly associated (P > .10) with high-risk drug-using behaviors but was more prevalent among IDUs with annual incomes of <$5,000 (P = .018). The occurrence of anti-HAV increased among homosexual males as the number of sexual partners increased (P < .001) but was similar to the age-adjusted prevalence (30.6%) estimated for the general United States population. IDUs are at increased risk for HAV infection; however, our data suggest that factors related to low socioeconomic status contribute more to the occurrence of HAV infection among IDUs than does injection drug use. IDUs and persons at risk for injection drug use should receive HAV vaccine.