Frequency Of Recurrent Disease Research Articles

Long-term survival in venous thromboembolic disease: rivaroxaban vs. warfarin – propensity score matching study

BackgroundVenous thromboembolic disease (VTE) is characterized by obstruction of venous blood flow by a thrombus. Survival data, frequency of disease recurrence, and bleeding rate in patients on anticoagulant therapy with warfarin compared to rivaroxaban in the Latin American population are limited in VTE.MethodsA retrospective cohort study with propensity score matching analysis was conducted in patients with pulmonary embolism and/or deep vein thrombosis anticoagulated with warfarin or rivaroxaban treated. Survival analysis was performed using a Kaplan-Meier curve for each of the intervention groups, and it was compared using a Log Rank test.ResultsOf 2193 potentially eligible patients with a suspected diagnosis of VTE, 505 patients entered the analysis; of these, 285 subjects were managed with warfarin and 220 anticoagulated with rivaroxaban. Major bleeding at 12 months occurred in 2.7% (6/220) of patients treated with Rivaroxaban, compared to 10.2% (29/285) in the Warfarin group in the unmatched population (p = 0.001). In the matched population, bleeding at 12 months occurred in 2.9% (6/209) of patients on Rivaroxaban and in 11.0% (23/209) of patients on Warfarin (p = 0.001). The survival rates at 6 months were 97.1% for Rivaroxaban and 97.6% for Warfarin (p = 0.76). At 12 months, the survival rates were 94.7% for Rivaroxaban and 95.7% for Warfarin (p = 0.61).ConclusionIn the treatment of VTE, there is no differences on 6 and 12-month survival or a reduction in the occurrence of new thromboembolic events when comparing rivaroxaban to warfarin. However, a lower risk of major bleeding is observed at 12 months with Rivaroxaban.

Reconstruction of Facial Skin Defects with Flap and Graft Techniques: A Comparative Study

Background: Reconstruction of facial skin defects is challenging. Skin flaps and grafts are well-known techniques for reconstructing these defects. The outcomes of the surgeries can vary depending on the surgical procedures and the patient's characteristics. Objectives: This study aimed to compare the results of reconstructing facial skin defects using skin grafts and flaps in patients referred to Imam Reza Hospital, Birjand, Iran. Methods: This quasi-experimental study was performed on 100 patients with tumors and traumatic lesions in the facial area referred to the plastic surgery service of Imam Reza Hospital, Birjand, Iran. For comparison, the data of 50 patients with skin grafts and 50 patients with flaps who underwent facial skin defect repair surgery were collected. Patients' demographic characteristics were extracted from their hospital records. The final reconstruction results were evaluated based on the presence or absence of aesthetic or functional complications three months after surgery. Results: The mean ages of participants were 64.6±14.0 and 58.3±19.1 in the flap and graft groups, respectively. Women comprised 26 (52%) of the flap and 22 (44%) of the graft groups. The mean size of lesions in the graft group was 21.3±17.3 cm and 4.7±3.9 cm in the flap group (P=0.001). The frequency of aesthetic and functional complications in the flap group was 13 (26%) and 9 (18%), and in the graft group was 24 (48%) and 15 (30%), respectively. The frequency of aesthetic complications in the flap group was significantly lower than that in the graft group (P=0.023). There was no significant difference between the two groups in terms of the frequency of functional complications (P=0.160). The frequency of disease recurrence was not significantly related to surgical technique (P=0.749). Furthermore, the lesion location had a significant association with the surgical technique (P=0.009); however, the number of surgeries had no significant association with the surgical technique (P=0.389). Conclusion: In general, except for when there is an indication for using a method, the reconstruction of facial skin defects using a skin flap will have better results than a skin graft.

Первый опыт применения тканеинженерных конструкций для хирургической коррекции опущения передней стенки влагалища

Objective. To study the effectiveness and safety of new surgical method for correcting the anterior vaginal wall prolapse using tissue-engineered constructs. Patients and methods. After preliminary experimental work on the creation and evaluation of the biocompatibility of tissueengineered constructs based on non-biodegradable (polypropylene and titanium endoprostheses) mesh implants with an autologous cellular component (rat and human dermal fibroblasts), 4 patients aged 44, 54, 70 and 75 years were examined. Inclusion criteria: anterior vaginal wall prolapse (stage II – III); consent to the installation of tissue-engineered construct. A fourstage surgical program providing for the correction of stage II-III anterior vaginal wall prolapse using tissue-engineered constructs of individual size was used. Results. In the early postoperative period, one patient was diagnosed with a small hematoma of the anterior vaginal wall. During the first month after surgery, one patient complained of gradual perineal pain, another patient – of frequent urination. Subsequently, these symptoms stopped. After 3, 6, 9, 12, 15 months after surgery, during the pelvic examination at rest, the Valsalva maneuver and transperineal ultrasound, no displacement of organs was detected, ultrasound clearly visualized a tissueengineered construct without displacement and deformation. Conclusion. We have developed an original method for correcting the prolapse of the anterior vaginal wall using tissueengineered constructs based on polypropylene and titanium with an autologous cellular component, which helps to optimize the results of surgical treatment, reduce the frequency of disease recurrence and the risk of developing mesh-related complications. Key words: pelvic organ prolapse, tissue-engineered constructs, surgical correction

Emergency Embolization of Pelvic Vessels in Patients With Locally Advanced Cervical Cancer and Massive Vaginal Bleeding: A Case Series in a Latin American Oncological Center.

PURPOSELocally advanced cervical cancer may present with uncontrollable vaginal bleeding in up to 70% of cases. Pelvic vessel embolization has been used as an urgent maneuver for achieving fast hemostatic control. This report describes outcomes of selective pelvic vessel embolization in patients with severe bleeding due to a locally advanced cervical cancer.METHODSIn this retrospective study, technical aspects, clinical variables, and bleeding-related morbidity were described. The frequency of recurrent disease and the vital status at 1 year of follow-up were determined. Analysis was performed with statistical software R, version 3.6.2. The setting was Instituto Nacional de Cancerología- Bogotá, Colombia, between January 2009 and July 2017.RESULTSA total of 47 patients were included. Median age was 44 years (range, 26-70 years). The pre-embolization median hemoglobin level was 7.9 g/dL (range, 5.0-11.3 g/dL). Blood transfusions were administered to 41 women (87.2%). Bleeding control was achieved in 95.7% of cases in the first 24 hours after the embolization. There were no major complications. In 17 cases (36.2%), minor complications were reported; the most common was pelvic pain. In 17.1% of cases, a second embolization was required. After 12 months of follow-up, 27.7% of patients were alive without disease, 44.7% were alive with disease, and 25.5% of them have died of cervical cancer progression.CONCLUSIONSelective pelvic vessel embolization is a useful alternative in patients with locally advanced cervical cancer and life-threatening bleeding. Its impact on recurrent disease and death due to oncologic cause is not clear.

Early Recurrence in Completely Resected IIIB and IIIC Melanoma Warrants Restaging Prior to Adjuvant Therapy

PurposeTo evaluate the results of restaging completely resected stage IIIB/C melanoma prior to start of adjuvant therapy.Patients and MethodsOne hundred twenty patients with stage IIIB or IIIC (AJCC 2009) melanoma who underwent complete surgical resection were screened for inclusion in our trial investigating adjuvant dendritic cell therapy (NCT02993315). All patients underwent imaging to exclude local relapse or metastasis before entering the trial. The frequency of recurrent disease within 12 weeks after resection and the method of detection were investigated.ResultsSixty-nine (58%) stage IIIB and 51 (43%) stage IIIC melanoma patients were screened. Median age was 54 (range 27–79) years. Twenty-two (18%) of 120 patients with completely resected stage IIIB/C melanoma had evidence of early recurrent disease, despite exclusion thereof by prior imaging. Median interval between resection and detection of relapse was 7.4 (range 4.3–10.7) weeks. Recurrence was asymptomatic in 17 (77%) patients, but metastasis was noticed by the patient or physician in 5 (23%). Eight patients with local relapse received local treatment with curative intent, and one was treated with systemic therapy. The remaining patients had distant metastasis, 1 of whom underwent resection of a solitary liver metastasis while 12 patients received systemic treatment.ConclusionsPatients with completely resected stage IIIB/C melanoma have high risk of early recurrence before start of adjuvant therapy. Restaging should be considered for high-risk melanoma patients before start of adjuvant therapy.

Support needs of people living with Mycobacterium ulcerans (Buruli ulcer) disease in a Ghana rural community: a grounded theory study.

Mycobacterium ulcerans (also known as Buruli ulcer) disease is a rare skin disease which is prevalent in rural communities in the tropics mostly in Africa. Mortality rate is low, yet morbidity and consequent disabilities affect the quality of life of sufferers. The aim of this paper is to use the grounded theory method to explore the support needs of people living with the consequences of Buruli ulcer in an endemic rural community in Ghana. We used the grounded theory research approach to explore the experiences of people living with Mycobacterium ulcerans in a rural district in Ghana and provide a basis to understand the support needs of this group. The key support needs identified were: functional limitations, fear and frequency of disease recurrence, contracture of limbs and legs, loss of sensation and numbness in the affected body area, lack of information from health professionals about self-care, feeling tired all the time, insomnia, lack of good diet, lack of access to prostheses, having to walk long distances to access health services, and loss of educational opportunities. The study discusses how the systematically derived qualitative data has helped to provide a unique insight and advance our understanding of the support needs of people living with BU and how they live and attempt to adapt their lives with disability. We discuss how the availability of appropriate interventions and equipment could help them self-manage their condition and improve access to skin care services. The support needs of this vulnerable group were identified from a detailed analysis of how those living with BU coped with their lives. A key issue is the lack of education to assist self-management and prevent deterioration. Further research into the evaluation of interventions to address these support needs is necessary including self-management strategies.

P0094 Tumour budding in oral squamous cell carcinomas as a prognostic factor

Background Small oral squamous cell carcinomas (OSCC) are characterised by a highly variable prognosis. New prognostic factors are needed to give patients the optimum treatment. Budding is defined as a small group of tumour cells or buds with 1–5 cells at the tumour to stroma border, and is accepted as a prognostic factor in colorectal cancer. The purpose of this study was to evaluate if tumour budding can be a prognostic factor for OSCCs. Methods Tumour-tissue from 58 patients with primary, small OSCC, at stages T1/T2, N0, and M0, was collected from the ENT department, Rikshospitalet, Oslo. After diagnosis, patients were primarily treated by surgery and 62% with postoperative radiotherapy. Follow-up information was obtained from their medical records. Budding was detected by immunohistochemistry using anti-pan-keratin antibodies, and tumour budding was scored in the most invasive part of the tumour, registrating the field with most buds (200× magnification). Findings were correlated with treatment and follow-up information. Findings All the carcinomas stained positively for pan-keratin. The tumours were split into two groups: low-budding ( Interpretation Tumour budding in the tumour front was detected in most of the OSCCs, and a high number of buds were associated with a higher frequency of recurrent disease. This indicates a possible clinical value for use of such scoring.

Abstract PD05-01: Next generation genomic sequencing (NGS) identifies molecular targets in inflammatory breast cancer (IBC)

Abstract BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of invasive breast cancer and is associated with poor outcome in spite of optimal multidisciplinary management. The disease is associated poor response to neoadjuvant chemotherapy and a peculiar pattern of recurrence (chest wall, nodes, CNS). There currently few distinct molecular alterations for effective therapeutic targeting in the advance setting. The availability of comprehensive cancer genomic testing using Next-Generation Sequencing (NGS) technology may identify a number of genomic alterations not assessed by traditional methods and provide opportunities for more effective treatment selection particularly in aggressive and uncommon diseases such as IBC. METHODS: Twenty-three patients with refractory metastatic IBC were included in this analysis. All patients underwent confirmatory biopsy and/or tissue collection. Tissue from metastastic lesions of patients with recurrent IBC was submitted as slides or FFPE blocks. NGS was performed by Foundation Medicine, Cambridge, MA. The entire coding sequence of 182 cancer-related genes (3,230 exons) plus 37 introns from 14 genes often rearranged in cancer were sequenced to high depth (>500X) All classes of genomic alterations were detected. RESULTS: The site distribution and frequency of disease recurrence included: soft tissue (19) lung (4), bone and liver (3), and brain (2). The disease subtype classification based on the expression of ER, PR and HER-2 were as follow: ER−, PR−, Her-2−, Basal-like or TN (65%); ER+ and/or PR+, HER-2− (grade3) or HER-2+, Luminal B (22%); ER−, PR−, HER2+ (13%). Genomic alterations were identified in all patients with various frequencies. Genetic mutations included: P53 (DNA-binding domain, splice site), PI3KCA (H1047R, R441N, E545K, K111E,); RB1; PTEN (D107Y); EGFR (L858R); ERBB2 (V777L, S310F) in a patient with TN disease; ESR1 D538G. Gene amplifications included: MYC (26%); CCND1 (22%); ERBB2 (in a patient with TN disease), MLC-1, CCNE1, CK4, K-RAS. One patient had evidence of discordant genomic abnormalities in two simultaneous sites of recurrence (skin and pleura) suggesting disease heterogeneity. Three patients were effectively treated with genomic alterations-guided therapies. CONCLUSIONS: Genomic sequencing of advanced IBC is feasible, identifies potential therapeutic targets and can advance our understanding of the molecular alterations of this aggressive disease. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD05-01.

A Vaxfectin®-adjuvanted HSV-2 plasmid DNA vaccine is effective for prophylactic and therapeutic use in the guinea pig model of genital herpes

Here we describe studies in the guinea pig model of genital herpes to evaluate a novel plasmid DNA (pDNA) vaccine encoding the HSV-2 glycoprotein D and UL46 and UL47 genes encoding tegument proteins VP11/12 and VP 13/14 (gD2/UL46/UL47), formulated with a cationic lipid-based adjuvant Vaxfectin®. Prophylactic immunization with Vaxfectin®-gD2/UL46/UL47 significantly reduced viral replication in the genital tract, provided complete protection against both primary and recurrent genital skin disease following intravaginal HSV-2 challenge, and significantly reduced latent HSV-2 DNA in the dorsal root ganglia compared to controls. We also examined the impact of therapeutic immunization of HSV-2 infected animals. Here, Vaxfectin®-gD2/UL46/UL47 immunization significantly reduced both the frequency of recurrent disease and viral shedding into the genital tract compared to controls. This novel adjuvanted pDNA vaccine has demonstrated both prophylactic and therapeutic efficacy in the guinea pig model of genital herpes and warrants further development.

Effects of herpes simplex virus type 2 glycoprotein vaccines and CLDC adjuvant on genital herpes infection in the guinea pig

Genital herpes simplex virus (HSV) infections are common but results from vaccine trials with HSV-2 glycoprotein D (gD) have been disappointing. We therefore compared a similar HSV gD2 vaccine, to a further truncated gD2 vaccine, to a vaccine with gD2 plus gB2 and gH2/gL2 and to a vaccine with only gB2 and gH2/gL2 in a guinea pig model of genital herpes. All vaccines were administered with cationic liposome-DNA complexes (CLDC) as an adjuvant. All vaccines significantly decreased the severity of acute genital disease and vaginal virus replication compared to the placebo group. The majority of animals in all groups developed at least one episode of recurrent disease but the frequency of recurrent disease was significantly reduced by each vaccine compared to placebo. No vaccine was significantly more protective than gD2 alone for any of the parameters described above. No vaccine decreased recurrent virus shedding. When protection against acute infection of dorsal root ganglia and the spinal cord was evaluated all vaccines decreased the per cent of animal with detectable virus and the quantity of virus but again no vaccine was significantly more protective than another. Improvements in HSV-2 vaccines may require inclusion of more T cell targets, more potent adjuvants or live virus vaccines.

Pneumonectomy for Lung Cancer After Preoperative Concurrent Chemotherapy and High-Dose Radiation

We studied the clinical characteristics and outcomes of patients undergoing pneumonectomy after preoperative concurrent chemoradiation for non-small cell lung cancer. Clinical records of patients with non-small cell lung cancer who underwent pneumonectomy at our institution between 1995 and 2005 after preoperative concurrent chemoradiation were reviewed retrospectively. Twenty-nine patients underwent pneumonectomy after preoperative concurrent chemoradiation. Of the 21 men and 8 women who were treated, 1 had stage IIB (T3N0M0) and the remainder had stage IIIA or IIIB non-small cell lung cancer. Mean patient age at surgery was 53.4 years. There were 15 right pneumonectomies, of which 2 were for pancoast tumors. All patients received concurrent preoperative chemoradiation. Mean total radiation dose was 61.1 Gy. All patients went on to have complete (R0) resection by pneumonectomy. Pathologic complete response was found in 16 patients (55.2%). All patients were discharged alive from the hospital after pneumonectomy. Median hospital length of stay was 5 days (mean 8.6). Ninety-day mortality after surgery was 3.4% (n = 1). Recurrences have been found in 11 patients (38%), including brain metastases (n = 6), bone metastases (n = 4), liver metastases (n = 2), and cervical lymph node metastases (n = 2). One patient had a contralateral new primary lung cancer develop 70 months after undergoing pneumonectomy. Estimated 5-year disease-free survival is 48%. Median survival time has not been reached. Pneumonectomy can be performed safely after preoperative concurrent chemoradiation, even with high-dose radiation. The frequency of disease recurrence in the brain underscores the need to evaluate the role of prophylactic cranial radiation in non-small cell lung cancer.

Differentiated operative therapy of thyroid autonomy (Plummer's disease).

The operative therapy of the autonomous thyroid deals almost exclusively with nodular goiters. There are only rare situations with purely diffuse autonomy in surgical patients. The endpoint of operative therapy is permanent elimination of clinically relevant autonomous function and thereby irreversible abolition of thyrotoxicosis, even in their latent form. Clinically relevant autonomous function normally ist linked to nodular structures of different size and different distribution, so that this aim corresponds automatically with the aim of complete removal of nodular structures, both in autonomous and in non-autonomous goiters. Function is best preserved by leaving a homogenous remnant of considerable size. In different particular clinical situations (for example pregnancy, suspicion of malignancy, recurrent goiter, intrathoracic goiter, thyrotoxic crisis, Marine-Lenhart-syndrome) the basic principal of operative strategy is varied according to the respective situations. Unsatisfactory operative results are mainly caused by incomplete removal of nodules, based on insufficient surgical performance of morphological and functional diagnostics, which is related to operative uniformity. An operative strategy, which ist "fitted to morphology" and "regarding function" and which we call "selective strategy", in our opinion ist highly appropriate, to avoid remnant nodules and remnant autonomy and to preserve an normal remnant, even in different position and of different size. This selective surgery ist applicable both to autonomous and non-autonomous goiter. Compared with the classic subtotal, uniform procedure the incidence of remnant nodules is reduced from about 50% to about 5 %. Remnant autonomy is almost excluded, when mistakes are avoided (about 1%). The incidence of recurrent goiter and recurrent thyrotoxicosis is lowered to under 5%--but up to now there are too few reliable long-term follow-up studies. The selective surgery strategy demands flexibility regarding operative tactics, which can be simply classified into 5 basic situations, which we relate to the operative procedure per thyroid lobe. It requires experience and competence in carefully dissecting and--when necessary--manipulating the recurrent laryngeal nerve und the parathyroid glands. Under these conditions it is followed by a comparatively low rate of complications (permanent recurrent laryngeal nerve paralysis and hypoparathyroidism under 1%, respectively). Thus, the old dilemma of thyroid surgery can be solved, which consists of radical operation with higher morbidity and lower frequency of recurrent disease on the one hand and more limited operative procedures with fewer complications but more frequent recurrencies on the other hand.

Delayed start of adjuvant 5-FU/leucovorin based chemotherapy in colon cancer is safe up to 12 weeks postoperatively

4056 Background: Postoperatively adjuvant chemotherapy with 5-Fluorouracil modulated by leucovorin alone or in combination with Oxaliplatin significantly reduce the risk of recurrence and prolong the disease free survival (DFS) in patients with a radical resection for colonic carcinoma. In all reported studies the chemotherapy has started within 6–8 weeks after surgery. Due to complications following surgery it is not always possible to start adjuvant chemotherapy within this time frame. The aim of the present retrospective study was to investigate the effect on risk of recurrence and effect on DFS in patients treated in clinical routine practice in one single institution. Methods: Between 1992 and 2004, 234 patients (121 females, 113 males) with a median age of 66 years (range 25–84 years) received weekly bolus 5-FU/leucovorin postoperatively for 6 months. 211 (90.2%) had a Dukes′ C tumour and 23 (9.8%) high risk Dukes′ B tumour. The median time from surgery and start of adjuvant therapy was 71 days (range 30–190 days). Patients were divided in three groups, where chemotherapy started within 6 weeks, 8 weeks and 12 weeks after surgery and the frequency of recurrent disease and DFS were compared between these groups. Results: Medium follow-up was 35.6 months (range 2,7- 140.6 months). Five patients (21.7%) with Dukes′ B tumours and 76 patients (36.0%) with Dukes′ C tumours recurred during the follow-up period. There were no differences in the proportion of Dukes′ B and C tumours between the three groups. Recurrent disease was more frequent but no significant difference in patients that started within 6 weeks (52.6%) compared with patients that started within 8 weeks (45.5%) and 12 weeks (35.5%). In all three groups there was a tendency to better DFS in patients that started later than 6 or 8 weeks, but these differences were not significant. Conclusions: Starting adjuvant 5-Fluorouracil/leucovorin alone later than 6–8 weeks do not negatively effect the risk of recurrent disease or DFS. No significant financial relationships to disclose.

Impact of Immunization with Glycoprotein D2/AS04 on Herpes Simplex Virus Type 2 Shedding into the Genital Tract in Guinea Pigs That Become Infected

In recent clinical trials, a vaccine that contained herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) and the adjuvant AS04 afforded HSV-seronegative women significant protection against HSV-2 genital disease and limited protection against infection. Similarly, in guinea pigs, immunization with the vaccine provided significant protection against genital HSV-2 disease but did not prevent mucosal infection. We explored the impact of immunization on the magnitude of latent virus infection and on the frequency and magnitude of virus reactivation as measured by both recurrent disease and viral shedding into the genital tract. Guinea pigs immunized with gD2/AS04 were shown by quantitative polymerase chain reaction (qPCR) analysis to have significantly less latent viral DNA in the ganglia than did naive control guinea pigs and to have a reduced incidence and frequency of recurrent disease. By contrast, all immunized guinea pigs shed virus into the genital tract with a frequency comparable to that seen in control guinea pigs. However, the amount of virus shed was significantly reduced, as measured by qPCR. These data suggest that immunization could affect transmission by altering viral shedding patterns.

Adult-Onset Still Disease in Southeast Brazil

Adult-onset Still disease (AOSD) has been described all over the world. Clinical presentations and prognosis have varied in different studies. The objective of this study was to determine the clinical presentation and the evolution of AOSD at a tertiary referral center in southeast Brazil. The clinical records of 16 patients were retrospectively studied to determine symptoms at diagnosis, follow up, and the medication prescribed. The mean age at onset was 30.8 years (range, 24-55 years; standard deviation [SD], 9.2 years) with a slight male prevalence (54.2%). All patients presented constitutional symptoms, fever, and skin rash. Liver involvement was observed in all cases, with hepatomegaly in 81.3%, increased liver enzymes in 50.0%, and hypergammaglobulinemia in 68.8%. Cardiac involvement was observed in 12.6%, pleuritis in 6.3%, and renal involvement in 25.0%. All patients presented leukocytosis with a predominance of neutrophils. Elevated ferritin levels were observed in 56.3%, and these levels were normalized after disease remission. Initial treatments included nonsteroidal antiinflammatory drugs and low-dosage corticosteroids in all patients; 43.8% also needed methotrexate. In 25.0% of cases, a monocyclic disease was observed; others had recurrent episodes. After a follow up of 6.9 years (SD, 1.2 years), carpal ankylosis was the main articular sequel, observed in 53.6% of the patients. AOSD is rare in southeast Brazil. Although less severe systemic manifestations, like serositis and pneumonitis, were observed, reversible liver involvement was common; the frequency of recurrent disease and carpal ankylosis was higher than in previous studies.

Development of HSV-specific CD4+ Th1 responses and CD8+ cytotoxic T lymphocytes with antiviral activity by vaccination with the HSV-2 mutant ICP10ΔPK

A growth compromised herpes simplex virus type 2 (HSV-2) mutant which is deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10ΔPK) protects from HSV-2 challenge in the mouse and guinea pig cutaneous and vaginal models and reduces the incidence and frequency of recurrent disease (Vaccine (17) (1999) 1951; Vaccine (19) (2001) 1879). The present studies were designed to identify the immune responses induced by ICP10ΔPK and define the component responsible for protective activity. We found that ICP10ΔPK elicits a predominant HSV-specific T helper type 1 (Th1) response, as evidenced by: (1) higher levels of HSV-specific IgG2a (Th1) than IgG1 (Th2) isotypes and (2) higher numbers of CD4+ IFN-γ than IL-10 secreting T cells in popliteal lymph nodes. This Th1 response pattern was associated with a significant increase in the levels of IL-12 produced by dendritic cells from ICP10ΔPK than HSV-2 immunized animals. Lymph node cells (LNCs) from ICP10ΔPK immunized mice had significantly higher levels of HSV-2 specific cytolytic activity than LNCs from mice immunized with HSV-2 and it was mediated by CD8+ T cells. CD8+ CTL were not seen in LNCs from HSV-2 immunized mice. In adoptive transfer experiments, CD8+ T cells and, to a lower extent, CD4+ T cells from ICP10ΔPK immunized mice inhibited HSV-2 replication, suggesting that they are involved in the protective immunity induced by ICP10ΔPK vaccination.

Frequency and CT findings of recurrent disease after lung transplantation.

To determine the frequency and computed tomographic (CT) findings of recurrence of the primary disease after lung transplantation at six North American lung transplantation centers. Medical records of 1,394 lung transplant recipients were reviewed to identify patients with recurrent primary disease. Their CT scans and pathologic specimens were reviewed. The frequency of disease recurrence in the six transplantation centers was 1% (15 of 1,394 patients), including six previously reported cases. Sarcoidosis recurred in nine (35%) of 26 transplants and was the most common disease to recur. Three (33%) of nine patients with recurrent sarcoidosis had correlative findings at CT. When present, CT findings were usually different at recurrence compared with pretransplantation CT findings. A relatively small percentage of patients are at risk for recurrence of primary disease following lung transplantation. Sarcoidosis is the most common disease to recur.

Clear Cell Carcinoma of the Uterine Cervix: Pathology and Prognosis in Surgically Treated Stage IB–IIB Disease in Women Not Exposed in Utero to Diethylstilbestrol

Objective. The purpose of this research was to compare the clinical behavior, pathology findings, and prognosis of surgically treated FIGO stage IB–IIB clear cell carcinomas of the cervix with those of squamous cell carcinomas and non-clear cell adenocarcinomas.Methods. Fifteen patients with clear cell adenocarcinomas of the cervix (8 FIGO stage IB, 7 FIGO stage IIB) were reviewed. The control group consisted of 444 squamous cell carcinomas and 59 non-clear cell adenocarcinomas. None of the patients had a history of in utero exposure to diethylstilbestrol. All patients underwent radical abdominal hysterectomy with systematic pelvic lymphadenectomy. All specimens were processed as serial giant frontal sections. The mean follow-up in the clear cell group was 83 (13–182) months. Statistical analysis was done with contingency tables, χ2 tests, and Fisher's exact test.Results. Twelve of the fifteen clear cell carcinomas (80%) were endophytic and tended toward deep cervical infiltration. Clear cell carcinomas extended to the uterine corpus significantly more often than squamous cell and non-clear cell adenocarcarcinomas (P < 0.001). The rates of parametrial involvement and pelvic lymph node involvement were 40 and 47%, respectively. Four patients (27%), all with positive pelvic nodes, developed recurrences an average of 14 (4–48) months after initial therapy. The extrapelvic sites of relapse were the lung, liver, and bone. Clear cell carcinomas had a worse 5-year survival rate (67%) than squamous cell carcinomas (80%) and non-clear cell adenocarcinomas (77%) but this was not statistically significant (P = 0.6). No significant differences were seen for age, growth pattern, parametrial and vaginal involvement, parametrial and pelvic lymph node metastases, frequency of recurrent disease, and time to first recurrence.Conclusion. The clinicopathologic findings and prognosis of surgically treated patients with stage IB–IIB clear cell carcinomas without exposure to diethylstilbestrol in utero are similar to those of patients with squamous cell carcinomas and non-clear cell adenocarcinomas.

Association between the HLA DQB1*0301 gene and human papillomavirus infection in high-grade cervical intraepithelial neoplasia.

This study describes the distribution of DQB1genes in Norwegian women treated for high-grade cervical intraepithelial neoplasia (CIN). Formalin-fixed, paraffin-embedded tissue sections from 170 biopsy specimens with diagnoses of CIN II (n = 54) or CIN III (n = 116) were DQB1-typed using allele-specific polymerase chain reaction. The follow-up period for cases was 13 to 15 years. The control material comprised blood samples and endocervical brushes from 213 women without CIN. Both cases and controls had previously been human papillomavirus (HPV)-typed. The DQB1*0301 allele was overrepresented among cases compared with controls (odds ratio [OR] = 1.8). Presence of CIN was related to HPV infection, and HPV 16 positivity was significantly associated with the presence of DQB1*0301 (OR 1.8). The DQBI*0301 allele was significantly more prevalent in CIN III than in CIN II cases. The lesions in two women recurred in the follow-up period, one of whom was carrying the DQB1*0301 allele. Women carrying the HLA-DQB1*0301 allele have an increased risk of developing CIN when infected by HPV 16, although there was not an increased frequency of recurrent disease among women carrying this allele.

Specific therapies for human papilloma virus infections

Human papillomavirus induces the hyperproliferation of epithelial cells, leading to a broad spectrum of human diseases, ranging from benign warts to malignant neoplasms, depending on the location of the lesion, the immune status of the patient and the type of human papillomavirus. Current therapies for human papillomavirus-associated diseases are based on the excision or ablation of dysplastic or malignant tissue, and are associated with a high frequency of recurrent disease, discomfort and costs. A better understanding of the viral replicative cycle and of the interaction between the virus and the host cell, particularly the cell cycle regulation, has opened new perspectives. Recently, new treatment modalities for human papillomavirus-induced lesions have been identified, including the use of antiviral/immunomodulatory therapies, such as cidofovir, antisense oligonucleotides, imiquimod and human papillomavirus vaccines.