HPV E6 oncoproteins and nucleic acids in neck lymph node fine needle aspirates and oral samples from patients with oropharyngeal squamous cell carcinoma.

Commercial assays measuring HPV E6 viral oncoproteins, E6/E7 mRNA or DNA were used to test neck lymph node fine needle aspirates (FNA) and oropharyngeal samples (saliva and oral swabs) from 59 Canadian patients with oropharyngeal squamous cell carcinomas (OPSCC). Overall agreements of p16 antigen staining of tumors to FNA tested for OncoE6™, Aptima HPV E6/E7 mRNA and cobas HPV DNA were 81.4% (k 0.53), 94.9% (k 0.83) and 91.1% (k 0.73) respectively. Using HPV presence in a subset of 25 tumors as the comparator, overall agreement was 64.0% (k 0.08) with OncoE6™, 88.0% (k 0.65) with Aptima HPV E6/E7 mRNA and 91.7% (k 0.70) with cobas HPV DNA. HPV testing of oropharyngeal samples yielded lower agreements with tumor markers; 23.7-24.0% (k 0.02), 55.9-68.0% (k 0.24-0.37) and 78.9-86.9% (k 0.49-0.58) in the 3 respective tests. HPV 16 was present in 93.7-100% of the samples tested and showed 100% genotype agreement between FNA and tumors. The high rates for HPV E6 oncoproteins and E6/E7 mRNA suggests most patients were experiencing transcriptionally active HPV-related OPSCC. Results from these commercial assays performed on FNA but not oropharyngeal samples showed moderate to very good agreements with p16 and HPV testing of tumors.

Lymphogranuloma venereum in Quebec: Re-emergence among men who have sex with men.

BACKGROUND: Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis genotypes L1, L2 and L3. This LGV is associated with significant morbidity and increased risk of HIV transmission. While fewer than two cases per year were reported in Quebec before 2005, LGV emerged in 2005-2006 with 69 cases, followed by a period of low incidence (2007-2012), and subsequent re-emergence since 2013. OBJECTIVES: To describe the incidence of LGV in Quebec and the characteristics of the affected population, including demographics and risk factors, clinical manifestations, laboratory tests, treatments and reinfection rates. METHODS: Descriptive data were collected from the notifiable diseases records through the Institut national de santé publique du Québec (INSPQ) infocentre portal. Questionnaires were obtained through the enhanced surveillance system and transmitted anonymously to the Quebec Ministry of Health. In-depth analysis was performed on cases from 2013 to 2016. RESULTS: There were 338 cases of LGV over the four-year period in Quebec. All cases were male, excluding one transsexual. Mean age was 41 years. Most lived in Montréal (81%) and were men who have sex with men (MSM; 99%). The majority (83%) reported four sexual partners or more in the last year, met mostly through the Internet (77%) and in saunas (73%). Frequency of sexual intercourse with out-of-province residents decreased in 2013-2016 (27%) compared with 2005-2012 (38%). History of STIs was frequent: 83% were HIV-infected, 81% reported previous syphilis and 78% previous gonorrhea. Recreational drug use was frequent (57%), reaching 71% in 2016. Most cases were symptomatic, a proportion which decreased in 2016 (68%) compared with 2013-2015 (82%; p=0.006). Clinical presentations included proctitis (86%), lymphadenopathy (13%) and ulcer/papule (12%). Reinfections, mostly within two years of first infection, occurred in 35 individuals (10%).Conclusion: The re-emergence of LGV in Quebec involves an urban subpopulation composed almost exclusively of MSM with STIs, who have a high number of partners and often use drugs.

Chlamydia and lymphogranuloma venereum in Canada: 2003-2012 Summary Report.

BACKGROUND: Chlamydia continues to be the most commonly reported sexually transmitted infection in Canada. Lymphogranuloma venereum (LGV), caused by certain serovars of Chlamydia trachomatis, is becoming established in some populations in a number of Western countries. OBJECTIVE: To identify trends in reported cases of chlamydia and LGV in Canada from January 1, 2003 to December 31, 2012. METHODS: Notifiable disease data on chlamydia were submitted to the Public Health Agency of Canada by provincial and territorial epidemiological units and summarized at the national level by age and sex. Confirmatory testing for suspected LGV cases and serovar subtyping were performed by the National Microbiology Laboratory (NML). Where possible, provincial/territorial health authorities use a standardized national case report form to collect enhanced epidemiological data on each case and to submit the data to the Agency. RESULTS: Rates of reported cases of chlamydia increased by 57.6%, from 189.6 to 298.7 per 100,000 between 2003 and 2012. The rate of reported cases of chlamydia among females (383.5 per 100,000) was almost twice as high as that among males (212.0 per 100,000), although the highest relative rate increase occurred among males. In both males and females, the rates of chlamydia were highest in those aged 20 to 24 years. From 2004 to 2012, 170 cases of LGV were reported to the Agency by provincial health authorities (including 104 confirmed and 66 probable cases). In 2012, case reports were received on 12 confirmed and probable cases, compared to 38 laboratory-positive cases confirmed by the NML. CONCLUSION: In Canada, as in many countries, chlamydia rates have markedly increased over the last 10 years, in part due to improved diagnosis through nucleic acid amplification (NAAT) testing. Consistent with trends in Europe and other countries, LGV is emerging in Canada among men who have sex with men (MSM).

Type-specific human papillomavirus infections and Pap test findings in Inuit and non-Inuit women in Nunavut, Canada.

OBJECTIVE: To determine the prevalence and distribution of type-specific human papillomavirus (HPV) infections and their association with cytological outcomes in women living in the Canadian territory of Nunavut. METHODS: Surveillance of type-specific HPV infection was conducted. Cervical specimens of all Inuit, First Nations and non-Aboriginal women in Nunavut who presented for a Pap test in any clinical setting between January 2008 and March 2009 were tested for HPV infection. The association between high-grade cervical lesions and HPV type was also examined. RESULTS: HPV results were available for 4,043 individual women (13 to 77 years). Of those with known ethnicity (N=4,033), 89.2% were Inuit, 0.4% were First Nations and 10.4% were non-Aboriginal. First Nations women were included in all analyses except those making comparisons by ethnicity, due to the small number of individuals in this group. Overall, 29.9% of women were found to be infected with HPV (any type) and 19.9% with any high-risk HPV (type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 or 59). Most often, women were infected with HPV 16 (6.4%) followed by HPV 31 (3.1%). There were no statistically significant differences between Inuit and non-Aboriginal (reference group) women 20 years of age and older regarding the prevalence of any HPV (odds ratios (OR): 1.19, 95% confidence intervals (CI): 0.92-1.54), high-risk HPV (OR: 1.06, 95% CI: 0.78-1.44) or HPV 16 and 18 (OR: 0.81, 95% CI: 0.51-1.27). HPV 31 was the only type that was significantly more frequent among Inuit than non-Aboriginal women (OR: 3.95, 95% CI: 1.24-12.54). There was no difference in the overall occurrence of cervical abnormalities between non-Aboriginal and Inuit women (p-value = 0.17). HPV 16 was strongly associated with cervical dysplasia, being present in 50.9% of specimens with a high-grade lesion. CONCLUSION: HPV is a significant public health issue in the territory of Nunavut. The findings presented in this article are similar to those in other studies among Inuit women, with prevalence of HPV being higher than in studies conducted among non-Inuit women in other regions of Canada. These results provide a baseline of HPV prevalence that precedes the introduction of the Nunavut HPV Immunization Program in 2010 and will allow for future evaluation. The high prevalence of HPV infection among women living in Nunavut can be reduced through immunization and associated high-grade cervical abnormalities mitigated by regular cervical screening.

Measles molecular epidemiology: What does it tell us and why is it important?

Measles molecular epidemiology was a key component of the verification of elimination of indigenous measles in Canada and is an invaluable tool during public health investigations, both to establish whether connections exist between concurrent measles cases and to indicate possible sources of importations. There are 24 distinct genotypes however the genotype is usually not sufficient to describe the complex molecular epidemiology of measles cases. The exact genetic sequence of the last 450 nucleotides of the nucleoprotein (N) gene (N-450) is used. The measles genome mutates very slowly and so cases within the same chain of transmission usually have identical N-450 sequences. In Canada, the National Microbiology Laboratory (NML) sequences the N-450 and deposits it into the WHO measles sequence database, MeaNS. This database can be used to identify other geographic regions where the measles sequence was detected, supporting or excluding connections. For commonly detected N-450 sequences, MeaNS designates a "sequence variant." Sequence variants are used as the defining characteristic of measles cases with identical sequences and this designation is fundamental to the description of measles molecular epidemiology both locally and globally. As progress is made towards global measles eradication, its genetic diversity decreases and distinct importations of measles from a single reservoir can be difficult to distinguish using current methods. Extending sequencing methods beyond the N-450 is required. While sequencing the entire hemagglutinin (H) gene, which is currently done routinely at the NML, can be helpful, whole genome sequencing will be required for effective molecular surveillance to monitor the sustained elimination of measles in Canada.insert text here.

Distribution of human papillomavirus types, cervical cancer screening history, and risk factors for infection in Manitoba.

OBJECTIVES: We conducted a study to investigate the prevalence of human papillomavirus (HPV) infections in an opportunistic sample of women in Manitoba, Canada. We inquired about risk factors associated with HPV infections and linked the HPV typing results with the cervical cancer screening history of the participants. METHODS: The study population included 592 women attending Papanicolaou (Pap) test clinics. After signing a consent form, participants were given a self-administered questionnaire on risk factors and received a conventional Pap test. Residual cells from the Pap tests were collected and sent for HPV typing. RESULTS: The mean age of the population was 43 years. A total of 115 participants (19.4%) had an HPV infection, 89 of whom had a normal Pap test. Of those who were HPV-positive, 61 (10.3%) had high-risk (Group 1) HPV. HPV-16 was the most prevalent type (15/115: 13.0% of infections). The most consistent risk factors for HPV infection were young age, Aboriginal ethnicity, higher lifetime number of sexual partners and higher number of sexual partners in the previous year. CONCLUSION: The prevalence of HPV types in Manitoba is consistent with the distributions reported in other jurisdictions. These data provide baseline information on type-specific HPV prevalence in an unvaccinated population and can be useful in evaluating the effectiveness of the HPV immunization program. An added benefit is in the validation of a proof of concept which links a population-based Pap registry to laboratory test results and a risk behaviour survey to assess early and late outcomes of HPV infection. This methodology could be applied to other jurisdictions across Canada where such capacities exist.

Type-specific prevalence of Human Papillomavirus infection among women in the Northwest Territories, Canada.

BACKGROUND: Certain types of Human Papillomavirus (HPV) are highly associated with cervical cancer and precursor lesions (dysplasia), but the distribution of HPVs in Northern Canada is largely unknown. This study determined the prevalences of HPV infection due to different virus types and the association of different virus types with cervical dysplasia in the Northwest Territories (NWT). METHODS: Between April 2008 and March 2009, women who underwent routine Pap testing in the NWT were included in the study. An in-house Luminex assay detected type-specific HPV infections. The HPV prevalence rates and population attributable risk fractions were calculated. RESULTS: In 5725 bio-samples, the overall HPV prevalence was 24.2%, and of the HPV-positive samples, 76.6% harbored high-risk types, 35.2% harbored multi-type infections, and 21.6% harbored HPV16 or 18 infections. The HPV prevalence was approximately 50% higher among Aboriginal than non-Aboriginal women. The age-specific HPV prevalence exhibited a U-shape distribution in the Aboriginal group. The prevalence of HPV16 or 18 infections found in high-grade lesions was 34.1%. Among this study population, 89.5% of the cases with cervical dysplasia were attributable to HPV infection, with 27.1% attributable to HPV16/18. CONCLUSION: The high prevalence of high-risk HPV in this population, particularly in the Aboriginal group, will require further studies to identify specific predictors of infection.

Genomic cartography of varicella-zoster virus: a complete genome-based analysis of strain variability with implications for attenuation and phenotypic differences.

In order to gain a better perspective on the true variability of varicella-zoster virus (VZV) and to catalogue the location and number of differences, 11 new complete genome sequences were compared with those previously in the public domain (18 complete genomes in total). Three of the newly sequenced genomes were derived from a single strain in order to assess variations that can occur during serial passage in cell culture. The analysis revealed that while VZV is relatively stable genetically it does posses a certain degree of variability. The reiteration regions, origins of replication and intergenic homopolymer regions were all found to be variable between strains as well as within a given strain. In addition, the terminal viral sequences were found to vary within and between strains specifically at the 3' end of the genome. Analysis of single nucleotide polymorphisms (SNPs) identified a total of 557 variable sites, 451 of which were found in coding regions and resulted in 187 different in amino acid substitutions. A comparison of the SNPs present in the two gE mutant strains, VZV-MSP and VZV-BC, suggested that the missense mutation in gE was primarily responsible for the accelerated cell spread phenotype. Some of the variations noted with high passage in cell culture are consistent with variations seen in the IE62 gene of the vaccine strains (S628G, R958G and I1260V) that may help in pinpointing variations essential for attenuation. Although VZV has been considered to be one of the most genetically stable human herpesviruses, this initial assessment of genomic VZV cartography provides insight into ORFs with previously unreported variations.

The diagnosis of genital herpes - beyond culture: An evidence-based guide for the utilization of polymerase chain reaction and herpes simplex virus type-specific serology.

Accurate identification of persons with genital herpes is necessary for optimal patient management and prevention of transmission. Because of inherent inaccuracies, clinical diagnosis of genital herpes should be confirmed by laboratory testing for the causative agents herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). Further identification of the HSV type is valuable for counselling on the natural history of infection and risk of transmission. Laboratory methods include antigen detection, culture, polymerase chain reaction (PCR) and conventional and type-specific serology (TSS). PCR has, by far, the greater sensitivity and should be the test of choice for symptomatic cases. HSV-2 TSS is indicated for patients with genital lesions in whom antigen detection, culture or PCR fail to detect HSV, and for patients who are asymptomatic but have a history suggestive of genital herpes. HSV-2 TSS is further indicated for patients infected with HIV. HSV-2 TSS along with HSV-1 TSS may be considered, as appropriate, in evaluating infection and/or immune status in couples discordant for genital herpes, women who develop their first clinical episode of genital herpes during pregnancy, asymptomatic pregnant women whose partners have a history of genital herpes or HIV infection, and women contemplating pregnancy or considering sexual partnership with those with a history of genital herpes. The above should be performed in conjunction with counselling of infected persons and their sex partners.

Long-term results of balloon dilation of benign bile duct strictures.

PURPOSE: To evaluate the results of percutaneous balloon dilation of benign bile duct strictures in a series of patients with a long follow-up period. MATERIAL AND METHODS: 56 patients with benign bile duct strictures underwent balloon catheter dilation. These patients had strictures of various origins: postsurgical, postlocal not surgical treatments, associated with gallstones, due to primary sclerosing cholangitis and to Mirizzi's syndrome. In 41 cases the diagnosis was made on the basis of radiological findings and history and in 15 cases on the basis of transluminal biopsy. RESULTS: In 87.5% of cases the treatment was immediately successful. There were no early recurrences, but 7 (21%) recurrences were seen over 1 year after treatment; of these, 57% underwent another balloon dilation procedure with a positive long-term outcome. CONCLUSION: The long-term success rate obtained in 72% of this series confirms that percutaneous bile duct dilation is a valid alternative to surgery without being burdened by complications; the procedure is also a valid alternative to the approach using endoscopic stents.

Prevalence of human papillomavirus in Mazandaran Province, Islamic Republic of Iran.

We report the prevalence of human papillomavirus (HPV) types in 100 cervical biopsy specimens in Mazandaran province. HPV DNA was detected in 78.6% of cervical carcinoma cases, 64.3% of dys/ metaplasia and 9% of normal cases. Significant correlation was found between the presence of HPV DNA and development of cervical carcinoma. HPV types 16 and 18 were detected in 60.6% of HPV-positive cervical carcinoma cases, whereas HPV31 and 33 were found in 21.2%, and HPV6 and 11 in 18.2%. Among HPV-positive dys/metaplasia cases, 55.6% were positive for HPV16 and 18, 22.3% for HPV6 and 11, and 11.1% for HPV31 and 33. Only HPV6 and 11 were detected in 4 (100%) normal biopsy specimens.

Prevalence of human papillomavirus in Mazandaran Province, Islamic Republic of Iran

We report the prevalence of human papillomavirus [HPV] types in 100 cervical biopsy specimens in Mazandaran province. HPV DNA was detected in 78.6% of cervical carcinoma cases, 64.3% of dys/ metaplasia and 9% of normal cases. Significant correlation was found between the presence of HPV DNA and development of cervical carcinoma. HPV types 16 and 18 were detected in 60.6% of HPV-positive cervical carcinoma cases, whereas HPV31 and 33 were found in 21.2%, and HPV6 and 11 in 18.2%. Among HPV-positive dys/metaplasia cases, 55.6% were positive for HPV16 and 18, 22.3% for HPV6 and 11, and 11.1% for HPV31 and 33. Only HPV6 and 11 were detected in 4 [100%] normal biopsy specimens

Diagnostic and interventional radiology in the post-operative period and follow-up of patients after rectal resection with coloanal anastomosis.

Surgical treatment of carcinoma of the distal third of the rectum with anal sphincter preservation is increasingly used in accredited cancer centers. This study aimed to evaluate the diagnostic usefulness of radiological investigations in the management of patients who had undergone resection with coloanal anastomosis for carcinoma of the rectum, in the immediate post-operative period, during closure of the protective colostomy and in the follow-up of symptomatic recanalized patients. A total of 175 patients who had undergone total rectal resection with end-to-side anastomosis for carcinoma of the distal third of the rectal ampulla, most of whom had received postoperative radiotherapy, were evaluated radiologically. In the postoperative period radiological investigation was ordered only for symptomatic patients to detect pathology of the anastomosis and the pouch sutures and was used direct film abdominal radiography and contrast-enhanced radiography of the rectal stump with a water-soluble radio-opaque agent. Before closure of the colostomy, 2 months after rectal excision or approximately 4 months after if postoperative radiotherapy was given, the anastomosis and pouch of all patients, even asymptomatic ones, were studied with water-soluble contrast enema to check for normal canalization. In the follow-up after recanalization radiological examinations were done to complete the study of the large intestine if the endoscopist was not able to examine it up to the cecum. Of the 175 patients examined radiologically during the postoperative period and/or subsequent follow-up, 95 showed no pathological findings. Seventy-nine patients had fistulas of the coloanal anastomosis or the pouch, 23 of which supplied a presacral collection. In the absence of severe sepsis, the only therapeutic measures were systemic antibiotics and washing of the surgical catheters to maintain efficient operation. In 2 patients in whom transanal drainage was performed radiologically the fistula was cured in 1 week. In 36 cases of cicatricial stenosis, 17 at the coloanal anastomosis and 19 at the pouch, radiological examination always detected the lesion, correctly defining its anatomical characterisitics, nature and extension. Of the 19 cases of stenosis treated radiologically, 15 recovered an adequate intestinal calibre for tients operated on, 21 cases of reccurrence were detected. Radiological examination was requested as the first investigation in only one of these cases, for a patient with subocclusion. Radiological investigations in patients who have undergone colonanal anastomosis are of read diagnostic value in the immediate post-operative period, during closure of the protective colostomy and in the follow-up of symptomatic recanalized patients.

Percutaneous gastrostomy in oncologic patients: analysis of results and expansion of the indications.

BACKGROUND: Percutaneous gastrostomy is generally performed for permanent enteral nutrition or gastric decompression. METHODS: In our series of oncologic patients, percutaneous gastrostomy was also used temporarily in some patients for enteral nutrition while awaiting functional recovery of swallowing, in preparation for surgery, or for the treatment of fistulas in the upper digestive tract. Fifty-one procedures were performed in 50 patients: 42 for feeding, eight for decompression, and one for transgastric drainage of a duodenal fistula. RESULTS: Of the 35 patients treated for permanent enteral nutrition, four are still alive, with a total survival time of 2,167 days. In three patients, gastrostomy was performed for temporary feeding and was removed once the ability to swallow was restored. In four patients, it was created to restore metabolic balance before surgery. In the patient with a duodenal fistula, healing was achieved in 19 days. The seven patients in whom the procedure was performed for decompression survived for a mean of 19.2 days. There was only one major procedure-related complication (peritonitis). CONCLUSIONS: Percutaneous gastrostomy is a safe, low-cost method that allows the patient to maintain essential nutrition without the discomfort of a nasogastic tube and therefore warrants wider and earlier use. We feel that its application should also be extended to temporary feeding of patients about to undergo long courses of chemotherapy and radiotherapy, which can lead to severe deterioration of nutritional status.

TP53 mutations and mdm2 protein overexpression in cholangiocarcinomas.

Tumor suppressor protein p53 is a positive regulator of MDM2 gene expression and the mdm2 protein can bind to p53, preventing the transactivation of p53 responsive genes, thus mimicking TP53 mutation. The authors looked for alterations that could affect, directly and indirectly, p53 function in 13 patients with extrahepatic cholangiocarcinoma. Molecular analysis by single strand conformation polymorphism and DNA sequencing revealed that TP53 gene mutations occurred in only 2 of 13 cholangiocarcinomas. High levels of mdm2 protein were found, by immunohistochemical staining, in 61% of the cholangiocarcinomas and in almost all specimens (70%) displaying stabilized p53 protein in the absence and in the presence of TP53 mutations. The finding of co-overexpressed mdm2 and p53 proteins in cholangiocarcinomas indicates that they can upregulate the expression of mdm2 protein to a level sufficient for binding and accumulating p53 in a presumably inactive complexed form. The presence of TP53 mutations or upregulation of MDM2 gene expression in 9 of the 13 cholangiocarcinomas strongly supports that the impairment of the p53 pathway is an important and specific step in cholangiocarcinoma pathogenesis. At variance with other authors, no alteration of p16ink4/CDKN2 gene was observed in all 13 cholangiocarcinomas.

In vivo study of polyurethane-coated Gianturco-Rosch biliary Z-stents.

PURPOSE: Prototypes of Gianturco-Rosch Z-stents coated with polycarbonate urethane (PCU) were placed in the biliary tree of pigs, in order to test their biomechanical behavior, stability, and biocompatibility. METHODS: The stents were surgically implanted in the common bile duct of three pairs of pigs, which were killed after 1, 3, and 6 months respectively. Explanted livers from pigs of the same race, age, and size were used to provide comparative data. The bile ducts were radiologically and histopathologically examined; the stents were processed and examined by scanning electron microscopy. RESULTS: No complications occurred and the animals showed a normal weight gain. The main bile duct appeared radiologically and macroscopically dilated, but the stents proved to be in place. Histologically, the bile duct epithelium was destroyed, but neither hyperplastic nor inflammatory fibrotic reactions of the wall were evident. Both the metallic structure and the polymeric coating of the stents were intact. A layer of organic material with a maximum thickness of approximately 3 micron was evident on the inner surface of the stents. CONCLUSION: The present in vivo study demonstrates the biocompatibility, efficacy, and stability of PCU-coated Gianturco-Rosch stents in the biliary environment.

Percutaneous intraductal sampling for cyto-histologic diagnosis of biliary duct strictures.

BACKGROUND: Percutaneous transhepatic biliary drainage (PTBD) allows ductal material to be collected for cyto-histologic examination. We evaluated the data from a large series of patients with a PTBD in whom endobiliary cyto-histologic sampling techniques were employed in order to define a strategy for their use in the diagnostic work-up. PATIENTS AND METHODS: Ductal samples for cyto-histologic examination were obtained from 409 consecutive patients with a PTBD for stenosing lesions of the biliary tree. Bile aspirate cytology was performed for all patients and ductal biopsy specimens were obtained, generally after negative cytology, from 49 of them (11.9%), all candidates for a therapeutic procedure. The cyto-histologic results of intraductal sampling were compared with pathologic surgical data in 210 patients and with clinical-radiologic follow-up in 199. RESULTS: Overall, 22 out of the 409 patients had a final diagnosis of benign stenosis and 177 had samples positive for neoplastic disease. The sensitivity of bile cytology was 43.8% while ductal biopsies showed a sensitivity of 60.4%. The combination of the two sampling techniques achieved a sensitivity of 65.1%. For both sampling methods the specificity was 100%. Hilar metastases from neoplastic lesions of the GI tract and primary lesions of the biliary ducts showed the highest sensitivity. CONCLUSION: Cyto-histologic assessment of stenosing lesions of the biliary ducts is mandatory when highly sophisticated interventions (e.g. wide hepatic resection or liver transplantation) or non-surgical treatments are envisaged. The collection of cyto-histologic samples from bile ducts, in patients with a percutaneous bile drainage, is an easy, safe and valuable method to obtain the diagnosis. In view of the absence of false positive results in our series and in others, intraductal biopsy serves no purpose when positive exfoliative cytology is positive for malignancy. In the presence of negative cytology it is felt that an intraductal biopsy should be mandatory when the choice of a therapeutic program depends on the result of the cyto-histologic diagnosis.

Evaluation of temperature distribution during hyperthermic treatment in biliary tumors: a computational approach.

A computational approach is adopted to predict the temperature distribution in the biliary tissue during hyperthermic treatments in biliary tumors. Two different models are developed: an axisymmetric model and a three-dimensional model. In the first model the Pennes bioheat transfer equation is applied. It is aimed at simulating the thermoregulatory effect of the capillary bed and it can also give a pressure criterion to determine whether the blood perfusion term should be included in the mathematical model. The second model is aimed at simulating the convective effect of the large hepatic vessels: A constant Nusselt number is assumed on the sides of the vessels. The simulations of the three-dimensional model have been carried out with and without capillary perfusion in the tissue, i.e., respectively in the worst case and in the best case that may occur during heating. The results show that it is possible to obtain therapeutic temperature values in the tissue for time intervals considered acceptable by physicians. Moreover, the model is able to give more precise information about the volumes of tumoral tissue heated above therapeutic temperatures with the hyperthermic technique considered.

Interventional radiology and radiotherapy for inoperable cholangiocarcinoma of the extrahepatic bile ducts.

AIMS AND BACKGROUND: To evaluate the effectiveness of external radiation therapy (ERT), alone or combined with endoluminal brachytherapy (BRT), following percutaneous transhepatic biliary drainage (PTBD) in the treatment of patients affected by inoperable cholangiocarcinoma. METHODS & STUDY DESIGN: From September 1980 to June 1996, 130 jaundiced patients affected by inoperable cholangiocarcinoma were submitted to PTBD at the Division of Radiology C of the National Cancer Institute of Milan. Nineteen were excluded from the present analysis due to the short survival after PTBD (< 30 days). The other 111 patients were divided into three groups according to the following therapy: no further treatment after palliative PTBD in 89 patients (80%, group 1); ERT in 10 patients (9%, group 2); ERT plus BRT in 12 patients (11%, group 3). All the ERT + BRT patients were enrolled after 1990 and were treated with high-energy photon beams followed by endobiliary insertion of one or two iridium-192 wires. RESULTS: Median overall survival among the 111 assessable patients was 126 days; for groups 1, 2 and 3 it was 108, 345 and 428 days, respectively. The patients submitted to radiotherapy (ERT alone or ERT + BRT) were evaluated by radiologic examinations after the end of radiation. In group 2, a partial remission in 3 cases, a progression of disease in 1 case, and no change in 6 cases were observed. Among the patients of group 3, complete remission in 5 and partial remission in 7 patients were achieved. In all the patients achieving complete remission, the PTBD could be removed. CONCLUSIONS: The combination of ERT plus BRT improves survival and quality of life of the patients submitted to PTBD for cholangiocarcinoma. Under the technical point of view, radiation treatment is easy to perform, but much caution is required in defining clinical and planning target volumes. Moreover, drainage during the radiation treatment has to be submitted to a very meticulous surveillance.

Comparative in vitro sensitivity of human cholangiocarcinoma and colon adenocarcinoma cells to anticancer agents.

We comparatively investigated the sensitivity of a human cholangiocarcinoma cell line (SG231) and an adenocarcinoma cell line (WiDr) to mitoxantrone (MX), taxol (TX), mitomycin C (MMC), doxorubicin (DX), cisplatin (CDDP) and 5-fluorouracil (5FU) by the sulforhodamine B assay. The lower susceptibility of SG231 to SFU, to CDDP, to DX and to MMC than WiDr was observed, whereas the sensitivity of the two cell lines to MX and TX was similar. We also investigated the ability of a chemical modulator, lonidomine (LND), and hyperthermia to enhance the cytotoxic activity of the different drugs in the SG231 cell line. No potentiation of MX or CDDP activity was observed after a 2 hours treatment in hyperthermic conditions (42 degrees C). Conversely, a slight potentiation of a 2 hours pretreatment with MX and DX was obtained by a 24 hours post treatment with LND.