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.

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.

Increase in intracellular Na+: transmembrane signal for rejoining of DNA strand breaks in proliferating lymphocytes.

Two early events in the mitogen-induced entry of murine splenocytes into proliferation are (a) a rapid rise in influx of Na+, causing its total internal concentration to increase by 42 +/- 7% within 2 h of culture with concanavalin A (Con A), and (b) rejoining of some 3000 DNA strand breaks per diploid genome within the same period. Con A did not induce rejoining in low Na+ (less than 9 mM) medium, but the process began directly when Na+ was added, at its usual concentration, to the growth medium. Incubation of cells with ouabain, an inhibitor of the Na+K+-ATPase, or monensin, a Na+ ionophore, caused an increase in the internal Na+ concentration in normal, but not in low, Na+ medium. In the former (but not in the latter) medium, both ouabain and monensin caused rejoining of the DNA strand breaks to occur in resting lymphocytes, i.e., in the absence of mitogen. Stimulation of splenocytes with Con A also resulted in a rapid but transient increase in the level of intracellular free Ca2+. This effect was also observed in the absence of extracellular Na+; however, deprivation of extracellular Ca2+ completely abolished this effect. Moreover, the intracellular free Ca2+ level was significantly higher in cells suspended in Na+-free buffer or medium. Since the Con A-induced rejoining of DNA strand breaks occurred in the absence of extracellular Ca2+ and removal of extracellular Na+ had no inhibitory effect on the Con A-induced increase in the level of intracellular free Ca2+, the Con A-stimulated repair could not have been mediated by the initial increase in Ca2+ influx. The early mitogen-induced increase in the internal Na+ concentration is a necessary and sufficient signal for the rejoining of breaks, an event that must occur before the proliferating lymphocytes can replicate their DNA.

Amino acid transport in pig lymphocytes. Enhanced activity of transport system asc following mitogenic stimulation.

Changes in neutral amino acid transport activity caused by addition of phytohaemagglutinin-P to quiescent peripheral pig lymphocytes have been evaluated by measurements of 14C-labelled neutral and analogue amino acids under conditions approaching initial entry rates. Utilizing methylaminoisobutyric acid, the best model substrate of System A, we confirmed our previous report (Borghetti, A.F., Kay, J.E. and Wheeler, K.P. (1979) Biochem. J. 182, 27-32) on the absence of this transport system in quiescent cells and its emergence following stimulation. Furthermore, we demonstrated the presence in quiescent cells of an Na+-dependent transport system for neutral amino acids that has been characterized as System ASC by several criteria including intolerance to methylaminoisobutyric acid, strict Na+-dependence, the property of transtimulation and specificity for pertinent substrates such as alanine, serine, cysteine and threonine. Analysis of the relationship between influx and substrate concentration revealed that two independent saturable components contribute to entry of alanine in quiescent cells: a low affinity (Km = approximately 4 mM) and a high affinity (Km = approximately 0.2 mM) component. The high affinity component could be inhibited in a competitive way by serine, cysteine and threonine, but methylaminoisobutyric acid did not change appreciably its constants. The enhanced activity of alanine transport through the ASC system observed in activated cells resulted from a large increase in the capacity (V) of the high affinity component without any substantial change in the apparent affinity constant (Km).

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.

Inherited diseases in North American Mennonites: focus on Old Colony (Chortitza) Mennonites.

The patterns of migration and the genetic disorders occurring among North American Mennonites are reviewed, and inherited conditions recently recognized in a religious and genetic isolate, the Old Colony (Chortitza) Mennonites, are described. Old Colony Mennonites are of Dutch/German origin and descend from approximately 400 founding families who settled in the Old Colony, Chortitza (the Ukraine, USSR) in the late 1700s, and then migrated to Canada and Central and South America in the past century. We investigated over 6 generations of a Canadian Old Colony kindred in which there was extensive intermarriage, and in whom 28 individuals developed diabetes mellitus. Insulin-dependent diabetes mellitus (IDDM) occurred in 14 affected individuals in 10 closely related sibships; the 11 living IDDM patients were all concordant for the immunogenetic marker HLA-DR4. Fourteen close relatives had other disorders of carbohydrate metabolism, including gestational diabetes and non-insulin-dependent diabetes mellitus. Other close relatives had autoimmune diseases, including rheumatoid arthritis, hyper- and hypothyroidism, multiple sclerosis, and red cell aplasia. Other inherited diseases, including Alport syndrome, congenital defects, and inborn errors of metabolism were also found in the kindred. In the almost exclusively (99%) Old Colony Mennonite public health district in which the kindred was ascertained, there were multiple cases of Tourette syndrome, of malformations (including congenital heart defects and cleft lip +/- palate), and familial clusters of inborn errors of metabolism. We report this Old Colony (Chortitza) Mennonite isolate because 1) there are large familial aggregations of tissue-specific autoimmune diseases, malformations, inborn errors of metabolism, and of some other conditions whose genetic basis is still unknown; 2) there are multiple cases of rare genetic conditions, 3) we have established a computerized genealogic data base on over 1,000 kindred members as well as a cryopreserved lymphocyte/DNA bank on over 100 closely related individuals with various genetic conditions; and 4) this religious isolate, which extends across North, Central, and South America, offers an excellent opportunity for studying the epidemiology and molecular genetics of both common and rare inherited diseases.

Suprapubic cystotomy as treatment for severe hemorrhagic cystitis after bone marrow transplantation.

We analyzed the success of suprapubic cystotomy in patients with severe hemorrhagic cystitis after bone marrow transplantation. Seventy-three out of 963 patients developed severe hemorrhagic cystitis which resulted in urinary tract obstruction after high-dose cytoreductive therapy. Eleven patients (15%) failed medical treatment and required emergency suprapubic cystotomy. Three of these patients died of other complications prior to resolution of HC. Of the remaining 8 patients who underwent surgery, 4 are alive. The mortality rate was significantly higher in patients who required surgery than in those who responded to medical therapy. Patients whose HC required surgery also had a greater transfusion requirement than those who responded to medical therapy. We conclude that surgical treatment of severe HC should be undertaken only after failure of medical therapy.

The occurrence of cholangitis after percutaneous biliary drainage: evaluation of some risk factors.

Sepsis of the biliary tract is often reported after percutaneous transhepatic biliary drainage (PTBD) and is considered a life-threatening condition. The authors studied 39 patients with biliary stenosis (35 with neoplastic stricture and four with benign disease) with the purpose of identifying some factors possibly associated with a higher risk of cholangitis. None of the patients complained of biliary sepsis at the first clinical examination. Several factors were taken into account and were statistically tested according to Miettinen rate ratios to differentiate patients in whom cholangitis would consequently develop: nature, site and extent of basic disease, type and functioning of PTBD, skin contamination at puncture site of PTBD, and bile contamination at PTBD and at follow-up. The presence of bacteria in the first bile (31.5%) was not related to a higher risk. All subjects showed bile contamination after PTBD, but cholangitis developed in only 15 patients, and it was always supported by enteric microorganisms. When we compared patients with cholangitis and subjects without infection, it was possible to demonstrate a statistically significant association of cholangitis and the following: nature of the stricture, presence of multiple intrahepatic biliary obstruction, neoplastic invasion or compression on the duodenum, and presence of Staphylococcus aureus on the skin at puncture site at drainage.

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.

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.

Polyurethane-coated, self-expandable biliary stent: an experimental study.

RATIONALE AND OBJECTIVES: We describe a self-expanding metallic biliary Gianturco-Rösch stent coated with polymeric material. The coating was designed to prevent the growth of neoplastic and reactive tissue within the biliary ducts. METHODS: The stents were coated with a solvent-casting technique, which consists of dissolving polyurethane (polyether urethane or polycarbonate urethane) pellets in a solvent (dimethylacetamide), dipping the stent in the solution, and completely evaporating the solvent. In vitro mechanical characterization of the stent was performed to determine the adhesion of the coating to the metallic cage, the best introducer caliber for implantation of the device, and the relationship between the stent's diameter and radial stress. RESULTS: Reports in the literature on the biostability of polycarbonate urethane compared with polyether urethane prompted us to use the former material to coat the stents. The solvent technique gives a smooth internal surface of the stent wall, leaving in relief the coated structure of the stent on the external surface. The functional tests demonstrated that the coating did not compromise the original characteristics of the stent in terms of self-expandability, axial flexibility, and increased radial rigidity of the device. CONCLUSION: Functional tests verified coating stability and device handling, which are the first steps toward in vivo experimentation.

Radiologic diagnosis of invasive carcinoma on adenomatous polyps of the colon.

The radiographic appearance at double contrast enema of 33 cases of invasive cancer on adenomatous polyps (AP) of the colon is reviewed. The radiologic diagnosis of malignancy was prospectively made in 54.5% of the cases. In 45.5% of the cases, malignancy was not suspected at the time of examination. The endoscopic appearance of these lesions was identical to that seen on the barium study. There are no radiologic criteria able to entirely rule out the possibility of a carcinomatous transformation of an AP. However, the radiologic features of malignancy (indentation of the intestinal wall and/or irregular outline of the surface of the polyp) have to be considered quite reliable.

Hysterosalpingography in the sequels of conisation of the uterine cervix.

A hysterosalpingographic survey was made of 65 women of reproductive age who had undergone conisation of the uterine cervix for carcinoma in situ or severe dysplasia at least one year before. None of the patients investigated radiologically had undergone uterine surgery before conisation. In a high percentage of cases morphological changes of the cervical canal and, less frequently, the isthmus were found. Most of the changes are attributable to scar retraction, and the hysterosalpingographic findings did not differ appreciably from those following other types of gynecological surgery, namely, segmental or total stenosis and ectasia of the cervical canal and isthmus. A control series of patients with preoperative and postoperative hysterosalpingograms is now under consideration to confirm the radiological findings and to correlate them with clinical data.

[Pleuroparenchymal and cardiomediastinal reactions in the radiotherapy of malignant lymphomas. (author's transl)]. / Reazioni pleuroparenchimali e cardiomediastiniche nella radioterapia dei linfomi maligni

The radiographic documentation for over 300 malignant lymphoma patients who received radiotherapy to the hilo-mediastinal regions at the National Cancer Institute of Milan is examined with a view to ascertaining the pleuroparenchymal and cardiomediastinal sequelae of irradiation in a fairly homogeneous series in respect of treatment techniques. Early and late lesions of varying severity, mild, marked and severe, were found in 60% of the patients. Only in 15% were the lesions severe; in 6% pronounced pleural effusions were found and in 1.2% exudative pericarditis. To identify the etiological factors, the lesions were correlated with several variables: patient age, disease stage, pretreatment condition of the intrathoracic organs, radiotherapeutic techniques and doses, and combined therapy with Bleomycin at the doses usually given in the treatment of lymphomas, where relevant. Of these factors only the radiotherapeutic technique (site and number of fields, division of dose) and especially the dose absorbed seem to be relatively closely related to the frequency and severity of the post-irradiation lesions. There seem to be other factors in the genesis of these lesions, probably related to individual reactivity, but for these we have no evaluation parameters.

[Radiological study of the topography and morphology of pulmonary cancer]. / Studio radiologico sulla topografia e morfologia del cancro polmonare

This study proposes a radiological, topographical and morphological classification of primary carcinoma of the lung based on a large radiographic case-series of the National Cancer Institute of Milan checked anatomopathologically. The aim is to standardise the X-ray findings and so make for easier understanding and more rewarding cooperation among those engaged on the diagnosis and treatment of this tumor. The classification of lung cancer into central and peripheral only is felt, in the light of present knowledge, to be inadequate. It is therefore suggested that central lung cancers be divided into purely endobronchial, endoperibronchial and exobronchial, taking into account both the repercussions on ventilation and extracentral spread. For peripheral lung carcinomas more detailed morphological and topographical features are considered in order to pinpoint the tumor and its hilomediastinal spread, especially in the case of paracentral tumors. A brief reference is made to the more relevant radiodiagnostic procedures.

A new set for transhepatic insertion of large caliber catheters for biliary drainage: technical and clinical report.

An original set for percutaneous insertion of large caliber (12-16 French) biliary drainages is described. The results obtained in the 70 patients submitted to biliary drainage with late complications due to malfunction of the standard 8.3 or 10 F catheters show the advantage of the set described. The correction of unsatisfactory levels of bilirubinemia was obtained in 100% of cases, the resolution of recurrent cholangitis in 84.2% and of bile leakage on the skin in 46.7%. The large caliber and the large side holes of the catheter, together with its length and its easy handling, allow resolution of many different problems of insufficient drainage present in patients with neoplastic involvement of bile ducts.

Percutaneous transhepatic biliary drainage in malignant obstructive jaundice.

Results obtained in 70 patients with neoplastic (primary or metastatic) biliary obstruction and submitted to percutaneous transhepatic biliary drainage indicate the effectiveness of the technique in relieving jaundice, improving general conditions and restoring liver function. In 25.4% of cases, the drainage allowed the patients to undergo surgical treatment of the neoplasm. In 74.6%, the drainage was left in place as definitive palliation. The complication rate was very low and similar to that described in the literature. At this time it is difficult to identify prognostic factors and foresee the results of percutaneous transhepatic biliary drainage, but the procedure is always indicated in patients at high operative risk or inoperable.

Feasibility of different combinations of chemotherapy (6 MOPP) plus radiotherapy in Hodgkin's disease.

During a preliminary clinical experience (1973-1977) we experimented three different sequences in associating 6 MOPP cycles (CT) with radiotherapy (RT) for the treatment of stage II and III Hodgkin's disease. A total of 55 consecutive previously untreated patients can be estimated to contribute in defining feasibility, immediate results and toxicity of the combined treatment. In this group of patients RT preceded CT in 20 cases (RT-6 MOPP), the opposite sequence (6 MOPP-RT) was preferred in 16 cases, whilst a split-course CT fitting in the RT (3 MOPP-RT-3 MOPP) was employed in 19 cases. Except for the sequence used with respect to irradiation, the CT was carried out in all the cases according to the classical scheme proposed by De Vita et al. (11). RT was effected with 60Co-teletherapy and a wide field or segmental sequential fields, having variable extension depending on the stage ("extended nodal irradiation" for stage II and III cases with lymph node involvement not below L3; "total nodal irradiation" for the remaining cases in stage III). The programmed doses were 45.0 Gy to the involved areas and 40.0 Gy to the clinically uninvolved regions for the RT-6 MOPP and 6 MOPP-RT groups. Doses of 35.0/30.0 Gy were planned for the 3 MOPP-RT-3 MOPP group. The three different groups are not homogeneous with regard to certain important clinical and pathological characteristics; in fact, a higher quota of stage III patients, with systemic symptoms and spleen positivity is present in the 6 MOPP-RT and 3 MOPP-RT-3 MOPP groups. The combined treatment has achieved a complete clinical remission in 18/20 patients in the RT-6 MOPP group (90.0%), in 12/16 patients of the 6 MOPP-RT group (75.0%), and in 17/19 cases in the 3 MOPP-RT-3 MOPP "sandwich" combination (89.5%). The average overall duration of the treatment was 48 weeks for the sandwich combination, 50 weeks for the RT-6 MOPP group, and 56 weeks for the 6 MOPP-RT association. As regards the sandwich combination, both CT and RT took a reasonable length of time to complete. On the contrary, both the medical treatment and irradiation required an excessively long time and were not well tolerated when preceded by either RT or CT in full doses. In particular, myelosuppression was less acute and prolonged in the 3 MOPP-RT-3 MOPP group, whereas the actual doses of CT and RT were higher than those which can be reached with respect to other groups. Three preliminary cycles of CT considerably reduce the target volumes and complications arising from RT. The first CT time gave an objective response greater than 50% in 9/9 cases of the 3 MOPP-RT-3-MOPP group with mediastinal involvement. In this group, rather considerable pulmonary complications were observed in 3/9 patients (33.3%) with respect to the 40% found for the 6 MOPP-RT group (2/5 cases) and the 67.7% for the RT-6 MOPP group (6/9 cases).