Markers of slow-healing peptic ulcer in the elderly

Little is known about ulcer outcome in the elderly. The aims of the present paper were to establish whether risk factors of slow-healing peptic ulcer can be demonstrated in the elderly and whether clinical differences exist between ulcer patients whose age of onset of the disease was before or after 65 years old. The short-term, open study, involving 1052 elderly patients (over 65 years) in 37 gastroenterology centers throughout Italy aimed to compare two schedules of ranitidine treatment: 150 mg twice daily versus 300 mg at bedtime. As nonsignificant differences were found between these two schedules, the sample was considered as a whole. It included 319 gastric ulcer (GU) patients, 699 duodenal ulcer (DU) patients, and 34 concomitant GU and DU cases. Ninety-three patients dropped out of the trial; 79/294 GU, 138/635 DU, and 10/30 GU+DU were found still unhealed after four weeks and 20 GU, 15 DU, and 1 GU+DU remained so after eight weeks. Statistical analysis was performed using likelihood-ratio and Pearson's chi-squared tests and Cox's models. Univariate analysis showed that the indicators of slow-healing GU were ulcer size (P=0.002) and persisting ulcer symptoms (P=0.0001); indicators of slow-healing DU were ulcer size (P=0.0001), persisting ulcer symptoms (P=0.0001), alcohol (P=0.0003), and NSAID (P=0.0088) consumption. DU patients taking antiplatelet drugs have significantly better results after four weeks and worse results after eight weeks (P=0.0352). Cox's models revealed that the persistence of ulcer symptoms is the most important factor predicting unhealing ulcers (GU,P=0.0008; DU,P=0.0002), while ulcer size is only important for DU (P=0.0215). Patients with ulcer disease onset before 65 years of age were more frequently males; DU subjects were more frequently smokers, with a family history of ulcer and no NSAID consumption. In conclusion, persistence of ulcer symptoms and ulcer size are indicators of slow-healing ulcer in the elderly; in the case of DU, NSAID and alcohol consumption may be additional factors.This study was performed under the auspices of the R. Farini Foundation for Gastrointestinal Research.Centers participating in the study: Alba (G. Prandi, R. Bianco); Asti (C. Moro, M. Grassini); Avezzano (A. de Sanctis, A. Sedici); Belluno (F. Costan Biedo, P. Olivieri); bussolengo (S. Adamo, G. Sartori); Cagliari (P. Loriga, C. Caschili); Castelfranco V. to (S. Bertazzo, G. Pesce); Castrovillari (S. Leone, G. Mollica); Conegliano V. to (G. Lollo, P. Lunardi); Cosenza (A. Belmonte, G. Manno); Cuneo (G. Ferro, A. Manca); Fano (M. Cuzzupoli, A. Olivieri); Fiesole (P. Ciani, L. Manneschi); Gorizia (E. Benedetti, S. Fayenz); Lanciano (S. Di Matteo, F. Cifani); Malo (C.F. Azzini, A. Pilotto); Monza (S. Magni, A. Lomazzi); Melito P.S. (G. Dattola); Napoli (B. De Luca, D. Di Cesare); Negrar (A. Geccherle, C. Manfrini); Novara (M. Del Piano, F. Montino); Orbassano (G. Emanueli, C. Calcamuggi); Oristano (A. Tuveri, M. Sau); Padova (R. Naccarato, F. Di Mario); Palermo (G. Barbagallo-Sangiorgi, S. Vigneri); Polistena (G. Gerace); Popoli (A. Pomidori, R. Lattanzio); Prato (A. Candidi-Tomasi, M. Lami); Reggio Calabria (P. Califano, C. Campolo); Roma (L. Capurso, M. Koch); Rovereto (A. Bernardi, M.C. Paler); S. Vito al Tagliamento (G. Tasca, A. Pighin); Scilla (G. Naim); Terni (A. Della Spoletina, F. Bellavigna); Torino (G. Babando, L. Lombardo); Venezia (M. Pasquino, M.E. Benvenuti); Vercelli (W. Giorgelli, G. Ardizzone).     

Factors affecting anal continence after restorative proctocolectomy

The aim of this multicentre study was to define the incidence of disordered continence after restorative proctocolectomy and ileoanal reservoir with respect to some factors which may influence the postoperative soiling rate. Two hundred and seven patients underwent the operation, 156 had their ileostomy closed and were all available for a functional assessment. Minor leakage was observed in 26.9% of cases, whereas 1.9% complained of troublesome faecal soiling. None had gross faecal incontinence. Patients over 45 years had significantly more soiling than those younger (45% vs 24%, p<0.05). Soiling was more prevalent in those with ulcerative colitis than with other diseases (35% vs 18% p<0.05). The soiling rate decreased after the first postoperative year from 34% to 21% (p<0.05). A bowel frequency higher than 5 evacuations/24 hours increased soiling from 20% to 48% (p<0.01). Pouchitis doubled the soiling rate from 26% to 50% (p<0.05) without there being any difference in sphincter function. Soiling was not significantly related to staged procedure, J-pouch, perineal complications or a long rectal cuff. Careful preoperative evaluation of the anal sphincter should be performed in older patients operated on for colitis as they are likely to leak during the first year following restorative proctocolectomy, especially in cases with diarrhoea or pouchitis.From the Italian Registry of the Ileoanal Reservoir: A. Bastagli, E. Contessini, L. Gennari, W. Montorsi, M. Fincato (Milano); E. Berti Riboli (Genova); G. Castiglioni, F. Crucitti, G. Cucchiara, G. Fegiz, G. Ribotta, V. Speranza (Roma); E. Cavina, F. Mosca (Pisa); U. Conti, A. Saccomani (Finale e Pietra Ligure); D. D'Amico, M. Lise (Padova); M. Dellepiane, E. Masenti, A. Paletto (Torino); R. Dionigi, C. Morone (Pavia); G. Gozzetti (Bologna); E. Landi (Ancona); F. Mazzeo, A. Renda (Napoli); U. Mercati (Perugia); A. Napolitano (Chieti); E. Pasquali (Verona); F. Prete (Bari); G. Stancanelli (Ravenna); F. Tonelli (Firenze).     

Effect of interferon-α on immunoglobulin production by peripheral blood mononuclear cells in multiple myeloma

Abstract: To test a hypothesis that interferon-α (IFN) treatment might restore normal immunoglobulin (Ig) production in multiple myeloma (MM), the effect of IFN on Ig isotype (IgG and IgA) production by peripheral blood (PB) and bone marrow (BM) mononuclear cells (MNCs) in MM patients was analyzed by ELISA. IFN at a concentration of 1000 U/ml was found to enhance IgA production by PB MNCs in IgA-MM and had a trend to stimulate IgG production in IgG-MM. The effect of IFN on nonparaprotein Ig isotype production was more variable, with mostly neutral or inhibitory effects being seen in both the MM subtypes. In contrast to the influences observed in MM patients, IFN at the same concentration inhibited both IgG and IgA production by PB MNCs in healthy controls. In studying BM cells, IFN was found to reduce IgA production in IgA-MM, but had a neutral effect on IgG production in IgG-MM. In the controls, the production of both the IgG and the IgA isotypes by BM MNCs was decreased by IFN. On the basis of these results it seems that the disease itself somehow affects the Ig-producing cells in MM, when measured as different responses of the cells to exogenous IFN in vitro. The results do not support the hypothesis that IFN treatment could restore normal Ig production in MM patients.     

Monoclonal gammopathy in rheumatic diseases

To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P?=?0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P?=?0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P?=?0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P?=?0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015–1.251), P?=?0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011–1.242), P?=?0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype switch, 1 progressed to multiple myeloma (MM), and another 2 experienced renal injuries attributed by monoclonal or polyclonal plasma cell interstitial infiltration. Seven (17.1%) of the 41 MG patients presented hematological neoplasias, 4 with MM, 2 with smoldering multiple myeloma, and 1 with B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The presence of light-chain MG was associated with the development of MM [OR 17.5 (95%CI 1.551–197.435), P?=?0.041], but not with an increased risk of lymphoma or SMM. MG was observed in patients with various rheumatic disorders, with SS being the most common type. The presence of MG might be associated with higher disease activity. The development of hematological neoplasias including MM and lymphoma was seen in this setting. Therefore, we recommend the screening for MG and close monitoring for potential malignant transformation in patients with rheumatic diseases as needed.     

Hepatitis C virus infection in households of anti-HCV chronic carriers in Italy: A multicentre case-control study

Summary To test the hypothesis that households of anti-HCV positive subjects might be at increased risk of HCV infection, a case-control study was carried out comparing 518 family members of 205 anti-HCV positive subjects (index carriers) with 281 family members of 100 anti-HCV negative subjects (index controls), consecutively observed in ten gastroenterology units in different Italian regions. The index carriers were age and sex matched to the index controls and their households were similar with respect to the main sociodemographic characteristics. Anti-HCV antibodies were found in 6.9% (36/518) of household members of index carriers and in 3.2% (9/281) of household members of index controls (p<0.05). The results of multiple logistic regression analysis showed that being over 50 years of age was the sole independent predictor for a household contact of the likelihood of being anti-HCV positive (O.R. 3.6; C.I. 95%=1.5–8.2). Being in the household of an anti-HCV index carrier was marginally associated to anti-HCV positivity (O.R. 2.0; C.I. 95%=0.9–4.6). No association was found for sex, area of residence, family size, lowest level of schooling, or any type of family relationship. These findings are not in compliance with the statement that household contacts of HCV carriers are at increased risk of HCV infection. The 3.2% anti-HCV prevalence rate observed among household contacts of anti-HCV negative index controls may suggest that the true anti-HCV prevalence in the general population in Italy is nearly 2.5 times as high as the 1.3% found in Italian blood donors.Additional collaborators:G. Pilleri, M. D.,M. Bernasconi, M. D. (Cagliari);O. G. Manghisi, M. D.,R. Cuppone, M. D. (Castellana Grotte);M. A. Freni, M. D.,A. Aiello, M. D.,A. Spadaro, M. D. (Messina);G. Raimondo, M. D.,G. Longo, M. D. (Messina);A. Picciotto, M. D.,E. Bordellini, M. D. (Genoa);M. Toti, M. D.,C. Nencioni, M. D. (Grosseto);M. Chiaramonte, M. D.,U. Lorenzoni, M. D. (Padua);A. Craxi, M. D.,L. M. Valenza, M. D. (Palermo);A. Andriulli, M. D.,F. Spirito, M. D.,A. Mangia, M. D. (S. Giovanni Rotondo);F. Bonino, M. D.,M. Baldi, M. D.,M. Capalbo, M. D. (Turin).     

Better quality of therapy with 5-ASA colonic foam in active ulcerative colitis

We evaluated the efficacy, tolerance, and acceptance of a new 5-ASA colonic foam versus 5-ASA liquid enema in the short-term treatment of active ulcerative colitis in a three-week prospective, randomized, investigator-blind study, enrolling 233 patients from 12 outpatient clinics in Italy. In arm 1 of the study, 117 patients with mild attacks received 2 g of 5-ASA as foam or enema at bedtime. In arm 2, 116 patients with moderate attacks were given 4 g of 5-ASA as foam or enema at bedtime. End points were defined as complete relief of symptoms, and endoscopic and histological evidence of remission or improvement. In patients with mild relapse, 34 of 63 (54%) treated with foam were in clinical remission after only 10 days compared with 17 of 51 (31%) treated with enemas (P<0.05). However, there was no statistically significant difference between foam (83%) and enema (74%) after three weeks. In patients with moderate relapse, a higher proportion of patients achieved complete clinical remission in the foam group (63%) compared with enema group (52%) after three weeks (difference 11%, 95% CI –7 to 29). No significant differences were observed in endoscopic and histological evaluation of colonic mucosa between treatment groups in either arm. 5-ASA foam was well tolerated. No unexpected adverse events were reported. Patient evaluation of therapy showed that foam was much better accepted than enema because foam was more comfortable, more practical, easier to retain, and interfered less with daily living. The results of this study suggest that 5-ASA foam may provide prompter remission of symptoms compared to liquid enema and it improves the quality of topical therapy in ulcerative colitis.This paper was presented in part at the Research Forum of the 92nd annual meeting of The American Gastrointestinal Association, New Orleans, May 18–24, 1991.The multicenter group included: M. Campieri, A. Belluzzi, G. Brunetti, P. Gionchetti, M. Miglioli, L. Barbara (Bologna); C. Prantera, A. Andreoli, E. Berto (Roma); P. Paoluzi, M.C. Di Paolo, A.O. Paoluzi (Roma); F. Pallone, F. Luzza (Catanzaro); M. Cottone, L. Oliva (Palermo); G. Bianchi Porro, S. Ardizzone, M. Petrillo (Milano); G. D'Albasio, G. Trallori (Firenze); G.C. Sturniolo, M.C. Montino (Padova); A. Pera, C. Barletti (Torino); R. de Franchis, G. Grandinetti, G.M. Meucci, M. Vecchi (Milano); P. Bianchi, M.C. Campanini, T. Ranzi (Milano); L. Capurso, C. Papi (Roma).Supported by a grant from Bracco and Giuliani (Milan, Italy).     

Effect of a Gluten-free Diet on the Risk of Enteropathy-associated T-cell Lymphoma in Celiac Disease

Patients with celiac disease have an increased rate of enteropathy-associated T-cell lymphoma, but conflicting data are available about the protective role of a gluten-free diet with regard to the development of this malignancy. We followed 1,757 celiac patients for a total period of 31,801 person-years, collecting data about the frequency of gluten intake and the incidence of the enteropathy-associated T-cell lymphoma. Out of the nine celiac patients who developed an intestinal lymphoma [standard morbidity ratio of 6.42 (95% CI = 2.9–12.2; P < 0.001)], only two kept a strict gluten-free diet after the diagnosis of celiac diasese and developed the malignancy after the peridiagnosis period of 3 years, dropping therefore the standard morbidity ratio to 0.22 (95%CI = 0.02–0.88; P < 0.001). The risk of developing an intestinal lymphoma for the celiac patients that used to have dietary gluten was significant (X² = 4.8 P = 0.01). These results show that a strict gluten-free diet is protective towards the development of enteropathy-associated T-cell lymphoma. Collaborating Centers Cattedra di Medicina Interna II, Univ. Cattolica, Roma, G.Gasbarrini, M.D., V. De Vitis, M.D.; Dipartimento di Pediatria, Univ. Federico II, Napoli, L. Greco, M.D., S. Auricchio, M.D.; Ospedale per gli infermi di Faenza-Azienda USL di Ravenna, D.Santini, M.D., F. Scaggiante M., M.D., Vincenzi M., Federici M.D.; Istituto Giannina Gaslini, Pediatria III, Genova, E. Castellano, M.D., A.Calvi, M.D.; Cattedra di Gastroenterologia, Dipartimento di Medicina Interna, Univ. Torino, Sategna-Guidetti, S. Grosso; Unità di Gastroenterologia, IRCCS Policlinico S. Matteo, Univ. Pavia, Campanella J., M.D., Corazza G.R., M.D.; Unita’ Operativa di Nutrizione Clinica, Ospedale S. Eugenio, Roma, G. Sandri, M.D., G. Giorgetti, M.D.; Monica Amici, Dipartimento di Medicina Interna, Policlinico S. Orsola-Malpighi, Bologna, U. Volta, M.D., C. Parisi, M.D.; Servizio di Gastroenterologia ed Endoscopia Digestiva, Ospedale USL 9, Treviso, S. Lo Perfido, M.D., ; Divisione di Gastroenterologia, IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Foggia, F. Perri, M.D., V. Festa M.D.,; Clinica di Gastroenterologia ed Epatologia, Univ. Perugia, M.A. Pelli, M.D., M.L. Cavalletti M.D.,; Unità Operativa di Gastroenterologia ed Endoscopia Digestiva, Ospedale di Circolo e Fondazione Macchi, Varese, S. Segato, M.D., M. Curzio M.D.,; Servizio di Gastroenterologia ed Endoscopia Digestiva, Dipartimento Oncologia, Ospedale S. Giovanni AS, Torino, M. Pennazio M.D.,, F.P. Rossini, M.D.; Cattedra di Gastroenterologia, Ist. di Clinica Medica II, Univ. La Sapienza, Roma, A. Picarelli M.D.; Divisione di Gastroenterologia, Ospedale Mauriziano Umberto I, Torino, A. Pera, M.D., E. Ercole M.D.; Unità Operativa di Gastroenterologia, Dip.to di Patofisiologia Clinica, Univ. Pol. “Careggi” Firenze, M.T. Passaleva; Clinica Pediatrica, Servizio di Gastroenterologia, Univ. La Sapienza, Roma, M. Barbato M.D.,; Istituto di Medicina Interna, Univ. Cagliari, P. Usai M.D.,, M.F. Dore M.D.,; Divisione di Gastroenterologia, Ospedale Regionale, Bolzano, F.Chilovi, M.D., L. Piazzi, M.D. L.Zancanella M.D., and Servizio di Gastroenterologia Pediatrica e Servizio di Gastroenterologia, Univ. Modena, V. Boarino, M.D., A. Ferrari M.D.     

BOOKS

Book reviewed in this article: D Zucker-Franklin, M F Greaves, C E Grossi & A M Marmont (eds) (1981) Atlas of blood cells. Function and pathology. Carola T. Kapff & James H Jandl (1981) Blood. Atlas and sourcebook of haematology. G Fermi & M F Perutz (1981) Haemoglobin and myoglobin. Vol 2 of “Atlas of molecular structures in biology”. Edited by D C Phillips & F M Richards. Karl Lennert (1981) Histopathology of non-Hodgkin's lymphomas (based on the Kiel classification). J H Sanderson & C E Phillips (1982) An atlas of laboratory animal haematology.     

Inhibition of binding of interferon-gamma to its receptor by salicylates used in inflammatory bowel disease.

5-Aminosalicylic acid (5ASA), 4ASA, their N-acetylated metabolites N-acetyl-5ASA and N-acetyl-4ASA, olsalazine, and colchicine impair interferon-gamma (IFN gamma) induced HLA-DR expression on a colonic cell line, HT-29. The mechanism of this effect is now reported. HT-29 cells were cultured with 50 U/ml IFN gamma with or without drug, and northern blot analysis was performed using a probe for the beta chain of the DR molecule. IFN gamma led to a noticeable increase in HLA-DR mRNA which was attenuated by the drugs. Analysis of the specific binding of increasing concentrations of 125I-IFN gamma by non-linear regression showed a Kd of 1.35 x 10(-10) M and 2.3 x 10(5) binding sites per HT-29 cell. Binding of 125I-IFN gamma was reduced by incubation with increasing concentrations of unlabelled IFN gamma but not with IFN alpha. Incubation with therapeutic concentrations of drugs led to the following reductions in binding: 10 mM 5ASA, 20% (p < 0.001); 10 mM N-acetyl-5ASA, 24% (p < 0.01); 10 mM 4ASA, 21% (p < 0.005); 10 mM N-acetyl-4ASA, 29% (p < 0.001); and 1 mM olsalazine, 29% (p < 0.001). Colchicine (10(-7) M) and 10(-5) M prednisolone had no effect. Incubation with higher concentrations of the drugs revealed a dose-response effect on binding with complete inhibition by 100 mM 4ASA and 10 mM olsalazine, and lesser degrees of inhibition by 100 mM 5ASA, N-acetyl-5ASA, and N-acetyl-4ASA. At concentrations found in the rectal lumen, the salicylates used in inflammatory bowel disease impair the binding of IFN gamma to its receptor on colonic epithelial cells.     

Incidence of pulmonary embolism in younger versus older patients using CT

OBJECTIVE: The aim of this study is to compare the incidence of pulmonary embolism (PE) on computed tomography (CT) studies between younger and older patients to determine if there is an age-related bias for overutilization of CT pulmonary angiography (CTPA) in younger patients. MATERIAL AND METHODS: Six hundred thirty-one consecutive CTPA cases for suspected acute PE between 11/10/2003 and 3/19/2004 were retrospectively studied. Of these 631 cases, 59 patients were found to have clots in the pulmonary arteries (ranging from central to subsegmental PA). CTPA was performed using multidetector CT at 1.25-mm collimation, 120 kVp, 320 mA. Patients were categorized by gender and age: A, less than 20 (n = 11); B, 20 to 29 (n = 44); C, 30 to 39 (n = 59); D, 40 to 49 (n = 90); E, 50 to 59 (n = 120); F, 60 to 69 (n = 114); G, 70 to 79 (n = 104); H, 80 to 89 (n = 72); I, 90 or more (n = 21). The incidences of PE were calculated in each gender and age group. To compare the incidence of PE between younger and older groups, they were divided into 2 groups at the ages of 40 (<39 and > or = 40), 50 (<49 and > or = 50), and 60 (<59 and > or = 60). Statistical analysis was performed using the chi test. RESULTS: The incidences of PE were 11.9% in males (A, 0%; B, 17.6%; C, 10%; D, 8.3%; E, 13.3%; F, 6.9%; G, 17.5%; H, 23.5%; I, 0%), 7.7% in females (A, 0%; B, 7.4%; C, 5.1%; D, 12.5%; E, 4.2%; F, 14.5%; G, 7.8%; H, 5.5%; I, 0%), and 9.4% in total patients (A, 0%; B, 11.1%; C, 6.8%; D, 11.1%; E, 7.5%; F, 10.5%; G, 11.5%; H, 9.7%; I, 0%). No significant differences in the incidences of PE were observed when patients were divided at the age of 40 (male, female, total; P=1.0, 0.6252, 0.7220), at the age of 50 (male, female, total; P = 0.6748, 0.6879, 1.0), or at the age of 60 (male, female, total; P = 0.8458, 0.7046, 0.6820). CONCLUSION: No statistically significant difference in the incidence of PE was observed between younger and older patients. Our findings suggest that there is no age-related bias for overutilization of CT angiography (CTA) in younger patients.     

Problems of staging colorectal cancer

Summary A total of 2994 cases of previously untreated colorectal carcinomas taken from the database of the International Cancer Patient Data Exchange Sytem of the UICC were analyzed. The objective was to compare pretherapeutic and postsurgical data and to investigate the impact of missing information on the quality of tumor staging under routine conditions. In clinical staging, a higher percentage of items were marked unknown in the questionnaires than in histopathological staging. The clinical and postoperative assessment of TNM stages Ib, II, and III frecuently diverged, indicating a low precision for clinical staging. Fistulae were rarely observed in either colon or rectum carcinoma.Authors for the International Cancer Patient Data Exchange System of the UICC. Members of the following institutions are cooperating in the ICPDES: Duke Comprehensive Cancer Center, Durham, NC (until 1983; Director; W.W. Shingleton; Representative for the ICPDES: E. Cox), University of Texas M.D. Anderson Hospital, Houston, TX (C.A. LeMaistre; UICC/CICA Coordinator for the ICPDES and International Data Center V.F. Guinee), Mayo Comprehensive Cancer Center, Rochester, MN (until 1983, C.G. Moertel; W.F. Taylor, H. Golenzer), Memorial Sloan-Kettering Cancer Center, New York, NY (P. Marks; S. Bretsky), Roswell Park Memorial Institute, Buffalo, NY (G.P. Murphy; W.W. Lane), Institut Jules Bordet, Bruxelles (W. Mattheiem), Fondation Bergonié, Bordeaux (C. Lagarde; M. Durand). Tumorzentrum Heidelberg/Mannheim (Ch. Herfarth; G. Wagner, G. Pfaff), Westdeutsches Tumorzentrum Essen (C.G. Schmidt, R. Pfeiffer), Országos Onkologiai Intézet, Budapest (S. Eckhardt, Z. Péter); Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (U. Veronesi; N. Cascinelii, R. Bufalino), Nederlands Kankerinstituut, Amsterdam (F. Cleton; E. Hamersma, European Data Center: R Zewuster), Rotterdamsch Radio—Therapeutisch Instituut (D. M. van der Veldt; J. W. van der Velden), All — Union Cancer Research Center of the USSR Academy of Medical Sciences, Moscow (N.N. Blokhin; I.V. Vardomskaya), Mount Vernon Hospital, Northwood, Middlesex (since 1982, P. Strickland; S. Dische), Cancer Institute, Chinese Academy of Medical Sciences, Beijing (since (1983, You-Hui Zhang; Jian-Zhang Wang). Our thanks to Prof. Dr. E. Weber, Heidelberg, for his support in the Biplot analysis     

Prognostic factors in elderly multiple myeloma patients aged 65 years or older: Comparison with nonelderly patients with multiple myeloma

Background:   Although age is a prognostic factor in multiple myeloma (MM), the prognostic factors in elderly MM patients may be different to those in nonelderly MM patients due to the patient's age. The difference in the significance of prognostic factors between elderly MM patients and the nonelderly MM patients was studied.
Methods:   Forty-two elderly MM patients aged 65 years or older were compared with 68 nonelderly MM patients, who were less than 65 years of age. The characteristics of the elderly patients included: aged 65–81 years (median, 72 years); female/male ratio of 22 : 20; 24 IgG type cases, 13 IgA type cases, one non-secretory case and four cases of Bence-Jones type; one case of stage I, 12 cases at stage II and 29 cases at stage III. The prognostic factors were evaluated by means of univariate analysis and Cox's multivariate analysis.
Results:   The median survival time was significantly shorter in the elderly MM patients (24 months) than in the nonelderly patients (50 months) ( P  < 0.01). Of the univariate prognostic factors, corrected serum Ca (cCa), hemoglobin, serum P, bone marrow plasma cell and uric acid were significant prognostic factors in the elderly MM patients, while nine factors including those listed here, were significant in nonelderly controls. Multivariate analysis showed that serum cCa was the only independent prognostic factor ( P  = 0.019) in elderly MM patients, while serum P and bone lesions were significant prognostic factors in nonelderly MM patients.
Conclusion:   Corrected serum c. (cCa) was an independent prognostic factor in elderly MM patients.     

Pleural fluid nucleic acid testing enhances pneumococcal surveillance in children

Background and objective: National surveillance of invasive pneumococcal disease (IPD) includes serotyping Streptococcus pneumoniae (SP) isolates from sterile site cultures. PCR is more sensitive and can identify more SP serotypes (STs) in culture‐negative samples. The aim of this study was to determine whether enhanced surveillance of childhood empyema, using PCR, provides additional serotype information compared with conventional surveillance. Methods: Pleural fluid (PF) from children with empyema were cultured and tested by PCR to identify SP, targeting the autolysin gene (lytA). Multiplex PCR‐based reverse line blot assay was used to identify SP STs. Corresponding IPD surveillance and serotype data were obtained from the National Notifiable Diseases Surveillance System (NNDSS). Results: Eighty‐nine children with empyema, aged ≤16 years, were recruited between April 2008 and March 2009, inclusive. SP was isolated from 5/84 (5.9%) PF cultures and by PCR in 43/79 (54.4%) PF samples. Serotypes were unidentifiable in 15 samples. The frequency of six serotypes (or serotype pairs) identified in 28 samples, including one with two serotypes, were: ST1, n = 4/29 (13.8%); ST3, n = 9/29 (31.0%); ST19A, n = 12/29 (41.4%); ST7F/7A, n = 1/29 (3.4%); ST9V/9A, n = 1/29 (3.4%); ST22F/22A, n = 2/29 (6.9%). Over the same period, 361 IPD patients, aged 16 years or less, were notified to NNDSS. Among 331 serotypeable NNDSS isolates (71.5% from blood), the frequencies of ST1 and 3 were significantly lower than in PF samples: ST1, n = 8/331 (2.4%; P < 0.05); ST3, n = 13/331 (3.9%; P < 0.0001). Conclusions: The use of PCR to identify and serotype SP in culture‐negative specimens provides additive information.     

Association study of IFNAR2 and IL10RB genes with the susceptibility and interferon response in HBV infection

Summary. A recent genome‐wide association study discovered that two polymorphisms, interferon (IFN) alpha receptor 2 (IFNAR‐2) F8S and interleukin 10 receptor (IL10RB) K47E, were associated with susceptibility to hepatitis B virus (HBV) infection in Africa. Here, we reevaluate the effects of the two polymorphisms on HBV susceptibility in the Chinese Han population, and extended the study to look at their association with IFN response in chronic hepatitis B (CHB). We included 341 patients with CHB and 341 unrelated controls presenting with asymptotic HBV self‐limited infection, who were well matched in age and sex. In the CHB group, 101 patients had been treated with peg‐IFN‐alpha‐2a for 48 weeks and followed up for 24 weeks to determine the clinical response, resulting 34 individuals with sustained virological response (SVR) and 67 individuals with nonsustained response (NR). Subgroups in the CHB group were divided according to the viral loads, HBeAg and maternal HBsAg status. The association with the susceptibility to HBV infection was only observed for IL10RB K47E when we compared the individuals with persistent HBV infection through nonmaternal transmission to the controls with asymptomatic self‐limited HBV infection. Further, we found that the IFNAR2‐8SS genotype was associated with HBeAg negative patients (OR = 0.316, 95% CI: 0.121–0.825, P = 0.019) and that the IFNAR2‐8F allele was associated with the risk to high viral loads (OR = 1.667, 95% CI: 1.148–2.420, P = 0.007). In addition, the IFNAR2‐8FF genotype predisposed to higher MxA gene induction and correlated with sustained IFN response (OR = 0.348, 95% CI: 0.129–0.935, P = 0.036). Haplotype analysis based on polymorphisms of three single‐nucleotide polymorphisms, MxA ?88 G/T, IFNAR‐2 F8S and IL10RB K47E showed that the haplotype distribution was significantly different between the SVR and NR groups (P = 0.040). This study suggests that IFNAR2 may play an important role in determining IFN response and clinical phenotypes of HBV infection in the Chinese Han population.     

Translocation t(11;14)(q13;q32) is the hallmark of IgM,IgE, and nonsecretory multiple myeloma variants

In an attempt to address the issue of cytogenetic features of multiple myeloma (MM) variants, we have analyzed a series of 8 IgM, 9 IgD, 2 IgE, and 14 nonsecretory (NS) MM cases using fluorescence in situ hybridization. A very high incidence (83%) of t(11;14)(q13;q32) was detected in the IgM (7 of 8), IgE (2 of 2), and NS (11 of 14) MM cases, but not in the IgD cases (2 of 9). Of note, no t(4;14) was observed in this cohort of patients. This increased incidence of t(11;14) was associated with 2 dominant features in these variants, namely, a "lymphoplasmacytic" presentation mainly in IgM MM and a lower secreting capacity in the others, 2 features previously associated with t(11;14). Of major interest, t(11;14) was never observed in Waldenstr?m macroglobulinemia or in IgG/IgA "lymphoplasmacytic" lymphomas. Thus, for unknown reasons, t(11;14) is the hallmark of IgM, IgE, and NS MM, (but not IgD MM), with a 5-fold increase of its incidence compared to that of IgG and IgA MM.     

老年人意义未明的单克隆免疫球蛋白血症的转归

目的 探讨老年人意义未明的单克隆免疫球蛋白血症(MGUS)的转归.方法 对我院14例MGUS患者转归进行回顾性分析,总结MGUS临床特征及转归时间,探讨单克隆免疫球蛋白浓度变化.结果 MGUS无多发性骨髓瘤(MM)的临床表现,从MGUS到MM转归时间为4～20年,平均10年;MM主要为IgA型和IgG型,其中IgA型6例,IgG型6例,轻链型2例;MGUS患者免疫球蛋白浓度总体呈现逐年上升趋势,呈折线型上升者占少数.结论 单克隆免疫球蛋白升高有向MM发展的可能,对于MGUS患者需密切观察,避免漏诊和误诊.     

Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg‐interferon and ribavirin therapy

Background and aims: Mutations in the core and NS5A region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. Genome‐wide association studies have revealed that the single‐nucleotide polymorphism (SNP) of interleukin 28B (IL28B) contributes to IFN response. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the core and NS5A region affect the response to IFN therapy. Methods: A total of 299 patients (157 men, 142 women; mean age, 55.9 ± 10.3 years) infected with HCV genotype 1b were studied. The fibrosis stage was diagnosed as F0 (n=23), F1 (n=121), F2 (n=62), F3 (n=32) and F4 (n=7) by liver biopsy. Results: Of the 299 patients, 138 achieved sustained virological response (SVR). On univariate analysis, predictors of SVR were age <60 years, male gender, higher platelet count, lack of fibrosis, non‐Q at core 70, mutant‐type interferon sensitivity‐determining region (ISDR) and IL28B genotype TT. The factors related to SVR on multivariate analysis were IL28B (P=0.0001), fibrosis (P=0.0111) and mutations in the core region70 (P=0.0267) and ISDR (P=0.0408). The best SVR was achieved in patients with non‐Q70, mutant‐type ISDR and T allele (74.5%), and the worst was achieved in patients with Q70, wild‐type ISDR and G allele (8.1%). Conclusions: The SNP of IL28B and mutations in the core region and NS5A are associated with IFN responsiveness. Both host and viral factors might be useful for predicting IFN response.     

Xeroderma pigmentosum patients from Germany: repair capacity of 45 XP fibroblast strains of the Mannheim XP Collection as measured by colony-forming ability and unscheduled DNA synthesis following treatment with methyl methanesulfonate and N-methyl-N-nitrosourea

Summary A total of 45 XP fibroblast strains from the Mannheim XP Collection (representatives of XP complementation groups A, C, D, E, F or G, I, and XP variants) were investigated for colony-forming ability (term: D₀ after treatment with up to ten doses of the methylating carcinogen MeSO₂OMe. As controls 16 fibroblast strains from normal donors were used. Except for 4 XP strains (1 from group C and 3 from group D) which, however, were borderline cases, none of the remaining 41 XP strains was found to be more sensitive than normal controls. This held true within the limits of an experimental accuracy (experimental variability of D₀ values) of ±7%. When weighted means were calculated for XP complementation groups and compared with that of normal donors at a significance level of 5%, no significant difference was detected. In contrast, after exposure of 6 XP group D strains to MeNOUr, a weighted mean D₀ value was obtained which was significantly decreasd by 27%. Unscheduled DNA synthesis (term: G₀ which serves as a measure of excision repair) after exposure to MeNOUr was quantitatively the same (exposure to MeNOUr was quantitatively the same (experimental varability: ±8%) both in the group of normal strains and in most of the XP complementation groups. Exceptions were group E and group F (or G) which had higher, and group I which had lower repair. Analogous G₀ values measured after exposure to MeSO₂OMe (experimental variability: ±13%), however, differed from that of the control strains: they were lower in XP complementation groups A, D, E, F (or G), and I. However, groups A, E, F (or G), and I including only 3 individual strains or less may be considered to be possibly ill-represented. Yet, group D including 11 XP strains did show reduction of the mean G₀ value by 35%. From this it is concluded that there are repair defects in XP group D strains with regrad to MeSO₂OMe-induced adducts. These defects seem to be small.Abbreviations XP xeroderma pigmentosum - MeSO₂OMe methyl methanesulfonate - MeNOUr N-methyl-N-nitrosourea - Me(NO)(NO₂)Gdn N-methyl-N-nitro-N-nitrosoguanidine - HEPES N-2-hydroxyethyl-piperazine-N-2-ethanesulfonic acid This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136     

Maintenance therapy with alpha-interferon following first-line VAD in multiple myeloma

Abstract: The aim of this study was to evaluate the response characteristics of vincristine, adriamycin and dexamethasone (VAD) as a first-line chemotherapy and to determine the efficacy of maintenance alpha-interferon (α-IFN) in multiple myeloma (MM). Between January 1985 and December 1994, a prospective trial was performed in stage II and III MM patients. The study population received only VAD with no maintenance therapy before 1990 (n = 31), and those recruited after 1990 (n = 33) were planned to be maintained with α-IFN (5 mU, 3 times per wk) during the plateau to a maximum of 2 yr. Median follow-up duration (44 vs. 39 months), time to response (3.4 vs. 3.5 months) and rate of objective response (61.3%, 19/31 and 63.6%, 21/33) were similar in VAD-only and VAD+IFN groups, respectively. The survival analyses revealed higher median progression-free (39.6 vs. 12 months) and overall survival (65+ vs. 24 months) durations in VAD+IFN group compared to VAD-only group. VAD regimen was well tolerated and IFN-related side effects were reversible. These findings denote that IFN maintenance prolongs the duration of response obtained by VAD.