Risk of lymphoid neoplasms in a Swedish population-based cohort of 337,437 patients undergoing appendectomy

Objective Appendectomy remains one of the most common surgical procedures, but possible long-term consequences for health and disease are incompletely investigated. The appendix forms part of the secondary lymphoid system and appendectomy has been associated with increased risks of hematolymphoproliferative malignancies in some studies. Materials and methods We examined the risk of lymphoid neoplasms in a large cohort of 337,437 appendectomised patients <60 years of age in Sweden 1975–2009. We estimated relative risks of non-Hodgkin lymphoma (NHL) and major subtypes, Hodgkin lymphoma (HL), chronic lymphocytic leukaemia (CLL), myeloma, and acute lymphoblastic leukaemia (ALL) versus the general population using standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Results There was no increased risk of NHL (SIR?=?0.97, 95%CI 0.88–1.06), major NHL subtypes, CLL (SIR?=?0.87, 95%CI 0.70–1.06), myeloma (SIR?=?1.14, 95%CI 0.96–1.33) or ALL (SIR?=?1.10, 95%CI 0.80–1.47) following appendectomy. An increased risk of HL was observed among patients diagnosed with appendicitis (SIR?=?1.29, 95%CI 1.07–1.54, p=0.007), especially individuals aged?<20 years at surgery (SIR?=?1.43, 95%CI 1.11–1.82), and for the nodular sclerosis subtype of HL (SIR?=?1.55, 95%CI 1.01–2.27). A marginally increased risk of myeloma was noted among men, but the association was limited to the first few years of follow-up. Conclusion Appendectomy is not associated with any notable increase in risk of lymphoid neoplasms. A small increased risk of HL following appendicitis (rather than appendectomy per se) could reflect a true association, or shared susceptibility to infection/inflammation among individuals prone to develop HL. The association observed for myeloma may be explained by chance or surveillance bias.     

Hodgkin's lymphoma in systemic lupus erythematosus

OBJECTIVE: In systemic lupus erythematosus (SLE), there is a well-documented increased risk of non-Hodgkin's lymphoma (NHL), but little is known about the risk of Hodgkin's lymphoma (HL). The purpose of our work was to describe the phenomenon of HL in SLE. METHODS: A multi-site cohort of 9547 SLE subjects was assembled; HL cases were ascertained through cancer registry linkage, and the standardized incidence ratio (SIR) for HL was determined. We also performed a literature search for HL cases in SLE, and compared these with our sample. Finally, we pooled results from our cohort study with two large population-based cohort studies providing SIR estimates for HL in SLE. RESULTS: Five cases of HL occurred in our SLE cohort during the observation interval, for an SIR of 2.4 (95% CI 0.8, 5.5). The literature review documented 13 HL case reports developing in patients with SLE. A pooled analysis combining our data with the other large cohort studies yielded a standardized incidence ratio of 3.16 (95% CI, 1.63-5.51) for HL in SLE. CONCLUSIONS: Data suggest that risk in SLE is increased not only for NHL, but also for other malignancies arising from B-lymphocytes, including HL.     

Cancer incidence in people with hepatitis B or C infection: a large community-based linkage study

BACKGROUND/AIMS: Risks of hepatocellular carcinoma (HCC) following hepatitis B and/or hepatitis C virus (HBV/HCV) infection are well known, those for other cancers are less well understood. The aim was to quantify the risk of cancers among persons diagnosed with HBV/HCV infections. METHODS: The data from a cohort of 39109 HBV, 75834 HCV, and 2604 HBV/HCV co-infected persons notified to the State health department, 1990-2002, were probabilistically linked to the Cancer Registry and standardised incidence ratios (SIRs) for cancer were calculated. RESULTS: The match rate for any cancer was 2.7%, 2.3% and 3.3% for HBV, HCV and HBV/HCV co-infected notifications. SIRs for HCC were 30.6 (95% CI 25.7-36.5), 22.7 (95% CI 19.1-26.5) and 30.3 (95% CI 13.6-67.5), respectively. Increased risk was detected for Burkitt's lymphoma and HBV (SIR 12.9, 95% CI 5.4-30.9) and immunoproliferative malignancies following HCV (SIR 5.6, 95% CI 1.8-17.5). CONCLUSIONS: The risk of HCC in the infected cohort was 20-30 times greater than in the uninfected population with SIRs two to three times greater than those for the other HBV/HCV infection associated cancers. The modest though significant risk of immunoproliferative malignancies associated with HCV infection is consistent with recent findings.     

Late non-relapse mortality among adult autologous stem cell transplant recipients: a nation-wide analysis of 1,482 patients transplanted in 1990-2003

Data on the incidence and causes of late (>100 d) non-relapse mortality (NRM) in autologous stem cell transplant (ASCT) recipients is limited. We have analysed NRM in a cohort of 1,482 adult patients who received ASCT in 1990-2003 in six Finnish transplant centres. The most common diagnoses included non-Hodgkin's lymphoma (NHL) (n = 542), multiple myeloma (MM) (n = 528), breast cancer (n = 132); Hodgkin's lymphoma (HL) (n = 86) and chronic lymphocytic leukaemia (CLL) (n = 63). Until September 2005, 646 patients (44%) have died. Late NRM was observed in 68 patients (4.6% of ASCT recipients; 11% of all deaths). There were 38 males and 30 females with a median age of 58 yr (20-69) at the time of ASCT. The median time to NRM was 27 months from ASCT (3-112). The risk of NRM was highest in patients with CLL (9.5%) and those with HL (8.1%) followed by MM and NHL (4.9% and 4.8%, respectively). The risk of late NRM was comparable in patients who received total body irradiation (TBI) and those who received chemotherapy-only regimens (6.7% vs. 4.3%). Another malignancy was the most common cause of late NRM (24 patients, 35% of late NRM). Twelve patients (0.8% of ASCT recipients) have died due to secondary haematological malignancy. Altogether 22 patients (32% of late NRM) died from infectious causes. Malignancies and late infections are important causes of NRM after ASCT. These facts point out the importance of prolonged follow-up in ASCT recipients.     

Intracellular lactic dehydrogenase and phosphohexose isomerase activity in leukaemia and malignant lymphoma

Intracellular activities of total lactic dehydrogenase (LDH) and phosphohexose isomerase (PHI) were investigated in the leukaemic cells of 14 patients with acute myeloid leukaemia (AML), five with chronic myeloid leukaemia (CML), seven with acute lymphoblastic leukaemia (ALL), 19 with chronic lymphocytic leukaemia (CLL), 16 with leukaemic non-Hodgkin's lymphoma (NHL) and in the lymphocytes of 14 normal persons. Intracellular total LDH-activity of the blasts of AML and ALL was in the same range as the normal lymphocytes. Patients with CLL and NHL had significantly lower levels ( P <0.01) of total intracellular LDH than the controls. Intracellular PHI activity was consistently lower in the lymphoid malignancies (ALL, CLL, NHL) than in normal lymphocytes ( P <0.05), or in leukaemic myeloblasts ( P <0.01). The intracellular LDH/PHI index of the leukaemic lymphoblasts was significantly elevated as compared to lymphocytes from normal subjects ( P <0.0001) or to leukaemic cells from patients with AML ( P <0.001), with CLL ( P < 0.0001) or with NHL ( P < 0.001). The patients with CLL and NHL, on the other hand, had significantly lower levels of LDH/PHI ratio than the normal subjects ( P <0.0001 and P <0.025 respectively).     

Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus

OBJECTIVE: To assess the risk of cancer in patients with systemic lupus erythematosus (SLE). METHODS: A population-based cohort of 5 715 hospitalised SLE patients was followed 1964-1995 through linkage of the Hospital Discharge Register to the National Swedish Cancer Register. RESULTS: In all, 443 malignancies occurred during the observation-period. The overall risk was increased by 25% (SIR= 1.25, CI 95% 1.14-1.37) and lymphomas constituted the major excess risk. The risk of non-Hodgkin's lymphoma (NHL) was nearly 3-fold increased (SIR = 2.86, CI 95% 1.96-4.04). There was also an increased risk of lung cancer (SIR= 1.73, CI 95% 1.25-2.32) and squamous cell skin cancer (SIR= 1.53, CI 95% 0.98-2.28), which was most pronounced at more than 15 years of follow-up. CONCLUSION: The major finding was a bimodal incidence pattern with an increased risk of lymphoma, mainly NHL, early during follow-up, but lung cancer and squamous skin cancer later on.     

Prevalence of familial malignancy in a prospectively screened cohort of patients with lymphoproliferative disorders

Increasing evidence points to a heritable contribution in the development of lymphoma. The goal of this study was to determine the rate of familial lymphoproliferative malignancy among consecutive lymphoma patients presenting to a tertiary care center and to enroll families with multiple affected first-degree relatives on a data and tissue collection study. Beginning in 2004 all new patients presenting to the Dana-Farber Cancer Institute with non-Hodgkin (NHL) or Hodgkin lymphoma (HL) or chronic lymphocytic leukaemia (CLL) were asked to complete a one-page self-administered family history questionnaire. 55.4% of 1948 evaluable patients reported a first-degree relative with a malignancy, with the highest rate among CLL probands. Lymphoid malignancies were particularly common, with 9.4% of all probands reporting a first-degree relative with a related lymphoproliferative disorder (LPD). This frequency was again highest for CLL, at 13.3% of CLL probands, compared to 8.8% of NHL probands and 5.9% of HL probands (P = 0.002). The prevalence of CLL was significantly increased in parents of CLL probands (P < 0.05), and a greater risk of NHL was seen in fathers of NHL probands than in mothers (P = 0.026). We conclude that familial aggregation of LPDs is common among newly diagnosed patients, varies significantly by diagnosis and contributes meaningfully to the population disease burden.     

Hepatitis C virus infection prevalence and liver dysfunction in a cohort of B-cell non-Hodgkin's lymphoma patients treated with immunochemotherapy

Several studies have reported a higher prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) than in the general population. Treatment for NHL includes the use of chemotherapeutic agents such as cytotoxic drugs, corticosteroids, and rituximab, which can be immunosuppressive and hepatotoxic. While reactivation of hepatitis B virus (HBV) when undergoing immunosuppressive therapy for haematological malignancies is a well-documented complication, data on HCV reactivation or liver function impairment after chemotherapy for NHL are controversial. From January 2006 to December 2009, 207 consecutive NHL patients treated with chemotherapy without rituximab (CHOP) or with rituximab (R-CHOP) were observed; screening for HCV infection and baseline liver function tests were performed in all patients. The prevalence of HCV infection was 9.2%. This prevalence is higher than that observed in the general population in Italy (3%). Among the HCV-infected subjects, the incidence of hepatitis flares was 26.3% vs 2.1% among the HCV-uninfected individuals. Although less frequent and less severe than in HBV-infected subjects, liver dysfunction can occur as a consequence of rituximab-containing regimens in HCV-infected patients with NHL. In the cases considered in this study, no patient treated with chemotherapy without rituximab developed hepatitis flares. The frequency and the severity of this complication vary in different reports. Therefore, we recommend the assessment of liver function and the screening of all patients with NHL for HCV infection before starting chemotherapy; we also recommend monitoring of liver function tests and HCV-RNA serum levels during treatment.     

Expression of CD66 in non-Hodgkin lymphomas and multiple myeloma

Objectives: ⁹⁰Y‐labeled anti‐CD66b monoclonal antibody clone BW 250/183 was developed for treatment of tumors. The aim of the study was the analysis of CD66 expression in lymphoproliferative malignancies to expand the potential of anti‐CD66‐based therapy. Patients and methods: Bone marrow samples from 260 patients were examined for the expression of CD66 on tumor cells in 104 B‐chronic lymphocytic leukemias (B‐CLL), 28 mantle cell lymphomas (MCL), 22 follicular lymphomas (FCL), 15 marginal zone lymphomas (MZL), 12 lymphoplasmacytic lymphomas (LPL), 13 diffuse large B cell lymphomas (DLBCL), 4 T‐non‐Hodgkin lymphomas (T‐NHL), 3 B‐NHL not otherwise specified (B‐NHL NOS), 3 B acute lymphoblastic leukemias (B‐ALL), and in 56 multiple myelomas (MM) by flow cytometry. Results: Positive (≥ 20%) expression of CD66abce clone Kat4c was detected in 76% of B‐CLL and 76.8% of MM. The highest number of CD66abce‐positive samples was in MCL and LPL (96.4% of 28 and 91.7% of 12 patients, respectively). Expression of CD66b clone BW 250/183 was examined in 114 of 260 samples. Positive expression was detected in 23.3% of B‐CLL (6/35), 17.1% of MM (7/30), and 21.4% of MCL (3/14) samples. Conclusion: The expression of CD66b compared to CD66abce was lower in all measured samples. Use of radiolabeled anti‐CD66b antibody for the treatment of lymphoproliferative diseases appears to have limited preclinical substantiation.     

Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and concurrent lymphoid malignancy

Allogeneic hematopoietic cell transplantation (HCT) can be curative for both myelodysplastic syndromes (MDS) and lymphoid malignancies. Little is known about the efficacy of allogeneic HCT in patients in whom both myeloid and lymphoid disorders are present at the time of HCT. We analyzed the outcomes in 21 patients with MDS and concurrent lymphoid malignancy when undergoing allogeneic HCT. A total of 17 patients had previously received extensive cytotoxic chemotherapy, including autologous HCT in 7, for non-Hodgkin lymphoma (NHL, n=7), Hodgkin lymphoma (HL, n=2), CLL (n=5), NHL plus HL (n=1), multiple myeloma (n=1) or T-cell ALL (n=1), and had presumably developed MDS as a consequence of therapy. Four previously untreated patients had CLL. A total of 19 patients were conditioned with high-dose (n=14) or reduced-intensity regimens (n=5), and were transplanted from HLA-matched or one Ag/allele mismatched related (n=10) or unrelated (n=9) donors; two patients received HLA-haploidentical related transplants, following a modified conditioning regimen. Currently, 2 of 4 previously untreated and 2 of 17 previously treated patients are surviving in remission of both MDS and lymphoid malignancies. However, the high non-relapse mortality among previously treated patients, even with reduced-intensity conditioning regimens, indicates that new transplant strategies need to be developed.     

Hepatitis C virus infection and lymphoproliferative diseases in France: a national study. The GERMIVIC Group

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by North American and southern European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). In order to evaluate the situation in France, we conducted a retrospective national study about the association of chronic HCV infection and LPD. 72 Internal Medicine and Infectious Diseases departments were contacted. Response rate was 51.4%. We recorded 43 LPD (19 males, 24 females): 31 B-cell-NHL, 4 Waldenstr?m's macroglobulinemia, 3 chronic lymphocytic leukemia, 2 multiple myeloma, 2 lymphomas of the mucosa-associated lymphoid tissue, and 1 Hodgkin's disease. Mean age at HCV diagnosis was 62 years (range 33-84). In 16 cases, LPD occurred in patients known to be HCV-infected. For 11 patients, LPD diagnosis preceded the diagnosis of HCV infection, whereas diagnosis was done simultaneously in 11 patients. For those with accurate infection date, mean interval between both events was 15.2 years. Fourteen patients had HCV extrahepatic manifestations: 9 mixed cryoglobulinemia, including 7 with NHL, 5 sicca syndrome (5 NHL), and both in one patient. Cohort of HCV-infected patients could be accurately determined for 16 departments, totaling 1,485 patients and 37 cases. Thus, from our data the frequency of LPD among HCV-infected patients approximates 2. 49%. Despite possible bias inherent to this retrospective study, our data support the hypothesis of HCV-associated LPD and particularly B-cell-NHL. In France, this association is much lower than in Italy. Further studies are needed to assess the precise role of HCV in the multistep process leading to monoclonal proliferation.     

Derivation and validation of a novel score for early prediction of severe CRS after CAR-T therapy in haematological malignancy patients: A multi-centre study

Chimeric antigen receptor T (CAR-T) cell therapy is highly effective in inducing complete remission in haematological malignancies. Severe cytokine release syndrome (CRS) is the most significant and life-threatening adverse effect of this therapy. This multi-centre study was conducted at six hospitals in China. The training cohort included 87 patients with multiple myeloma (MM), an external validation cohort of 59 patients with MM and another external validation cohort of 68 patients with acute lymphoblastic leukaemia (ALL) or non-Hodgkin lymphoma (NHL). The levels of 45 cytokines on days 1–2 after CAR-T cell infusion and clinical characteristics of patients were used to develop the nomogram. A nomogram was developed, including CX3CL1, GZMB, IL4, IL6 and PDGFAA. Based on the training cohort, the nomogram had a bias-corrected AUC of 0.876 (95% CI = 0.871–0.882) for predicting severe CRS. The AUC was stable in both external validation cohorts (MM, AUC = 0.907, 95% CI = 0.899–0.916; ALL/NHL, AUC = 0.908, 95% CI = 0.903–0.913). The calibration plots (apparent and bias-corrected) overlapped with the ideal line in all cohorts. We developed a nomogram that can predict which patients are likely to develop severe CRS before they become critically ill, improving our understanding of CRS biology, and may guide future cytokine-directed therapies.     

Expression of C-IAP1, C-IAP2 and SURVIVIN discriminates different types of lymphoid malignancies

(De-)regulation of apoptosis plays an important role in normal and malignant lymphopoiesis. Apoptosis-regulating genes of the BCL-2 family and the recently identified inhibitors of apoptosis (IAP) family have been implicated in different types of non-Hodgkin lymphoma (NHL). To investigate whether expression of specific apoptosis-regulating genes correlated with different types of lymphoid malignancies, we measured the expression of five BCL-2 family genes, four IAP family genes and SMAC by real-time quantitative polymerase chain reaction in patient samples. In total, 137 samples from B- and T-cell acute lymphoblastic leukaemia (ALL), B-cell chronic lymphocytic leukaemia (CLL), six different NHL types and three control tissue types were analysed. The data were further analysed using cluster and discriminant analysis. Three specific expression patterns were identified for CLL, ALL and NHL respectively. CLL samples, as well as B-ALL and follicular lymphoma samples showed high similarity in the expression of these apoptosis-regulating genes and could be distinguished from each other and other diseases and controls. Discriminant analysis identified three members of the IAP family, C-IAP1, C-IAP2 and SURVIVIN, as the most informative genes to discriminate between these lymphoid malignancies.     

Malignancies associated with chronic hepatitis C: case report and review of the literature

Hepatocellular carcinoma (HCC) is a well-known consequence of hepatitis C virus (HCV) infection mainly in cirrhotic patients. Associations of other malignancies such as cholangiocellular carcinoma and B-cell malignancies with HCV are less well known. Here we review pathophysiological aspects of malignancies associated with HCV infection. A case report of HCV-related HCC and B-cell lymphoma illustrates the increased risk for HCV-infected patients to develop other malignancies besides HCC.     

The efficacy of VAD chemotherapy for refractory lymphoid malignancies

Thirty patients with refractory lymphoid malignancies [multiple myeloma (MM): 8, plasma cell leukemia (PCL): 2, acute lymphocytic leukemia (ALL): 5, chronic myelogenous leukemia in blast crisis: 1, chronic lymphocytic leukemia in blast crisis: 1, adult T-cell leukemia: 1, non-Hodgkin lymphoma (NHL): 9, Hodgkin's disease (HD): 3] were treated with VAD regimen (vincristine, doxorubicin, dexamethasone). Of 28 evaluable patients, 4 patients achieved complete response or remission [MM1, ALL1, NHL1, HD1], 10 attained partial response or remission [MM5, PCL1, NHL3, HD1], and 2 patients with MM attained minor response. The remission duration ranged from 1 month to over 14 months. The response rate was high in patients with MM (75%) and lymphoma (60%), however 4 patients with T-cell malignancies achieved no response except one with NHL. In three patients who showed resistance to VAD, diltiazem was administered in addition to VAD and one patient with MM had response. Atrio-ventricular block was also observed in one patient during the period of diltiazem administration. Nine patients developed documented infections, 5 of which suffered from candida infections. From these observations, we concluded that VAD regimen might be useful as a salvage therapy especially in patients with MM and lymphoma.     

Promising therapy results for lymphoid malignancies in children with chromosomal breakage syndromes (Ataxia teleangiectasia or Nijmegen-breakage syndrome): a retrospective survey

Children with chromosomal instability syndromes have an increased risk of developing lymphoma and leukaemia. The treatment of these malignancies is hampered by therapy-associated toxicity and infectious complications. This retrospective analysis evaluated the therapy outcome of 38 children with Ataxia teleangiectasia or Nijmegen-breakage syndrome with acute lymphoblastic leukaemia (ALL, n = 9), Non-Hodgkin lymphoma (NHL, n = 28) and Hodgkin lymphoma (HL, n = 1). All patients with NHL or ALL were treated in accordance to Berlin-Frankfurt-Münster (BFM)- or Co-operative study group for childhood ALL (CoALL)-oriented chemotherapy schedules. 22 patients received significantly reduced-intensity chemotherapy. After a median follow-up of 3·7 years the 10-year overall survival was 58%. Dosage-reduction of chemotherapeutic drugs seemed to have no disadvantages and reduced toxic side effects. On the other hand, reduced-intensity chemotherapy did not prevent second malignancies, which occurred in ten patients with a 10-year incidence of 25%. After individual treatment approaches three of these patients with second malignancies were in complete clinical remission for more than 5 years. We conclude that BFM- or CoALL-oriented chemotherapy is effective and can be administered in children with AT or NBS. Moreover, we show that even second lymphoid malignancies can successfully be treated in these patients.     

Role of the CD40 and CD95 (APO-1/Fas) antigens in the apoptosis of human B-cell malignancies

Ligation of CD40 inhibits apoptosis and stimulates proliferation of normal B cells, whereas ligation of CD95 (APO-1/Fas) induces apoptosis of activated lymphocytes. Aberrant signalling through the CD40 and CD95 antigens could thus participate in the pathogenesis of lymphoid malignancies. The expression and function of CD40 and CD95 on neoplastic B cells from patients with acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and non-Hodgkin’s lymphoma (NHL) were examined. CD40 was expressed by all 30 B-cell tumours, whereas CD95 was detected on neoplastic B cells in only one of 10 cases of ALL, two of 10 cases of CLL, and three of 10 cases of NHL. Incubation with an agonistic CD95 monoclonal antibody (MoAb) did not augment apoptosis in any of the unstimulated B-cell neoplasms. CD40 triggering did not consistently inhibit spontaneous apoptosis, but ultimately stimulated the growth of neoplastic B cells in most cases. Furthermore, CD40 activation led to up-regulation of the CD95 antigen in all 30 B-cell neoplasms. Ligation of CD95 on CD40-activated tumour cells augmented apoptosis in five of 10 ALL, three of 10 CLL, and nine of 10 NHL cases. The degree of apoptosis induced by CD95 triggering was greater for NHL cells than for ALL cells or CLL cells. Bcl-2 expression by ALL and NHL cells was substantially decreased after in vitro culture, whereas Bcl-2 expression by CLL cells was not significantly changed. However, there was no correlation between the level of Bcl-2 expression and sensitivity to CD95-mediated apoptosis. Thus, factors other than levels of CD95 and Bcl-2 determine susceptibility of malignant B cells to apoptosis after CD95 triggering. CD40-activated lymphoma cells appear to be very sensitive to CD95-mediated apoptosis, suggesting potential strategies for treatment of NHL. Elucidation of the mechanisms underlying resistance of ALL and CLL cells to CD95 triggering may facilitate the development of novel therapeutic approaches to these diseases as well.     

Risk of myocardial infarction associated with chronic hepatitis C virus infection: a population-based cohort study

Hepatitis C virus (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis. However, it remains unclear if HCV infection increases the risk of acute myocardial infarction (MI). To determine whether HCV infection is an independent risk factor for acute MI among adults followed in general practices in the United Kingdom (UK), a retrospective cohort study was conducted in The Health Improvement Network, from 1996 through 2008. Patients ≥18 years of age with at least 6 months of follow-up and without a prior history of MI were eligible for study inclusion. HCV-infected individuals, identified with previously validated HCV diagnostic codes (n = 4809), were matched on age, sex and practice with up to 15 randomly selected patients without HCV (n = 71 668). Rates of incident MI among patients with and without a diagnosis of HCV infection were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards regression, controlling for established cardiovascular risk factors. During a median follow-up of 3.2 years, there was no difference in the incidence rates of MI between HCV-infected and -uninfected patients (1.02 vs 0.92 events per 1000 person-years; P = 0.7). HCV infection was not associated with an increased risk of incident MI (adjusted HR, 1.10; 95% confidence interval [CI], 0.67-1.83). Sensitivity analyses including the exploration of a composite outcome of acute MI and coronary interventions yielded similar results (adjusted HR, 1.16; 95% CI, 0.77-1.74). In conclusion, HCV infection was not associated with an increased risk of incident MI.     

The risk of lymphoma development in autoimmune diseases: a meta-analysis

BACKGROUND: The risk of development of non-Hodgkin lymphoma (NHL) in autoimmune patients has been investigated in several cohort studies. These studies revealed inconclusive results. To shed some light on this controversy, we conducted a meta-analysis of all available cohort studies linking systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sj?gren syndrome (pSS) to the risk of NHL development. METHODS: We searched the PubMed database (1974 to April 2005) for English-language cohort studies using the key words systemic lupus erythematosus, SLE, rheumatoid arthritis, RA, Sj?gren syndrome, or SS; non-Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All cohort studies that used established diagnostic criteria for SLE, RA, and pSS; had histologic confirmation of NHL; and provided standardized incidence rates (SIRs) were included in the meta-analysis. RESULTS: The 20 studies chosen for the analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis suggested extreme heterogeneity among the studies (P < .01; I2 > 70%), high risk of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3-17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA, the random effects SIRs of NHL with conventional antirheumatic treatment, cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7-9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively. CONCLUSIONS: Rheumatic disease may present a potential risk factor for development of NHL. In this regard, we focused on the underlying pathophysiologic mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying potential for and background of NHL development.     

Hepatocellular carcinoma and other primary liver cancers in hepatitis C patients in Sweden - a low endemic country

Summary.  The aim of this study was to assess the risk of hepatocellular carcinoma (HCC) and other primary liver cancers (PLC) in the nationwide cohort of hepatitis C virus (HCV) infected patients in Sweden. The basis was the total HCV-cohort notified in 1990–2004, after excluding 3238 people also reported with hepatitis B, the study cohort consisted of 36 126 people contributing an observation time of 246 105 person-years. The most common route of transmission was intravenous drug use (57%). The national Cancer Registry was used for follow-up, and 354 developed PLC (mainly HCC), of whom 234 were eligible for statistical analysis. The PLC incidence in the HCV cohort was compared with the incidence in the general population, and a standardized incidence ratio (SIR) was calculated for six different strata according to estimated duration of infection. The highest relative risk, SIR: 46 (95% CI: 36–56) was found in the stratum 25–30 years with HCV infection and SIR: 40 (95% CI: 31–51) in the stratum 30–35 years with infection. In the entire community-based HCV cohort in Sweden we found a highly increased risk of liver cancer compared to the general population. The highest relative risk was among people who had been infected for more than 25 years.