Risk of lymphoma subtypes by occupational exposure in Southern Italy

Background

Occupational exposure is known to play a role in the aetiology of lymphomas. The aim of the present work was to explore the occupational risk of the major B-cell lymphoma subtypes using a case–control study design.

Methods

From 2009 to 2014, we recruited 158 lymphoma cases and 76 controls in the provinces of Bari and Taranto (Apulia, Southern Italy). A retrospective assessment of occupational exposure based on complete work histories and the Carcinogen Exposure (CAREX) job-exposure matrix was performed.

Results

After adjusting for major confounding factors, farmers showed an increased risk of diffuse large B-cell lymphoma (DLBCL) [odds ratio (OR)?=?10.9 (2.3–51.6)] and multiple myeloma (MM) [OR?=?16.5 (1.4–195.7)]; exposure to the fungicide Captafol was significantly associated with risk of non-Hodgkin lymphoma (NHL) [OR?=?2.6 (1.1–8.2)], particularly with the risk of DLBCL [OR?=?5.3 (1.6–17.3)].

Conclusions

Agricultural activity seems to be a risk factor for developing lymphoma subtypes, particularly DLBCL, in the provinces of Bari and Taranto (Apulia Region, Southern Italy). Exposure to the pesticides Captafol, Paraquat and Radon might be implicated.

Trial registration

Protocol number UNIBA 2207WEJLZB_004 registered 22/09/2008.

     

Occupational risk factors for cancer of the central nervous system: A case-control study on death certificates from 24 U.S. states

The risk of cancer of the central nervous system (CNS) by industry and occupation was investigated with a case-control analysis of the death certificates of 28,416 cases and 113,664 controls, selected from over 4.5 million deaths in 24 U.S. states between 1984 and 1992. Industries showing consistent increases in risk by gender and race included textile mills, paper mills, printing and publishing industries, petroleum refining, motor vehicles manufacturing, telephone and electric utilities, department stores, health care services, elementary and secondary schools, and colleges and universities. CNS cancer risk was increased for administrators in education and related fields, secondary school teachers, and other education- and health-related occupations. The application of job-exposure matrices to the industry/occupation combinations revealed a modest increase in risk for potential contact with the public at work and exposure to solvents. Occupational exposure to electromagnetic fields (EMF) was not associated with CNS cancer, although an association was observed with a few EMF-related occupations and industries. Agricultural exposures were associated with significant risk increases among white women and white men. Further work is required to investigate in more detail specific occupational exposures or possible confounders responsible for the observed associations. Am. J. Ind. Med. 33:247–255, 1998. © 1998 Wiley-Liss, Inc.     

Post-natalizumab clinical and radiological findings in a cohort of multiple sclerosis patients: 12-month follow-up

There is an urgent need to identify the best strategies to prevent the loss of natalizumab (N) beneficial effects after its suspension. The objective is to evaluate the clinical and radiological disease activity and to test the efficacy of immunomodulatory/immunosuppressive drugs (IT) after N suspension. Clinical and radiological data from 54 patients 2 years before treatment (pre-N), during treatment (on-N) and after interruption, during 1-year follow-up (post-N) were retrospectively collected. Annualized relapse rate (ARR), expanded disability status scale (EDSS), presence of new T2 lesions and Gd+ (gadolinium enhancing) T1 lesions were evaluated. Pre-N ARR at 1 year was 1.74 while post-N ARR was 0.94 (p = 0.0053). We observed that post-N disease activity never raised over pre-N levels, neither post-N ARR nor post-N EDSS. In patients retreated with N after suspension, post-N ARR was significantly lower than pre-N ARR (p = 0.017), but not in patients treated with other IT or in patients not treated with any disease modifying drugs (DMD). The mean time of freedom from new T2 lesions and new Gd+ lesions was lower in post-N period compared to on-N (T2 lesions p = 0.0000, Gd+ lesions p = 0.0000). In conclusion, a “rebound” pattern was not identified in our cohort, though the disease activity rapidly returned after N, regardless of the treatment used.     

Targeting the cancer initiating cell: the ultimate target for cancer therapy

An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the original therapeutic approach or they have acquired mutations which confer resistance to the primary therapy. In experimental mouse tumor transplant models, CICs have the ability to transfer the tumor to immunocompromised mice very efficiently while the BCs are not able to do so as effectively. Often CICs display increased expression of proteins involved in drug resistance and hence they are intrinsically resistant to many chemotherapeutic approaches. Furthermore, the CICs may be in a suspended state of proliferation and not sensitive to common chemotherapeutic and radiological approaches often employed to eliminate the rapidly proliferating BCs. Promising therapeutic approaches include the targeting of certain signal transduction pathways (e.g., RAC, WNT, PI3K, PML) with small molecule inhibitors or targeting specific cell-surface molecules (e.g., CD44), with effective cytotoxic antibodies. The existence of CICs could explain the high frequency of relapse and resistance to many currently used cancer therapies. New approaches should be developed to effectively target the CIC which could vastly improve cancer therapies and outcomes. This review will discuss recent concepts of targeting CICs in certain leukemia models.     

Antibodies against lytic and latent Kaposi's sarcoma-associated herpes virus antigens and lymphoma in the European EpiLymph case-control study

Background:

Kaposi''s sarcoma-associated herpes virus is associated with primary effusion lymphoma and multicentric Castleman''s disease.

Methods:

Seropositivity to lytic and latent Kaposi''s sarcoma herpes virus (KSHV) antigens were examined in 2083 lymphomas and 2013 controls from six European countries.

Results:

Antibodies against KSHV latent and lytic antigens were detectable in 4.5% and 3.4% of controls, respectively, and 3.6% of cases (P>0.05). The KSHV seropositivity was associated with splenic marginal zone lymphoma (SMZL) (odds ratio (OR)=4.11, 95% confidence interval (CI)=1.57–10.83) and multiple myeloma (OR=0.31, 95% CI=0.11–0.85).

Conclusion:

The KSHV is unlikely to contribute importantly to lymphomagenesis among immunocompetent subjects. However, the observed association with SMZL may underline a chronic antigen mechanism in its aetiology.     

Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma

Cytogenetic analysis in myeloma reveals marked chromosomal instability. Both widespread genomic alterations and evidence of aberrant class switch recombination, the physiological process that regulates maturation of the antibody response, implicate the DNA repair pathway in disease pathogenesis. We therefore assessed 27 SNPs in three genes (XRCC3, XRCC4 and XRCC5) central to DNA repair in patients with myeloma and controls from the EpiLymph study and from an Irish hospital registry (n = 306 cases, 263 controls). For the haplotype-tagging SNP (htSNP) rs963248 in XRCC4, Allele A was significantly more frequent in cases than in controls (86.4 versus 80.8%; odds ratio 1.51; 95% confidence interval 1.10-2.08; P = 0.0133), as was the AA genotype (74 versus 65%) (P = 0.026). Haplotype analysis was performed using Unphased for rs963248 in combination with additional SNPs in XRCC4. The strongest evidence of association came from the A-T haplotype from rs963248-rs2891980 (P = 0.008). For XRCC5, the genotype GG from rs1051685 was detected in 10 cases from different national populations but in only one control (P = 0.015). This SNP is located in the 3'-UTR of XRCC5. Overall, these data provide support for the hypothesis that common variation in the genes encoding DNA repair proteins contributes to susceptibility to myeloma.     

Determination of compounds with anticholinesterase activity in commercial drugs by a new enzyme sensor

A suitable enzyme sensor for the analysis of anticholinesterase compounds of pharmaceutical interest is described. It is based on the competitive inhibiting properties of these compounds on the enzyme butyrylcholinesterase and it is constituted by a hydrogen peroxide amperometric electrode modified by a superimposed Nylon membrane containing two chemically immobilized biological mediators (butyrylcholinesterase and choline oxidase). Some applications to the analysis of several pharmaceutical forms containing different compounds showing anticholinesterase activity are also reported and evaluated.     

Mortality from lung cancer among Sardinian patients with silicosis

The mortality of 724 subjects with silicosis, first diagnosed in 1964-70 in the Sardinia region of Italy, was followed up through to 31 December 1987. Smoking, occupational history, chest x ray films, and data on lung function were available from clinical records for each member of the cohort. The overall cohort accounted for 10,956.5 person-years. The standardised mortality ratios (SMRs) for selected causes of death (International Classification of Diseases (ICD) eighth revision) were based on the age specific regional death rates for each calendar year. An excess of deaths for all causes (SMR = 1.40) was found, mainly due to chronic obstructive lung disease, silicosis, and tuberculosis with an upward trend of the SMR with increasing severity of the International Labour Office (ILO) radiological categories. Twenty two subjects died from lung cancer (SMR = 1.29, 95% confidence interval (95% CI) = 0.8-2.0). The risk increased after a 10 and 15 year latency but the SMR never reached statistical significance. No correlation was found between lung cancer and severity of the radiological category, the type of silica (coal or metalliferous mines, quarries etc), or the degree of exposure to silica dust. A significant excess of deaths from lung cancer was found among heavy smokers (SMR = 4.11) and subjects with airflow obstruction (SMR = 2.83). A nested case-control study was planned to investigate whether the association between lung cancer and airway obstruction was due to confounding by smoking. No association was found with the ILO categories of silicosis or the estimated cumulative exposure to silica. The risk estimate for lung cancer by airflow obstruction after adjusting by cigarette consumption was 2.86 for a mild impairment and 7.23 for a severe obstruction. The results do not show any clear association between exposure to silica, severity of silicosis, and mortality from lung cancer. Other environmental or individual factors may act as confounders in the association between silicosis and lung cancer. Among them, attention should be given to chronic airways obstruction as an independent risk factor for lung cancer in patients with silicosis.     

Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case–control study

Objectives:This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts.Methods:We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case–control study, conducted in six European countries in 1998–2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education.Results:We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01–4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00–4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95–4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively).Conclusions:Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.     

Nipple-Sparing Mastectomy: Are We Providing Proper Prophylactic Antibiotic Coverage?

Background

Infection after nipple-sparing mastectomy (NSM) and implant-based reconstruction (IBR) can be a devastating complication. The retained nipple may act as a portal or nidus for different ductal organisms, and as such, the bacteriology of surgical-site infections (SSIs) in this setting may not be adequately covered by current antibiotic recommendations. This study sought to evaluate SSI and reconstruction outcomes in relation to antibiotic choice and identify the different microbial species implicated.

Methods

A prospective database was reviewed for patients who underwent NSM with IBR from 2010 to 2019. Patient characteristics, operative details, antibiotic regimens, and subsequent treatment details were evaluated. The study analyzed SSI incidence, timing, and type of causative organisms.

Results

The study analyzed 571 NSMs with IBR performed for 347 patients (55% with direct implants and 45% with tissue expanders). The preoperative antibiotics consisted of cephalosporin alone for 65% of the patients, a more broad single-antibiotic use for 12% of the patients, and dual-coverage antibiotics for 20% of the patients. During a median follow-up of 1.7 years, SSI developed in 12% of the reconstructions, with 6% requiring prosthesis removal. The most common SSI organism cultured was Staphylococcal species. Neither pre- nor postoperative antibiotic choice was associated with incidence of infection, type of bacteria, or need for prosthetic explanation.

Conclusion

For patients undergoing NSM with IBR, a more aggressive antibiotic choice is not associated with an improved SSI rate. Patient and treatment factors continue to carry the highest risk for SSI.