AIDS-related primary central nervous system lymphoma: = a Norwegian national survey 1989=E2=80=932003

Primary = central=20 nervous system lymphoma (PCNSL) is a frequent complication in = acquired=20 immunodeficiency syndrome (AIDS). The objective of this survey was = to=20 investigate incidence, clinical features, radiological findings,=20 histologic diagnosis, treatment and outcome for all patients with=20 histologically verified AIDS-related PCNSL diagnosed in Norway in=20 1989=E2=80=932003.

Methods

We identified = the=20 patients by chart review of all cases recorded as PCNSL in The = Norwegian=20 Cancer Registry (by law recording all cases of cancer in Norway) = and all=20 cases recorded as AIDS-related PCNSL in the autopsy registry at a = hospital=20 having 67% autopsy rate and treating 59% of AIDS patients in = Norway, from=20 1989 to 2003. Histologic material and radiological images were = reviewed.=20 We used person-time techniques to calculate incidence rates of = PCNSL among=20 AIDS patients based on recordings on AIDS at the Norwegian = Surveillance=20 System for Communicable Diseases (by law recording all cases of = AIDS in=20 Norway).

Results

Twenty-nine = patients had=20 histologically confirmed, newly diagnosed AIDS-related PCNSL in = Norway=20 from 1989=E2=80=932003. Only 2 patients had this diagnosis = established while=20 alive. AIDS patients had 5.5% lifetime risk of PCNSL. Their = absolute=20 incidence rate of PCNSL per 100 person-years was 1.7 (95%CI: = 1.1=E2=80=932.4) and=20 decreased during the consecutive 5-year periods from 3.6, to 2.5, = and to=20 0.4 (p < 0.001). Median survival from initial symptom of PCNSL = was 2.3=20 months, but one patient was still alive 4 years after completed=20 radiotherapy.

Conclusion

This is the = first=20 national survey to confirm decreasing incidence of AIDS-related = PCNSL.=20 Despite dismal survival in most patients, the possibility of long = term=20 survival should prompt more aggressive diagnostics in suspected = PCNSL.

Competing=20 interests

Authors'=20 contributions

Pre-pub= lication=20 history

References

Background

Primary central nervous system lymphoma (PCNSL) has been = diagnosed in=20 at least 2% of individuals infected with human immunodeficiency = virus=20 (HIV) [1],=20 and in 9=E2=80=9314% of acquired immunodeficiency syndrome = (AIDS)-autopsies [2-4].=20 PCNSL is, after toxoplasmosis, the most common cause of focal = brain=20 lesions in AIDS patients [1,5].=20 The reported median survival in AIDS-related PCNSL is = 1.0=E2=80=932.5 months with=20 supportive care only [6,7]=20 and 2.0=E2=80=935.5 months with whole brain radiation therapy [1,8].=20 The incidence of PCNSL among AIDS patients has been reported to = decline in=20 the era of highly active antiretroviral therapy (HAART), = introduced in=20 1996 [8-14].

Few studies on AIDS related PCNSL were population based [3,9,15-17].=20 This survey is, to the best of our knowledge, the first comprising = a whole=20 country. Its objective was to investigate incidence, clinical = features,=20 radiological findings, histologic diagnosis, treatment and outcome = for all=20 patients with histologically verified AIDS-related PCNSL diagnosed = in=20 Norway in 1989=E2=80=932003.

Competing=20 interests

Authors'=20 contributions

Pre-pub= lication=20 history

References

Methods

This study complied with the Helsinki Declaration. The Regional = Committee for Medical Research Ethics, the Directorate for Health = and=20 Social Affairs and The Data Inspectorate approved the study and = waived=20 informed consent.

Norway (population of 4.2 million in 1989 and 4.6 million in = 2003) has=20 mandatory cancer reporting to the Norwegian Cancer Registry. This = national=20 registry recorded 180 patients with PCNSL diagnosed from 1 January = 1989 to=20 31 December 2003. Medical records of all patients were reviewed.=20 Histologically verified AIDS-related PCNSL was found in 23 of the = 180=20 patients (98 had non-AIDS PCNSL and 59 no PCNSL) [18].=20 During the studied 15-year period Ullevaal University Hospital = treated 59%=20 (423/723) of reported new cases of AIDS in Norway and autopsied = 67%=20 (186/278) of their AIDS deaths. A search in their AIDS autopsy = registry=20 identified 6 additional cases of AIDS-related PCNSL.

This study sample thus consisted of 29 AIDS patients with=20 histologically verified PCNSL; 27 were diagnosed and treated at = Ullevaal=20 University Hospital. Clinical features, histologic diagnosis, = radiological=20 findings, treatment and outcome were registered. HAART was defined = as the=20 administration of three or more antiretroviral agents including a = protease=20 inhibitor or non-nucleoside reverse transcriptase inhibitor. One=20 pathologist (AKG) re-examined histologic material of all these = patients=20 from biopsy (n =3D 2) or autopsy (n =3D 27) and reclassified it = according to=20 the current WHO-classification (2001). For immunohistochemistry, = the=20 antibodies CD3, CD20 and Ki67 were used as a minimum. Epstein-Barr = virus=20 hybridization was performed in 25 patients. Twenty-six patients = had a=20 complete autopsy of the entire body (excluding systemic lymphoma). = The=20 remaining 3 patients underwent biopsy (n =3D 2) or autopsy (n =3D = 1) of the=20 brain only; none of them had signs of lymphoma at chest- and = abdomen=20 imaging (n =3D 3) or bone marrow biopsy (n =3D 2). Cause of death = was=20 established from medical records, autopsy reports and death=20 certificates.

In 14 included patients (1 of 12 diagnosed in = 1989=E2=80=931993, 13 of 17=20 diagnosed in 1994=E2=80=932003) images from computed tomography = (CT) (in 14) and=20 magnetic resonance imaging (MRI) (in 4) prior to histologic = diagnosis were=20 available for review. (In Norway hospitals are not obliged to = store=20 radiological images for more than 10 years.) A neuroradiologist = (JK) and a=20 general radiologist (ISH) reviewed the images, first individually = and then=20 together. Results are based on consensus from the joint = review.

Number of new cases with AIDS and number of AIDS deaths in = Norway each=20 year were obtained from MSIS (The Norwegian Surveillance System = for=20 Communicable Diseases). Named AIDS reporting from laboratories and = clinicians to this national surveillance system has been mandatory = in=20 Norway since 1983 [19].

Statistical analyses

We = calculated=20 absolute incidence rates of PCNSL among persons with AIDS based on = numbers=20 of newly diagnosed AIDS-related PCNSL and numbers of patients = living with=20 AIDS the same year (PYAR; Person-Years-At-Risk) (data from MSIS). = Trend=20 test and 95% confidence interval (CI) for incidence was calculated = according to the Poisson distribution.

Duration of survival was calculated as time between date of = first=20 symptom attributable to PCNSL and date of death or January = 1^st=202008. Survival curves were calculated and plotted using the = method=20 of Kaplan and Meier. All p-values in the analyses are two-sided. = The=20 analyses were performed with Stata 9.0 (College Station, TX) and = SPSS 14.0=20 (Chicago, IL).

Competing=20 interests

Authors'=20 contributions

Pre-pub= lication=20 history

References

Results

In Norway the absolute incidence rate of PCNSL among AIDS = patients per=20 100 person-years in 1989=E2=80=932003 was 1.7 (95%CI: = 1.1=E2=80=932.4) and decreased from=20 3.6, to 2.5, and to 0.4 the consecutive 5-year periods (p < = 0.001)=20 (Figure 1).=20 The average annual incidence rate of AIDS-related PCNSL among = inhabitants=20 in Norway was 0.44 per million (95%CI: 0.30=E2=80=930.64). The = proportion of=20 AIDS-deaths diagnosed with concomitant PCNSL was 5.5% (28/508). = This=20 proportion was stable over time (5.3% (12/227), 6.0% (13/215) and = 4.6%=20 (3/66) in 1989=E2=80=931993, 1994=E2=80=931998 and = 1999=E2=80=932003, respectively; Fischer's=20 Exact Test: p =3D 0.96).

Figure=20 1 AIDS-related=20 PCNSL in Norway: new cases, incidence rates and = Person-Years-At-Risk=20 (PYAR). New cases diagnosed with AIDS-related PCNSL = (a),=20 annual incidence rate per 100 Person-Years-At-Risk (PYAR) = (b) and=20 PYAR (c) the three 5-year periods: = 1989=E2=80=931993,=20 (more ...)

Patient characteristics are listed in Table 1.=20 Twenty-six (90%) of the 29 patients were male. Mean age at = diagnosis of=20 PCNSL was 39.0 years. The histologic diagnosis was diffuse large = B-cell=20 lymphoma in all patients. Only 2 patients had this diagnosis = established=20 while alive (in 2000 and 2003, based on open biopsy). = Immunohistochemistry=20 was positive with CD20 and Ki67 and negative with CD3 in 29/29 = (100%).=20 Epstein-Barr virus hybridization was positive in 25/25 (100%). = Polymerase=20 chain reaction (PCR) of the cerebrospinal fluid (CSF) performed = prior to=20 death demonstrated positive Epstein-Barr virus DNA in 3/5 (60%) = and=20 negative Toxoplasma gondii DNA in 2/2 (100%).

Table=20 1

Characteristics of=20 AIDS patients with PCNSL in Norway during 1989=E2=80=932003 = (n =3D=20 29).

Review of CT/MRI in 14 patients revealed no brain lesion in 1 = (7%), a=20 single lesion in 2 (14%), and multiple (2=E2=80=937) lesions in 11 = (79%) patients.=20 In the patient with no lesion, CT one week prior to death = indicated=20 hydrocephalus. All together, 37 lesions (36 at CT and 9 at MRI) = were=20 identified; involving the lobes in 11 patients (79%) and the deep=20 structures of the brain in 8 patients (57%) (Table 1).=20 All lesions enhanced after intravenous contrast injection; 75% = showed=20 ring-enhancement both at CT (27/36) and MRI (6/8) (Figure 2).

Figure=20 2 AIDS-related=20 PCNSL in Norway: imaging findings at CT and MRI. = Contrast=20 enhanced CT in 3 patients demonstrating lesions with=20 ring-enhancement in the frontal lobes (a), cerebellum (b) = and basal=20 ganglia (c). MRI (d-f) in another patient with lesion in=20 the=20 (more ...)

The two patients diagnosed while alive received whole brain = radiation;=20 no patients received cancer chemotherapy. HAART was given to 4/7 = (57%)=20 diagnosed after the introduction of HAART in Norway (August 1996). = In 3=20 patients HAART was started mean (median, range) 4.3 (3.0, = 2=E2=80=938) months=20 prior to first symptom of PCNSL and was continued after symptom = debut.=20 Only one of these had a favourable clinical and haematological = response,=20 with normalization of CD4 cell count; this response was first = achieved=20 after PCNSL was diagnosed. In one patient HAART was started after = PCNSL=20 was diagnosed and gave no favourable response. Toxoplasma therapy = was=20 given to 20/29 (69%) patients; 2 responded with clinical = improvement and=20 regress of imaging findings but both died rapidly after their = symptoms=20 relapsed 1 and 15 months after initial toxoplasma therapy,=20 respectively.

Median survival from first symptom attributable to PCNSL was = 2.3 (95%=20 CI: 1.5=E2=80=933.2) months. Only 21% (6/29) and 7% (2/29) were = alive at 6 months=20 and 1 year, respectively (Figure 3),=20 but one patient has survived for 4.5 years. In this patient PCNSL = was=20 established by biopsy 3 months after debut of personality changes; = he=20 received HAART and radiotherapy and was alive > 4 years after = completed=20 radiotherapy. All deaths (n =3D 28) were caused by AIDS and PCNSL. = Autopsy=20 revealed cerebral toxoplasmosis in addition to PCNSL in 1 patient = (not=20 responding to toxoplasma therapy).

Figure=20 3

Survival=20 curve for patients with AIDS-related PCNSL in = Norway.=20 Kaplan-Meier survival curve with 95% confidence interval for = patients with AIDS-related PCNSL (n =3D 29). Median survival = from=20 first symptom attributable to PCNSL was 2.3 (95% CI:=20 1.5=E2=80=933.2)=20 (more ...)

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Authors'=20 contributions

Pre-pub= lication=20 history

References

Discussion

Different from non AIDS-related PCSNL in Norway [18],=20 the incidence of AIDS-related PCNSL in Norway decreased in = 1989=E2=80=932003.=20 Previous single- and multicenter studies [8-12]=20 have also found decreasing incidence of AIDS-related PCNSL in the = era of=20 HAART. However, to our knowledge, this is the first national = survey to=20 confirm these findings.

Our survey had both strengths and limitations. It was based on = case=20 reporting to a national cancer registry and a comprehensive search = for=20 non-reported cases in the autopsy registry at the hospital = treating most=20 AIDS patients in Norway. Furthermore, all cases were = histologically=20 verified. However, due to the small sample size and the very few = patients=20 diagnosed and treated while alive, we could not assess prognostic = factors.=20 Also, most radiological images from 1989=E2=80=931993 were = unavailable. The=20 imaging results should still be quite representative for the years = 1994=E2=80=932003 since images were reviewed for 76% (13/17) of = the patients from=20 this time period.

Our figures for incidence rate (1.7 per 100 person-years) and = lifetime=20 risk (5.5%) of PCNSL among AIDS patients are in the upper range of = figures=20 in other studies [1,6,9,15,20].=20 Lower incidence rates were reported from the US [9,15]:=20 the absolute incidence rate of brain lymphoma per 1000 = person-years among=20 AIDS patients was 4.7 in 1981=E2=80=931990 [15]=20 and 8.4 and 1.1 in 1988=E2=80=931995 and 1996=E2=80=932000 [9],=20 respectively. Although not truly comparable with rates among AIDS=20 patients, reported incidence rates of PCNSL per 1000 person-years = among=20 HIV-infected individuals in Europe were 0.3=E2=80=935.3 in = 1983=E2=80=932002 [11]=20 and 0.4=E2=80=938.3 in 1994=E2=80=932000 [10].

Autopsy in all AIDS patients is needed to truly estimate the = incidence=20 of AIDS-related PCNSL. In our study, 93% (27/29) had the diagnosis = of=20 PCNSL first established by autopsy. None of these patients had a = biopsy=20 performed while alive, and 15% (4/27) of them had no focal brain = lesion on=20 imaging (Table 1),=20 so PCNSL was unexpected. Furthermore, PCNSL was considered a = likely=20 differential diagnosis prior to death in only 35% (8/23) of those = with=20 focal brain lesions, whereas cerebral toxoplasmosis was considered = likely=20 in 91% (21/23).

The short median survival from first symptom attributable to = PCNSL (2.3=20 months) was similar to survival times in other larger materials = (1.0=E2=80=932.8=20 months) [8,16,17].=20 However, lack of a prompt diagnosis of PCNSL may have excluded = patients=20 with very poor performance status from optimal treatment. Long = time=20 survival of more than 4.5 years was achieved in one patient = treated with=20 radiotherapy and HAART. Similar cases have been reported by others = [7,21].

Good performance status, higher CD4 count, whole brain = irradiation and=20 HAART have favourable impact on survival in AIDS-related PCNSL [1,8,22,23].=20 Early diagnosis, to ensure optimal treatment before the = performance status=20 has declined, is thus essential. In our study, all but 4 of the 27 = patients first diagnosed at autopsy had focal brain lesion(s) on = CT/MRI,=20 which should raise the suspicion of PCNSL. Furthermore, 17 of 19 = patients=20 with focal lesion(s) who received toxoplasma therapy, showed no = clear=20 response. None of these 17 patients underwent stereotactic or open = biopsy=20 which may be partly explained by the bad performance status (WHO = 2=E2=80=934) in=20 most of them (77%, 13/17).

Delayed diagnosis of PCNSL is a concern with empiric toxoplasma = therapy=20 [1,22].=20 To reduce this delay, brain biopsy is advised when there is = clinical or=20 radiological deterioration during the first week of initial = toxoplasma=20 therapy or lack of clinical improvement within 2 weeks [1,24].=20 Also, PCNSL can be diagnosed without awaiting toxoplasma therapy = or=20 biopsy, based on CSF Epstein-Barr virus DNA and ²⁰¹Tl=20 single-photon emission computed tomography (SPECT). Combining = these two=20 methods, a rapid, accurate and minimally invasive diagnosis may be = achievable, although the accuracy of this diagnostic approach is = not fully=20 clarified in the era of HAART [2].

The present MRI/CT findings are similar to those in = toxoplasmosis [1,25].=20 MRI and CT can seldom differentiate lymphoma from toxoplasmosis = [1,20].=20 If available, diffusion or perfusion MRI, magnetic resonance = spectroscopy,=20 positron emission tomography and SPECT [1,25]=20 might help to select patients for biopsy versus empiric toxoplasma = therapy. So might PCR examination of the CSF to detect = Ebstein-Barr virus=20 DNA or Toxoplasma gondii DNA [1,2],=20 but none of these tests are completely specific. Biopsy is often = needed,=20 but should be weighted against its relatively high procedural risk = in AIDS=20 patients [1].=20 Further research on the combination of less invasive diagnostic = procedures=20 is required to reduce the need for biopsy.

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Conclusion

This national survey showed decreasing incidence rate of = AIDS-related=20 PCNSL in Norway during 1989=E2=80=932003. AIDS patients in Norway = had a 5.5%=20 lifetime risk of PCNSL, emphasizing the importance of PCNSL as=20 organ-specific manifestation of AIDS. Despite dismal survival in = most=20 patients (median 2.3 months), the possibility of long term = survival should=20 prompt more aggressive diagnostics in suspected = PCNSL.

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Competing interests

The authors declare that they have no competing=20 interests.

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Authors' contributions

ISH, OM and AE conceived of the study and obtained ethical = approvals.=20 ISH collected the data, performed the data analyses and drafted = the=20 manuscript. JK and ISH reviewed the imaging material. AKG reviewed = the=20 histopathological material. OM, AE and OD contributed in the=20 interpretation of data. All authors have critically revised the = manuscript=20 and have given final approval of the version to be=20 published.

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Pre-publication history

The pre-publication history for this paper can be accessed = here:

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Acknowledgements

This study received funding from Western Norway Regional Health = Authority and Haakon and Sigrun =C3=98degaard's Foundation. The = study sponsors=20 were not involved in study design, data=20 collection/interpretation/analysis, writing of the manuscript or = the=20 decision to submit the manuscript for publication.

Competing=20 interests

Authors'=20 contributions

Pre-pub= lication=20 history

References

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Articles=20 from BMC Cancer = are=20 provided here courtesy of
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'this' to reuse same window, else ""=0A= // windowname: Reference name for window=0A= // additional: Attributes for window.open, from:=0A= // width, height, resizable, scrollbars, toolbar, location, = directories,=0A= // status, menubar, copyhistory.=0A= // Notes: Book version always provides menubar, toolbar, etc.=0A= //=0A= function startTargetBook(link,windowname,width,height,additional)=0A= {=0A= startTarget(link,windowname,width,height,additional)=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function startTarget(link,windowname,width,height, additional)=0A= {=0A= if(! window.focus)=0A= return;=0A= =0A= var sizestring =3D ",width=3D" + width + ",height=3D" + height;=0A= var opt =3D = "menubar=3Dno,toolbar=3Dno,status=3Dno,scrollbars=3Dyes,resizable=3Dyes,d= ependent=3Dyes,location=3Dno";=0A= var allOptions =3D opt + sizestring;=0A= if (additional) { allOptions =3D allOptions + ',' + additional; }=0A= =0A= windowname =3D String(windowname).replace(/-/g, "_")=0A= var moveToXDefault =3D 75=0A= var moveToYDefault =3D 50=0A= =0A= var moveToX =3D moveToXDefault=0A= var moveToY =3D moveToYDefault=0A= =0A= try {=0A= if (window.screen.width && width > 0)=0A= moveToX =3D Math.ceil((window.screen.width - width)) - 15=0A= moveToX =3D (moveToX > 0 ? moveToX : moveToXDefault)=0A= =0A= if (window.screen.height && height > 0)=0A= moveToY =3D Math.ceil((window.screen.height - height)) - 50=0A= moveToY =3D (moveToY > 0 ? moveToY : moveToYDefault)=0A= }=0A= catch (e) {}=0A= =0A= var wLeftTopCornerOptions =3D ',left=3D' + moveToX + ',top=3D' + = moveToY + ',screenX=3D' + moveToX + ',screenY=3D' + moveToY=0A= =0A= allOptions =3D allOptions + wLeftTopCornerOptions=0A= =0A= w =3D window.open ("", windowname, allOptions)=0A= w.focus()=0A= =0A= link.target=3Dwindowname=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function focuswin(windowname)=0A= {=0A= windowname =3D String(windowname).replace(/-/g, "_")=0A= w =3D = window.open("",windowname,"menubar=3Dyes,scrollbars=3Dyes,toolbar=3Dyes,l= ocation=3Dyes,status=3Dyes,directories=3Dyes,resizable=3Dyes");=0A= w.focus();=0A= =0A= return true;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseString (inStr)=0A= {=0A= var outStr =3D ''=0A= =0A= for (i =3D0; i <=3D inStr.length; i++)=0A= {=0A= outStr =3D inStr.charAt(i) + outStr=0A= }=0A= =0A= return outStr=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseAndReplaceString (inStr, findStr, newStr)=0A= {=0A= return reverseString(inStr).replace(findStr, newStr)=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function initUnObscureEmail (className, innerHTML)=0A= {=0A= =0A= try{=0A= if (window.addEventListener)=0A= window.addEventListener('load', function() {unObscureEmail = (className, innerHTML)}, false)=0A= else if (window.attachEvent)=0A= window.attachEvent('onload', function() {unObscureEmail = (className, innerHTML)})=0A= }catch(e){=0A= }=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function unObscureEmail (className, innerHTML)=0A= {=0A= try {=0A= if (typeof(unObscuredEmails) =3D=3D 'undefined')=0A= unObscuredEmails =3D new Array()=0A= =0A= if (! 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