High dose chemotherapy with autologous stem cell support for patients with histologically transformed B-cell non-Hodgkin lymphomas. A Norwegian multi centre phase II study

We present a prospective phase II study of patients with relapse after chemotherapy showing transformation of follicular lymphoma to diffuse large B-cell lymphoma, performed before rituximab was included in standard treatment. Patients in complete (CR) or partial remission (PR) after salvage chemotherapy were eligible for high-dose chemotherapy with autologous stem cell support (HDT). Forty-seven patients from five Norwegian centres were included, of whom 30 (63%) received HDT. Eighteen (60%) achieved CR, seven (23%) PR and five (10%) had progressive disease following HDT. Median follow-up for the surviving patients was 75 months; median progression-free (PFS) and overall survival (OS) were 26 and 47 months, respectively. Median OS for all patients was 43 months, compared to only 10 months for patients not eligible for HDT. Patients receiving CD34(+) enriched/B-cell depleted grafts had inferior PFS and a trend for inferior OS compared to patients receiving non-purged grafts (Log Rank 0·025 and 0·151, respectively). In conclusion, two thirds of patients with transformation of follicular lymphoma were eligible for HDT. The majority of patients achieved CR and a considerable number had prolonged OS. The use of in vitro purged grafts did not result in a survival benefit compared to that of non-purged grafts.     

Renal masses in the adult patient: the role of percutaneous biopsy

Although percutaneous renal mass biopsy with cross-sectional imaging guidance has long been considered to be safe and accurate, there have been recent advances in imaging, interventional, and cytologic techniques that have increased the role of percutaneous biopsy in the diagnosis of renal masses. Today, biopsy plays a fundamental role in the care of patients with a renal mass. Biopsy results are used to confirm the diagnosis of renal cancers, metastases, and infections, and there is increasing evidence to suggest that biopsy can help subtype and grade many primary renal cancers. Because a considerable fraction of small solid renal masses are benign and do not need treatment, there is an increasing need to diagnose them. Biopsy after a full imaging work-up can help prevent unnecessary and potentially morbid surgical and ablation procedures in a substantial number of patients. Although more data are needed to understand the overall accuracy of biopsy for the diagnosis of benign lesions, many can be diagnosed with the aid of biopsy findings. This article reviews reported experience with percutaneous renal mass biopsy, discusses the technical factors that contribute to results, and details seven specific clinical settings that should prompt the clinician to consider percutaneous biopsy when encountering a renal mass.     

Acute peripheral facial palsy in adults

Objective To collect epidemiological data of peripheral facial palsy, and especially to chart the incidence and clinical characteristics of Lyme associated facial palsy.Material and methods We included consecutive adult patients presenting with peripheral facial palsy in Vest–Agder County from January 1997 to December 1998. The facial palsy was graded according to the House and Brackman facial function scoring system,and cerebrospinal fluid and serum samples were examined for Borrelia burgdorferi antibodies and virus antibodies. Final outcome was evaluated by follow up visits or telephone interview.Results Sixty nine patients were included and followed until complete recovery, or for 5 years. Ten per cent were caused by Lyme disease, 17% by virus infection, 4% by other causes and 68% were classified as Bell’s palsy. All patients with Lyme facial palsy had additional neurological symptoms, and 87% reported constitutional complaints. The overall final outcome was good with complete recovery in 77%, slight sequelae in 20% and moderate sequelae in 3%. No patients experienced severe sequelae. Two of 28 patients examined with neurography had absent compound muscle action potentials in orbicularis oculi. Both made good recovery with only slight sequelae.Conclusions Peripheral facial palsy is a common disorder with a favourable prognosis. Lyme disease seems to be an infrequent cause of facial palsy in patients without constitutional symptoms or additional neurological findings.     

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Background

Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder.

Methods

MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests.

Results

In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group.

Conclusion

The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.     

Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial

BACKGROUND: Use of intravenous penicillin and ceftriaxone to treat Lyme neuroborreliosis is well documented, although oral doxycycline could be a cost-effective alternative. We aimed to compare the efficacy of oral doxycycline with intravenous ceftriaxone for the treatment of Lyme neuroborreliosis. METHODS: From April, 2004, to October, 2007, we recruited consecutive adult patients from nine hospitals in southern Norway into a non-inferiority trial. Inclusion criteria were neurological symptoms suggestive of Lyme neuroborreliosis without other obvious causes, and presence of any of the following: a CSF white-cell count of more than five per mL; intrathecal production of specific Borrelia burgdorferi antibodies; or acrodermatitis chronicum atrophicans. Patients were randomly allocated to receive 200 mg oral doxycycline or 2 g intravenous ceftriaxone once per day for 14 days, in a double-blind, double-dummy design. A composite clinical score (range 0 to 64, 0=best) was based on standardised interviews and clinical neurological examination. The primary outcome was reduction in clinical score at 4 months after the start of treatment. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT00138801. FINDINGS: Of 118 patients who underwent randomisation, 102 completed the study (mean clinical score at baseline 8.5 [SD 4.1]). 4 months after the start of treatment, mean score improvement in the doxycycline group (n=54) was 4.5 (95% CI 3.6 to 5.5) points and that in the ceftriaxone group (n=48) was 4.4 (3.4 to 5.4) points (95% CI for difference between groups -0.9 to 1.1; p=0.84). 26 (48%) patients in the doxycycline group and 16 (33%) in the ceftriaxone group had total recovery (95% CI for difference between groups -4% to 34%; p=0.13). Side-effects possibly related to treatment were reported in 21 (37%) and 26 (46%) patients in these groups, respectively (-28% to 9%; p=0.30). Three patients discontinued ceftriaxone treatment owing to adverse events. INTERPRETATION: Oral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis.     

Rectal Cancer in the Young Patient

Purpose The purpose of this national study was to evaluate the results of treatment for young rectal cancer patients. Methods This prospective study from the Norwegian Rectal Cancer Project includes all 2,283 patients younger than aged 70 years with adenocarcinoma of the rectum from November 1993 to December 1999. Patients younger than aged 40 years (n = 45), 40 to 44 years (n = 87), 45 to 49 years (n = 153), and 50 to 69 years (n = 1998) were compared for patient and tumor characteristics and five-year overall survival. Patients treated for cure (n = 1,354) were evaluated for local recurrence, distant metastasis, and disease-free survival. Results Patients younger than aged 40 years had significantly higher frequencies of poorly differentiated tumors (27 vs. 12–16 percent; P = 0.014), N2-stage (37 vs. 13–18 percent; P = 0.001), and distant metastases (38 vs. 19–24 percent; P = 0.019) compared with older patients. Among those treated for cure, 56 percent of the patients younger than aged 40 years developed distant metastases compared with 20 to 26 percent of the older patients (P = 0.003). Overall five-year survival was 54 percent for patients younger than aged 40years compared with 71 to 88 percent for the older patients (P = 0.029). Age younger than 40 years was a significant independent prognostic factor and increased the risk for metastasis and death. Conclusions Patients younger than aged 40 years had a more advanced stage at the time of diagnosis and poor prognosis compared with older patients. Young patients treated for cure more often developed distant metastases and had inferior survival. From the Norwegian Gastrointestinal Cancer Group and the Norwegian Rectal Cancer Group. Supported by a grant from the Norwegian Cancer Society.     

Transanal Excision vs. Major Surgery for T1 Rectal Cancer

PURPOSE The purpose of this national study was to examine the long-term results of transanal excision compared with major surgery of T1 rectal cancer.METHODS This prospective study from the Norwegian Rectal Cancer Project included all 291 patients with a T1M0 tumor within 15 cm from the anal verge treated by anterior resection, abdominoperineal resection, Hartmann’s procedure, or transanal excision in the period from November 1993 to December 1999.RESULTS Two hundred fifty-six patients were treated by major surgery and 35 patients by transanal excision. None of the patients had neoadjuvant therapy. Macroscopic tumor remnants (R2) occurred in 17 percent (6/35) of the transanal excisions, while major surgery obtained 100 percent R0 resections. Eleven percent of the patients treated with major surgery had glandular involvement. There were no significant differences according to tumor localization, size, or differentiation between Stage I and Stage III tumors. Patients treated with transanal excision were older than patients having major surgery (mean age, 77 vs. 68 years, P < 0.001). After curative resection (R0, R1, Rx) the five-year rate of local recurrence was 12 percent (95 percent confidence interval, 0–24) in the transanal excision group compared with 6 percent (95 percent confidence interval, 2–10) after major surgery (P = 0.010). The overall five-year survival was 70 percent (95 percent confidence interval, 52–88) in the transanal excision group compared with 80 percent (95 percent confidence interval, 74–85) in the major surgery group (P = 0.04) and the five-year disease-free survival was 64 percent (95 percent confidence interval, 46–82) in the transanal excision group compared with 77 percent (95 percent confidence interval, 71–83) in the major surgery group (P = 0.01).CONCLUSIONS The main problem of transanal excision for early rectal cancer in the present study was the inability to remove all the malignancy. Patients treated with transanal excision had significantly higher rates of local recurrence compared with patients who underwent major surgery. Patients who had transanal excision had inferior survival, but they were older than those who had major surgery.From the Norwegian Gastrointestinal Cancer Group and the Norwegian Rectal Cancer Group.This work was supported by a grant from the Norwegian Cancer Society.Presented at the XXth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Budapest, Hungary, June 6 to 10, 2004.