Fulminant liver failure after vancomycin in a sulfasalazine-induced DRESS syndrome: fatal recurrence after liver transplantation

DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is a rare drug hypersensitivity reaction with a significant mortality. We describe a 60-year-old man with polyarthritis treated with sulfasalazine who developed DRESS and fulminant liver failure after additional vancomycin treatment. Liver histology revealed infiltration of granzymeB+ CD3+ lymphocytes in close proximity to apoptotic hepatocytes. After a superurgent liver transplantation and initial recovery, the patient developed recurrent generalized exanthema and eosinophilia, but only moderate hepatitis. Histology showed infiltration of FasL+ lymphocytes and eosinophils in the transplanted liver. Treatment with high-dose methylprednisolone was unsuccessful. Postmortem examination revealed extensive necrosis of the liver transplant. This case report illustrates that patients with DRESS may develop fulminant liver failure and that DRESS recurrence can recur in the transplanted liver. Histological and immunological investigations suggest an important role of granzymeB and FasL mediated cell death in DRESS associated hepatitis.

Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century

The current therapeutic strategy in breast cancer is to identify a target, such as estrogen receptor (ER) status, for tailoring treatments. We investigated the patterns of recurrence with respect to ER status for patients treated in two randomized trials with 25 years' median follow-up. In the ER-negative subpopulations most breast cancer events occurred within the first 5-7 years after randomization, while in the ER-positive subpopulations breast cancer events were spread through 10 years. In the ER-positive subpopulation, 1 year endocrine treatment alone significantly prolonged disease-free survival (DFS) with no additional benefit observed by adding 1 year of chemotherapy. In the small ER-negative subpopulation chemo-endocrine therapy had a significantly better DFS than endocrine alone or no treatment. Despite small numbers of patients, "old-fashioned" treatments, and competing causes of treatment failure, the value of ER status as a target for response to adjuvant treatment is evident through prolonged follow-up.

Perception of atrial fibrillation before and after radiofrequency catheter ablation: relevance of asymptomatic arrhythmia recurrence.

BACKGROUND The objective of this study was to assess the incidence and impact of asymptomatic arrhythmia in patients with highly symptomatic atrial fibrillation (AF) who qualified for radiofrequency (RF) catheter ablation. METHODS AND RESULTS In this prospective study, 114 patients with at least 3 documented AF episodes together with corresponding symptoms and an ineffective trial of at least 1 antiarrhythmic drug were selected for RF ablation. With the use of CARTO, circumferential lesions around the pulmonary veins and linear lesions at the roof of the left atrium and along the left atrial isthmus were placed. A continuous, 7-day, Holter session was recorded before ablation, right after ablation, and after 3, 6, and 12 months of follow-up. During each 7-day Holter monitoring, the patients recorded quality and duration of any complaints by using a detailed symptom log. More than 70,000 hours of ECG recording were analyzed. In the 7-day Holter records before ablation, 92 of 114 patients (81%) had documented AF episodes. All episodes were symptomatic in 35 patients (38%). In 52 patients (57%), both symptomatic and asymptomatic episodes were recorded, whereas in 5 patients (5%), all documented AF episodes were asymptomatic. After ablation, the percentage of patients with only asymptomatic AF recurrences increased to 37% (P<0.05) at the 6-month follow-up. An analysis of patient characteristics and arrhythmia patterns failed to identify a specific subset who were at high risk for the development of asymptomatic AF. CONCLUSIONS Even in patients presenting with highly symptomatic AF, asymptomatic episodes may occur and significantly increase after catheter ablation. A symptom-only-based follow-up would substantially overestimate the success rate. Objective measures such as long-term Holter monitoring are needed to identify asymptomatic AF recurrences after ablation.

Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.

BACKGROUND Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. METHODS The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. FINDINGS From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. INTERPRETATION Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. FUNDING US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

Recurrence due to neoplastic seeding in head and neck cancer: report of two cases and review of the literature

AIMS AND BACKGROUND Tumor progression due to seeding of tumor cells after definitive treatment for squamous cell carcinomas of the head and neck is an uncommon condition that can considerably worsen the outcome of patients with head and neck cancer. METHODS AND STUDY DESIGN We report two cases of recurrence due to neoplastic seeding from oropharyngeal and oral cancer, respectively. We performed a literature review with MEDLINE as the main search engine. RESULTS Seeding was found to occur most often in tracheotomy scars and gastrostomy sites. The oral cavity, hypopharynx and oropharynx were the primary sites in most cases, and advanced tumor stage seemed to be a risk factor for seeding. Treatment options include salvage surgery, which requires thorough resections, radiotherapy when possible, and palliative management. The prognosis of such events is poor. CONCLUSION Although neoplastic seeding is a well-known phenomenon in cancer surgery, many questions remain unanswered, especially regarding preventive measures and management strategies.

Accelerated partial breast irradiation with interstitial brachytherapy as second conservative treatment for ipsilateral breast tumour recurrence: multicentric study of the GEC-ESTRO Breast Cancer Working Group

PURPOSE To analyse the clinical outcome after salvage lumpectomy and multi-catheter brachytherapy (MCB) for ipsilateral breast tumour recurrence (IBTR). MATERIAL AND METHODS Between 09/00 and 09/10, 217 patients presenting an IBTR underwent lumpectomy and MCB (low, pulsed, or high-dose rate). Survival rates without second local recurrence (2nd LR), distant metastasis (DM), and overall survival (OS) were analysed as well as late effects and cosmetic results. Univariate and multivariate analyses (MVA) based on IBTR data were performed to find prognostic factors for 2nd LR, DM, and OS. RESULTS Median follow-up after the IBTR was 3.9 years [range: 1.1-10.3]. Five and 10-year actuarial 2nd LR rates were 5.6% [range: 1.5-9.5] and 7.2% [range: 2.1-12.1], respectively. Five and 10-year actuarial DM rates were 9.6% [range: 5.7-15.2] and 19.1% [range: 7.8-28.3], respectively. Five and 10-year actuarial OS rates were 88.7% [range: 83.1-94.8] and 76.4% [range: 66.9-87.3], respectively. In MVA, histological grade was prognostic factor for 2nd LR (p=0.008) and OS (p=0.02); while tumour size was prognostic factor for DM (p=0.03). G3-4 complication rate was 11%. Excellent/good cosmetic result was achieved in 85%. CONCLUSION This study suggests that in case of IBTR, lumpectomy plus MCB is feasible and effective in preventing 2nd LR with an OS rate at least equivalent to those achieved with salvage mastectomy.

Local recurrence after retropubic radical prostatectomy for prostate cancer does not exclusively occur at the anastomotic site

What's known on the subject? and What does the study add? Local recurrence after radical prostatectomy (RP) for clinically organ-confined prostate cancer is largely assumed to occur at the anastomotic site, as reflected in European and North American guidelines for adjuvant and salvage radiotherapy after RP. However, the exact site of local recurrence often remains undetermined. The present study shows that roughly one out of five patients with local recurrence after RP has histologically confirmed tumour deposits at the resection site of the vas deferens, clearly above the anastomotic site. This should be considered when offering ‘blind’ radiotherapy to the anastomotic site in patients with biochemical recurrence alone. Objective To determine the anatomical pattern of local recurrence and the corresponding clinical and pathological variables of patients treated with retropubic radical prostatectomy (RRP). Patients and Methods In all, 41 patients with biopsy confirmed local recurrence after extended pelvic lymph node dissection and RRP performed between January 1992 and December 2009 at a single tertiary referral academic centre were retrospectively studied. The site of local recurrence as assessed on computed tomography or magnetic resonance imaging was reviewed. Two sites were identified: the vesicourethral anastomotic site and the cranial resection margin of the surgical bed, where the vas deferens was transected and clipped. Age and serum prostate-specific antigen (PSA) level at RRP, pathological tumour and nodal stage, Gleason score, tumour location, surgical margin status, age and serum PSA level at the time of local recurrence, and time to diagnosis of local recurrence were assessed for the two sites and compared with the chi-square or Wilcoxon rank sum tests as appropriate. Results Local recurrence occurred at the anastomotic site in 31/41 (76%) patients and at the resection site of the vas deferens in nine of 41 (22%) patients. One patient had distinct lesions at both sites. There was no significant difference in any of the clinical and pathological variables between patients with local recurrence in the former and latter site. Conclusion Most local recurrences after RRP occur exclusively at the anastomotic site. However, 22% of locally recurrent cases had tumour at the resection site of the vas deferens. This should be taken into account when considering adjuvant or salvage radiation therapy.

Lake sediments as archives of recurrence rates and intensities of past flood events

Palaeoflood hydrology is an expanding field as the damage potential of flood and flood-related processes are increasing with the population density and the value of the infrastructure. Assessing the risk of these hazards in mountainous terrain requires knowledge about the frequency and severness of such events in the past. A wide range of methods is employed using diverse biologic, geomorphic or geologic evidences to track past flood events. Impact of floods are studied and dated on alluvial fans and cones using for example the growth disturbance of trees (Stoffel and Bollschweiler 2008; Schneuwly-Bollschweiler and Stoffel 2012: this volume) or stratigraphic layers deposited by debris flows, allowing to reconstruct past flood frequencies (Bardou et~al. 2003). Further downstream, the classical approach of palaeoflood hydrology (Kochel and Baker 1982) utilizes geomorphic indicators such as overbank sediments, silt lines and erosion features of floods along a river (e.g. Benito and Thorndycraft 2005). Fine-grained sediment settles out of the river suspension in eddies or backwater areas, where the flow velocity of the river is reduced. Records of these deposits at different elevations across a river’s profile can be used to assess the discharge of the past floods. This approach of palaeoflood hydrology studies was successfully applied in several river catchments (e.g. Ely et al. 1993; Macklin and Lewin 2003; O’Connor et al. 1994; Sheffer et al. 2003; Thorndycraft et al. 2005; Thorndycraft and Benito 2006). All these different reconstruction methods have their own advantages and disadvantages, but often these studies have a limited time coverage and the records are potentially incomplete due to lateral limits of depositional areas and due to the erosional power of fluvial processes that remove previously deposited flood witnesses. Here, we present a method that follows the sediment particle transported by a flood event to its final sink: the lacustrine basin.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

Influence of intervertebral disc fenestration at the herniation site in association with hemilaminectomy on recurrence in chondrodystrophic dogs with thoracolumbar disc disease: a prospective MRI study

OBJECTIVE To describe the influence of fenestration at the disc herniation site on recurrence in thoracolumbar disc disease of chondrodystrophoid dogs. STUDY DESIGN Prospective clinical study. ANIMALS Chondrodystrophic dogs (n=19). METHODS Dogs were divided into 2 groups: group 1 (9 dogs) had thoracolumbar disc extrusion (Hansen type I) treated by hemilaminectomy and concomitant fenestration of the affected intervertebral disc and group 2 (10 dogs) had hemilaminectomy without fenestration. All dogs had 3 magnetic resonance imaging (MRI) examinations: preoperatively, immediately postoperatively to assess removal of herniated disc material, and again 6 weeks after surgery. RESULTS There were 13 male and 6 female dogs; mean age, 7.1 years. Thoracolumbar disc herniation was confirmed with MRI. Immediate post surgical MRI revealed that the herniated disc removal was complete in all but 1 dog and that fenestration did not lead to complete removal of nucleus pulposus within the intervertebral disc space. On the 3rd MRI examination, none of the group 1 dogs had further disc material herniation at the fenestrated site. Six of the 10 group 2 dogs had a recurrence of herniation leading to clinical signs in 3 dogs (pain in 2 dogs, paresis in 1 dog). CONCLUSION In thoracolumbar disc herniation, fenestration of the affected intervertebral disc space prevents further extrusion of disc material. CLINICAL RELEVANCE Fenestration reduces the risk of early recurrence of disc herniation and associated postoperative complications.

Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study.

BACKGROUND Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. FINDINGS Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1-9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65-0·76]) and radical prostatectomy (4·0 [1·6-9·7]; p=0·0024; AUC 0·57 [0·52-0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2-12]; p=0·019; AUC 0·67 [0·61-0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0-19]; p=0·0015; AUC 0·74 [95% CI 0·65-0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4-6·0]; p=0·0039; AUC 0·68 [95% CI 0·63-0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures. INTERPRETATION This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. FUNDING Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.

Treatment and outcomes of urethral recurrence of urinary bladder cancer in women after radical cystectomy and orthotopic neobladder: a series of 12 cases

INTRODUCTION The incidence, treatment, and outcome of urethral recurrence (UR) after radical cystectomy (RC) for muscle-invasive bladder cancer with orthotopic neobladder in women have rarely been addressed in the literature. PATIENTS AND METHODS A total of 12 patients (median age at recurrence: 60 years) who experienced UR after RC with an orthotopic neobladder were selected for this study from a cohort of 456 women from participating institutions. The primary clinical and pathological characteristics at RC, including the manifestation of the UR and its treatment and outcome, were reviewed. RESULTS The primary bladder tumors in the 12 patients were urothelial carcinoma in 8 patients, squamous cell carcinoma and adenocarcinoma in 1 patient each, and mixed histology in 2 patients. Three patients (25%) had lymph node-positive disease at RC. The median time from RC to the detection of UR was 8 months (range 4-55). Eight recurrences manifested with clinical symptoms and 4 were detected during follow-up or during a diagnostic work-up for clinical symptoms caused by distant metastases. Treatment modalities were surgery, chemotherapy, radiotherapy, and bacillus Calmette-Guérin urethral instillations. Nine patients died of cancer. The median survival after the diagnosis of UR was 6 months. CONCLUSIONS UR after RC with an orthotopic neobladder in females is rare. Solitary, noninvasive recurrences have a favorable prognosis when detected early. Invasive recurrences are often associated with local and distant metastases and have a poor prognosis. © 2014 S. Karger AG, Basel.