Histologic characteristics and tumor spread of recurrent glottic carcinoma: analysis on whole-organ sections and comparison with tumor spread of primary glottic carcinomas

BACKGROUND: The assessment of the precise tumor extent of recurrent glottic carcinomas is a challenge. METHODS: The histologic characteristics of 29 recurrent glottic carcinomas after radiation failures, initially classified as T1 and T2, were analyzed on whole-organ slices. The growth patterns of 21 recurrent prT3 and prT4 and 52 primary pT3 and pT4 carcinomas were compared. RESULTS: Fifteen of 29 (52%) recurrent carcinomas were under-staged by imaging studies and endoscopy. Most recurrent carcinomas presented with multicentric tumor foci, whereas most primary carcinomas with a concentric tumor growth pattern (p < .05). Undifferentiated dissociated tumor cells were observed more often in the vicinity of recurrent tumor foci than of the primary tumor mass (p < .05). CONCLUSION: Recurrent glottic carcinomas are often under-staged and present with multiple tumor foci dispersed in different regions of the larynx. If voice-preserving salvage surgery is considered as a treatment option, these facts should be kept in mind.

Recurrent ischemic colitis in a patient with leiden factor V mutation and systemic lupus erythematous with antiphospholipid syndrome

Ischemic colitis results from insufficient blood supply to the large intestine and is often associated with hypercoagulable states. The condition comprises a wide range presenting with mild to fulminant forms. Diagnosis remains difficult because these patients may present with non-specific abdominal symptoms. We report a 51- year-old female patient with known Leiden factor V mutation as well as systemic lupus erythematous along with antiphospholipid syndrome suffering from recurrent ischemic colitis. At admission, the patient complained about abdominal pain, diarrhea and rectal bleeding lasting for 24 hours. Laboratory tests showed an increased C-reactive protein (29.5 mg/dl), while the performed abdominal CT-scan revealed only a dilatation of the descending colon along with a thickening of the bowel wall. Laparotomy was performed showing an ischemic colon and massive peritonitis. Histological examination proved the suspected ischemic colitis. Consecutively, an anti-coagulation therapy with coumarin and aspirin 100 was initiated. Up to the time point of a follow up examination no further ischemic events had occurred. This case illustrates well the non-specific clinical presentation of ischemic colitis. A high index of suspicion, recognition of risk factors and a history of non-specific abdominal symptoms should alert the clinicians to the possibility of ischemic disease. Early diagnosis and initiation of anticoagulation therapy or surgical intervention in case of peritonitis are the major goals of therapy.

Oral sirolimus for prevention of recurrent infrainguinal arterial obstructions after surgical and endovascular revascularizations

No data are currently available on the role of oral sirolimus in the prevention of recurrent stenosis in the periphery. We report the effects of oral sirolimus in the prevention of recurrent infrainguinal obstructions in patients with complex peripheral arterial disease. Three patients with ischemic rest pain of the lower limbs and repeated short-term need for surgical and/or endovascular revascularization: 9 times within 12 months, 7 times within 15 months, 11 times within 26 months, respectively. Oral sirolimus on a case by case basis, resulted in less frequent restenosis and longer intervention-free intervals: three re-interventions within 37 months in the first patient, one balloon angioplasty within 17 months in the second, and three re-interventions within 21 months in the third patient, respectively. Side effects, in particular dyspepsia and diarrhoea, were mild and tolerable. To our knowledge, this is the first report to show that oral sirolimus was successfully administered in patients with recurrent excessive neointimal proliferation after revascularization of peripheral arterial lesions lowering the necessity of re-intervention and hence prolonging intervention-free intervals.

Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes

BACKGROUND: Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS: We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS: We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1x10(-7)). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS: We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype.

Pegylated interferon-alpha2a/ribavirin treatment of recurrent hepatitis C after liver transplantation

Hepatitis C virus (HCV) infection invariably recurs after liver transplantation (LT), leading to significant morbidity and mortality. Although the combination of pegylated interferon-alpha (IFN-alpha)/ribavirin is the preferred treatment for these patients, the optimal schedule remains undetermined. In an uncontrolled trial, 19 patients with HCV infection recurring after LT received pegylated IFN-alpha(2a), 180 mug weekly, and ribavirin, 10 mg/kg body weight daily, for 48 weeks. The proportion of patients with undetectable HCV RNA in their serum after 12 weeks of treatment was 53%. Five patients (26%) dropped out of the study due to intolerance (in 2 cases), depression (in 1), or infectious complications (in 2). A sustained virological response (SVR), defined as undetectable serum HCV RNA 24 weeks after the end of treatment, was observed in 9/19 patients (47%). SVR was associated with an early virological response after 12 weeks of therapy (P<0.001) and a treatment duration >80% (P=0.02), but not with baseline HCV RNA level or a cumulative dose of pegylated IFN-alpha(2a) or ribavirin >80% of the scheduled dose. All 4 patients with genotype 2 or 3 reached SVR, as compared with 33% of patients with genotype 1 or 4 (P=0.03). A 48-week course of pegylated IFN-alpha(2a)/ribavirin therapy is effective in patients with recurrent HCV infection after LT.

Treatment of recurrent rejection in heart transplantation: cytolytic therapy or bolus steroids?

OBJECTIVES: The treatment of recurrent rejection in heart transplant recipients has been a controversial issue for many years. The intent of this retrospective study was to perform a risk-benefit analysis between treatment strategies with bolus steroids only versus anti-thymocyte globulins (RATG; 1.5 mg/kg q 4 days). METHODS: Between 1986 and 1993, 69 of 425 patients (17 male, 52 female; mean age 44 +/- 11 years) who had more than one rejection/patient per month (rej/pt per mo) in the first 3 postoperative months were defined as recurrent rejectors. RESULTS: Repetitive methylprednisolone bolus therapy (70 mg/kg q 3 days) was given in 27 patients (group M; 1.4 +/- 0.2 rej/pt per mo) and RATG therapy for one of the rejection episodes of the 42 remaining patients (group A; 1.5 +/- 0.2 rej/pt per mo). The quality of triple drug immunosuppression in the two study groups was comparable. The rejection-free interval (RFI) following RATG treatment in group A was 21.6 +/- 10 days and 22 +/- 11 in group M. In group M, 3 of 27 patients (11%) had a rejection treatment-related infection (2 bacterial; 1 viral) versus 6 of the 42 patients of group A (14.2%; bacterial 1, viral 5). During postoperative months 3-24, 0.15 +/- 0.12 rej/pat per mo were observed in group M and 0.21 +/- 0.13 rej/pat per mo in group A (n.s.). In this 21-month period cytolytic therapy for rejection was initiated in 8 of the remaining 21 patients of group M (38%) and 15 of the remaining 37 patients of group A (40.5%). The absolute survival and the individual causes of death were not affected by the type of initial treatment of recurrent rejection. The actuarial freedom of graft atherosclerosis is comparable in the two groups with 78% in group A versus 79% in group M free of graft atherosclerosis at 3 years postoperatively. CONCLUSIONS: A comparison of cytolytic therapy versus repeated applications of bolus steroids for treatment of recurrent rejection reveals no significant difference in the long-term patient outcome with respect to the incidence of future rejection episodes and survival.

Comparison of the receptor FGFRL1 from sea urchins and humans illustrates evolution of a zinc binding motif in the intracellular domain

BACKGROUND: FGFRL1, the gene for the fifth member of the fibroblast growth factor receptor (FGFR) family, is found in all vertebrates from fish to man and in the cephalochordate amphioxus. Since it does not occur in more distantly related invertebrates such as insects and nematodes, we have speculated that FGFRL1 might have evolved just before branching of the vertebrate lineage from the other invertebrates (Beyeler and Trueb, 2006). RESULTS: We identified the gene for FGFRL1 also in the sea urchin Strongylocentrotus purpuratus and cloned its mRNA. The deduced amino acid sequence shares 62% sequence similarity with the human protein and shows conservation of all disulfides and N-linked carbohydrate attachment sites. Similar to the human protein, the S. purpuratus protein contains a histidine-rich motif at the C-terminus, but this motif is much shorter than the human counterpart. To analyze the function of the novel motif, recombinant fusion proteins were prepared in a bacterial expression system. The human fusion protein bound to nickel and zinc affinity columns, whereas the sea urchin protein barely interacted with such columns. Direct determination of metal ions by atomic absorption revealed 2.6 mole zinc/mole protein for human FGFRL1 and 1.7 mole zinc/mole protein for sea urchin FGFRL1. CONCLUSION: The FGFRL1 gene has evolved much earlier than previously assumed. A comparison of the intracellular domain between sea urchin and human FGFRL1 provides interesting insights into the shaping of a novel zinc binding domain.

Prospective study of exclusive strontium-/yttrium-90 beta-irradiation of primary and recurrent pterygia with no prior surgical excision. Clinical outcome of long-term follow-up

PURPOSE: To evaluate the consecutive treatment results regarding pterygium recurrence and the efficacy of exclusive strontium-/yttrium-90 beta-irradiation for primary and recurrent pterygia and to analyze the functional outcome. PATIENTS AND METHODS: Between October 1974 and December 2005, 58 primary and 21 recurrent pterygia were exclusively treated with strontium-/yttrium-90 beta-irradiation with doses ranging from 3,600 to 5,500 cGy. The follow-up time was 46.6 +/- 26.7 months, with a median of 46.5 months. RESULTS: The treatment led to a size reduction in all pterygia (p < 0.0001). Neither recurrences nor side effects were observed during therapy and follow-up in this study. Best-corrected visual acuity increased (p = 0.0064). Corneal astigmatism was reduced in recurrent pterygia (p = 0.009). CONCLUSION: Exclusive strontium-/yttrium-90 beta-irradiation of pterygia is a very efficient and well-tolerated treatment, with remarkable aesthetic and rehabilitative results in comparison to conventional treatments, especially for recurrent lesions which have undergone prior surgical excision.

Imaging of chronic recurrent multifocal osteomyelitis of childhood first presenting with isolated primary spinal involvement

OBJECTIVE: Initial presentation with primary spinal involvement in chronic recurrent multifocal osteomyelitis of childhood (CRMO) is rare. Our objective was to review the imaging appearances of three patients who had CRMO who initially presented with isolated primary spinal involvement. DESIGN AND PATIENTS: The imaging, clinical, laboratory and histology findings of the three patients were retrospectively reviewed. Imaging included seven spinal MR imaging scans, one computed tomography scan, nine bone scans, two tomograms and 16 radiographs. These were reviewed by two musculoskeletal radiologists and a consensus view is reported. All three patients presented with atraumatic spinal pain and had extensive bone spinal pathology. The patients were aged 11, 13 and 12 years. There were two females and one male. RESULTS AND CONCLUSIONS: The initial patient had thoracic T6 and T8 vertebra plana. Bone scan showed additional vertebral body involvement. Follow-up was available over a 3 year period. The second patient had partial collapse of T9 and, 2 years later, of C6. Subsequently extensive multifocal disease ensued and follow-up was available over 8 years. The third patient initially had L3 inferior partial collapse and 1 year later T8 involvement with multifocal disease. Follow-up was available over 3 years. The imaging findings of the three patients include partial and complete vertebra plana with a subchondral line adjacent to endplates associated with bone marrow MR signal alterations. Awareness of the imaging appearances may help the radiologist to include this entity in the differential diagnosis in children who present with spinal pathology and no history of trauma. Histopathological examination excludes tumor and infection but with typical imaging findings may not always be necessary.