Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation.

Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases.

Capecitabine and oxaliplatin as second-line treatment in patients with carcinoma of unknown primary site.

BACKGROUND: Treatment of patients with carcinoma of unknown primary site (CUP) remains a challenge, and no effective second-line treatment has been identified. In CUP patients who are non-responsive or relapse early after first-line platinum/taxane-based regimens, it is likely that gastrointestinal (GI) tract tumours may be overrepresented. These patients could be candidates for GI tract-directed therapy. We here report the results obtained with oxaliplatin and capecitabine as second-line therapy in 25 recurrent/refractory CUP patients following first-line treatment with paclitaxel, cisplatin and gemcitabine. PATIENTS AND METHODS: Patients received capecitabine orally (1000 mg/m(2)) twice daily, days 1-14, and oxaliplatin (130 mg/m(2)) intravenously on day 1 in a three-week schedule. RESULTS: Twenty-five CUP patients received a median of three cycles of capecitabine and oxaliplatin as second-line treatment. Histopathological assessments suggested the primary site to be of GI tract origin in the majority of the patients (76%). We found an objective response rate of 13%, a median progression-free survival and overall survival rate of 2.3 and 3.9 months, respectively, and 32% of patients alive at one year after initiation of second-line therapy. The regimen was well tolerated by most patients. CONCLUSIONS: This study, demonstrates that there is still a significant need for improved second-line therapy in CUP patients.

Paclitaxel, cisplatin and gemcitabine in treatment of carcinomas of unknown primary site, a phase II study.

BACKGROUND: The present study was conducted to evaluate the efficacy and toxicity of a combination of paclitaxel, cisplatin and gemcitabine in patients with carcinoma of unknown primary site (CUP). PATIENTS AND METHODS: Patients with CUP, ECOG performance status 0-1 and age between 18 and 65 years old were treated with paclitaxel 175 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1 and gemcitabine 1000 mg/m(2) day 1 and 8 in a three-week schedule. RESULTS: Ninety-eight patients were enrolled between 1998 and 2008. Ninety-one patients had target lesions according to the RECIST guidelines. The overall response rate was 42.9% (39 patients), including five complete responses (5.5%) and 34 partial responses (37.4%). The median survival time was 10.7 months, and the survival rates at one and two years were 42% and 14%, respectively. The most frequent grade 3 or more adverse events were neutropenia and thrombocytopenia. There were 3 treatment-related deaths. CONCLUSIONS: Combination of paclitaxel, cisplatin and gemcitabine is an active regimen in patients with CUP with response and survival rates at least similar to other platinum- and taxane-containing regimens. The treatment was well tolerated by most patients although neutropenia and thrombocytopenia were relatively common. The present regimen represents an attractive regimen in younger CUP patients with a good performance status.

Relevance of computerized tomography in the preoperative evaluation of patients with vulvar cancer: a prospective study.

BACKGROUND: The purpose of the study was to determine whether inclusion of computerized tomography (CT) in the prospective evaluation of vulvar cancer changed the surgical treatment strategy in terms of detection of lymph node metastases, tumor spread and comorbidity, and additionally to examine the logistical influence of adding further examinations prior to treating out-hospital patients referred from geographically distant areas. METHODS: During an 8 month period we conducted a prospective study of patients with newly diagnosed or recurrent vulvar cancer consecutively referred to Copenhagen University Hospital, Rigshospitalet. The patients underwent a gynecological examination, chest x-ray and a preoperative CT scanning of the chest, abdomen and pelvis. It was registered whether the radiological findings regarding the extent of the tumor, lymph node involvement, incidental findings and comorbidity changed the surgical treatment plan. Further, the logistical influence of the long referral distances was registered. RESULTS: Thirty patients with a median age of 69 years (range 44-93 years) were included in the study. CT did not significantly change the initial surgical treatment plan for the patients. CT did not reveal lymph node enlargement outside the inguinofemoral area and was inaccurate compared to the sentinal node examination of the local lymph nodes. CT diagnosed no cases with distant metastases from the primary malignancy, but two cases with a secondary malignant disease were found. CONCLUSIONS: CT scanning has no clinical impact as a routine screening examination prior to surgery. It may delay treatment, but can add important information when clinically indicated.

[Extracorporeal membrane oxygenation of a child with severe chemical pneumonia]. / Ekstrakorporal membranoxygenering af et barn med svær kemisk pneumoni.

This case presents a thirteen months old child with severe acute respiratory distress syndrome after ingestion of lamp oil (hydrocarbon). Mechanical ventilation including high-frequency oscillation could not stabilise the course, and the child developed pneumothorax and emphysema. Treatment was changed to veno-arterial extracorporeal membrane oxygenation (ECMO) on the third day. After nine days of ECMO and further two days of conventional ventilatory treatment he was extubated, and four months later the child presented with normal X-ray of the lungs and without any signs of disease.

The BoneXpert method for automated determination of skeletal maturity.

Bone age rating is associated with a considerable variability from the human interpretation, and this is the motivation for presenting a new method for automated determination of bone age (skeletal maturity). The method, called BoneXpert, reconstructs, from radiographs of the hand, the borders of 15 bones automatically and then computes "intrinsic" bone ages for each of 13 bones (radius, ulna, and 11 short bones). Finally, it transforms the intrinsic bone ages into Greulich Pyle (GP) or Tanner Whitehouse (TW) bone age. The bone reconstruction method automatically rejects images with abnormal bone morphology or very poor image quality. From the methodological point of view, BoneXpert contains the following innovations: 1) a generative model (active appearance model) for the bone reconstruction; 2) the prediction of bone age from shape, intensity, and texture scores derived from principal component analysis; 3) the consensus bone age concept that defines bone age of each bone as the best estimate of the bone age of the other bones in the hand; 4) a common bone age model for males and females; and 5) the unified modelling of TW and GP bone age. BoneXpert is developed on 1559 images. It is validated on the Greulich Pyle atlas in the age range 2-17 years yielding an SD of 0.42 years [0.37; 0.47] 95% conf, and on 84 clinical TW-rated images yielding an SD of 0.80 years [0.68; 0.93] 95% conf. The precision of the GP bone age determination (its ability to yield the same result on a repeated radiograph) is inferred under suitable assumptions from six longitudinal series of radiographs. The result is an SD on a single determination of 0.17 years [0.13; 0.21] 95% conf.