Haematopoietic stem cell transplantation and oral complications

De ontwikkeling van nieuwe procedures heeft ertoe geleid dat een hematopoëtische stamceltransplantatie tegenwoordig ook kan worden toegepast bij patiënten die vroeger niet hiervoor in aanmerking kwamen, zoals ouderen. Tevens leiden deze ontwikkelingen tot verschuivingen in het spectrum van complicaties als gevolg van hematopoëtische stamceltransplantatie. In dit artikel komen de belangrijkste principes van hematopoëtische stamceltransplantatie aan de orde en de verschillende orale complicaties die hierbij kunnen optreden: mucositis, infecties, bloedingen, graft-versus-hostziekte, xerostomie, hyposialie, smaakverandering, secundaire tumoren, osteoporose, osteonecrose en groei- en ontwikkelingsstoornissen. Tot slot wordt aandacht besteed aan de rol van mondzorgverleners bij een hematopoëtische stamceltransplantatie.New haematopoietic stem cell transplantation procedures make the treatment available to patients who previously did not qualify, such as the elderly. In addition, the spectrum of oral complications associated with haematopoietic stem cell transplantation has altered as a result of the recent developments. This article is a review of the main principles of haematopoietic stem cell transplantation and provides information on oral complications which may develop, such as mucositis, infections, bleeding, graft-versus-host disease, xerostomia, hyposalivation, altered taste, secondary tumors, osteoporosis, osteonecrosis and growing and developing disturbancies. Finally, the role of dental care providers in cases of haematopoietic stem cell transplantation is addressed.</p

Haematopoietic stem cell transplantation and oral complications

De ontwikkeling van nieuwe procedures heeft ertoe geleid dat een hematopoëtische stamceltransplantatie tegenwoordig ook kan worden toegepast bij patiënten die vroeger niet hiervoor in aanmerking kwamen, zoals ouderen. Tevens leiden deze ontwikkelingen tot verschuivingen in het spectrum van complicaties als gevolg van hematopoëtische stamceltransplantatie. In dit artikel komen de belangrijkste principes van hematopoëtische stamceltransplantatie aan de orde en de verschillende orale complicaties die hierbij kunnen optreden: mucositis, infecties, bloedingen, graft-versus-hostziekte, xerostomie, hyposialie, smaakverandering, secundaire tumoren, osteoporose, osteonecrose en groei- en ontwikkelingsstoornissen. Tot slot wordt aandacht besteed aan de rol van mondzorgverleners bij een hematopoëtische stamceltransplantatie.New haematopoietic stem cell transplantation procedures make the treatment available to patients who previously did not qualify, such as the elderly. In addition, the spectrum of oral complications associated with haematopoietic stem cell transplantation has altered as a result of the recent developments. This article is a review of the main principles of haematopoietic stem cell transplantation and provides information on oral complications which may develop, such as mucositis, infections, bleeding, graft-versus-host disease, xerostomia, hyposalivation, altered taste, secondary tumors, osteoporosis, osteonecrosis and growing and developing disturbancies. Finally, the role of dental care providers in cases of haematopoietic stem cell transplantation is addressed.</p

A New Method for Isolation of Interstitial Fluid from Human Solid Tumors Applied to Proteomic Analysis of Ovarian Carcinoma Tissue

Major efforts have been invested in the identification of cancer biomarkers in plasma, but the extraordinary dynamic range in protein composition, and the dilution of disease specific proteins make discovery in plasma challenging. Focus is shifting towards using proximal fluids for biomarker discovery, but methods to verify the isolated sample's origin are missing. We therefore aimed to develop a technique to search for potential candidate proteins in the proximal proteome, i.e. in the tumor interstitial fluid, since the biomarkers are likely to be excreted or derive from the tumor microenvironment. Since tumor interstitial fluid is not readily accessible, we applied a centrifugation method developed in experimental animals and asked whether interstitial fluid from human tissue could be isolated, using ovarian carcinoma as a model. Exposure of extirpated tissue to 106 g enabled tumor fluid isolation. The fluid was verified as interstitial by an isolated fluid:plasma ratio not significantly different from 1.0 for both creatinine and Na+, two substances predominantly present in interstitial fluid. The isolated fluid had a colloid osmotic pressure 79% of that in plasma, suggesting that there was some sieving of proteins at the capillary wall. Using a proteomic approach we detected 769 proteins in the isolated interstitial fluid, sixfold higher than in patient plasma. We conclude that the isolated fluid represents undiluted interstitial fluid and thus a subproteome with high concentration of locally secreted proteins that may be detected in plasma for diagnostic, therapeutic and prognostic monitoring by targeted methods

A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

<p>Abstract</p> <p>Background</p> <p>The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS.</p> <p>Method</p> <p>Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m²iv days 1 and 4, ifosfamide 1500 mg/m²iv days 1 - 4, doxorubicin 50 mg/m²day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA.</p> <p>Result</p> <p>Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far.</p> <p>Conclusion</p> <p>The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01382030">NCT01382030</a>, EudraCT 2004-002501-72</p

Ovarian cancer molecular pathology.

Peer reviewe