Boudewijn E.C. Plaat

Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: Differences in clinical outcome and expression of multidrug resistance proteins

PURPOSE Several studies have reported clinical behavior and chemotherapy resistance in leiomyosarcomas, but these studies did not differentiate between soft tissue leiomyosarcomas (LMS) and malignant gastrointestinal stromal tumors (GIST). Multidrug resistance (MDR) has been associated with the expression of P-glycoprotein (P-gp), multidrug resistance protein (MRP(1)), and lung resistance protein (LRP). The aim of the present study was to compare LMS and GIST with respect to clinical outcome and MDR parameters. PATIENTS AND METHODS Clinical outcome was evaluated in 29 patients with a primary deep-seated LMS and 26 patients with a primary malignant GIST. Paraffin-embedded material, available for 26 patients with LMS and 25 with GIST, was used for immunohistochemical detection of P-gp, MRP(1), LRP, and c-kit. RESULTS Mean overall survival (OS) was 72 months for LMS patients and 31 months for GIST patients (P: <.05). Metastases occurred in 16 (59%) of 27 assessable LMS patients and in 10 (56%) of 18 assessable GIST patients. LMS predominantly metastasized to the lungs (14 of 16 patients), whereas GIST tended to spread to the liver (five of 10 patients) and the abdominal cavity (three of 10 patients; P: <.001). P-gp and MRP(1) expression was more pronounced in GIST than in LMS (P: <.05): the mean percentage of P-gp expressing cells was 13.4% in patients with LMS and 38.4% in patients with GIST, and the mean percentage MRP(1) expressing cells was 13.3% in patients with LMS and 35.4% in patients with GIST. LRP expression did not differ between LMS and GIST. c-kit was expressed in 5% of the LMS patients and in 68% of the GIST patients. CONCLUSION LMS patients have a better survival than GIST patients, and the metastatic pattern is different. Expression of MDR proteins in LMS is less pronounced than in GIST.

Computer-assisted cytogenetic analysis of 51 malignant peripheral-nerve-sheath tumors: Sporadic Vs. neurofibromatosis-type-1-associated malignant schwannomas

Cytogenetic studies in small groups of patients with malignant peripheral‐nerve‐sheath tumors (MPNST) revealed complex karyotypes with no consistent changes. A computer‐assisted cytogenetic analysis using a cytogenetic database was performed to determine recurrent cytogenetic alterations in 51 MPNSTs (44 from the literature and 7 new cases) and to allow direct cytogenetic comparison between NF‐1‐associated and sporadic MPNSTs. Significant loss (p < 0.05) was observed in the chromosomal regions 9p2, 11p1, 11q2 and 18p1. Also, loss in 1p3, 9p1, 11q1, 12q2, 17p1, 18q1‐q2, 19p1, 22q1, X and Y was detected. Gain of chromosomal material was found in chromosome 7, especially 7q1 (p < 0.05). Most involved breakpoints were: 1p13, 1q21, 7p22, 9p11, 17p11, 17q11, 22q11. Cytogenetic differences between NF‐1‐associated and sporadic MPNSTs included a relative loss of chromosomal material in NF‐1‐associated MPNSTs in 1p3, 4p1 and 21p1‐q2 and a relative gain in 15p1‐q1. Differences in breakpoints between the NF‐1 associated and the sporadic MPNST group were observed in 1p21‐22 (28% of NF‐1 vs. 0% of sporadic MPNSTs), 1p32‐34 (17% vs. 0%), 8p11‐12 (7% vs. 27%) and 17q10‐12 (24% vs. 7%). This approach, in which the cytogenetic results of various reports are combined, shows that losses in 9p2 and gains in 7q1 could be of oncogenetic importance in MPNSTs. Loss of 17q1, on which the NF‐1 gene has been located (17q11.2), is not a common cytogenetic finding in NF‐1‐associated MPNSTs. The observed differences between NF‐1‐associated and sporadic MPNSTs might reflect different oncogenetic pathways. Int. J. Cancer 83:171–178, 1999.

The impact of comorbidity on treatment-related side effects in older patients with laryngeal cancer

The standard treatment of elderly head and neck patients is controversial. The goal of this study was to evaluate the relationship between co-morbidity and complications in elderly laryngeal cancer patients treated with different modalities. Retrospective analysis of patients 75 years old and older with laryngeal cancer (n=139) and patients 65 years old and younger as a reference control group (n=289) diagnosed in our department between 1997 and 2007 has been performed. Pretreatment co-morbidity (ACE-27), treatment-related complications and one- and six-month death rates have been analyzed. Co-morbidity rate was more pronounced in the elderly group, but did not result in more complications. Correlation has been found between co-morbidity and complication in the whole patients group, but not in the elderly group. By multivariate analysis, in all age groups radiation therapy (vs. total laryngectomy) and tumor stage were predictors of complications but co-morbidity and age were not. According to our study there is no reason to treat elderly laryngeal cancer patients differently. The weaker relation between co-morbidity and complications emphasizes the importance of careful pre-treatment evaluation in elderly.

Expression of P-glycoprotein, multidrug resistance-associated protein 1, and lung resistance-related protein in human soft tissue sarcomas before and after hyperthermic isolated limb perfusion with tumor necrosis factor-α and melphalan

Multidrug resistance (MDR) is associated with expression of P‐glycoprotein (P‐gp), multidrug resistance‐associated protein 1 (MRP1), and lung resistance‐related protein (LRP). Tumor necrosis factor (TNF‐α) is able to modify the expression of these three proteins in different cell types. The effect of TNF‐α in the clinical situation on patients with soft tissue sarcomas (STS) is indeterminate.

Clinico-Pathological Data and Prognostic Factors in Completely Resected AJCC Stage I-III Liposarcomas

Background: In general, although biological behavior and prognosis of liposarcomas (LPS) are more favorable compared with most other soft tissue sarcomas (STS), prognosis can vary widely depending on tumor characteristics, especially histological subtype and tumor grade.Patients and Methods: All consecutive, completely resected stage I-III LPS (as determined by the American Joint Committee on Cancer staging guidelines), treated at the Groningen University Hospital from 1977–2000, were analyzed.Results: A total of 69 patients, 35 males and 34 females, median age 51 (range 11–80) years, were reviewed. After a median follow-up of 71 (range 5–231) months, the overall local recurrence and metastasis rate at five years after diagnosis were 27% and 16%, respectively. Retroperitoneal localization was a significant negative prognostic factor regarding local recurrence; dedifferentiation, grade II-III, and deep location regarding distant metastasis; and dedifferentiation, grade II-III, stage II-III, size .20 cm and non-radical resection regarding survival.Conclusions: LPS have a relatively mild biologic behavior, with the exception of very large, deeply located, dedifferentiated and/or grade II-III LPS. Radical resection is important for diseasespecific survival. LPS have a relatively mild biologic behavior, with the exception of very large, deeply located, dedifferentiated and/or grade II-III LPS.

Narrow band imaging is a new technique in visualization of recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP) is a rare, benign, wart‐like disease for which no curative treatment exists. The goal of treatment is total surgical removal of the epithelial lesions to keep the airway open and the voice sufficient. Therefore, it is essential to visualize all papillomatous lesions. The present study aims to evaluate the sensitivity of additional use of narrow band imaging (NBI) in detecting RRP during microlaryngoscopy.

Clinical recommendations on the treatment of neuroendocrine carcinoma of the larynx : A meta-analysis of 436 reported cases

Current recommendations on the treatment of neuroendocrine carcinoma of the larynx (NCL) are based on anecdotal evidence. With this meta‐analysis, our purpose was to provide clinicians with more substantiated guidelines in order to improve the treatment outcome of the patients affected with NCL.

Expression of multidrug resistance proteins, P-gp, MRP1 and LRP, in soft tissue sarcomas analysed according to their histological type and grade

The biological behaviour of different histological types and grades of soft tissue sarcomas (STS) varies. This might result in a differing sensitivity to cytotoxic drugs. Cross-resistance to functionally and structurally distinct natural-product drugs, known as multidrug resistance (MDR), is associated with the overexpression of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and lung resistance-related protein (LRP). The purpose of this study was to evaluate the expression of P-gp, MRP1 and LRP in STS according to their histological type and grade. In 141 chemotherapy-naive STS patients, the expression of the three MDR proteins was detected by immunohistochemistry. Nine histological types were documented. These were 19% grade 1, 34% grade 2 and 47% grade 3 tumours. Expression of P-gp and LRP was observed more frequently than the expression of MRP1 (P<0.0001). P-gp expression was most pronounced in malignant fibrous histiocytoma (MFH), but was low in leiomyosarcomas. MRP1 was expressed in most malignant peripheral nerve sheath tumours (MPNST). LRP was strongly expressed in MFH and unspecified sarcomas, but was low in liposarcomas. MRP1 and LRP expression was significantly more common in grades 2 and 3 compared with grade 1 tumours. P-gp expression was correlated with MRP1, especially in grade 3 STS. In conclusion, P-gp, MRP1 and LRP are expressed in the majority of STS, but this expression varies according to the histological type. MRP1 and LRP, but not P-gp expression, were found to be correlated to tumour grade. MDR might contribute to the observed differences in clinical behaviour within the heterogeneous group of STS.

Co-morbidity and treatment outcomes of elderly pharyngeal cancer patients: A matched control study

Treatment choice in elderly pharyngeal cancer patient is disputed. This study was aimed to asses association of co-morbidity, complications and survival in different treatment modalities of pharyngeal cancer patients. Retrospective analysis of pharyngeal cancer patients, diagnosed between 1997 and 2007 in a tertiary referral hospital was performed. Patients 75years and older (n=42), were matched with two control patients 64years and younger (n=84). Co-morbidity (ACE-27), treatment related complications and survival data were assessed and analyzed. Frequency of co-morbidity was similar in both age groups, although discarding alcohol abuse resulted in higher incidence of co-morbidity in the elderly group. Complication rate was not significantly different. In a multivariate analysis only stage found to be a significant predictor of complications. Survival estimates adjusted to sex, age and birth cohort revealed co-morbidity to be a significant predictor for survival in elderly and young patients. No evidence has been found to treat elderly pharyngeal cancer patients differently than younger ones. Treatment related complications are not predicted by co-morbidities in young and elderly patients; however survival is predicted by comorbidity. Therefore thorough pre-treatment evaluation and care necessary in the elderly population.

Narrow Band Imaging Improves Observer Reliability in Evaluation of Upper Aerodigestive Tract Lesions

Visualization by endoscopy is essential in the diagnosis of upper aerodigestive tract lesions. Recent studies showed that narrow band imaging (NBI) increases the diagnostic potential of conventional white light imaging (WLI) by highlighting the superficial vessels. The objective of this study was to evaluate whether the use of NBI would influence inter‐ and intraobserver agreement while making diagnostic decisions using rigid endoscopy of the upper aerodigestive tract.