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Biomedical subjects

H J Hoekstra

Publications and source records attributed to H J Hoekstra.

At least 55 records · Page 3Linked to original sources

Hyperthermic isolated limb perfusion in the management of extremity sarcoma.

High local drug concentrations can be achieved in a limb with minimal systemic toxicity with the technique of hyperthermic isolated limb perfusion (HILP). The currently most successful drugs are still Tumor Necrosis Factor alpha (TNFalpha) and melphalan. With HILP, as an induction chemotherapy treatment of locally advanced primarily irresectable soft tissue sarcomas of a limb, a limb salvage rate of 71% can be achieved, with a minimal treatment related morbidity. For the HILP is no upper age limit. Systemic inflammatory response syndrome is currently seldom seen. The exact working mechanisms of TNFalpha are still unknown. Experimental work is now directed to the development of drugs sensitizing the tumor vasculature to the effects of TNFalpha. In the clinical HILP setting are currently lower doses of TNFalpha in combination with melphalan investigated. Although multidrug resistance (MDR) is a major issue in effectiveness of chemotherapy in human cancer treatment, HILPs with TNFalpha and melphalan did not induce MDR in sarcomas. The future research in HILP with TNFalpha is directed in increasing tumor sensitivity for TNF with lowering the dosage without decreasing tumor response.

Antineoplastic Agents↗

Is sentinel node biopsy beneficial in melanoma patients? A report on 200 patients with cutaneous melanoma.

AIM: The aim of this study was to evaluate the reliability and clinical impact of sentinel node biopsy, including preoperative lymphoscintigraphy and intraoperative lymphatic mapping in patients with cutaneous melanoma of the head, neck, trunk or extremities. METHODS: Two hundred patients (103 women, 97 men), median age 57 (range 21-86) years with cutaneous melanoma > or =1.0mm Breslow thickness and clinically negative lymph nodes participated in a single institutional prospective study from May 1995 to January 2000. Primary melanoma sites included: 22 head and neck (11%), 67 trunk (34%), 29 upper extremity (14%) and 82 lower extremity (41%). The median Breslow thickness was 2.5 (range 1.0-20.0)mm. Preoperative dynamic and static lymphoscintigraphy, intraoperative blue dye and a gamma detection probe were used. If histological examination with HE or IHC showed metastases, therapeutic lymph node dissection (TLND) was performed. RESULTS: Sentinel node(s) could be identified in 197 patients (99%); 393 sentinel nodes (mean: 2.0 per patient, range 1-7) were removed from 241 basins. Three procedures failed in the head and neck region. In 167 patients, the sentinel nodes were both blue and radioactive (85%); in 26 patients, they were only radioactive (13%) and in four patients only blue (2%). In total, 150 patients had tumour-negative sentinel nodes (76%). During a median follow-up of 47 (range 24-79) months, nodal recurrence in a negative mapped basin was documented in six patients of which isolated recurrence was in two patients and recurrence together with locoregional recurrence in four patients (false negative rate 6/54=11%). Estimated three-year recurrence-free survival in the node-negative patients and node-positive patients was 83 and 66% respectively (P<0.05). The overall survival at three years was 92 and 73% respectively (P<0.05). CONCLUSION: Sentinel node biopsy provides accurate staging and important prognostic information. The final place of sentinel node biopsy is still undefined, and therefore sentinel node biopsy is still considered as an experimental surgical staging procedure.

Adult↗

New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma.

The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research, new diagnostic techniques, such as Positron Emission Tomography and the introduction of the sentinel lymph node biopsy with advanced laboratory methods such as immuno-histochemical markers, and reverse transcriptase polymerase chain reaction, have been developed to facilitate early detection of metastatic melanoma. The role of these new techniques on the staging and surgical treatment of melanoma is discussed in this paper.

Biomarkers, Tumor↗

Routine chest X-rays have no additional value in the detection of relapse during routine follow-up of patients treated with chemotherapy for disseminated non-seminomatous testicular cancer.

BACKGROUND: The routine follow-up of patients with disseminated non-seminomatous testicular cancer (DNSTC) treated with the combination of orchidectomy, polychemotherapy, and if needed, resection of the residual mass, consists of regular physical examinations, chest X-rays (CXR) and tumor marker assessments. Most guidelines for this routine follow-up originate from multi-center trials. In order to estimate the value of CXR in the detection of tumor relapse after complete remission, we reviewed all patients with disseminated testicular cancer treated with chemotherapy at the University Hospital Groningen. PATIENTS AND METHODS: Three hundred and fifty-three consecutive patients with DNSTC treated between February 1977 and February 1999 at our institution were reviewed. Two hundred and ninety (82.2%) patients, who were in complete remission after cisplatin-containing chemotherapy followed by, if necessary, resection of the residual mass, entered this analysis. The follow-up schedule consisted of regular physical examinations, tumor marker assessment (lactate dehydrogenase, beta-human chorionic gonadotropin and alpha-FP) and CXR. In all patients the first diagnostic sign of tumor relapse was documented. RESULTS: During a median follow-up of 107 months (range 8-261) a tumor relapse was documented in 33 patients (11.4%). Median time to relapse was 17 months (range 6-179) after the start of chemotherapy. In 27 patients, tumor relapse was first detected by a rise in tumor markers. Two patients presented their relapse with neurological complaints. Both were diagnosed with brain metastasis. In four patients the relapse was detected by both increase in tumor markers and abnormalities in the physical examination. In none of the 33 relapsed patients was routine CXR during follow-up involved in the detection of tumor recurrence. All but one of the relapsed patients had elevated tumor markers before the start of chemotherapy. The total number of CXR made during follow-up in all 290 patients was 10 160; none were diagnostic for the detected relapses. CONCLUSIONS: These data suggest that routine CXR has no additional value in the detection of tumor relapses during follow-up after chemotherapy in the subset of patients who present their DNSTC with increased tumor markers and are in complete remission after treatment. In order to save valuable resources, CXR can be omitted from the follow-up schedule after chemotherapy for marker-positive non-seminomatous testicular cancer in complete remission.

Adolescent↗

[Resection of the sciatic nerve with preservation of leg function].

Four patients, three women aged 32, 65 and 77 years and one man aged 51 years, had a soft tissue tumour of the upper dorsal thigh or gluteal region. They were treated by resection of both the sciatic nerve and the tumour. This resulted in a good functional outcome with limited functional disturbances. In the case of the three women, metastases of their malignant schwannoma, sarcoma, or liposarcoma respectively were found after several months to years; 2 of them died from these. The man was treated on several occasions for local recurrences of the malignancy. Patients with soft tissue sarcomas involving the sciatic nerve are often treated by amputating the affected limb. Nerve resection is a good alternative for complete tumour resection whilst still preserving the limb.

Adult↗

Soft tissue sarcoma--compliance with guidelines.

BACKGROUND: Because soft tissue sarcomas (STS) are rare, guidelines for the diagnosis and treatment of patients with STS were developed. Because the diagnostic management is essential for definitive treatment, adherence to these guidelines is important. METHODS: Primary STS registered by the Comprehensive Cancer Center North-Netherlands from January 1989 to January 1996 were analyzed retrospectively with regard to adherence to the diagnostic guidelines. Urogenital, gastrointestinal STS, and Kaposi sarcomas were excluded. RESULTS: Three hundred fifty-one STS patients were analyzed. In the specialized center, 69% of patients were age < 60 years, whereas, in district hospitals, 63% of patients were age > 60 years. With increased age, referral to the center declined in a linear fashion. For all guidelines, adherence was significantly better in the center. In district hospitals, patient volume had no significant influence on compliance with the guidelines, except for the management of patients with STS > or = 3 cm. In district hospitals, where fewer than 15 patients were treated in the 7-year period, significantly more often, an inadequate biopsy or even no biopsy procedure was performed prior to resection. CONCLUSIONS: In many aspects of the diagnostic process of STS, existing guidelines were not followed, especially in community hospitals. Adherence to all individual guidelines was significantly better in the specialized center. To improve compliance with future STS guidelines, appropriate guideline development, dissemination, and implementation programs should be developed. Concentration of patients with STS in a limited number of hospitals and intensified collaboration with specialized centers seem advisable. Special attention should be paid to older patients, who significantly more often were not referred to a specialized center.

Adolescent↗

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-alpha and melphalan.

BACKGROUND: 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-alpha) is able to modify the expression of these three proteins in different cell types. The effect of TNF-alpha in the clinical situation on patients with soft tissue sarcomas (STS) is indeterminate. METHODS: Thirty-seven patients with a locally advanced extremity STS underwent hyperthermic isolated limb perfusion (HILP) with TNF-alpha and melphalan; 15 patients received additional interferon gamma. Clinical and histologic responses were documented and used to define the overall response. Samples before and after HILP were analyzed immunohistochemically for P-gp, MRP1, and LRP. Samples were scored as negative or positive (< or = 5% or > 5% positive tumor cells). RESULTS: Six patients had an overall complete response, 25 patients had a partial response, and 4 patients with STS revealed no change; in 2 patients, the response remained unclear. The percentage STS samples that were positive for all three proteins dropped from 92% before HILP to 85% after HILP. P-gp positive samples were encountered more often than MRP1 positive samples (P < 0.05). The percentage of samples that were negative for all three MDR proteins increased after HILP from 6% to 16%. MDR status had no significant correlation with tumor response. CONCLUSIONS: HILP with TNF-alpha and melphalan results in excellent overall tumor response in patients with locally advanced STS. STS more often are positive for P-gp than for MRP1. MDR status in patients with STS is not predictive for tumor response after HILP. Data from the current study suggest that the combination of TNF-alpha and melphalan does not induce MDR positive STS: a result with clinical importance when consecutive, adjuvant, doxorubicin-containing chemotherapy is considered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era.

BACKGROUND: The current study reviews chronologic changes in the long term outcome of patients with metastatic nonseminomatous testicular germ cell tumors (NSTGCT) who were treated at a single institution during the past two decades. The 10-year survival of prognostic subgroups according to the classification of the International Germ Cell Consensus Classification Group (IGCCCG) and various other prognostic classifications is examined in time to evaluate whether cumulative experience has led to an improved outcome of patients with metastatic NSTGCT and to explore differences in outcome of prognostic subgroups. METHODS: Two hundred ninety-nine patients with metastatic NSTGCT who were treated with cisplatin-based polychemotherapy during the period from 1977 to 1996 were staged retrospectively according to the Royal Marsden (RM) classification and the following prognostic classifications: IGCCCG, Indiana, Medical Research Council (MRC), and European Organization for Research and Treatment of Cancer (EORTC). The numbers of patients who were treated during the periods 1977-1986 and 1987-1996 were 146 and 153, respectively. Survival curves were constructed using the Kaplan-Meier method, and disease specific 10-year survival rates of prognostic subgroups treated during the two consecutive 10-year periods were compared using the log rank test. RESULTS: The median follow-up of surviving patients during the periods 1977-1986 and 1987-1996 was 14.7 years (range, 0.2-20.6 years) and 7.0 years (range, 0.4-11.4 years), respectively. The actuarial disease specific 10-year survival rate of patients with metastatic NSTGCT increased from 76% during the period 1977-1986 to 88% during the period 1987-1996 (relative risk [RR], 0.51; 95% confidence interval [95% CI], 0.29-0.89; P < 0.05). The 10-year survival rates of patients with good, intermediate, and poor prognoses according to the IGCCCG classification were 95%, 74%, and 37%, respectively, during the period 1977-1986 and 94%, 87%, and 66%, respectively, during the period 1987-1996. Patients with a poor prognosis according to the IGCCCG classification showed the greatest increase in 10-year survival (RR, 0.43; 95% CI, 0.18-1.04; P = 0.06). Analysis using the RM, Indiana, and EORTC classifications also showed an improved 10-year survival rate of patients with a poor prognosis who were treated during 1987-1996 compared with those who were treated during 1977-1986. CONCLUSIONS: The 10-year survival rate of patients with metastatic NSTGCT who were treated with cisplatin-based chemotherapy significantly increased from 76% during the period 1977-1986 to 88% during the period 1987-1996. This improvement during the cisplatin era resulted mainly from an increase in the survival of patients with metastatic disease who had a poor prognosis. These results indicate that the management of patients with NSTGCT is still improving.

Adolescent↗

Continuous leakage measurement during hyperthermic isolated limb perfusion.

BACKGROUND: Continuous measurement of perfusate leakage into the systemic circulation is of the utmost importance and can be performed with the help of radioactive tracers. The purpose of this study was to assess changes in the perfusion leakage rate between two periods: 1977-1990 and 1991-2000, and to determine the factors responsible for these changes. METHODS: During the 1991-2000 period, 119 patients underwent HILP mainly for locally recurrent melanoma or locally advanced soft tissue sarcoma. HILP was performed with melphalan (33%) or in combination with TNFalpha (65%). There were 67 iliacal, 12 femoral, 25 popliteal, and 15 axillary perfusions performed. Leakage into the systemic circulation was monitored continuously with the help of 131I-albumin and a stationary scintillation detector placed above the heart. RESULTS: The median maximum leakage was 2.7% (range 0%-21%) which is significantly less than the previous period (1977-1990) where leakage of 8% (range 0%-30%) was reported (P < .05). A statistical difference in leakage was detected among perfusion locations where the iliac and femoral vessels showed more leakage than the axillary and popliteal vessels (P < .05). Furthermore, there appeared to be significantly less leakage when TNFalpha was used than when melphalan was the sole drug (P < .05). CONCLUSIONS: Nowadays leakage from isolated perfusions into the systemic circulation is further minimized compared with the days when melphalan was the sole drug used. Increased awareness about TNFalpha leakage, continuous external monitoring with 131I-albumin as the main isotope, flow rate regulation in the perfusion circuit, and regulation of the patient's systemic blood pressure have all been major contributors to this improvement.

Adolescent↗

Cancer surgery in the elderly.

Surprisingly, cancer in the elderly is frequently treated in a poor manner, and the behaviour of the disease in elderly patients is often poorly understood. Cancer treatment varies significantly with age, the percentage of patients receiving definitive treatment declines with increasing age, and there is a decline in survival of cancer with age. One of the contributing factors may be that physicians are less likely to recommend specialist consultation for elderly patients. One has to keep in mind that cancer surgery in the elderly, without any co-morbidity, is safe, and that, nowadays, the morbidity and mortality increases minimally with the age of the patient. In contrast, the morbidity and mortality is 2-3 fold as high in the elderly cancer patients with co-morbidity compared with younger cancer patients. A better public education of the elderly may increase cancer awareness, and therefore decrease the risk of developing symptoms that require emergency surgery, with a subsequent three times increase in the mortality rate. Surgeons treating elderly cancer patients should realise that performance status is more important than age, and should always keep in mind the three major questions as recently formulated by Balducci; (1) is the patient going to die of cancer or with cancer, (2) is the patient able to tolerate the surgery and possible surgical-related complications, and (3) is the patient likely to suffer the complications of cancer during her/his life? The increased number of surgical treatment options in elderly cancer patients will lead to an increase in overall cancer survival in elderly cancer patients, and contribute to an improvement in their quality of life. Surgical oncologists should focus on how to manage the most common cancers in elderly people such as breast, colorectal, lung and prostate, as well as take an active part in palliative treatments.

Aged↗

Sexual functioning after treatment for testicular cancer--review and meta-analysis of 36 empirical studies between 1975-2000.

Literature concerning sexual functioning after treatment for testicular cancer from 1975-2000 is reviewed. After a literature search in Medline and Psylit was conducted, as well as a search for cross-references made, a meta-analysis was performed. To describe sexual functioning, several aspects of the sexual response cycle were used: sexual desire, sexual arousal, erection, and orgasm; ejaculatory function, sexual activity, and sexual satisfaction were used as well. The number of patients included in the studies as well as treatment modalities were taken into account. A total of 36 relevant studies was screened (28 retrospective and 7 prospective studies), concerning 2,786 cases of testicular cancer. Meta-analysis revealed that ejaculatory dysfunction was reported most frequently and was related to surgery in the retroperitoneal area. Erectile dysfunction was related to irradiation, but was reported least frequently. Other sexual functions were not related to treatment modality. Meta-analysis revealed no deterioration of sexual functioning in the course of time, except a decrease in sexual desire and an increase in sexual satisfaction. Retrospective studies reported more sexual dysfunction than did prospective studies. Detailed analysis of separate studies, however, revealed a wide variation in reported sexual morbidity, as well as in assessment methods. Somatic consequences of disease and treatment may reduce ejaculation; however, other aspects of sexual functioning are not clearly related to disease- or treatment-related factors and may instead refer to a psychological vulnerability caused by one's confrontation with a life-threatening, genito-urinary disease, such as testicular cancer.

Erectile Dysfunction↗

Gastrointestinal complications in lung transplant survivors that require surgical intervention.

BACKGROUND: Lung transplantation is widely accepted as a treatment for end-stage lung disease. At present, information regarding the incidence and outcome of acute gastrointestinal complications in lung transplant survivors is limited. METHODS: Since 1990, 127 lung transplantations have been performed in 125 patients: 73 males (58 per cent) and 52 females (42 per cent) of median age 43 (range 9-64) years. Patients received a standard induction and maintenance regimen of immunosuppression. RESULTS: At a median follow-up of 2.6 (range 0-8.6) years the overall survival rate was 68 per cent. An acute abdomen requiring surgical intervention was diagnosed in 12 patients (10 per cent). The median time following lung transplantation was 19 (range 3-68) months. Eight cases of bowel perforation, two of appendicitis, one of colitis, one of cholecystitis, and one pneumoperitoneum were encountered. Four Hartmann procedures, two sigmoid resections, one small bowel resection, two appendicectomies, a subtotal colectomy, a cholecystectomy and an exploratory laparotomy were performed with minimal morbidity and no postoperative death. CONCLUSION: Lung transplant survivors are at increased risk of developing an acute abdomen because of the use of high-dose immunosuppressive agents. Physicians who evaluate lung transplant patients for an acute abdomen should have a low threshold for surgical intervention.

Abdomen, Acute↗

Soft tissue carcinoma in the retroperitoneum: an often neglected diagnosis.

AIMS: Successful surgical treatment of patients with retroperitoneal soft tissue sarcoma (RSTS) is based on pre-operative planning that starts with a correct pre-operative diagnosis. In a population-based study, we determined which patients were initially treated for assumed other conditions. The effect of an erroneous diagnosis on the installed treatment was analysed. METHOD: With the help of the Dutch Network and National Database for Pathology (PALGA), data were collected on 143 patients in the Netherlands in whom a primary RSTS was found and confirmed histologically between 1 January 1989 and 1 January 1994. Satisfactory clinical information was obtained on 138 patients, 64 males and 74 females (54%). The median age was 60 (range 18-88) years. RESULTS: At the time of actual treatment 37% of the patients with RSTS were assumed to have another disorder (group 1 n=51), whereas 87 patients were diagnosed as having RSTS (group 2). In group 1, an acute presentation was more common (18 vs 2% P=0.002), and the tumour was less often palpable at physical examination (43 vs 69% P=0.004), while clinical work-up less frequently included CT-imaging (57 vs 89% P<0.001) and a biopsy (29 vs 77% P<0.001). Although tumours in group 1 were smaller (median diameter 13 vs 19 cm P<0.05), this was not reflected in a better operative result: less patients underwent complete tumour resection (51 vs 57%) and more patients underwent surgery for tumours that proved to be irresectable (14 vs 1% P=0.004). CONCLUSIONS: (1) More than one-third of patients with RSTS are misdiagnosed and inappropriately treated; and (2) biopsies and cross-sectional imaging improve diagnosis.

Adolescent↗

Locoregional recurrence of retroperitoneal soft tissue sarcoma: second chance of cure for selected patients.

BACKGROUND: Locoregional recurrence of a retroperitoneal soft tissue sarcoma (RSTS) may offer a second chance of curative surgical treatment. In a population-based study the proportion of patients developing isolated locoregional recurrences (LR) was determined and the outcome of these patients was analysed. METHOD: In a retrospective nationwide study, data were collected on 142 patients treated between 1 January 1989 and 1 January 1994 for primary RSTS. In patients who had been treated radically for their primary sarcoma (77/142, 54%), the pattern of recurrence was evaluated. Factors predictive of survival for patients with LR were studied. RESULTS: After a median follow-up of 86 (range 60-101) months, 32 patients (42%) had developed LR, and distant metastasis (DM) had been diagnosed in 17 patients (22%). Median disease-free interval between the initial operation and the establishment of LR or DM was 22 and 19 months, respectively. Five-year cumulative survival of patients with established LR was 37% in comparison with 11% for patients with DM (P=0.062). Factors predictive of favourable outcome in patients with LR were the absence of multifocal recurrence (n=13 P=0.01), lipomatous histomorphology (n=20 P=0.02), and a complete resection of recurrent sarcoma (n=17 P=0.04). CONCLUSION: After a median follow-up of 7 years following radical treatment of a primary RSTS, 42% of the patients had developed isolated locoregional recurrences. A complete resection of recurrent disease, lipomatous histomorphology and the absence of multifocal growth influenced prognosis favourably.

Adult↗

Isolated limb perfusion: the European experience.

Isolated limb perfusion (ILP) is a method of cancer treatment allowing the administration of high doses of anticancer agents in a limb surgically isolated from systemic circulation. By using continuous leakage monitoring and using the drug melphalan, a high complete remission rate is obtained in patients with melanoma. In patients with sarcomas, ILP with tumor necrosis factor and melphalan represents a neoadjuvant treatment for limb-sparing surgery. This treatment is the first demonstration of an active anti-angiogenic regimen in the clinic.

Antineoplastic Agents↗