Heimen Schraffordt Koops

Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas: The cumulative multicenter European experience

OBJECTIVE The objective of the study was to achieve limb salvage in patients with locally advanced soft tissue sarcomas that can only be treated by amputation or functionally mutilating surgery by performing an isolated limb perfusion (ILP) with tumor necrosis factor (TNF) + melphalan (M) as induction biochemotherapy to obtain local control and make limb-sparing surgery possible. SUMMARY BACKGROUND DATA To increase the number of limb-sparing resections in the treatment of locally advanced extremity soft tissue sarcoma, preoperative radiation therapy or chemotherapy or a combination of the two often are applied. The ILP with cytostatic agents alone is another option but rarely is used because of rather poor results. The efficacy of the application of TNF in ILP markedly has changed this situation. METHODS In 8 cancer centers, 186 patients were treated over a period of almost 4.5 years. There were 107 (57%) primary and 79 (43%) recurrent sarcomas, mostly high grade (110 grade III; 51 grade II; and 25 very large, recurrent, or multiple grade I sarcomas). The composition of this series of patients is unusual: 42 patients (23%) had multifocal primary or multiple recurrent tumors; median tumor size was very large (16 cm); 25 patients (13%) had known systemic metastases at the time of the ILP. Patients underwent a 90-minute ILP at 39 to 40 C with TNF + melphalan. The first 55 patients also received interferon-tau. A delayed marginal resection of the tumor remnant was done 2 to 4 months after ILP. RESULTS A major tumor response was seen in 82% of the patients rendering these large sarcomas resectable in most cases. Clinical response rates were: 33 complete response (CR) (18%), 106 partial response (PR) (57%), 42 no change (NC) (22%), and 5 progressive disease (PD) (3%). Final outcome was defined by clinical and pathologic response: 54 CR (29%), 99 PR (53%), 29 NC (16%), and 4 PD (2%). At a median follow-up of almost 2 years (22 months; range, 6-58 months), limb salvage was achieved in 82%. Regional toxicity was limited and systemic toxicity minimal to moderate, easily managed, with no toxic deaths. CONCLUSIONS In the setting of isolated limb perfusion, TNF is an active anticancer drug in patients. The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.

Detection of unknown occult primary tumors using positron emission tomography

The potential of positron emission tomography (PET) with 18F‐fluoro‐2‐deoxy‐D‐glucose (FDG) to detect primary tumors after unsuccessful conventional diagnostic workup was assessed in patients with metastatic disease from an unknown primary tumor.

Frozen section investigation of the sentinel node in malignant melanoma and breast cancer.

Background: Intraoperative frozen section investigation allows immediate regional lymph node dissection when the sentinel node contains tumor. The purpose of this study was to determine the sensitivity of frozen section diagnosis of the sentinel node in melanoma and breast cancer patients.Methods: A total of 177 sentinel nodes from 99 melanoma patients and 444 lymph nodes from 262 breast cancer patients were assessed by frozen section investigation. Nodes were bisected, and a complete cross-section was obtained for frozen section. Step sections at three levels were made of the remaining lymphatic tissue and were stained with hematoxylin and eosin and S100/HMB45 (melanoma) or CAM5.2 (breast cancer) to obtain a final pathological diagnosis.Results: Frozen section investigation revealed metastases in 8 of 17 node-positive melanoma patients (47%). Seventy-one of 96 breast cancer patients (74%) with lymph node metastases were identified with frozen section. The specificity was 100% and 99%, respectively.Conclusion: The sensitivity of intraoperative frozen section investigation of sentinel nodes was 47% in melanoma patients and 74% in breast cancer patients. Frozen section examination allows immediate axillary lymph node dissection in the majority of node-positive breast cancer patients. Frozen section analysis is not recommended in patients with melanoma.

Sentinel node biopsy for melanoma in the head and neck region

Lymphatic drainage in the head and neck region is known to be particularly complex. This study explores the value of sentinel node biopsy for melanoma in the head and neck region.

Function and complications after ablative and limb-salvage therapy in lower extremity sarcoma of bone.

The functional results and the complications after several limb‐saving and ablative treatments because of lower extremity bone sarcoma were evaluated.

The significance of the doctor-patient relationship in coping with cancer

The uncertainty and anxiety experienced by cancer patients and their ways of coping with uncertainty and anxiety were studied on the basis of a questionnaire completed by 418 patients. The study shows that 28.2% of the patients had a low and 33.5% had a high uncertainty score, while 50% had a low and 9% had a high anxiety score. Four ways of coping with uncertainty and anxiety can be distinguished, of which the use of self-instruction means was most common. Expert help proved to be important for reduction of uncertainty. For reduction of anxiety the support of the home environment and of fellow-patients was also of importance. The implications of these findings for the doctors performance and for the care of cancer patients are discussed.

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

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.

Results of isolated regional perfusion in the treatment of malignant soft tissue tumors of the extremities

High‐grade soft tissue sarcomas of the extremities continue to pose problems of local disease control and deaths from distant metastases. Between 1969 and 1976, eight patients with primary and six with recurrent high‐grade soft tissue sarcomas of the extremities were treated by isolated regional perfusion with cytostatics and local excision. None received systemic adjuvant chemotherapy or external‐beam radiotherapy. During the follow‐up (median, 13 years) five patients (36%) developed distant metastases. One was cured after resection of a pulmonary metastasis. In one other patient (7%) recurrent local disease was diagnosed after 48 months; he was cured after resection of the local lesion followed by postoperative external beam radiotherapy. The actuarial 5‐year and 10‐year survival was 69%. Treatment caused no cardiovascular complications and there was no postoperative mortality.

Cytogenetics of carcinoma in situ of the testis

Carcinoma in situ (CIS) of the testis is the precursor lesion of most testicular germ cell tumors (TGCTs). Karyotyping of CIS is important for a better understanding of the pathogenesis of TGCTs and the progression to invasive cancer. We karyotyped three cases of CIS. All three cases showed a numerical abnormal chromosomal pattern. In one case, two copies of the germ cell tumor marker i(12p) were found.

Effects of multiple-drug chemotherapy (cis-diammine-dichloroplatinum, bleomycin, and vinblastine) on the maturation of retroperitoneal lymph node metastases of nonseminomatous germ cell tumors of the testis. No evidence for De Novo induction of differentiation.

Investigating the mechanisms underlying maturation of metastases of nonseminomatous germ cell tumors on administration, of chemotherapy, the histologic characteristics of primary testis tumors was compared to the histologic characteristics of their retroperitoneal metastases in three historical patient groups. The metastases in Group I (20 patients) were not treated; those in Groups II (nine patients) and III (24 patients) were treated, respectively, with three cycles of dactinomycin and with four cycles of cis‐diammine‐dichloroplatinum, vinblastine, and bleomycin, before retroperitoneal lymph node dissection. In Group III there was a significant increase of metastases consisting of differentiated teratoma only, as compared to the metastases of Group I. However, both with and without chemotherapy, the metastases contained fewer areas of differentiated teratoma than the primary lesions. Metastases containing differentiated teratoma with and without other components, with one exception in Group III, were derived from primary tumors containing mature areas as well. Components other than mature teratoma were almost completely eradicated in Group III. These findings strongly suggest that selective destruction of components other than differentiated teratoma causes the mature histologic characteristics in the metastases upon administration of chemotherapy. The results do not support the hypothesis of induction of differentiation by the chemotherapeutic agents.