Helle Klyver

Spontaneous regression of metastases from melanoma: review of the literature.

Regression of metastatic melanoma is a rare event, and review of the literature reveals a total of 76 reported cases since 1866. The proposed mechanisms include immunologic, endocrine, inflammatory and metastatic tumour nutritional factors. We conclude from this review that although the precise mechanisms remain unknown, some event must trigger the immune system to produce a stronger than normal response that results in regression of the melanoma metastases. Immunologic studies of patients with regression may disclose the underlying mechanisms and lead to new therapies of disseminated melanoma.

Spontaneous regression of metastases from malignant melanoma: a case report.

A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence of therapy, which is considered inadequate to exert a significant influence on neoplastic disease. The incidence of spontaneous regression of metastases from malignant melanoma is approximately one per 400 patients, and possible mechanisms include immunologic, endocrine, inflammatory and tumour nutritional factors. Our patient engaged in alternative therapies and was taking a number of different dietary supplements, none of which can be medically recommended, but the combination of which possibly strengthened the immune system and thereby the host defense against the melanoma metastases.

CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta-analysis.

It is possible that reduced function of DNA repair and cell-cycle control genes increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with increased risk of malignant melanoma. First, we performed case-control studies of 1,152 Danish and 752 German individuals with malignant melanoma compared with 9,142 Danish and 3,718 German controls. Second, we performed a meta-analysis of CHEK2*1100delC and malignant melanoma, involving 2,619 cases and 17,481 controls. Third, we examined the risk of malignant melanoma associated with CHEK2*1100delC heterozygosity in an analysis stratified for sun exposure, as well as for subtype and location on the body. The odds ratios for malignant melanoma for CHEK2(*)1100del heterozygotes compared with those for noncarriers were 2.01 (95% confidence interval (CI), 1.03-3.91) in Danes, 1.42 (95% CI, 0.46-4.31) in Germans, and 1.79 (95% CI, 1.02-3.17) in Danes and Germans combined. In a meta-analysis, the odds ratio of malignant melanoma for CHEK2*1100delC heterozygotes compared with that for noncarriers was 1.81 (95% CI, 1.07-3.05). Stratifications did not alter these results. CHEK2*1100delC heterozygotes have a twofold risk of malignant melanoma compared with noncarriers.

Extensive screening for primary tumor is redundant in melanoma of unknown primary

For decades, patients in our institution with metastastic melanoma of unknown primary have been subjected to extensive examinations in search of the primary tumor. This retrospective study questions the results, and thus the feasibility of these examinations. Of 103 patients diagnosed with unknown primary tumor during the period 1986–2006, 39 (38%) presented primarily with a cutaneous or a subcutaneous metastasis, and 63 (61%) with a lymph node metastasis. One patient presented with a bone metastasis (1%). Eighty‐seven patients (84%) were examined by an ophthalmologist. A choroidal melanoma was suspected as the primary tumor in one patient. Eighty‐four patients (82%) were examined by an oto‐rhino‐laryngologist, whereby no primary tumor was found. Ninety‐five patients (92%) were examined by sigmoideoscopy/rectoscopy. No primary tumor was found. Of the 36 women, 32 had a gynecological examination (89%), revealing no primary tumor. We conclude, that only one possible (but not verified) primary tumor was disclosed by various specialists examinations of 103 patients referred with the diagnosis metastatic melanoma with no primary tumor. Special screenings can thus be considered as redundant. Thus, for patients referred with metastastic melanoma of unknown primary, we recommend that a detailed history is obtained, and a standard physical examination performed, in addition to a histopathological review and CT/PET for staging. J. Surg. Oncol. 2011; 104:724–727.

Sentinel Node Detection in Melanomas Using Contrast-Enhanced Ultrasound

Background: Sentinel node (SN) biopsy has proven to be a useful clinical method based on the combination of radionuclide tracer principles and the dye technique. Contrast-enhanced ultrasound (CEUS) has been used successfully for detection of SN in animals, but the use of CEUS has not been reported in humans. Purpose: To investigate the possible use of CEUS in detecting SN in patients with malignant melanomas (MM), and to improve the method by using different concentrations of contrast agent and various positions of the extremity. Material and Methods: Ten patients with MM on an extremity and one healthy volunteer were included. One milliliter of a contrast agent (Sonovue; Bracco, Milan, Italy) was injected subcutaneously on both sides of the scar from the excised tumor. Contrast-enhanced lymph channels and lymph nodes (LNs) were searched for using low-mechanical-index CEUS and by stimulated acoustic emission. Afterward, lymphoscintigraphy was performed and the patient operated. During surgery, the SNs were located via scintigraphic findings, gamma-probe signals, and blue-dye visualization of lymph channels and LNs. Before the human study, a study of 10 mice was performed to exclude possible tissue damage, as the contrast agent was not registered for subcutaneous administration. Results: In one patient, two contrast-enhanced inguinal LNs were visualized by CEUS, corresponding to two inguinal SNs found by scintigraphic imaging. No contrast-enhanced lymph channels or LNs were visualized in any other patients or in the volunteer. No tissue damage was observed in the 10 mice. Conclusion: This study does not support the use of CEUS for detection of SNs in humans. However, the application of CEUS for the investigation of SNs is still not fully explored in humans, and an alternative setup and/or contrast agent might provide better results.

Radionuclide leakage monitoring during hyperthermic isolated limb perfusion for treatment of local melanoma metastasis in an extremity

The aim is to describe the importance of leakage monitoring in hyperthermic isolated limb perfusion (ILP). It is generally recommended that leakage should not exceed 10% because of risk of systemic toxicity.

Radiation exposure to surgical staff during hyperthermic isolated limb perfusion with 99mTechnetium labeled red blood cells

Purpose: Hyperthermic isolated limb perfusion (HILP) is an effective method in the treatment of recurrent melanomas and soft tissue sarcomas. To avoid systemic toxicity, leakage from the limb perfusate into the systemic circulation is real-time monitored by administration of a radioactive agent to the limb circuit. This has made HILP safe for the patient. However, the radiation exposure to the surgical staff has never been measured and could be a limiting factor for the use of HILP. The purpose of the present study was to measure and evaluate the radiation exposure to the surgical staff performing HILP with 99mTechnetium labeled red blood cells. Materials and methods: Thirteen patients had HILP performed in 11 lower limbs and two upper limbs at our inpatient clinic between October 2006 and February 2007. The surgeon and nurse had thermoluminescence dosimetry (TLD) chips attached to the finger pulp and to the ring area of the left fourth finger, as well as an electronic dosimeter attached to the anterior lining of the trousers. The anesthesiologist and perfusion technologist also carried electronic dosimeters. Results: The surgeon had the highest radioactive exposure with an average dose per procedure to the finger pulp of 16.2 µSv, to the ring area of 8.5 µSv, and to the abdominal wall of 4.2 ± 0.6 µSv. Conclusions: HILP with 99mtechnetium-labeled red blood cells does not constitute a safety risk to the operating team with respect to radioactive exposure. Routine dose monitoring of the staff or special precautions for fertile women are not necessary.