Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease.

Early versus delayed excision of lymph node metastases is still being assessed in malignant melanoma. In the present retrospective, multicentre study, the outcome of 314 patients with positive sentinel lymphonodectomy (SLNE) was compared with the outcome of 623 patients with delayed lymph node dissection (DLND) of clinically enlarged lymph node metastases. In order to avoid the lead-time bias, survival was generally calculated from the excision of the primary tumour. Survival curves were constructed using the Kaplan-Meier product-limit estimate. Cox's proportional hazards model was used to perform a multivariate analysis of factors related to overall survival. Compared with SLNE and early performed complete lymph node dissection, DLND yielded a significantly higher number of lymph node metastases. Median and mean tumour thickness were nearly identical in the two therapy groups. The estimated 3-year overall survival rate was 80.1+/-2.8% (+/-standard error of the mean (SEM)) in patients with positive SLNs, and 67.6+/-1.9% in patients with DLND (5-year survival rates 62.5+/-5.5 and 50.2+/-5.4%, respectively). The difference between the two survival curves was statistically significant (P=0.002). Using multifactorial analysis, SLNE (P=0.000052), American Joint Committee on Cancer (AJCC) Breslow thickness category (P<0.000001), age (P=0.01) and gender (P=0.028) were independent predictors of overall survival. The location of the primary tumour (P=0.59) was non-significant. Considering only those centres with sufficient data for epidermal ulceration, this risk factor was also significant. In cutaneous malignant melanoma, early excision of lymphatic metastases, directed by the sentinel node procedure, provides a highly significant overall survival benefit.

Sentinel lymphonodectomy in nonmelanoma skin malignancies.

BACKGROUND: Whereas the value of sentinel lymphonodectomy (SLNE) in malignant melanoma is established, experience with SLNE in nonmelanoma skin cancers is limited. OBJECTIVES: The feasibility of SLNE in nonmelanoma skin tumours is evaluated. METHODS: Thirty-seven patients with high-risk nonmelanoma skin tumours underwent SLNE: 11 squamous cell carcinomas (SCCs), seven Merkel cell carcinomas (MCCs), five cutaneous lymphomas, eight adnexal carcinomas and six other skin cancers, all clinical stage N0. RESULTS: In nine patients (four MCCs, two SCCs, three lymphomas) the sentinel lymph nodes (SLNs) showed histological evidence of microinvolvement. In five of these nine patients, radical lymph node dissection (RLND) was performed, revealing further micrometastases in three patients (two SCCs, one MCC). No patient with negative SLN showed tumour dissemination during the follow-up over a mean of 2.5 years (range 2 months to 4.5 years, median 2.4 years). CONCLUSIONS: Our data provide evidence that SLNE is a minimally invasive and highly sensitive staging tool in selected patients with high-risk nonmelanoma skin cancers.

The Augsburg experience: histological aspects and patient outcomes.

In Augsburg, sentinel lymphonodectomy (SLNE) was introduced into melanoma treatment in 1994. Diagnostic accuracy has been improved by early identification of sentinel lymph node (SLN) micrometastases and even more by their histomorphometric assessment. The S classification defines three categories of SLN metastases, S1 to S3, supplemented by S0 in the absence of metastasis. It is the leading predictor for the status of the remaining regional lymph nodes and an independent prognosticator for distant metastasis and survival. This should find consideration in adjuvant therapy trials. The pivotal question of whether SLN-guided surgery itself achieves survival benefit has been approached by a follow-up study that compared 387 SLNE-treated patients with 473 patients from the pre-SLNE era. In contrast to nonsignificant differences in patients with thin and very thick primary tumors, death from intermediate-thickness melanoma (1.51 to 4 mm) occurred significantly more often in the watch-and-wait group versus the SLNE group. These results must be validated by prospective randomized trials (e.g., NCI 29605).

Prognostic and therapeutic implications of sentinel lymphonodectomy and S-staging in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine neoplasm of the skin with a high propensity for early lymph node metastasis and subsequent distant spread. Optimal treatment and prognostic factors are poorly defined. OBJECTIVE: The purpose of this study is to assess the prognostic and therapeutic relevance of sentinel lymphonodectomy in MCC. METHODS: Five patients with biopsy-proven MCC underwent gamma-probe-guided sentinel lymphonodectomy assisted by lymphatic mapping. From each sentinel lymph node (SLN), a series of paraffin sections was histologically and immunohistochemically examined for the presence of micrometastases, which were then staged according to the recently published S classification. RESULTS: Four of the 5 patients showed metastatic disease in the SLNs, 3 of which were classified as S(2), 1 as S(3). Only 1 of the S(2) patients demonstrated additional positive nodes at completion lymphonodectomy. The patient staged as S(3) refused a radical lymph node dissection and died within 1 year due to widespread metastasis. CONCLUSIONS: Sentinel lymphonodectomy is a low-morbidity procedure which enables an early detection and exact staging of regional lymph node metastases with potentially high prognostic and therapeutic relevance in MCC.

A micromorphometry-based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma.

BACKGROUND: The sentinel lymph nodes (SLNs) as the primary targets for lymphatic metastases can be removed selectively by gamma probe-guided sentinel lymph nodectomy (SLNE) in nearly all patients with cutaneous melanoma. Correspondingly high standards in terms of specificity, sensitivity, and microstaging are required for the evaluation of SLNs. METHODS: Since 1995, the authors have performed SLNE in 389 lymph node regions (LNRs) on 342 patients with melanoma. The harvested 636 SLNs and a further 1394 nonsentinel lymph nodes (non-SLNs) were evaluated by standardized, semiserial section histology, including immunohistochemistry. For each LNR, this technique permitted routine S classification using two simple morphometric parameters: the number of tumor-involved, 1-mm slices of the SLNs (n) and the centripetal depth of metastatic cell invasion (d). S1 was defined by 1 < or = n < or = 2 and d < or = 1 mm, equivalent to localized peripheral tumor cell deposits; S2 was defined by n > 2 and d < or = 1 mm, indicating more extended peripheral metastases; S3 was defined by d > 1 mm in SNLs with deeper metastatic infiltration; and S0 meant no detectable tumor cells (n = 0). RESULTS: The authors diagnosed 325 SLNs as S0, 24 SLNs as S1, 22 SLNs as S2, and 18 SLNs as S3. The occurrence of at least one melanoma-positive non-SLN subsequent regional completion lymph node dissection (RCLND) significantly increased from 0 of 12 in S1 SLNs to 2 of 13 in S2 SLNs and 9 of 15 in S3 SLNs (P = 0.001; chi-square test). Like the T classification of the primary melanoma, the S classification proved to be a highly significant predictor for distant metastasis (P < 0.001). It turned out to be an independent factor of influence on distant metastasis and survival in multivariate Cox analyses, which included tumor thickness, primary tumor site, patient gender, and patient age as covariates. CONCLUSIONS: The data presented recommend the S-staging concept as a promising option to fill a gap between the T and conventional N component of the pTNM classification. If its predictive capacity can be confirmed in multicenter studies, then the S classification may become the decisive criterion for or against RCLND, and a combined T plus S staging system will help to improve prognostically relevant stratification of melanoma patients in adjuvant therapy trials.

The predictive value of the sentinel lymph node in malignant melanomas.

At the beginning of a lymphogenous metastasizing process in malignant melanomas, the first tumor cells are found in the so-called sentinel lymph node (SLN), defined as the first tumor-draining lymph node. Its removal and histopathological examination enable us to discover metastases of malignant melanomas long before their possibility of detection by any other method. Since the beginning of 1995, we have performed more than 350 gamma-probe-guided sentinel lymphonodectomies (gamma-SLNE), without any clinical evidence of metastases as determined by lymphoscintigraphy. Using gamma-SLNE, the detection and excision of the SLN succeeded in nearly all patients. The SLNs were fixed in formalin, completely cut into 1-mm thin slices and stained for routine H&E histology and with S-100 and HMB-45. In persons with melanomas thinner than 0.75 mm, we never found micrometastases. However, the SLNs were positive in melanomas from 0.76 to 1.50 mm in about 7% of patients, in melanomas from 1.51 to 4.00 mm in about 21% and in tumors thicker than 4 mm in about 44%. In primary melanomas with satellite or in-transit metastases, the SLNs contained metastases in 75% of patients. Normally, a radical lymph node dissection (RLND) follows, as it is considered to be the necessary consequence following detection of tumor cells. The lymph nodes of the RLNDs contained further metastases in about 30% of patients. The probability of the involvement of lymph nodes other than the SLN correlates with the extension of tumor cells in the SLN. During our 4-year-follow-up, we observed only a single lymph node recurrence in a patient with a negative SLN (false negative rate of about 0.4%). The development of systemic metastasis correlates not only with the Breslow tumor thickness, but also with the extent of the involvement of the melanoma metastasis in the SLN. Summarizing, it can be said that gamma-SLNE has revolutionized melanoma surgery. Based on our data, it is absolutely necessary in the staging of malignant melanoma. In our opinion, the existing classification systems for staging lymph node involvement have to be revised in light of the results of SLNE.

Secondary lymph node involvement from primary cutaneous large B-cell lymphoma of the leg: sentinel lymph nodectomy as a new strategy for staging circumscribed cutaneous lymphomas.

BACKGROUND: Primary cutaneous large B-cell lymphoma of the leg (LBCLL) is a recently defined type of non-Hodgkin's lymphoma. It forms a separate category in the new classification of primary cutaneous lymphomas elaborated by the European Organization for Research and Treatment of Cancer. It is associated with a less favorable prognosis than the most frequently occurring types of primary cutaneous B-cell lymphoma. METHODS: The authors present four patients with the typical clinicopathologic constellation of LBCLL. Three of them died during the years 1993-1996. The authors reviewed their courses. The fourth patient was staged by sentinel lymph nodectomy (SLNE), i.e., the selective surgical removal and histologic examination of the first draining lymph node associated with the cutaneous tumor. RESULTS: The courses of the three previous patients were characterized by secondary involvement of regional lymph nodes followed by systemic dissemination of the lymphoma in a third step. Although the conventional staging of the fourth patient had been negative for any extracutaneous lymphoma manifestation, the SLNE revealed initial regional lymph node involvement, which had decisive implications for the choice of therapy. CONCLUSIONS: SLNE may gain a prominent role in the staging of circumscribed cutaneous lymphomas, in addition to its already established position in melanoma management. Further positive effects of SLNE are 1) better distinction of primary cutaneous lymphomas with secondary lymph node involvement from primary lymph node lymphomas with skin manifestation, and 2) better insight into the biology of different primary cutaneous lymphoma types.

[Finger tip necroses after dihydroergotamine medication in limited systemic scleroderma]. / Fingerkuppennekrosen nach Dihydroergotaminmedikation bei limitierter systemischer Sklerodermie.

A 78 year old women developed acute fingertip necrosis just a few days after starting dihydroergotamine. The lesions healed in 3 weeks after the medication was stopped. The patient had suffered from Raynaud syndrome for 5 years and limited systemic sclerosis was diagnosed during the necrotic episode. Advanced age and microangiopathies are contraindications to the use of ergot-containing preparations.

Tree-pollen allergy is efficiently treated by short-term immunotherapy (STI) with seven preseasonal injections of molecular standardized allergens.

The efficacy and tolerance of short-term immunotherapy (STI) by seven preseasonal injections of tree-pollen allergens (ALK7 Frühblühermischung) was investigated in a double-blind, placebo-controlled, multicenter study with 111 rhinoconjunctivitis patients. Nasal and bronchial symptoms simultaneously analyzed, and nasal symptoms as a single end point, but not the overall score of nasal, bronchial, and conjunctival symptoms, showed a significantly lower increase with STI during birch-pollen exposure (both P=0.033, n=105, Mann-Whitney U-test). However, a selective analysis with patients from centers with high recruitment figures (n> or =10 patients, n=29 STI, n=32 placebo) showed a significantly lower increase of nasal, bronchial, and overall symptom score (STI 11.0 vs placebo 18.0, P=0.001, U-test). STI had equidirected effects on conjunctival, nasal, and bronchial symptoms analyzed as multiple end points, although conjunctival symptoms were not significantly different as a single end point. The seasonal increase in drug use was reduced by 62% in the STI group compared with placebo (P=0.032, t-test). Specific IgG4 increased only after STI (P<0.001); IgE was not significantly different. Eosinophil cationic protein remained unchanged with STI, but significantly increased with placebo in the pollen season (P=0.003). STI was well tolerated. In conclusion, STI was shown to be efficacious and safe for the treatment of patients with tree-pollen rhinoconjunctivitis.

[Erythema necrolyticum migrans after rectal adenocarcinoma]. / Erythema necrolyticum migrans nach Rektumadenokarzinom.

Necrolytic migratory erythema (NME) is mostly associated with a pancreatic-A-cell-glucagonoma and is considered to be a well-defined cutaneous paraneoplastic syndrome. We report on a 74-year old female who atypically developed a NME after surgical treatment of a rectal adenocarcinoma. Continuous staging and laboratory investigation over four years gave no evidence of any metastasis or further neoplasia.

Primary therapy of malignant melanomas: sentinel lymphadenectomy.

BACKGROUND: Each melanoma is drained by one or, occasionally, several individual lymph nodes within the nearest lymph node region (sentinel lymph node). OBJECTIVE: By histopathologic examination of the removed sentinel lymph node (SLN), it is possible to select patients clinically according to stage I or II (UICC classification), but who, microscopically, represent stage III. METHODS: Sentinel lymphadenectomies (SLNEs) were performed initially by the vital blue dye technique, and later by gamma-probe guidance only. The removed SLNs were examined by hematoxylin and eosin as well as immunohistochemical stains (S100, and HMB 45). RESULTS: We have performed 115 gamma-probe-guided SLNEs in 100 patients. The SLN could be found in all cases. In pT3 + 4 melanomas, 27.5% of the SLNs were positive; in only one patient with a pT2 tumor were micrometastases found. CONCLUSIONS: gamma-Probe-guided SLNE is a reliable procedure with minimal complications that should be performed in all pT3 + 4 (intraoperative frozen section histology) melanomas without clinically evident metastases.

[Lung edema and erosive gastroduodenitis as a sequela of inappropriate use of an adrenaline dose aerosol after wasp sting]. / Lungenödem und erosive Gastroduodenitis als Folge unsachgemässer Anwendung eines Adrenalin-Dosisaerosols nach Wespenstich.

Epinephrine (adrenaline) is an important drug in the treatment of severe anaphylactic reactions. Along with other drugs such as H1-antihistamines and glucocorticosteroids, it is found in every first aid kit for at-risk individuals, such as those who are allergic to insect stings. Subcutaneous or intramuscular injections if carried out by an untrained individual or the patient himself might give rise to potential problems. Therefore, it is common to prescribe epinephrine pressure aerosol as a safer alternative. If epinephrine aerosol is overused, it can cause serious problems. A patient developed by self-medication following a wasp sting lung edema as well as an erosive gastroduodenitis. She consumed two aerosol vials each of which contained about 73 mg of adrenaline. In order to avoid such incidents it is crucial that every doctor provides his or her patient with sufficient oral and written information regarding the correct use fo epinephrine inhalers.