Clinical outcome of stage I/II melanoma patients after selective sentinel lymph node dissection: long-term follow-up results.

PURPOSE: Although sentinel lymph node (SLN) status is part of the new American Joint Committee on Cancer staging system, there is no final proof that the SLN procedure in melanoma patients influences outcome of disease. This study investigated the accuracy of the SLN procedure and clinical outcome in melanoma patients after at least 60 months of follow-up. PATIENTS AND METHODS: Between 1993 and 1996, 209 patients with stage I/II cutaneous melanoma underwent selective SLN dissection by the triple technique. If the SLN contained metastatic disease, a completion lymphadenectomy was performed. Survival analyses were performed using the Kaplan-Meier approach. Factors associated with survival were analyzed using the Cox proportional hazards regression model. RESULTS: The success rate was 99.5%. Median follow-up was 72 months. Forty patients (19%) had a positive SLN. The false-negative rate was 9%. Five-year overall survival was 87% for the entire group and 92% and 67% for SLN-negative and SLN-positive patients (P <.0001), respectively. All patients with a positive SLN and a Breslow thickness < or = 1.00 mm survived, and SLN-positive patients with a Breslow thickness less than 2.00 mm tend to have a better prognosis compared with SLN-negative patients with a Breslow thickness greater than 2.00 mm. SLN status (P =.002), Breslow thickness (P =.002), and lymphatic invasion (P =.0009) were all found to be independent prognostic factors for overall survival. CONCLUSION: With a success rate of 99.5% and a false-negative rate of 9% after long-term follow-up, the triple-technique SLN procedure is a reliable and accurate method. Survival data seem promising, although a therapeutic effect is still questionable. As shown in this study, not all SLN-positive patients have a poor prognosis.

No indication for performing sentinel node biopsy in melanoma patients with a Breslow thickness of less than 0.9 mm.

In thin melanomas, the involvement of regional nodes is very uncommon. Recent sentinel node (SN) studies have confirmed the absence of positive regional lymph nodes in melanomas < 0.76 mm and a 5% positivity in melanomas between 1.0 and 1.99 mm. The chance of regional lymph node involvement - and therefore whether it is relevant to perform the SN procedure - seems to depend on the Breslow thickness of the primary tumour. However, a Breslow thickness cut-off point has not yet been established. We evaluated a melanoma population that had undergone an SN procedure to determine this point, so that the procedure can be restricted to a smaller group of patients in future. In a total of 348 patients with proven American Joint Committee on Cancer (AJCC) stages I or II cutaneous melanoma with a Breslow thickness > or = 0.5 mm the triple technique was used, consisting of preoperative visualization of the lymph channels from the initial site of the melanoma towards the SN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabelled lymph nodes. In melanomas thinner than 0.90 mm, no positive SN was found (95% confidence interval 0-5%). This group consisted of 75 patients (22%), with a median follow-up of 31 months. Our data suggest that this procedure need no longer be indicated for almost a quarter of the patient population, because the cut-off point for nodal involvement appears to be a Breslow thickness of 0.90 mm.

The sentinel lymph node status is an important factor for predicting clinical outcome in patients with Stage I or II cutaneous melanoma.

BACKGROUND: In a cohort of patients, the authors investigated whether and to what extent the sentinel lymph node (SLN) status contributes to predicting the probability of remaining disease free for at least 3 years. In addition, several traditional prognostic factors were analyzed: Breslow thickness, Clark invasion level, ulceration, lymphatic invasion, location, type of the melanoma, and age and gender of the patient. METHODS: In 263 consecutive patients with proven American Joint Committee on Cancer Stages I and II cutaneous melanoma, the triple technique SLN procedure was used, i.e., preoperative visualization of the lymph channels from the initial site of the melanoma toward the SLN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and lymph nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabeled lymph nodes. Median follow-up time was 48 months (range, 36-84 months). Multivariate logistic regression analysis was performed to examine the influence of the SLN status and several other prognostic factors on a minimum 3-year disease free survival. RESULTS: In 20% of patients, the SLN proved to be tumor positive. For SLN negative patients, the 5-year disease free survival rate was 91% (+/- 2.4%), and for SLN positive patients it was 49% (+/- 9%). Five variables showed a strong and statistically significant independent prognostic association with outcome, i.e., SLN status (P = 0.0007), thickness of primary melanoma (1.01-2.0 mm; P = 0.04), ulceration (P = 0.05), and lymphatic invasion (P = 0.01) of primary melanoma, and age (40-50 years; P = 0.01). CONCLUSIONS: The SLN status-along with Breslow thickness, ulceration, lymphatic invasion, and age--seems to have strong additional value in predicting a minimum 3-year disease free period after the SLN procedure. Patients with a positive SLN have a poorer prognosis than those with a negative SLN.

Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver.

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.

Immune-stimulating effects of low-dose perioperative recombinant granulocyte-macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma.

BACKGROUND: Surgery induces a postoperative immunosuppression, thereby possibly facilitating the outgrowth of pre-existing occult metastases or the seeding of disseminated tumour cells in patients with primary colorectal carcinoma operated on with curative intent. The hypothesis that adjuvant therapy with perioperative recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) would minimize postoperative immunosuppression was investigated in this pilot study. METHODS: Patients were allocated randomly to receive daily subcutaneous injections with either saline (n = 8) or rhGM-CSF 2.8 microg per kg body-weight (n = 8) from 3 days before operation until 4 days afterwards. Phytohaemagglutinin (PHA) skin test reactivity, monocyte human leucocyte antigen (HLA) DR expression and the extent of the acute-phase response, by determination of white blood cell count and differentiation, plasma interleukin (IL) 6 levels and body temperature in the perioperative period, were examined. RESULTS: rhGM-CSF treatment minimized postoperative suppression in PHA skin test reactivity and increased the numbers of neutrophils and monocytes while enhancing the expression of HLA-DR in the postoperative period. Additionally, both postoperative plasma IL-6 levels and the incidence of fever tended to be higher in the rhGM-CSF group. CONCLUSION: In this pilot study, perioperative administration of low-dose rhGM-CSF stimulated certain immune functions that are normally depressed after operation. The implications for the antitumour responses directly after operation and the formation of liver metastases are currently under investigation.

Major liver resection results in a changed plasma amino acid pattern as reflected by a decreased Fischer ratio which improves by bactericidal/permeability increasing protein.

BACKGROUND/AIMS: Major liver resection results in a high morbidity and mortality, and endotoxin plays a role in post-resection hepatic failure. Severe hepatic failure as seen in hepatitis and cirrhosis may be accompanied by hepatic encephalopathy and is characterized by a typical plasma amino acid pattern reflected by a decreased Fischer ratio. This study was performed to evaluate the plasma amino acid pattern in patients undergoing major liver surgery receiving placebo or the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). PATIENTS AND METHODS: Forty-eight patients were randomized in this phase II, dose escalation, multicenter trial. Plasma amino acid profiles were determined preoperatively, and on the first (day 1) and third (day 3) postoperative day. RESULTS: In the placebo group the Fischer ratio decreased significantly on both postoperative days. Administration of rBPI21 also resulted in a decreased Fischer ratio on day 1, but not on day 3. Highly elevated alanine plasma levels were observed on day 1 in placebo-treated patients, whereas rBPI21 prevented this elevation. Plasma alanine levels on day 1 correlated with the duration of post-resection hepatic failure. CONCLUSIONS: Major liver resection results in a decreased Fischer ratio and a rise in plasma alanine levels. Plasma levels of alanine on the first postoperative day correlated with the duration of the post-resection hepatic failure. rBPI21 improved the Fischer ratio and prevented the rise of plasma alanine levels.

Reliability of the sentinel node procedure in melanoma patients: analysis of failures after long-term follow-up.

BACKGROUND: The sentinel node (SN) concept assumes that early lymphatic metastases, if present, always are found first in the SN. The aim of this study was to determine the reliability of this procedure by establishing the success rate and number of failed procedures during a follow-up period of at least 2 years. METHODS: From August 1993 to November 1996, 204 consecutive patients with stage I and II cutaneous melanoma underwent SN biopsy by a triple technique. Preoperatively, all patients underwent (dynamic) lymphoscintigraphy. A gamma probe and blue dye helped localize the SN(s) during surgery, and these nodes subsequently were excised. These lymph nodes were step-sectioned and examined by routine and immunohistochemical staining. If the SN contained tumor cells, a lymphadenectomy was performed at a later date. RESULTS: The median follow-up time was 42 months. The success rate was 99%. Three patients developed a recurrence in the negative SN basin during follow-up, without simultaneous appearance of (locoregional) metastases. CONCLUSIONS: With a 99% success rate and a 1.5% rate of failed SN procedures (7% false-negative rate) after a median follow-up of 3.5 years, we concluded that the combined triple technique approach of detecting the SN was a reliable method to accurately identify and retrieve the SN.