Practice patterns and outcomes for anorectal melanoma in the USA, reviewing three decades of treatment: is more extensive surgical resection beneficial in all patients?

INTRODUCTION: Historically, the treatment of anorectal melanoma has been abdominoperineal resection (APR), but more recently local resection alone. Although treatment at melanoma centers has become less aggressive, the adoption of this approach and related outcomes across the USA is unknown. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients treated for anorectal melanoma (1973-2003). Treatment patterns and survival were studied. Frequency of treatment was compared using the chi-square test; survival was calculated using the Kaplan-Meier method. RESULTS: The 183 patients identified from the SEER database had a median age of 68 years. Of the 143 patients whose data were included, 51 underwent APR and 92 underwent transanal excision (TAE). Despite similar pathologic characteristics, median survival was similar in the two groups: 16 months for APR and 18 months for TAE (P = ns). Five-year survival also was similar in the two groups: 16.8% for APR and 19.3% for TAE (P = ns). The rate of APR was 27.0% between 1973 and 1996, as compared with 43.2% between 1997 and 2003 (P = ns). CONCLUSION: This study, the largest series to analyze widespread practice patterns and outcomes for anorectal melanoma in the USA, did not reveal a survival difference comparing TAE with APR. Moreover, the study did not reveal a trend toward less aggressive surgical resection. Since the extent of surgical intervention did not correlate with survival or extent of primary tumor, APR should be reserved for selected patients in whom TAE is not technically feasible.

The learning curve with single-port cholecystectomy.

OBJECTIVES: Single-port surgery is a rapidly advancing technique in laparoscopic surgery. Currently, there is limited evidence on the learning curve and practicality of performing single-port laparoscopic cholecystectomy. METHODS: Single-port cholecystectomy was performed on 20 consecutive patients for biliary dyskinesia, symptomatic cholelithiasis, or acute cholecystitis. The Tri-Port was placed in the umbilicus, and a combination of straight and articulating instruments were utilized. Patient characteristics and outcomes were reviewed, and a comparison was made with the prior 20 consecutive laparoscopic cholecystectomies performed using the 3-port technique. RESULTS: Characteristics were similar in both groups. The 3-port cholecystectomy had a mean time of 65.7 minutes, and patients had an average body mass index of 28.16. The first single-port cholecystectomy took 160 minutes with sequential improvement to the sixth case of 66 minutes with a mean of 68.2 minutes for the last 15 single-port cases. The average patient body mass index was 30.24. No major complications occurred. CONCLUSION: The largest series to date of single-port cholecystectomy for multiple degrees of biliary disease is presented. This study validates that this technique can be applied effectively and performed in comparable operative times to traditional 3-port cholecystectomy with a learning curve of approximately 5 cases.

A prospective trial comparing 1% lymphazurin vs 1% methylene blue in sentinel lymph node mapping of gastrointestinal tumors.

BACKGROUND: Methylene blue (M), as a dye in sentinel lymph node mapping (SLNM), has been introduced as an alternative to lymphazurin (L) after the recent shortage of L. M has been evaluated in breast cancer in multiple studies with favorable results. Our study compares L with M in the SLNM of gastrointestinal (GI) tumors. METHODS: Between Jan 2005 and Aug 2008, 122 consecutive patients with GI tumors were enrolled. All patients (pts) underwent SLNM with either L or M by subserosal injection of 2-5 mL of dye. Efficacy and rates of adverse reactions were compared between the two dyes. Patients were prospectively monitored for adverse reactions including anaphylaxis, development of blue hives, and tissue necrosis. RESULTS: Of 122 pts, 60 (49.2%) underwent SLNM using L and 62 (50.8%) underwent SLNM using M. Colon cancer (CrCa) was the most common site in both groups. The success rate of L and M in SLNM was 96.6% and 96.7%, respectively, with similar numbers of total number of lymph nodes per pt, SLNs per pt (<3), nodal positivity, skip metastasis, and accuracy. The only adverse reaction in the L group was oxygen desaturation >5% in 5% (3/60) of pts, compared with none in the M group. Cost per vial of L was $210 vs $7 for M. CONCLUSION: The success rate, nodal positivity, average SLNs per patient, and overall accuracy were similar between L and M. Absence of anaphylaxis and lower cost make M more desirable than L in SLNM of GI tumors.

Comparative analysis of bone marrow micrometastases with sentinel lymph node status in early-stage breast cancer.

Bone marrow micrometastases (BMM) and sentinel lymph node (SLN) status are both prognostic factors in breast cancer (BRCa) patients (pts). A definitive relationship between the two has not yet been proven and the data available is controversial. Thus, a retrospective study was conducted to determine the relationship of BM status and SLN status in pts with early BRCa (T1/T2). All female pts with early BRCa (T1/T2) operated upon by a single surgeon were included in the study. Prior to surgery, all pts underwent bone marrow aspiration from the posterior superior iliac spine bilaterally. Subsequently, pts underwent SLN biopsy and definitive primary breast surgery. BM samples were examined by using a Cytokeratin Detection Kit using CAM 5.2 monoclonal antibody. All pts with BMM underwent repeat BM analysis 6 months after completing all treatments. Data was collected for SLN, BM, estrogen receptor/progesterone receptor (ER/PR), and human epidermal growth factor receptor 2 (Her-2/neu) status and analyzed using chi-square (chi (2)) analysis or Fischer's exact test. A total of 270 consecutive pts with early BRCa were studied. SLN mapping was successful in all pts. SLN metastases (mets) were detected in 28.9% (78/270) pts. Of the 270 pts, 77.0% (208/270) had T1 disease. BMM were detected in 9.6% (26/270) pts, of whom 69.2% (18/26) were found to have BMM unilaterally. BMM were detected in 11.5% (9/78) pts with SLN mets versus 8.9% (17/192) in pts with node-negative disease (p = 0.65). Of the pts with T1 BRCa, BMM were observed in 9.1% (19/208) pts versus 11.3% (7/62) in pts with T2 BRCa (p = 0.6). In pts with ER/PR-negative (-ve) BRCa, BMM were found in 7.7% (2/26) pts versus 9.9% (24/242) in pts with ER/PR-positive (+ve) BRCa (p = 0.27). BMM were detected in 12.3% (9/73) pts with Her-2/neu +ve BRCa and in 8.6% (16/187) pts with Her-2/neu -ve BRCa (p = 0.11). After completion of adjuvant therapy all pts with BMM (n = 26) converted to BM negative status. We conclude that BM status did not correlate with SLN status and occurs independently of lymphatic metastasis possibly through a different mechanism. BMM occur in node-negative pts and may assist in identifying pts at high risk for disease recurrence. Obtaining bone marrow aspirate from two locations resulted in a significant increase in detection of micrometastases.

A rare cause of primary hepatic neoplasm: malignant peripheral nerve sheath tumor in the age of modern liver surgery.

Primary malignant peripheral nerve sheath tumor (MPNST) of the liver is rare. Histologic identification of spindle cells from a biopsy specimen and the potential clinical diagnoses are discussed. Potential metastatic and primary spindle cell lesions, as well as their impact on treatment decisions are considered. This was successfully treated with ablation assisted surgical resection and minimal blood loss.

The biologic significance of micrometastatic disease and sentinel lymph node technology on colorectal cancer.

The sentinel lymph node (SLN) technique has practical applications in multiple solid tumors including colorectal carcinoma. Identifying the SLN(s) provides better staging of the regional lymphatics beyond standard H&E analysis. This additional information assists in predicting biology and may be useful in guiding adjuvant therapy. We postulate the era of sentinel node has ushered in a new generation of node-negative patients; patients that have an exceptionally favorable outcome when compared to historic controls.

Management of T2 gallbladder cancer: are practice patterns consistent with national recommendations?

BACKGROUND: The national recommendation for the management of localized T2 gallbladder cancer (GBCA) is radical cholecystectomy. Although reported survival for localized T2 disease has been poor, groups have documented improvement with radical resection. We hypothesized that a discrepancy exists between national recommendations and current practice patterns. METHODS: Patients diagnosed with localized T2 GBCA between 1988 and 2002 were identified from the Surveillance, Epidemiology, and End Results registry. Age, sex, race, ethnicity, extent of surgery, and overall survival were assessed. Surgical procedure was categorized as cholecystectomy alone (CS), cholecystectomy plus lymph node dissection (CS+LN), radical cholecystectomy (RCS), or other. Survival calculations were made using the Kaplan-Meier method and compared with the log-rank test. RESULTS: Of 382 patients with pathologically confirmed T2 GBCA, 280 were women. The median patient age was 75 years. A total of 238 patients underwent CS, 76 underwent CS+LN, and 14 underwent RCS. The remaining 54 patients underwent a lesser or no procedure and were excluded from comparative analysis. The median survival was 14 months for all patients and 14, 14, and 8 months for subgroups treated with CS, CS+LN, and RCS, respectively. Rates of 5-year survival were 23%, 24%, and 36% for CS, CS+LN, and RCS subgroups, respectively. There was no significant difference in survival rates between RCS and CS+LN, or between RCS and CS. CONCLUSIONS: The majority of patients with T2 GBCA in the United States are not managed according to current national recommendations.

Prognostic impact of micrometastases in colon cancer: interim results of a prospective multicenter trial.

OBJECTIVE: The 25% rate of recurrence after complete resection of stage II colon cancer (CC) suggests the presence of occult nodal metastases not identified by hematoxylin and eosin staining (H&E). Interim data from our ongoing prospective multicenter trial of sentinel node (SN) biopsy indicate a 29.6% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs in CC. We hypothesized that these MM have prognostic importance. METHODS: Between March 2001 and August 2006, 152 patients with resectable colorectal cancer were enrolled in the trial. IHC and quantitative RT-PCR (qRT) assay were performed on H&E-negative SNs. Results were correlated with disease-free survival. RESULTS: The sensitivity of lymphatic mapping was significantly better in CC (75%) than rectal cancer (36%), P<0.05. Of 92 node-negative CC patients 7 (8%) were upstaged to N1 and 18 (22%) had IHC MM. Four patients negative by H&E and IHC were positive by qRT. At a mean follow-up of 25 months, 15 patients had died from noncancer-related causes, 12 had developed recurrence, 5 had died of CC (2 with macrometastases, 3 with MM), and 7 were alive with disease. The 12 recurrences included 4 patients with SN macrometastases and 6 with SN MM (2 by IHC, 4 by qRT). One of the 2 SN-negative recurrences had other positive lymph nodes by H&E. All patients with CC recurrences had a positive SN by either H&E/IHC or qRT. No CC patient with a negative SN by H&E and qRT has recurred (P=0.002). CONCLUSION: This is the first prospective evaluation of the prognostic impact of MM in colorectal cancer. These results indicate that the detection of MM may be clinically relevant in CC and may improve the selection of patients for adjuvant systemic chemotherapy. Patients with CC who are node negative by cumulative detection methods (H&E/IHC and qRT) are likely to be cured by surgery alone.

Association of angiogenesis markers with lymph node metastasis in early colorectal cancer.

HYPOTHESIS: We hypothesized that p53 mutations (mp53) are associated with decreased expression of thrombospondin 1 (TSP-1) and that decreased TSP-1 expression is associated with lymph node metastases. DESIGN: A retrospective study of lymphatic mapping and pathologic determination of angiogenesis markers in primary colorectal cancer. SETTING: Tertiary care cancer institute. PATIENTS: Sixty-one patients with colorectal cancer underwent lymphatic mapping. Lymph nodes that stained negative by hematoxylin-eosin were examined with immunohistochemistry for micrometastases. Primary tumors were analyzed by immunohistochemistry for mp53 and TSP-1 expression. The t test and the Mann-Whitney U test were used to examine the mean difference in TSP-1 expression between tumors. MAIN OUTCOME MEASURES: Mutant p53 expression, TSP-1 expression, and metastatic progression. RESULTS: Thirty-six of the 61 patients (59%) had nodal metastases shown by hematoxylin-eosin or immunohistochemistry in the sentinel node (N2, N1, N1mi, or N0[i+]). Patients with a truly negative sentinel node (pN0[i-][sn]) had significantly higher TSP-1 expression compared with those with some degree of nodal metastases (57.7 vs 30.1; P < .001). Acquisition of mp53 was associated with a decreased mean TSP-1 expression. Tumors without mp53 expression had a mean TSP-1 optical density value of 51.3 while tumors with elevated mp53 had a mean TSP-1 optical density value of 31.8 (P < .03). CONCLUSIONS: Patients with primary colorectal cancer with low TSP-1 expression, with or without detection of mp53 gene product, are more likely to harbor lymph node metastasis than patients with higher expression. Patients with a truly negative sentinel node (pN0[i-][sn]) frequently have higher expression of TSP-1 that may have inhibited metastatic progression. Further studies will investigate the relationship between mp53, TSP expression, and disease progression.

The prognostic effect of micrometastases in previously staged lymph node negative (N0) colorectal carcinoma: a meta-analysis.

BACKGROUND: The prognostic relevance of lymphatic micrometastases in colorectal carcinoma is unclear. To determine the prognostic significance of micrometastases in colorectal cancer, a meta-analysis was performed on all studies, which reported 3-year disease-free survival (DFS) and overall survival (OS). METHODS: Published studies selected for meta-analysis contained sufficient data from which to extrapolate estimates of 3-year DFS and/or OS. From 1991-2003, 25 studies re-examined N0 lymph nodes by serial sectioning and immunohistochemical (IHC) staining or reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Eight studies (566 patients) with IHC detected micrometastases and three (173 patients) with RT-PCR micrometastases were used to determine DFS and OS. Weighted estimates of 3-year survival were combined across studies within each group, and the combined survival estimates were compared across groups using a binomial test. RESULTS: Micrometastases were identified in all IHC studies; upstaging, including N1, N1mi and N0(i+), was achieved in 32% (179/566 patients). All RT-PCR studies identified micrometastases; upstaging to N0(mol+) was achieved in 37% (64/173 patients). There was a statistically significant difference in 3-year OS between RT-PCR positive N0(mol+) patients (77.8%) and those for whom micrometastases were not detected (96.6%) (P < .001). CONCLUSION: The prognostic value of micrometastases detected retrospectively by RT-PCR is significant in AJCC stage II colorectal patients. Studies utilizing RT-PCR performed a more complete nodal analysis when compared to studies using IHC techniques. RT-PCR may also be more specific for the detection of clinically relevant micrometastases compared to IHC detected cytokeratins. Prospective studies are needed to evaluate the potential benefit of systemic chemotherapy in patients with molecular metastases.

Lymphatic mapping and sentinel node analysis: current concepts and applications.

Since the introduction of sentinel node biopsy in 1990 as a minimally invasive surgical technique for the diagnosis of melanoma lymphatic metastases, the number of applications has expanded. We review applications and the current status of sentinel node biopsy in melanoma, breast, colon, gastric, esophageal, head and neck, thyroid, and lung cancer. Variations on techniques specific to each organ are explained, and the current role of sentinel node biopsy in diagnosis and treatment is discussed.

The efficacy of B-type natriuretic peptide for early identification of blood loss in traumatic injury.

BACKGROUND: Because B-type natriuretic peptide (BNP) secretion has a direct linear correlation with intravascular volume status, it was assessed as an initial marker for blood loss (BL) in polytrauma patients. METHODS: Hemodynamically unstable trauma patients between 18 and 45 years had serial BNP levels and hemoglobin (Hgb) levels obtained on admission, at 8 and 24 hours, and every morning during resuscitation. RESULTS: The 14 patients were categorized into 2 groups based on the 24-hour trend in Hgb levels: clinically significant blood loss (Hgb decrease >3 g/dL) or no clinical blood loss (Hgb decrease <3 g/dL). On admission, the 5 patients in the no blood loss group had normal BNP levels, whereas the 9 patients in the BL group had below-normal BNP levels. Because patients in the BL category were resuscitated, their BNP levels normalized. CONCLUSIONS: BNP levels below normal are indicative of intravascular volume loss in traumatically injured patients.