The role of sentinel lymph node mapping in colon cancer: detection of micro-metastasis, effect on survival, and driver of a paradigm shift in extent of colon resection.

Unlike in breast cancer and melanoma, sentinel lymph node mapping in colon cancer is primarily used as an aid to the pathologist for accurate nodal staging. The study was undertaken to review the incidence of micro-metastasis and its impact on survival when treated with chemotherapy. The study was also undertaken to see if SLNM could guide limited colon resection in early T stage tumor as a paradigm shift. SLNM was done by subserosal injection of a blue dye. SLNs were ultra-staged by multilevel sectioning and remaining Specimen was then examined by conventional method. For the last 245 patients the specimen was divied ex vivo into two segments as segment A containing the tumor bearing portion of the colon and SLNs with attached mesentery, while segment B include distal part of the colon with attached mesentery. Nodal staging was separately examined. Of the 354 Pts, SLNM was successful in 99.9% of Pts with an average no of SLN/ Pt = 2.8 and total nodes 17.8/pt. Survival was directly related negatively with stage and nodal status. Pts with +ve LN did much better with chemotherapy than without chemotherapy. With 245 Pts, specimen A Vs B, no Pts had +ve node in specimen B with -ve LN in specimen A. SLNM results in more node/Pt, more positive node/Pt ,and more micro-metastasis who when treated with chemotherapy survive longer. Limited segmental resection in early T stage is possible when done with guidance by SLNM without compromising biology.

Detection and prognostic impact of micrometastasis in colorectal cancer.

Review of literature was performed on studies with prognostic impact of micrometastasis in colorectal cancer. Among 16 studies included, micrometastasis was detected in 26.5% of patients. Most analysis revealed that micrometastasis carries a poorer prognosis compared to node negative disease (NND). The results of those studies were compared with our pilot study of 109 patients with colon cancer, showing improved prognosis of micrometastasis after being upstaged and treated with chemotherapy when compared with NND.

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.

Challenging the conventional treatment of colon cancer by sentinel lymph node mapping and its role of detecting micrometastases for adjuvant chemotherapy.

All colon cancer patients with lymph node (LN) positive disease are treated with chemotherapy. Patients with node negative disease are usually cured by surgery alone. Yet about 20% of patients develop recurrence within 5 years despite node negative status. This may often be the result of missed micrometastases by conventional examination. Sentinel lymph node (SLN) mapping was developed to find those nodes detected by blue dye which was ultrastaged to detect micrometastases. Consecutive patients, underwent SLN mapping with the blue dye with success rate of 99.2%. Average number of LN was 18.3, average number of SLN was 3/patient and overall nodal positivity was 45%. Ten patients had skip metastases. Overall survival of 235 patients was 84 months with survival of node negative patients 97 months versus 68 months for node positive patients. For stage I-IV patients, overall survival was as follows: stage I-115 months, stage II-90 months, stage III-84 months and stage IV-24 months respectively. Patients with micrometastases after chemotherapy had average survival of 108 months versus those without chemotherapy was 50 months. Thus, SLN mapping techniques is highly successful, easily reproducible and finds micrmoetastases in over 15% of patients which could have been missed by conventional pathological examination. These patients when treated with adjuvant chemotherapy have similar survival as those of node negative disease. Similarly, patients without any nodal metastases after SLN mapping and ultrastaging, may be considered as true node negative disease and may avoid further adjuvant chemotherapy.

Tumor size predicts long-term survival in colon cancer: an analysis of the National Cancer Data Base.

BACKGROUND: American Joint Committee on Cancer uses tumor size for "T" staging of many solid tumors for its effect on prognosis. However, tumor size has not been incorporated in tumor (T), nodal status (N), metastasis (M) staging for colon cancer. Hence, the National Cancer Data Base was used to determine whether tumor size correlates with TNM staging and survival. METHODS: For the 300,386 patients, tumor size was divided into S1 (0 to 2 cm), S2 (>2 to 4 cm), S3 (>4 to 6 cm), and S4 (>6 cm). Statistical comparison was done for TNM stage, grade, and nodal status with tumor size. Kaplan-Meier survival analysis was done for each "S" stage. RESULTS: Of the 300,386 patients, 13% were classified as S1, 39% S2, 30% S3 and 18% as S4. Right colon was the most common site (48%). Tumor size positively correlated with grade, T stage, and nodal stage. Tumor size was inversely associated with survival. CONCLUSION: Tumor size is positively correlated with important prognostic factors and negatively impacted survival.

Primary brain tumors in adults.

Primary malignant brain tumors account for 2 percent of all cancers in U.S. adults. The most common malignant brain tumor is glioblastoma multiforme, and patients with this type of tumor have a poor prognosis. Previous exposure to high-dose ionizing radiation is the only proven environmental risk factor for a brain tumor. Primary brain tumors are classified based on their cellular origin and histologic appearance. Typical symptoms include persistent headache, seizures, nausea, vomiting, neurocognitive symptoms, and personality changes. A tumor can be identified using brain imaging, and the diagnosis is confirmed with histopathology. Any patient with chronic, persistent headache in association with protracted nausea, vomiting, seizures, change in headache pattern, neurologic symptoms, or positional worsening should be evaluated for a brain tumor. Magnetic resonance imaging is the preferred initial imaging study. A comprehensive neurosurgical evaluation is necessary to obtain tissue for diagnosis and for possible resection of the tumor. Primary brain tumors rarely metastasize outside the central nervous system, and there is no standard staging method. Surgical resection of the tumor is the mainstay of therapy. Postoperative radiation and chemotherapy have improved survival in patients with high-grade brain tumors. Recent developments in targeted chemotherapy provide novel treatment options for patients with tumor recurrence. Primary care physicians play an important role in the perioperative and supportive treatment of patients with primary brain tumors, including palliative care and symptom control.