Danielle M. Hari

AJCC Cancer Staging Manual 7th Edition Criteria for Colon Cancer: Do the Complex Modifications Improve Prognostic Assessment?

BACKGROUND The 7th edition of the AJCC Cancer Staging Manual (AJCC-7) includes substantial changes for colon cancer (CC), which are particularly complex in patients with stage II and III disease. We used a national cancer database to determine if these changes improved prediction of survival. STUDY DESIGN The database of the Surveillance, Epidemiology and End Results Program was queried to identify patients with pathologically confirmed stage I to III CC diagnosed between 1988 and 2008. Colon cancer was staged by the 6(th) edition of the AJCC Cancer Staging Manual (AJCC-6) and then restaged by AJCC-7. Five-year disease-specific survival and overall survival were compared. RESULTS After all exclusion criteria were applied, AJCC-6 and AJCC-7 staging was possible in 157,588 patients (68.9%). Bowkers test of symmetry showed that the number of patients per substage was different for AJCC-6 and AJCC-7 (p < 0.001). The Akaike information criteria comparison showed superior fit with the AJCC-7 model (p < 0.001). However, although AJCC-7 staging yielded a progressive decrease in disease-specific survival and overall survival of patients with stage IIA (86.3% and 72.4%, respectively), IIB (79.4% and 63.2%, respectively), and IIC (64.9% and 54.6%, respectively) CC, disease-specific survival and overall survival of patients with stage IIIA disease increased (89% and 79%, respectively). Subset analysis of patients with >12 lymph nodes examined did not affect this observation. CONCLUSIONS The AJCC-7 staging of CC does not address all survival discrepancies, regardless of the number of lymph nodes examined. Consideration of other prognostic factors is critical for decisions about therapy, particularly for patients with stage II CC.

Surgery for Distant Melanoma Metastasis

Traditionally, distant metastatic melanoma has a poor prognosis owing to lack of efficacious, U.S. Food and Drug Administration-approved systemic therapy and the limited use of surgical resection as a therapeutic option. More recently, new biological therapies such as vemurafenib (Zelboraf) and ipilimumab (Yervoy) have shown strong promise and dramatically improved the landscape of stage IV melanoma therapy. Although there are numerous single-institution studies advocating the role for therapeutic surgical intervention, many remain skeptical of nonpalliative surgery for metastatic melanoma. Surgical resection of advanced melanoma has been proven to be effective as long as all disease is removed (R0). Patient selection is paramount. The combination of newer systemic therapies and surgical resection is currently under investigation. Understanding the tumor biology of melanoma and its mechanism of metastatic spread is essential to developing the most efficacious treatment strategy.

A 21-year analysis of stage I gallbladder carcinoma: is cholecystectomy alone adequate?

OBJECTIVES Gallbladder carcinoma (GBC) is a rare disease that is often diagnosed incidentally in its early stages. Simple cholecystectomy is considered the standard treatment for stage I GBC. This study was conducted in a large cohort of patients with stage I GBC to test the hypothesis that the extent of surgery affects survival. METHODS The National Cancer Institutes Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients in whom microscopically confirmed, localized (stage I) GBC was diagnosed between 1988 and 2008. Surgical treatment was categorized as cholecystectomy alone, cholecystectomy with lymph node dissection (C + LN) or radical cholecystectomy (RC). Age, gender, race, ethnicity, T1 sub-stage [T1a, T1b, T1NOS (T1 not otherwise specified)], radiation treatment, extent of surgery, cause of death and survival were assessed by log-rank and Coxs regression analyses. RESULTS Of 2788 patients with localized GBC, 1115 (40.0%) had pathologically confirmed T1a, T1b or T1NOS cancer. At a median follow-up of 22 months, 288 (25.8%) had died of GBC. Five-year survival rates associated with cholecystectomy, C + LN and RC were 50%, 70% and 79%, respectively (P < 0.001). Multivariate analysis showed that surgical treatment and younger age were predictive of improved disease-specific survival (P < 0.001), whereas radiation therapy portended worse survival (P = 0.013). CONCLUSIONS In the largest series of patients with stage I GBC to be reported, survival was significantly impacted by the extent of surgery (LN dissection and RC). Cholecystectomy alone is inadequate in stage I GBC and its use as standard treatment should be reconsidered.

Staging of Regional Lymph Nodes in Melanoma A Case for Including Nonsentinel Lymph Node Positivity in the American Joint Committee on Cancer Staging System

IMPORTANCE Survival varies widely in patients with stage III melanoma. The existence of clinical significance for positive nonsentinel lymph node (NSLN) status would warrant consideration for incorporation into the American Joint Committee on Cancer staging system and better prediction of survival. OBJECTIVE To evaluate whether disease limited to sentinel lymph nodes (SLNs) represents different clinical significance than disease spread into NSLNs. DESIGN, SETTING, AND PARTICIPANTS The database of the John Wayne Cancer Institute at Saint Johns Health Center, Santa Monica, California, was queried for all patients with SLNs positive for cutaneous melanoma who subsequently underwent completion lymph node dissection. MAIN OUTCOMES AND MEASURES Disease-free survival, melanoma-specific survival (MSS), and overall survival. RESULTS A total of 4223 patients underwent SLN biopsy from 1986 to 2012. Of these patients, 329 had a tumor-positive SLN. Of the 329, 250 patients (76.0%) had no additional positive nodes and 79 (24.0%) had a tumor-positive NSLN. Factors predictive of NSLN positivity included older age (P = .04), greater Breslow thickness (P < .001), and ulceration (P < .02). Median overall survival was 178 months for the SLN-only positive group and 42.2 months for the NSLN positive group (5-year overall survival, 72.3% and 46.4%, respectively). Median MSS was not reached for the SLN-only positive group and was 60 months for the NSLN positive group (5-year MSS, 77.8% and 49.5%, respectively). On multivariate analysis, NSLN positivity had a strong association with recurrence (hazard ratio [HR], 1.75; 95% CI, 1.23-2.50; P = .002), shorter overall survival (HR, 2.24; 95% CI, 1.48-3.40; P < .001), and shorter MSS (HR, 2.23; 95% CI, 1.46-3.07; P < .001). To further control for the effects of total positive lymph nodes, comparison was done for patients with only N2 disease (2-3 total positive lymph nodes); the results of this comparison confirmed the independent effect of NSLN status (MSS; P = .04). CONCLUSIONS AND RELEVANCE Nonsentinel lymph node positivity is one of the most significant prognostic factors in patients with stage III melanoma. Subclassification of melanoma by NSLN tumor status should be considered for the American Joint Committee on Cancer staging system.

Small bowel carcinoid: Location isn’t everything!

AIM To investigate the prognostic significance of the primary site of disease for small bowel carcinoid (SBC) using a population-based analysis. METHODS The Surveillance, Epidemiology and End Results (SEER) database was queried for histologically confirmed SBC between the years 1988 and 2009. Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method and compared using Log rank testing. Log rank and multivariate Cox regression analyses were used to identify predictors of survival using age, year of diagnosis, race, gender, tumor histology/size/location, tumor-node-metastasis stage, number of lymph nodes (LNs) examined and percent of LNs with metastases. RESULTS Of the 3763 patients, 51.2% were male with a mean age of 62.13 years. Median follow-up was 50 mo. The 10-year OS and DSS for duodenal primaries were significantly better when compared to jejunal and ileal primaries (P = 0.02 and < 0.0001, respectively). On multivariate Cox regression analysis, after adjusting for multiple factors, primary site location was not a significant predictor of survival (P = 0.752 for OS and P = 0.966 DSS) while age, number of primaries, number of LNs examined, T-stage and M-stage were independent predictors of survival. CONCLUSION This 21-year, population-based study of SBC challenges the concept that location of the primary lesion alone is a significant predictor of survival.

SOX10 expression in a gangliocytic paraganglioma--a case report.

We present a case of a 49-year-old woman who underwent a pancreaticoduodenectomy for symptomatic treatment of an obstructive periampullary duodenal mass initially found on CT imaging. Histologically, the tumor showed a triphasic pattern including small round cells, a spindle-cell component and ganglion cells of varying size. Furthermore, the tumor was surrounded by a proliferation of pancreatic ducts. These features led to the diagnosis of a gangliocytic paraganglioma arising in an ectopic pancreas. Sections of the tumor were then stained for SOX10, a neural crest transcription factor, and it was shown to be positive in the ganglion cells. The exact origin of gangliocytic paragangliomas has not yet been clearly defined. However, this finding of aberrant expression of SOX10 supports the idea of these lesions being neoplastic in nature.

New Palpable Mass in Right Breast

A 55-year-old postmenopausal female presents with a new mass in her right breast. She states that the mass has been there for about 3 months and has slowly grown in size. She first noticed it when she was taking a shower. The mass is not painful. She reports no nipple discharge, no nipple inversion, and no skin changes. She had her first menstrual period at age 11. Her only pregnancy was at age 35. Her mother and sister both had breast cancer. On physical examination, she has a 2 cm palpable, hard, ill-defined, immobile, non-tender mass in the upper outer quadrant of her right breast. There is no palpable axillary or supraclavicular adenopathy.

New Onset of Painless Jaundice

A 68-year-old man presents to the emergency department complaining of fatigue and intermittent vague abdominal pain. He denies nausea or vomiting, but “does not have much of an appetite these days.” He reports having lost almost 20 lbs in the past 2 months. He was recently diagnosed with type 2 diabetes, but has no other medical problems and no previous surgeries. His stools have become lighter in color and his urine is much darker than before. His social history is negative for alcohol use, but he has a 50+ pack-year smoking history before quitting last year. He has no significant family history. On exam, he has a yellow hue to his eyes and tongue, along with scratch marks on his skin. A non-tender mass is palpated in the right upper quadrant of the abdomen. Laboratory testing reveals total and direct bilirubin of 18 mg/dL (normal 0.2–1.3 mg/dL) and 9.2 mg/dL (<0.3 mg/dL), respectively, and alkaline phosphatase elevated at 215 μ/L (33–131 μ/L). Liver transaminases are mildly elevated. CA 19-9 and CEA levels are normal.

Abnormal Screening Mammogram

A 40-year-old woman sees her doctor for an annual physical exam. She is healthy and does not take any medications. She has a family history of breast cancer. Her physical examination is normal with no palpable breast masses. Her doctor recommends that she gets a screening mammography as part of her routine health maintenance screening, which she agrees to do. A week later, she gets a call from her doctor to inform her that she had an abnormal mammogram (BI-RADS 4). Her left breast was found to have multiple clusters of fine linear microcalcifications, with the largest cluster measuring 2 mm in diameter.