Validation of a gastric cancer nomogram using a cancer registry.

BACKGROUND: A Memorial Sloan Kettering (MSKCC) nomogram predicts disease specific survival (DSS) for gastric adenocarcinoma. The goal of this study is to use a cancer registry to compare nomogram predicted survival with actual survival in the general population. METHODS: All patients undergoing surgery for gastric adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database (1988-2012) were studied. RESULTS: 6954 patients were identified. Majority of cancers were in the antrum (30.2%), and had intestinal histology (73.7%). Median follow-up was 8.2 years. Five year DSS for nomogram risk groups (0-25%, 26-50%, 51-75%, and 76-100%) was 23%, 48%, 57%, and 81% respectively. Actual DSS was 7-15% lower than nomogram predicted DSS. Relative to patients in the 76-100% 5-year DSS risk group, patients in the 0-25%, 26-50%, and 51-75% groups had significantly higher risks of death with hazard ratios of 6.84 (95%CI 6.12-7.65), 3.30 (95%CI 2.83-3.86), and 2.64 (95%CI 2.30-3.03), respectively (all P < 0.001). The concordance index for 5-year nomogram predicted DSS was 0.68 (95%CI 0.67-0.69). CONCLUSIONS: The MSKCC gastric cancer nomogram over-estimates DSS from gastric cancer in the general population and has a moderate concordance index. Predictive tools generated at specialized institutions may not perform as well in the general population.

Impact of breast reconstruction on the decision to undergo contralateral prophylactic mastectomy.

BACKGROUND: In the last decade, there has been increasing use of contralateral prophylactic mastectomy (CPM) in patients with unilateral breast cancer and ductal carcinoma-in-situ (DCIS) undergoing mastectomy. Although many factors have been proposed to explain this trend, the impact of breast reconstruction on CPM has not been studied. METHODS: A retrospective review of patients with unilateral invasive breast cancer or DCIS from Surveillance, Epidemiology, and End Results registry data (2004-2008) was conducted. Characteristics of patients undergoing CPM and reconstruction were evaluated. RESULTS: A total of 102,674 patients diagnosed with DCIS or stage I to III infiltrating breast cancer underwent mastectomy for their primary lesion. Of these, 16,197 patients (16 %) underwent a CPM. A significantly higher proportion of women undergoing CPM had reconstruction performed (46 %) than those patients not undergoing CPM (15 %) (p < 0.001). Of the 20,760 patients (20 %) who underwent reconstruction, 7410 (36 %) had implant reconstruction, 7705 (37 %) tissue reconstruction, and 1941 (9 %) combined tissue/implant reconstruction; there were no data for 3,702 (18 %). There was an increasing trend of patients undergoing reconstruction from 2004 (n = 3390, 16.3 %) to 2008 (n = 5406, 26 %) (p < 0.001). On multivariable analysis, significant variables predicting CPM included age <45 years, stage I disease (odds ratio [OR] 1.44, 95 % confidence interval [CI] 1.35-1.54), lobular histology (OR 1.15, 95 % CI 1.11-1.20), and undergoing breast reconstruction (OR 3.58, 95 % CI 3.41-3.75). CONCLUSIONS: Besides age, undergoing reconstructive surgery is the factor most strongly associated with CPM. This suggests that apart from risk reduction, the availability of and/or patient willingness to undergo breast reconstruction may influence the decision to undergo CPM.

Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype.

BACKGROUND: The significance of androgen receptor (AR) expression in triple-negative breast cancer (TNBC) is unclear, and published studies so far have been inconclusive. METHODS: A tissue microarray was constructed using tissue obtained from 119 patients with primary TNBC and stained for AR expression. Other tissue types obtained included recurrent TNBC, normal breast tissue, adjacent ductal carcinoma-in situ (DCIS), lymph node (LN) and distant metastases. Positive AR expression was defined as ≥10% nuclear staining. RESULTS: Epithelial tissue was present and evaluable in 94 TNBC patients with a total of 177 tissue cores. AR expression in TNBC was 22 of 94 (23%). AR expression was higher in normal breast tissue (88%) and adjacent DCIS (73% overall). All LN metastases from AR-positive TNBC patients were also AR positive; in addition, no AR-negative TNBC patient had AR-positive LNs. AR expression was associated with older patient age (63 vs. 57 years, respectively, p = 0.051) and LN metastases (p = 0.033). Locoregional recurrence and overall/disease-specific survival were similar between AR-positive and AR-negative patients, although AR-positive patients had more advanced disease. On multivariate analysis, the presence of LN metastases was associated with poorer recurrence-free survival in AR-positive patients (hazard ratio, 4.34) (p = 0.031). CONCLUSIONS: The AR is expressed in normal breast tissue, and expression decreases with advancement to DCIS and invasive cancer. AR-positive TNBC was more common in older patients and had a higher propensity for LN metastases. AR-positive TNBC may represent a breast cancer subtype with unique features that may be amenable to treatment with alternative targeted therapies.

Atypical ductal hyperplasia on core biopsy: an automatic trigger for excisional biopsy?

INTRODUCTION: Excisional biopsy is currently recommended for atypical ductal hyperplasia (ADH) diagnosed on core needle breast biopsy (CNB), due to risk of upstaging to invasive or in situ carcinoma (DCIS). The study goal was to identify patients who may potentially forego excisional biopsy if the risk of upstaging is low. METHODS: We conducted a retrospective review of patients diagnosed with ADH on CNB who underwent excisional biopsy at one institution (5/2000-5/2011). We evaluated the upstaging rate and clinicopathologic factors associated with increased upstaging risk. RESULTS: A total of 114 cases of ADH were diagnosed on CNB. The median patient age was 64 years. On mammography, a mass/density/area of distortion was present in 23 % of cases; calcifications were present in 77 %. Most biopsies (79 %) were performed stereotactically. Twenty lesions (18 %) were upstaged to infiltrating carcinoma (5 %) or DCIS (13 %). Residual ADH was present in 43 biopsies (38 %). On univariate analysis, significant variables associated with upstaging included age >50 years, a mass lesion on mammography, and shorter length of biopsy core (p < 0.05). No patient ≤50 years of age was upstaged. Three patients who were not upstaged (3 %) developed ipsilateral disease (2 DCIS and 1 infiltrating ductal carcinoma) at a median time of 37 months. CONCLUSIONS: The rate of upstaging when ADH is diagnosed on CNB at our institution is 18 %, and routine excisional biopsy is currently recommended for all patients. However, patients <50 years old with focal atypia only and no residual calcifications postbiopsy may represent a low-risk group who could potentially avoid excisional biopsy.

Underuse of curative surgery for early stage upper gastrointestinal cancers in the United States.

BACKGROUND: Surgery is the cornerstone of potentially curative therapy for upper gastrointestinal cancer. We analyzed the patterns of treatment regarding the use of surgery for early-stage upper gastrointestinal cancer in the United States. METHODS: The Surveillance, Epidemiology, and End Research database was used to identify patients with cancer of the esophagus, stomach, pancreas, liver, gallbladder, biliary tract, or duodenum (2004-2007). Only patients with potentially resectable stage I and II disease were selected. The primary outcome measure was the use of curative intent surgery. The secondary outcomes were the predictors of surgery. RESULTS: We identified 29,249 patients with a median age of 69 years. Only 54% of the patients underwent cancer-directed surgical resection, ranging from 28% for liver cancer to 89% for gallbladder cancer. The remaining patients underwent either local excision (8%) or no surgery (38%). Among the no surgery group, most patients (79%) were documented as "not being recommended for resection." The independent variables on multivariate analysis predictive of a nonoperative approach included black race, age older than 75 years, tumor size greater than 5 cm, and high poverty level (P < 0.001). Patients who did not undergo surgery had worse median and overall survival at 3 years than patients undergoing surgery (11 months versus 36 months and 14% versus 43%, respectively; P < 0.001). CONCLUSIONS: Almost one half of patients with early-stage upper gastrointestinal cancer did not receive potentially curative surgery, with an adverse effect on overall survival. A combination of demographic, tumor, and socioeconomic factors were predictive of a lack of surgical resection.

Radioactive seed localization for nonpalpable breast lesions: review of 1,000 consecutive procedures at a single institution.

INTRODUCTION: Radioactive seed localization (RSL) is an alternative to wire localization for nonpalpable breast lesions, with reported lower rates of positive surgical margins. METHODS: A retrospective review of all consecutive RSL procedures performed at a single institution from 01/2003 through 10/2010 was conducted. RESULTS: One thousand RSL breast procedures were performed in 978 patients. Indications for RSL included invasive carcinoma (52%), in situ carcinoma (22%), atypical hyperplasia (11%), and suspicious percutaneous biopsy findings (15%). A total of 1,148 seeds were deployed using image guidance, with 76% placed ≥1 day before surgery. Most procedures (86%) utilized one seed. A negative margin was achieved at the first operation in 97% of patients with invasive carcinoma and 97% of patients with ductal carcinoma in situ (DCIS). An additional 9% of patients with invasive carcinoma and 19% of patients with DCIS had close (≤2 mm) margins, and underwent re-excision. Sentinel lymph node biopsy was successfully performed in 99.8% of cases. Adverse events included 3 seeds (0.3%) not deployed correctly on first attempt and 30 seeds (2.6%) displaced from the breast specimen during excision of the targeted lesion. All seeds were successfully retrieved, with no radiation safety concerns. Local recurrence rates were 0.9% for invasive breast cancer and 3% for DCIS after mean follow-up of 33 months. There was no evidence of a learning curve. CONCLUSIONS: RSL is a safe, effective procedure that is easy to learn, with a low incidence of positive/close margins. RSL should be considered as the method of choice for localization of nonpalpable breast lesions.

Use of preoperative magnetic resonance imaging for invasive lobular cancer: good, better, but maybe not the best?

BACKGROUND: Invasive lobular cancer (ILC) of the breast is difficult to diagnose clinically and radiologically. It is hoped that preoperative magnetic resonance imaging (MRI) can improve evaluation of extent of disease. METHODS: Patients diagnosed with ILC at a single institution from 2001 to 2008 who underwent clinical breast examination (CBE), mammography, ultrasound, and MRI were studied retrospectively. Concordance between tumor size on imaging/CBE and pathologic size was defined as size within ± 0.5 cm. Pearson correlation coefficients (R) were calculated for each modality. Local recurrence and re-excision rates were compared with those patients with ILC who did not undergo preoperative MRI. RESULTS: Seventy patients with ILC had all imaging modalities, including CBE, performed preoperatively. The sensitivity for detection of ILC by MRI was 99%. MRI-based tumor size was concordant with pathologic tumor size in 56% of tumors. MRI overestimated tumor size by >0.5 cm in 31% of tumors. Correlation of tumor size on imaging with final pathology was better for MRI (R = 0.75) than for mammography (R = 0.65), CBE (R = 0.63), or ultrasound (R = 0.45, all P < 0.01). Preoperative MRI was associated with lower reoperation rates for close/positive margins (P > 0.05). CONCLUSIONS: For ILC, MRI has better sensitivity of detection and correlation with tumor size at pathology than CBE, mammography, or ultrasound. However, 31% of cases are overestimated by MRI, and correlation remains only at 0.75. The select use of MRI for preoperative estimation of tumor size in ILC is supported by our data, but the need for improvement and refinement of imaging remains.

Papillary lesions on core breast biopsy: excisional biopsy for all patients?

Excisional biopsy has been recommended for papillary lesions diagnosed on core needle biopsy (CNB) because a significant proportion of cases are upstaged to in situ/invasive cancer after surgical excision. The study goals were to identify patients at lowest risk of upstaging in whom excisional biopsy may potentially be avoided. We retrospectively evaluated 46 patients with a papillary lesion on CNB. Six patients were upstaged overall (13%), to intraductal papillary carcinoma (7%), invasive papillary carcinoma (4%), and mixed invasive ductal/lobular carcinoma (2%). The upstaging rate for patients with atypia on CNB was higher than for patients without atypia (33 vs 3%, P = 0.011). No patient younger than 65 years was upstaged to in situ or invasive carcinoma, and the mean lesion size was also higher among patients who were upstaged (P > 0.05). Patients younger than 65 years with small papillary lesions lacking atypia on CNB may therefore represent a low-risk group that may be offered close clinical and radiologic follow-up.

The role of toll-like receptor-4 in the development of multi-organ failure following traumatic haemorrhagic shock and resuscitation.

Haemorrhagic shock and resuscitation (HS/R) following major trauma results in a global ischaemia and reperfusion injury that may lead to multiple organ dysfunction syndrome (MODS). Systemic activation of the immune system is fundamental to the development of MODS in this context, and shares many features in common with the systemic inflammatory response syndrome (SIRS) that complicates sepsis. An important advancement in the understanding of the innate response to infection involved the identification of mammalian toll-like receptors (TLRs) expressed on cells of the immune system. Ten TLR homologues have been identified in humans and toll-like receptor-4 (TLR4) has been studied most intensively. Initially found to recognise bacterial lipopolysaccharide (LPS), it has also recently been discovered that TLR4 is capable of activation by endogenous 'danger signal' molecules released following cellular injury; this has since implicated TLR4 in several non-infectious pathophysiologic processes, including HS/R. The exact events leading to multi-organ dysfunction following HS/R have not yet been clearly defined, although TLR4 is believed to play a central role as has been shown to be expressed at sites including the liver, lungs and myocardium following HS/R. Multi-organ dysfunction syndrome remains an important cause of morbidity and mortality in trauma patients, and current therapy is based on supportive care. Understanding the pathophysiology of HS/R will allow for the development of targeted therapeutic strategies aimed at minimising organ dysfunction and improving patient outcomes following traumatic haemorrhage. A review of the pathogenesis of haemorrhagic shock is presented, and the complex, yet critical role of TLR4 as both a key mediator and therapeutic target is discussed.

Granular-cell tumor of the anterior abdominal wall.

We report a case of granular-cell tumor (GCT) arising in the subcutaneous tissue of the abdominal wall and describe its radiologic and histologic characteristics. The differential diagnosis of a mass in this site may include multiple benign and malignant stromal lesions. In this case, the presentation, location, and radiological features suggested a desmoid tumor (aggressive fibromatosis). Treatment of the mass involved surgical excision with negative margins, and histological analysis confirmed the presence of a benign GCT. We report a case of this rare, benign tumor to allow the radiologist and pathologist to consider this disease in the differential diagnosis when presented with similar cases.

Validation of the updated 7th edition AJCC TNM staging criteria for gastric adenocarcinoma.

INTRODUCTION: The recently published 7th edition of the American Joint Committee on Cancer (AJCC) TNM staging criteria for gastric adenocarcinoma contains important revisions to T and N classifications, as well as overall stage grouping. Our goal was to validate the new staging system using a cancer registry. METHODS: Retrospective review of gastric cancer patients from Surveillance, Epidemiology, and End Results (SEER) registry data (2004-2007). Patients were staged according to both 6th and 7th edition criteria, and 3-year disease-specific survival was compared. RESULTS: Thirteen thousand five hundred forty-seven patients with gastric adenocarcinoma were identified with complete staging information. When using 7th edition criteria, there was an increase in the number of patients classified as stage III (23% vs. 13%), and a decrease in patients classified as stage IV (47% vs. 53%). Statistically significant differences in 3-year disease-specific survival were observed for all T and N categories and re-staging the same population according to the 7th edition criteria improved survival discrimination. Multivariate analysis revealed statistically significant differences in survival and linear progression of hazard ratios for each stage grouping. CONCLUSIONS: The 7th edition AJCC staging criteria for gastric adenocarcinoma demonstrate better survival discrimination and risk stratification than previous criteria.