Predictive factors for lymph node metastasis in early gastric cancer with signet ring cell histology and their impact on the surgical strategy: analysis of single institutional experience

Background

The prognosis of early gastric cancer (EGC) with signet ring cell histology is more favorable than other undifferentiated gastric adenocarcinomas. An accurate assessment of potential lymph node metastasis is important for the appropriate treatment of EGC with signet ring cell histology. Therefore, this study analyzed the predictive factors associated with lymph node metastasis in patients with this type of EGC.

Methods

A total of 136 EGC with signet ring cell histology patients who underwent D2 radical gastrectomy were reviewed in this study. The clinicopathologic features were analyzed to identify predictive factors for lymph node metastasis.

Results

The overall rate of lymph node metastasis in EGC with signet ring cell histology was 10.3%. Using a univariate analysis, the risk factors for lymph node metastasis were identified as the tumor size, depth of tumor invasion, and lymphovascular invasion. The multivariate analysis revealed that tumor size >2 cm, submucosal invasion, and lymphovascular invasion were independent risk factors of lymph node metastasis (P < 0.05).

Conclusions

The risk of lymph node metastasis of EGC with signet ring cell histology was high in those with tumor sizes ≥2 cm, submucosal tumors, and lymphovascular invasion. A minimally invasive treatment, such as endoscopic resection, might be possible in highly selective cases of EGC with signet ring cell histology with intramucosal invasion, tumor size <2 cm, and no lymphovascular invasion.     

Factors associated with decision to pursue mastectomy and breast reconstruction for treatment of ductal carcinoma in situ of the breast

Background

Factors influencing the treatment of ductal carcinoma in situ with mastectomy and reconstruction are poorly understood.

Methods

A retrospective cohort study of 196 patients presenting to one institution was performed.

Results

Forty-seven patients (24.0%) were treated with mastectomy, while 149 (76.0%) underwent breast-conserving surgery. Of the mastectomy patients, 28 (59.6%) elected for reconstruction. On bivariate analysis, patients who opted for mastectomy were younger than those treated with breast-conserving surgery (median age, 51.8 vs 56.5 years; P = .017) and had higher grade tumors (50.0% vs 34.6% grade 3, P = .009). Among patients treated with mastectomy, those who opted for reconstruction were younger than those forgoing reconstruction (49.4 vs 56.9 years, P = .024). Race, ductal carcinoma in situ tumor size, and histologic subtype were not associated with the decision to pursue mastectomy or reconstruction (P > .05 for all).

Conclusions

In patients with ductal carcinoma in situ, the decision to pursue mastectomy and reconstruction appears to be driven by younger patient age and higher tumor grade.     

Private insurance is the strongest predictor of women receiving breast conservation surgery for breast cancer

Background

It is widely accepted that mastectomy and breast-conserving surgery (BCS) with irradiation yield similar results, yet many women continue to receive mastectomy. This study evaluates factors contributing to surgical decision-making in breast cancer. Registry data were obtained on all patients treated at the Southwest Cancer Treatment and Research Center (SWCTRC) between 2002 and 2006. Patient demographics, including age and race, and insurance type, tumor characteristics, surgical procedure performed, lymph node status, stage, adjuvant therapy, and outcome were analyzed against mastectomy versus BCS using bivariate and multivariate analysis.

Results

There was a higher proportion of uninsured patients in the mastectomy cohort, which also included more patients with later stage disease, larger tumor size, and a higher number of lymph node metastases. The only independent predictors of BCS were fewer lymph node metastases and having insurance. Patients with private insurance were almost 4 times more likely to receive BCS (odds ratio 3.90, 95% confidence interval 1.20-12.67).

Conclusions

Insurance status is an important predictor determining whether a patient receives BCS or mastectomy for breast cancer.     

The impact of lymph node disease in extremity soft-tissue sarcomas: a population-based analysis

Background

Because of the low incidence of regional lymph node metastasis, node-positive soft-tissue sarcoma patients remain poorly characterized. Our objective was to assess regional lymph node metastasis in extremity sarcoma patients using a large population database.

Methods

The Surveillance, Epidemiology, and End Results database was queried for extremity sarcoma patients. Clinicopathologic data and outcomes were examined to evaluate the significance of regional lymph node metastasis.

Results

Of 7,159 patients without distant metastasis, 64 patients had identified regional lymph node metastasis (.9%). Regional lymph node metastasis was associated with younger age, tumor grade, size, invasion, and tumor subtype. Excluding distant metastasis, lymph node status was the strongest prognostic factor (hazards ratio = 5.1, P < .001).

Conclusions

Isolated regional lymph node metastasis is rare in extremity sarcoma patients. However, in the absence of distant metastasis, lymph node status is the most important prognostic factor. The management of positive lymph nodes remains uncertain although diagnosing lymph node metastasis may identify early biologically aggressive disease.     

Outcomes and prognostic factors in superficial spreading melanoma

Background

Prognostic factors and risk factors for positive sentinel lymph node (SLN) biopsy results are important to identify in superficial spreading melanoma (SSM).

Methods

A single-center database and a prospective clinical trial database were reviewed for all patients with diagnoses of SSM. Logistic regression, Kaplan-Meier survival analysis, and univariate and multivariate Cox models were used.

Results

A total of 1,643 patients with SSM were identified. Independent risk factors for positive SLN biopsy results were Breslow thickness (BT) ≥2.0 mm, age <60 years, and presence of ulceration. BT ≥2.0 mm, ulceration, lymphovascular invasion, and positive SLN and positive non-SLN biopsy results were independent risk factors for worse disease-free survival. Independent overall survival risk factors included BT ≥2.0 mm, age ≥60 years, ulceration, nonextremity tumor location, lymphovascular invasion, and positive SLN biopsy results.

Conclusions

BT, ulceration, lymphovascular invasion, and SLN and non-SLN status are important risk factors for SSM.     

Risk factors contributing to the difference in prognosis for papillary versus micropapillary thyroid carcinoma

Background

The aggressiveness of papillary thyroid carcinoma (PTC) was evaluated by comparing conventional PTC with papillary thyroid microcarcinoma (PTMC). Risk factors associated with differences in clinical and pathologic features were analyzed to provide appropriate surgical management.

Methods

A total of 539 patients with papillary carcinoma who underwent total thyroidectomy were retrospectively reviewed. The median follow-up period was 32 months.

Results

Of 539 patients, 311 (57.7%) had PTMC, and 228 (42.3%) had conventional PTC. No differences between patients with PTMC and those with PTC were observed in age, gender, and multifocality. PTMC was associated with less frequent bilaterality (P = .002), lymph node metastasis (P < .001), thyroid capsule invasion (P < .001), and disease recurrence (P < .001), and a higher rate of incidental diagnosis (P = .001). There was no statistically significant difference between the prevalence of lymph node metastasis at diagnosis and disease recurrence rate between nonincidental PTMC and conventional PTC (P > .05).

Conclusions

Incidental PTMC had significantly fewer aggressive tumor features. Nonincidental PTMC presented with aggressive characteristics similar to those of conventional PTC and should be treated likewise. The authors suggest routine total thyroidectomy followed by an adequate exploration of the central neck compartment as a safe treatment.     

Therapy choices and quality of life in young breast cancer survivors: a short-term follow-up

Background

Premenopausal women represent approximately 35% of new breast cancer diagnoses. Diagnosis and treatment may lead to substantial disruption in quality of life (QOL).

Methods

Premenopausal patients (aged 18 to 50 years) treated for nonmetastatic breast cancer completed a mailed questionnaire. Multiple self-reported QOL measures and clinical data were collected. Cluster analysis and Cronbach's α were used to validate the survey. Analysis of variance was performed for specific interventions. Lower interference scores conveyed higher QOL.

Results

The response rate was 49.8%. Cronbach's α was 0.96. Immediate contralateral prophylactic mastectomy (CPM) carried the highest interference (mean, 3.3148) with sexuality compared with no CPM (mean, 2.85) or delayed CPM (P = .03). Breast conservation had the least interference with appearance (P < .01) and work and finances (P = .02).

Conclusions

Therapeutic mastectomy and CPM with or without reconstruction may adversely affect QOL. These findings suggest that the choice and timing of interventions may significantly affect patient satisfaction.     

Regional recurrence in the era of sentinel lymph node biopsy

Background

The incidence of all-location regional recurrence after sentinel lymph node biopsy is not well documented. This study attempts to identify risk factors.

Methods

A prospectively maintained database was queried to identify patients with a regional recurrence of breast cancer after a first operation for invasive unilateral breast cancer. Patients with regional recurrence were compared with those alive and disease free at 5 years.

Results

Twenty-one of 1,060 patients (2%) experienced a regional recurrence. Most patients (95%) underwent sentinel lymph node biopsy as their axillary staging. Those with regional recurrences had larger tumors (P < .001), higher stage disease (P < .001), more estrogen receptor– and triple-negative breast cancers (P < .001), and more positive lymph nodes (P = .007). Mastectomy (P = .001) and receipt of neoadjuvant and/or chemotherapy (P < .001) were more common among those with regional recurrences.

Conclusions

Regional recurrence of breast cancer occurs infrequently. Risk factors include high-risk cancers, higher stage at presentation, nodal involvement, and need for therapies reflecting higher risk biology.     

Factors which affect the use of lumpectomy and mastectomy in an underinsured,safety net hospital population

Background

This study was performed to evaluate variables that affect the use of mastectomy and lumpectomy in an underinsured population.

Methods

A retrospective review of all patients who underwent breast cancer operations from July 2001 to February 2011 at a safety net hospital was performed. Univariate and multivariate analyses were performed to identify variables, which were associated with the type of operation.

Results

Of the 412 patients, 81% of the patients were underinsured or uninsured. Most patients (58%) presented with clinical stage 2A/B disease. Mastectomy was performed in 37% of patients and lumpectomy in 63%. In multivariate analysis, clinical tumor size (P = .035) and pathologic stage (P = .003) remained associated with mastectomy, while use of preoperative chemotherapy (P = .004) and type of surgeon (P = .001) was associated with lumpectomy.

Conclusions

Most patients underwent lumpectomy despite later stage at presentation. Preoperative chemotherapy was associated with increased likelihood of lumpectomy.     

Variations in clinicopathologic characteristics of thyroid cancer among racial ethnic groups: analysis of a large public city hospital and the SEER database

Background

Clinicopathologic variables influence the treatment and prognosis of patients with thyroid cancer.

Methods

A retrospective analysis of public hospital thyroid cancer database and the Surveillance, Epidemiology and End Results 17 database was conducted. Demographic, clinical, and pathologic data were compared across ethnic groups.

Results

Within the public hospital database, Hispanics versus non-Hispanic whites were younger and had more lymph node involvement (34% vs 17%, P < .001). Median tumor size was not statistically different across ethnic groups. Similar findings were demonstrated within the Surveillance, Epidemiology and End Results database. African Americans aged <45 years had the largest tumors but were least likely to have lymph node involvement. Asians had the most stage IV disease despite having no differences in tumor size, lymph node involvement, and capsular invasion.

Conclusions

There is considerable variability in the clinical presentation of thyroid cancer across ethnic groups. Such disparities persist within an equal-access health care system. These findings suggest that factors beyond socioeconomics may contribute to such differences.     

High Expression of Angiopoietin-1 is Associated with Lymph Node Metastasis and Invasiveness of Papillary Thyroid Carcinoma

Background

We investigated the expression of angiopoietins in patients with papillary thyroid carcinoma (PTC) and the role of angiopoietins as biomarkers predicting the aggressiveness of PTC.

Methods

Expression of angiopoietins was evaluated by immunohistochemistry of tumor specimens from patients with PTC. We demonstrated potential correlations between expression of angiopoietins and clinicopathologic features.

Results

High expression of Ang-1 was positively correlated with a tumor size >1 cm, capsular invasion, extrathyroid extension, lymphovascular invasion, lymph node metastasis, and recurrence (P < 0.05). Moreover, multivariate analysis revealed that high expression of Ang-1 was an independent risk factor for lymph node metastasis (P < 0.001, odds ratio [OR] = 62.113) and lymphovascular invasion (P = 0.027, OR 4.405). However, there was no significant correlation between Ang-2 and clinicopathologic features.

Conclusions

Our results suggest that Ang-1 can serve as a valuable prognostic biomarker for lymph node metastasis and invasiveness in patients with PTC.

     

p27 expression in post-treatment rectal cancer: a potential novel approach for predicting residual nodal disease

Background

Expression profiles of p21, p27, p53, Ki-67, and thymidylate synthase may be associated with response to neoadjuvant chemoradiation. The relationship between post-treatment protein expression and regional lymph node involvement has not been fully explored.

Methods

Tumor cores from 126 rectal cancer patients underwent immunohistochemical analysis for the aforementioned proteins. Staining indices (SIs) using percentage of stained cells and staining intensity were calculated for 10 tumor cores per patient. SI for each marker was compared between node negative and node positive patients.

Results

Twenty-six (20.6%) cancer patients had a pathologic complete response and 37 had inadequate tissue or cancer cells, leaving 63 for analysis. Thirty-seven (58.7%) cancer patients were node negative and 26 (41.3%) were node positive. There was an association between increased p27 SI and nodal positivity (P = .04).

Conclusion

Increased p27 expression in post-treatment rectal cancer is associated with nodal positivity and may determine which patients are suitable for local excision.     

Prognostic Factors for Occult Inguinal Lymph Node Involvement in Penile Carcinoma and Assessment of the High-Risk EAU Subgroup: A Two-Institution Analysis of 342 Clinically Node-Negative Patients

Background

The European Association of Urology (EAU) guidelines advise an elective bilateral lymphadenectomy in clinically node-negative (cN0) patients with high-risk penile carcinoma (≥pT2, G3, or lymphovascular invasion [LVI]).

Objective

Our aim was to assess prognostic factors for occult metastasis and to determine whether current EAU guidelines accurately stratify patients at high risk.

Design, setting, and participants

Data of 342 cN0 patients with histologically proven invasive penile squamous cell carcinoma who had undergone the current dynamic sentinel node biopsy (DSNB) protocol were analysed. A complete ipsilateral inguinal lymphadenectomy was only done if the sentinel node was tumour positive.

Measurements

The presence of occult metastasis was established by preoperative ultrasound and tumour-positive fine-needle aspiration cytology, tumour-positive sentinel nodes, and groin metastases during follow-up after a negative DSNB procedure. Median follow-up was 31 mo.

Results and limitations

Sixty-eight of 342 patients (20%) and 87 of 684 groins (13%) had occult nodal involvement including 6 patients (2%) with a groin metastasis after negative DSNB. Corpus spongiosum invasion, corpus cavernosum invasion, histologic grade, and LVI were each significant prognosticators for occult metastasis on univariate analysis. On multivariate analysis, grade (odds ratio [OR]: 3.3 for intermediate and 4.9 for poor, respectively) and LVI (OR: 2.2) remained predictive factors. In total, 245 patients (72%) were classified high risk according to EAU guidelines. Among them, the incidence of occult metastasis was 23% (57 of 245). A potential limitation of this study is the lack of external review.

Conclusions

Histologic grade and LVI are independent prognostic factors for occult metastasis in penile carcinoma. Although both predictors are incorporated into the current EAU guidelines, the stratification of patients needing a lymph node dissection is inaccurate. Approximately 77% of high-risk patients (188 of 245) would have had a negative bilateral inguinal lymphadenectomy. For the time being, DSNB is considered a more suitable staging method than EAU risk stratification for an accurate determination of patients who require lymph node dissection.     

Epidermal growth factor receptor overexpression is a marker for adverse pathologic features in papillary thyroid carcinoma

Background

Epidermal growth factor receptor (EGFR) overexpression (EGFR-H) is implicated in thyroid carcinoma disease progression; however, the clinicopathologic significance of EGFR-H in tumors that harbor EGFR and/or v-Raf murine sarcoma viral oncogene homolog B1 (BRAF)(V600E) mutations is unknown.

Methods

Tissue microarrays from 81 patients who had undergone thyroidectomy for carcinoma from 2002–2011 were scored for EGFR expression using immunohistochemistry. Somatic mutations in EGFR exons 19 and 21 and BRAF were analyzed. Correlations between the EGFR immunohistochemistry, EGFR, and BRAF(V600E) mutations and the clinicopathologic features were assessed.

Results

EGFR-H was detected in 39.5% of carcinomas (n = 32) from patients with papillary (PTC, 46.2%, n = 18), follicular (29.6%, n = 8), and anaplastic (100.0%, n = 6) but not medullary (0.0%, n = 9) thyroid carcinoma. BRAF(V600E) mutations were identified in 22.2% of the carcinoma cases (n = 18, 15 PTCs and 3 anaplastic thyroid carcinomas). No somatic EGFR mutations were detected in any subtype. On PTC univariate analysis, EGFR-H correlated with increasing stage, extrathyroid extension, tumor capsule invasion, adverse pathologic features (any demonstration of extrathyroid extension, tumor capsule invasion, lymphovascular invasion, lymph node metastasis, and/or distant metastasis), and BRAF(V600E) mutations. On multivariate analysis, EGFR-H correlated with BRAF(V600E) mutations. In BRAF wild-type PTCs, the correlation between EGFR-H and adverse pathologic features approached statistical significance (P = 0.065).

Conclusions

EGFR-H could be an important biomarker for aggressive PTCs, particularly in BRAF wild-type PTCs. Despite EGFR-H in PTC, follicular thyroid carcinoma, and anaplastic thyroid carcinoma by immunohistochemistry, somatic EGFR mutations were absent. Therefore, future investigations of EGFR should consider histologic and immunohistochemical methods, in addition to molecular profiling of thyroid carcinomas. This multimodal approach is particularly important for future clinical trials testing anti-EGFR therapy.     

Accurate axillary lymph node dissection is feasible after neoadjuvant chemotherapy

Background

Recently, lower axillary lymph node retrieval after neoadjuvant chemotherapy was reported. We did not have this experience, and retrospectively analyzed our axillary lymph node dissections (ALNDs).

Methods

One hundred ninety-one patients who had ALND after neoadjuvant chemotherapy were compared with 192 patients with primary ALND after a positive sentinel node biopsy.

Results

There were no differences in the mean number of nodes retrieved between the neoadjuvant group and the primary surgery group: 16.3 (range 4-38) and 15.8 (range 6-33), respectively (P = .4); or in the retrieval of fewer than 10 lymph nodes: 13/191 (7%) and 11/192 (6%) (P = .7). The number of cases with retrieval of more than 20 lymph nodes was higher in the neoadjuvant group: 42/191 (22%) versus 26/192 (13%) (P = .03). In the neoadjuvant group, 150/191 (79%) patients had residual lymph node metastasis after neoadjuvant chemotherapy.

Conclusion

Our results show the feasibility and need to remove enough lymph nodes to provide precise prognostic information and adequate local control.     

Pathologic Nodal Staging Score for Bladder Cancer: A Decision Tool for Adjuvant Therapy After Radical Cystectomy

Background

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard of care for high-risk non–muscle-invasive and muscle-invasive bladder cancer (BCa).

Objective

To develop a model that allows quantification of the likelihood that a pathologically node-negative patient has, indeed, no positive nodes.

Design, setting, and participants

We analyzed data from 4335 patients treated with RC and PLND without neoadjuvant chemotherapy at 12 international academic centers.

Interventions

Patients underwent RC and PLND.

Outcome measurements and statistical analysis

We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative as a function of the number of examined nodes.

Results and limitations

Overall, the probability of missing a positive node decreases with the increasing number of nodes examined (52% if 3 nodes are examined, 40% if 5 are examined, and 26% if 10 are examined). The proportion of having a positive node increased proportionally with advancing pathologic T stage and lymphovascular invasion (LVI). Patients with LVI who had 25 examined nodes would have a pNSS of 80% (pT1), 88% (pT2), and 66% (pT3–T4), whereas 10 examined nodes were sufficient for pNSS exceeding 90% in patients without LVI and pT0–T2 tumors. This study is limited because of its retrospective design and multicenter nature.

Conclusions

We developed a tool that estimates the likelihood of lymph node (LN) metastasis in BCa patients treated with RC by evaluating the number of examined nodes, the pathologic T stage, and LVI. The pNSS indicates the adequacy of nodal staging in LN-negative patients. This tool could help to refine clinical decision making regarding adjuvant chemotherapy, follow-up scheduling, and inclusion in clinical trials.     

The fate of unscreened women in colon cancer: impact on staging and prognosis

Background

Several nationwide reports show lower female participation in colon cancer screening. We therefore assessed for outcome differences in women of screening age presenting for surgical treatment of colon cancer patients.

Methods

All patients over 50 years undergoing surgery for first-onset colon cancer at Massachusetts General Hospital (2004 to 2011) were included. Differences between (unscreened) women and the remaining population in presentation characteristics and subsequent morbidity and mortality were assessed.

Results

We included 919 patients (49.1% female). Women were less often diagnosed through screening (26.4 vs 32.7%, P = .036). Unscreened women were at significantly higher risk (all P < .001) for having high-grade tumors (Relative risk [RR] = 1.61), lymph node metastasis (RR = 1.36), and distant metastasis (RR = 2.26) on pathology, leading to higher colon cancer-related mortality (RR = 1.72).

Conclusion

Unscreened women present with more advanced colon cancer and higher mortality, confirming that disparities in screening lead to ever-increasing disparities in outcomes.     

Neoadjuvant therapy reduces the incidence of nodal micrometastases in esophageal adenocarcinoma

Background

We evaluated the impact of neoadjuvant chemoradiotherapy (CRT) on nodal micrometastases (NMMs) in esophageal adenocarcinoma (EAC) patients with histologically negative nodes ([y]pN0).

Methods

Of 48 consecutively treated patients with neoadjuvant CRT, we selected 20 EAC ypN0 patients (group 1). These patients were matched with 20 pN0 EAC patients who had surgery alone (group 2). Harvested (y)pN0 lymph nodes were examined immunohistochemically (anti-CK8/18 [CAM 5.2]) according to a validated sentinel node protocol. A 3rd group (n = 11) staged as ypN1 after neoadjuvant CRT was used as the control group.

Results

Upstaging to NMM+ occurred in 2 patients (10%) in group 1 and in 8 patients (40%) in group 2 (P = .028). Disease-free and overall survival rates in NMM+ patients in group 1 were worse compared with NMM− patients (P = .014 and P = .003, respectively) but comparable with ypN1 patients (n = 11).

Conclusions

A 30% reduction of NMM+ was obtained after neoadjuvant treatment in (y)pN0 patients. NMM+ after CRT had a negative impact on survival in ypN1 patients. These data warrant further investigation in larger prospective datasets.     

Risk factors associated with lymphedema after lymph node dissection in melanoma patients

Background

Secondary lymphedema is a frequent complication after lymphadenectomy in melanoma patients, although few studies in melanoma adequately characterize risk factors for lymphedema, and of these, sample size is limited. This study aims to identify risk factors associated with the lymphedema after axillary lymph node dissection (ALND) and inguinal lymph node dissection (ILND) in a more robust cohort of melanoma patients.

Methods

We identified 269 ALND or ILND melanoma patients treated between 2008 and 2014. Demographic, clinical, and postoperative data were collected by review of the electronic medical record. Univariate and multivariate analysis were used to determine independent predictors of lymphedema.

Results

Fifty-six (20.8%) of the patients developed lymphedema after lymph node dissection with a median staging group of 3. ILND (odds ratio [OR] = 4.506, P < .001, 95% confidence interval [CI]: 2.289 to 8.869) and peripheral vascular disease (PVD; OR = 3.849, P = .020, 95% CI: 1.237 to 11.975) were significant predictors of lymphedema in multivariate analysis. Obese body mass index approached significance (OR = 1.802, P = .069, 95% CI: .955 to 3.399).

Conclusions

PVD and ILND were the 2 factors associated with the highest risk of lymphedema in melanoma surgery with PVD increasing risk 2-fold in ILND patients and 3-fold in ALND patients. These findings may improve surgeon-patient communication of care goals and surgical risk assessment.