BACKGROUND:

The tumor microenvironment after treatment with ipilimumab is not well described. Furthermore, the safety of surgery for patients being treated with ipilimumab for metastatic melanoma has not been well reported. This study analyzed the safety of surgery and the immune phenotype of tumors resected while on ipilimumab.

METHODS:

From our prospective melanoma database, we identified patients undergoing surgery for any indication within 30 days of receiving a dose of induction ipilimumab or while on maintenance ipilimumab therapy. Surgical toxicity was graded 1-5 by the Clavien classification. Tumor-infiltrating lymphocytes were classified by flow cytometry and compared with peripheral blood.

RESULTS:

23 patients were identified who underwent 34 operations a median of 27 weeks after initiation of ipilimumab (1-123 weeks). Subcutaneous resections were the most frequent, followed by intra-abdominal and nodal procedures. Grade 1 or 2 wound complications were seen in 22 % of patients. No Grade 3-5 complications were seen. Analysis of the T cell infiltrate and matched peripheral blood from ten patients showed an elevated % of CD4(+)FOXP3(+) T-regulatory cells and a 2.8-fold lower ratio of CD8(+)/CD4(+)FOXP3(+) in the tumor compared with blood (p = 0.02). In addition, all CD8(+) T cells had a higher expression of PD-1 in the tumor, compared with peripheral blood.

CONCLUSIONS:

Surgery for patients on ipilimumab is safe. This study highlights the immunosuppressive phenotype in tumors not responding to immunotherapy. The high percentage of T-regulatory cells and low T-effector cells in progressive tumors suggests a possible mechanism of immune escape.

BACKGROUND:

Current rates of survival for gastric cancer patients are much improved compared with those of the past. The purpose of our study was to analyze the survival of gastric cancer patients according to time period and to examine how different prognostic factors are related to changing survival rates.

METHODS:

We analyzed data from 7,757 patients who underwent curative gastrectomy after diagnoses of gastric cancer at Samsung Medical Center from 1994 to 2006. Clinicopathologic characteristics and prognostic factors were analyzed retrospectively, with patients divided into period I, from 1994 to 2001, and period II, from 2002 to 2006.

RESULTS:

The 5-year, disease-free survival rate of patients with gastric cancer increased significantly from 76.7 % during period I to 85.9 % during period II (p < 0.001). The prognosis of the patient who underwent surgery during period I was worse than that of the patient in period II. When multivariate analyses were performed for each time period, independent prognostic factors for period I included patient age >60 years, tumor located in the whole stomach, tumor size, stage, vascular invasion, perineural invasion, and adjuvant chemotherapy. For period II, tumor size, vascular, and adjuvant chemotherapy were no longer independent prognostic risk factors.

CONCLUSIONS:

The disease-free survival of gastric cancer improved and prognostic factors changed over time. Active, concurrent chemoradiotherapy together with radical gastric resection performed by an expert surgeon seemed to contribute to the improvement in the survival rates of gastric cancer.

BACKGROUND:

The objective of this study was to critically evaluate current literature on outcomes following multivisceral resection (MVR) in colorectal cancer (CRC). Adequate surgical resection with clear margins is imperative in achieving long-term survival in colorectal cancer. Where there is adherence to or invasion of adjacent organs, (MVR) may be needed to achieve complete disease clearance.

METHODS:

A systematic review of MVR in CRC was performed. Pubmed/Medline and Cochrane databases were searched for English language articles from 1995 to 2012 using a predefined strategy. Retrieved abstracts were independently screened for relevance and data extracted from selected studies by 2 researchers. Results are reported as weighted means.

RESULTS:

Included were 22 studies comprising 1575 patients (87.0 % primary colorectal cancer; 13.0 % recurrent, 63.8 % rectal; 36.2 % colon). The most common organs resected were the bladder and reproductive organs. The perioperative mortality was 4.2 % with morbidity of 41.5 % (95 % CI, 40.8-42.2 %). The overall 5-year survival rate was 50.3 % (95 % CI, 49.9-50.8 %). Surgery for recurrence was associated with worse outcomes than primary tumors with 5-year survival 19.5 % (95 % CI, 17.8-21.1 %) for recurrent rectal cancer and primary rectal tumors 5-year overall survival 52.8 % (95 % CI, 52.0-53.8 %). R0 resection was the strongest factor associated with long-term survival.

CONCLUSIONS:

Multivisceral resection provides the best possibility of long-term survival in locally advanced primary colorectal cancer in which a clear margin has been achieved.

BACKGROUND:

Little is known about the effects of diagnostic ureteroscopy on intravesical recurrence after nephroureterectomy.

METHODS:

This study was designed to determine the effect of diagnostic ureteroscopy on intravesical recurrence after nephroureterectomy. From 2004 to 2010, 446 patients underwent nephroureterectomy for upper urinary tract cancer at our tertiary medical center. We included 115 patients who underwent preoperative diagnostic ureteroscopy and 281 patients who did not. This study analyzed the impact of the reported risk factors and diagnostic ureteroscopy for intravesical recurrence after nephroureterectomy by multivariate Cox regression model.

RESULTS:

The rates of metastasis and cancer-specific mortality did not differ significantly between the two groups. Diagnostic ureteroscopy was associated with a higher incidence of intravesical recurrence in patients with (p = 0.02) and without (p = 0.016) a previous history of bladder cancer. Ureter tumor biopsy (p = 0.272) and ureter involvement (p = 0.743) were not associated with the rate of intravesical recurrence in this study. Multivariate Cox regression analysis showed that only bladder cancer history (p < 0.001), multifocal tumor (p = 0.05), and diagnostic ureteroscopy (p = 0.05) were independently associated with intravesical recurrence.

CONCLUSIONS:

Diagnostic ureteroscopy for upper urinary tract cancer was not associated with metastasis and cancer-specific mortality. However, ureteroscopy was associated with an increased incidence of intravesical tumor recurrence. Methods of prevention should be considered to decrease intravesical recurrence and avoid repeated surgical interventions or the development of advanced bladder disease in patients at risk.

BACKGROUND:

Breast cancer subtypes (BCS) determined from immunohistochemical staining have been correlated with molecular subtypes and associated with prognosis and outcomes, but there are limited data correlating these BCS and axillary node involvement. This study was conducted to assess whether BCS predicted for nodal metastasis or was associated with other clinicopathologic features at presentation.

METHODS:

Patients with stage I/II disease who underwent breast-conserving surgery and axillary surgical assessment with available tissue blocks underwent a institutional pathological review and construction of a tissue microarray. The slides were stained for estrogen receptor, progesterone receptor, and HER-2/neu (HER-2) for classification into BCS. Nodal involvement and other clinicopathologic features were analyzed to assess associations between BCS and patient and tumor characteristics. Outcomes were calculated a function of BCS.

RESULTS:

The study cohort consisted of 453 patients (luminal A 48.6 %, luminal B 16.1 %, HER-2 11.0 %, triple negative 24.2 %), of which 22 % (n = 113) were node positive. There were no significant associations with BCS and pN stage, node positivity, or absolute number of nodes involved (p > 0.05 for all). However, there were significant associations with subtype and age at presentation (p < 0.001), method of detection (p = 0.049), tumor histology (p < 0.001), race (p = 0.041), and tumor size (pT stage, p < 0.001) by univariate and multivariate analysis. As expected, 10-year outcomes differed by BCS, with triple negative and HER-2 subtypes having the worse overall (p = 0.03), disease-free (p = 0.03), and distant metastasis-free survival (p < 0.01).

CONCLUSIONS:

There is a significant association between BCS and age, T stage, histology, method of detection, and race, but no associations to predict nodal involvement. If additionally validated, these findings suggest that BCS may not be a useful prognostic variable for influencing regional management considerations.

INTRODUCTION:

The role of primary tumor excision in patients with stage IV breast cancer is unclear. Therefore, a meta-analysis of relevant studies was performed to determine whether surgical excision of the primary tumor enhances oncological outcome in the setting of stage IV breast cancer.

METHODS:

A comprehensive search for relevant published trials that evaluated outcomes following excision of the primary tumor in stage IV breast cancer was performed using MEDLINE and available data were cross-referenced. Data were extracted following review of appropriate studies by authors. The primary outcome was overall survival following surgical removal of the primary tumor.

RESULTS:

Data from ten studies included 28,693 patients with stage IV disease of whom 52.8 % underwent excision of the primary carcinoma. Surgical excision of the primary tumor in the setting of stage IV breast cancer was associated with a superior survival at 3 years (40 % (surgery) versus 22 % (no surgery) (odds ratio 2.32, 95 % confidence interval 2.08-2.6, p < 0.01). Subgroup analyses for selection of patients for surgery or not, favored smaller primary tumors, less competing medical comorbidities and lower metastatic burden (p < 0.01). There was no statistical difference between the two groups regarding location of metastatic disease, grade of tumor, or receptor status.

CONCLUSIONS:

Patients with stage IV disease undergoing surgical excision of the primary tumor achieve a superior survival rate then their nonsurgical counterparts. In the absence of robust evidence, this meta-analysis provides evidence base for primary resection in the setting of stage IV breast cancer for appropriately selected patients.