Central nervous system relapse in patients with untreated her2-positive esophageal or gastroesophageal junction adenocarcinoma

Abstract

Although HER2-positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2-positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2-targeted therapies that penetrate the blood-brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative-intent surgery during a time period (1980-1997) when no patient received HER2-targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow-up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2-positive (vs -negative) primary tumors showed a higher 5-year cumulative incidence of CNS relapse as first recurrence (5.8% vs 1.2%; P =.0058) and at any time (8.3% vs 2.4%; P =.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (P =.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; P =.001). These are the first data in a non-breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2-positive EACs have a predilection for CNS metastases. This article is protected by copyright. All rights reserved.

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Routine sampling of internal mammary lymph nodes during microsurgical breast reconstruction—Experience based on 524 microsurgical breast reconstructions

Purpose

Exploration of the internal mammary vessels during microsurgical reconstruction presents an ideal opportunity for identifying and sampling the internal mammary lymph node (IMLN) basin.

Methods

A retrospective review of patients undergoing microsurgical breast reconstruction using the internal mammary vessels as recipient vessels was conducted from March 2000 to December 2014. Patient demographics, tumor characteristics, preoperative lymph node mapping, reconstructive timing, and outcomes were studied.

Results

A total of 524 microsurgical breast reconstructions in 516 patients were performed using the internal mammary vessels. IMLNs were sampled in 53 immediate and 42 delayed breast reconstructions. Eight (seven in the immediate and one in the delayed group) of the sampled nodes were positive for cancer metastasis, for an incidence of 8.4% in identified lymph nodes. All patients with metastatic IMLNs subsequently received local-regional radiation and chemotherapy. All patients were alive, and six were disease-free at the conclusion of the study period, which had an average follow up of 67.3 months.

Conclusion

Incidentally encountered IMLNs during microsurgical breast reconstruction are frequently positive. With negligible downside and the possibility to provide additional information for treatment, the procedure should be encouraged. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Tumor regression grade in gastric cancer: Predictors and impact on outcome

Background

The clinical value and prognostic implications of histologic response to neoadjuvant chemotherapy in gastric cancer is unknown.

Methods

Tumor regression grade (TRG) was recorded in 58 gastric cancer patients identified from two institutional surgical databases. TRG 1a/b represented histologic responders (<10% viable tumor), while TRG 2/3 represented non-responders (>10% viable tumor).

Results

TRG 1a/b was recorded in 10 patients (17%), while 48 patients (83%) had a TRG 2/3 response. Larger tumor size (OR 0.24; 95%CI 0.09, 0.64; P = 0.004) and clinical downstaging (OR 30.0; 95%CI 3.26, 276; P = 0.003) were the only factors predictive of histologic response. TRG 1a/b responders had 3-year survival of 70.0% and an estimated overall survival of >69.8 months compared to 38.2% and 22.8 months in non-responders; however, this trend was not statistically significant (P = 0.535). While TRG could not predict survival (OR 2.40; 95%CI 0.46, 12.57; P = 0.300), patient age (OR 1.06; 95%CI 1.00, 1.11; P = 0.035), and the number of positive lymph nodes (≥7; OR 0.05; 95%CI 0.07, 0.27; P < 0.001) were independent predictors of survival.

Conclusions

Few gastric cancers demonstrate histologic response to neoadjuvant chemotherapy. While TRG may be a valid marker for treatment response, its predictive value and clinical application in gastric cancer remains unclear. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Assessing the impact of common bile duct resection in the surgical management of gallbladder cancer

Background

Although radical re-resection for gallbladder cancer (GBC) has been advocated, the optimal extent of re-resection remains unknown. The current study aimed to assess the impact of common bile duct (CBD) resection on survival among patients undergoing surgery for GBC.

Methods

Patients undergoing curative-intent surgery for GBC were identified using a multi-institutional cohort of patients. Multivariable Cox-proportional hazards regression was performed to identify risk factors for a poor overall survival (OS).

Results

Among the 449 patients identified, 26.9% underwent a concomitant CBD resection. The median number of lymph nodes harvested did not differ based on CBD resection (CBD, 4 [IQR: 2–9] vs. no CBD, 3 [IQR: 1–7], P = 0.108). While patients who underwent a CBD resection had a worse OS, after adjusting for potential confounders, CBD resection did not impact OS (HR = 1.40, 95%CI 0.87–2.27, P = 0.170). Rather, the presence of advanced disease (T3: HR = 3.11, 95%CI 1.22–7.96, P = 0.018; T4: HR = 7.24, 95%CI 1.70–30.85, P = 0.007) and the presence of disease at the surgical margin (HR = 2.58, 95%CI 1.26–5.31, P = 0.010) were predictive of a worse OS.

Conclusions

CBD resection did not yield a higher lymph node count and was not associated with an improved survival. Routine CBD excision in the re-resection of GBC is unwarranted and should only be performed selectively. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Lymphocyte to monocyte ratio and prognostic nutritional index predict survival outcomes of hepatitis B virus-associated hepatocellular carcinoma patients after curative hepatectomy

Introduction

Lymphocytes are an integral part of lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI). Both LMR and PNI which reflect body's inflammatory and nutritional status can be obtained from routine blood and biochemical test conveniently. Little evidence concerning the prognostic value of LMR and PNI in hepatocellular carcinoma (HCC) patients has been published. This study aimed to investigate the prognostic value of LMR and PNI in hepatitis B virals (HBV)—associated HCC patients who underwent curative hepatectomy.

Methods

Between January 2008 and June 2013, 450 surgically treated HCC patients were retrospectively analyzed. Clinicopathological parameters, LMR and PNI were collected and compared. The multivariate analysis was performed to indentify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) rates were also compared.

Results

Tumor size, vascular invasion, alpha fetoprotein level, LMR and PNI were independent prognostic factors for OS. Tumor number, tumor size, vascular invasion, LMR and PNI were independent prognostic factors for RFS. Either a high LMR or PNI could predict favorable OS and RFS in surgically treated HCC patients and vice versa.

Conclusions

Both LMR and PNI were significant independent predictors that can predict survival outcomes in HBV-associated HCC patients who received curative hepatectomy. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Efficacy and Safety of Induction Chemotherapy in Esophageal Cancer with Airway Involvement

Abstract

Purpose

Esophageal cancer with tracheobronchial involvement (TBI) has a poor prognosis. Radical therapy carries the risk of inducing tracheoesophageal fistula (TEF) and treatment-related mortality. Induction chemotherapy followed by reassessment for radical therapy may decrease morbidity and improve outcome.

Methods

This is a retrospective analysis of esophageal cancer patients with TBI who received induction chemotherapy. Airway involvement was defined as bronchoscopic appearance of a bulge into the lumen, restricted or immobile mucosa, frank infiltration, TEF, or stridor, which was clinically due to airway obstruction from the esophageal lesion.

Results

Eighty-three patients were included over 5 years; 97.6 % had squamous histology. All patients received taxane and platinum combination induction chemotherapy; 90.5 % of patients received chemotherapy without dose delays, and 77.8 % patients did not require a dose reduction or modification. The 31.7 % patients had a clinically significant ≥grade 3 toxicity. The objective response rate was 67 % among the patients who underwent restaging scans following induction chemotherapy; 79.5 % of the patients could receive radical intent therapy, either concurrent chemoradiotherapy, or radiation alone, or surgery in one patient. The TEF complication rate was 6 % during the course of therapy. At a median follow-up of 28 months in surviving patients, the estimated median PFS was 8 months (95 % CI 5.5–10.5) and the estimated median OS was 17 months (95 % CI 5.6–28.4). Patients who received radical therapy had a significantly better PFS and OS, p = 0.000.

Conclusions

Induction chemotherapy may improve the outcome of patients with esophageal cancer involving the airway and may help select patients for curative treatment and lower the risk of TEF development.

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Combination of carmustine and selenite effectively inhibits tumor growth by targeting androgen receptor, androgen receptor-variants and Akt in preclinical models: New hope for patients with prostate cancer

Abstract

Despite established androgen receptor (AR) antagonists, AR/AR-variants signaling remain a major obstacle for the successful treatment of castration resistant prostate cancer (CRPC). In addition, CRPC cells adapt to survive via AR-independent pathways to escape next generation therapies. Therefore, there is an urgent need for drugs that can target these signaling pathways in CRPC. In the present study, we sought to determine whether carmustine and selenite in combination could induce apoptosis and inhibit growth of CRPC in-vitro and in-vivo. CRPC (22Rv1, VCaP and PC-3) cell culture and xenograft mouse model were used. Combination of carmustine and selenite treatment significantly increased reactive oxygen species, apoptosis and growth inhibition in CRPC cells with down regulation of anti-apoptotic (Bcl-2 and Mcl-1) and proliferative proteins (c-Myc and cyclin-D1). This effect was associated with complete reduction of AR/AR-variants, AR-V7, PSA and significant induction of p27Kip1. Combination treatment substantially abolished phospho-Akt, phospho-GSK-3β and anchorage-independent growth in AR-positive and AR-negative cells. Consistent with in-vitro results, combination treatment effectively induced apoptosis and completely inhibited xenograft tumor growth and markedly reduced AR/AR-variants, AR-V7, PSA, and Bcl-2 in xenograft tumors without causing genotoxicity in host mice. Individual agent treatment showed only partial effect. The combination treatment showed a significant synergistic effect. The present study is the first to demonstrate that the combination of carmustine and selenite treatment completely suppressed CRPC tumor growth by reducing AR/AR-variants and Akt signaling. Our findings suggest that the combination of carmustine and selenite could constitute a promising next-generation therapy for successful treatment of patients with CRPC. This article is protected by copyright. All rights reserved.

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