Clinical Impact of Intraoperative Cytological Assessment of Bone Resection Margins in Patients with Head and Neck Carcinoma

Abstract

Background

Surgical treatment of head and neck squamous cell carcinoma (HNSCC) patients often results in complex defects, affecting functional structures. Frozen sections are valuable to guide resections and control for adequate margins; however, intraoperative assessment of bone remains challenging.

Objective

The objective of this study was to evaluate the clinical impact of an intraoperative cytological assessment of bone margins (ICAB) on resection status and patient outcome.

Methods

ICAB analysis (n = 267) was implemented in 102 patients during resection of HNSCC for a guided resection of affected bone. The cytological findings were compared with the final histological results of the corresponding bone margins, and the surgical consequences, R1 rates, and patient outcome of the ICAB intervention group were compared with an equal control group of 100 patients.

Results

ICAB revealed a sensitivity of 94.4 % [95 % confidence interval (CI) 81.3–99.3], specificity of 97.4 % (95 % CI 94.4–99.0), positive predictive value of 85.0 % (95 % CI 70.2–94.3), and negative predictive value of 99.1 % (95 % CI 96.9–99.9). Osseous R1 resections were reduced from 8 to 2.9 % (∆R1 = 5.1 %; p = 0.113), rendering a relative risk reduction (RRR) of 63.2 % with a number needed to treat (NNT) of 19.57. ICAB influenced final resection status, with a reduction of R1 resections from 17 to 7.8 % (∆R1 = 9.2 %; p = 0.026), with an RRR of 59.65 % and an NNT of 9.66. The ICAB intervention group revealed a higher disease-free survival [p(log-rank) = 0.045] and overall survival [p(log-rank) = 0.014] according to multivariable analysis.

Conclusion

ICAB, applied as a routine diagnostic tool to supplement frozen sections, can help to reduce R1 resections in order to improve patient outcome.

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A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma

Abstract

Background

Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion.

Method

We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites.

Results

Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group.

Conclusion

Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].

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Sentinel Node Mapping in Cervical and Endometrial Cancer: Indocyanine Green Versus Other Conventional Dyes—A Meta-Analysis

Abstract

Background

Historically, blue dyes, ⁹⁹Tc or a combination of the two tracers have been used for sentinel lymph node (SLN) mapping in cervical and endometrial cancer patients. Indocyanine green (ICG), as a tracer, has been recently introduced in this setting. Our goal was to assess the differences in overall and bilateral detection rates as well as in false-negative rates among the different tracers.

Methods

The electronic databases PubMed, MEDLINE, and Scopus were searched in January 2016 by searching the terms "sentinel lymph node" and "dye" and "indocyanine green," and "cervical cancer" or "endometrial cancer." Series comparing different tracers injected intracervically and reporting the detection rate and/or SLN false-negative rate were selected.

Results

Forty-five studies were retrieved. Six studies including 538 patients met selection criteria. Compared with blue dyes, ICG SLN mapping had higher overall (odds ratio [OR] 0.27; 95 % confidence interval [CI] 0.15–0.50; p < 0.0001) and bilateral detection rates (OR 0.27; 95 % CI 0.19–0.40; p < 0.00001). No differences were found between ICG and ⁹⁹TC, although these results are based on data of a single series. No differences in overall and bilateral detection rates were found between ICG and the combination of blue dyes and ⁹⁹TC. The pooled analysis of false-negative rates data showed no difference in false-negative rates between tracers.

Conclusions

In cervical and endometrial cancer, ICG SLN mapping seems to be equivalent to the combination of blue dyes and ⁹⁹TC in terms of overall and bilateral detection rates. Its safety profile and ease of use may favor its employment respect to conventional tracers.

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Do LORIS Trial Eligibility Criteria Identify a Ductal Carcinoma In Situ Patient Population at Low Risk of Upgrade to Invasive Carcinoma?

Abstract

Background

The Surgery Versus Active Monitoring for Low-Risk DCIS (LORIS) trial is studying the safety of monitoring core-biopsy diagnosed low-risk ductal carcinoma in situ (DCIS) without excision. We sought to determine the incidence and characteristics of synchronous invasive carcinoma found in LORIS-eligible women who underwent excision, as this knowledge is essential in assessing the safety of observation alone.

Methods

Women meeting LORIS eligibility criteria (age ≥46 years, screen-detected calcifications, non-high-grade DCIS diagnosed by core biopsy, absence of nipple discharge, or strong family history of breast cancer) who underwent surgical excision from 2009 to 2012 were identified. Histologic findings of excision specimens were reviewed.

Results

Overall, 296 LORIS-eligible cases were identified; 58 (20 %) had invasive carcinoma on final pathology (90 % invasive ductal, 78 % >1 mm in size, 21 % high grade, 3 % triple negative, 9 % HER2 amplified). Of these, 18 (31 %) were pT1b or larger and 3 (5 %) were pN1. Among eligible upgraded cases, 90 % received radiation, 89 % received endocrine therapy, and 18 % were recommended chemotherapy. Women upgraded to invasive carcinoma were more likely to have intermediate-grade DCIS on core biopsy and to have undergone mastectomy.

Conclusions

Among LORIS-eligible women, 20 % had invasive carcinoma at surgical excision that was heterogeneous in grade, size, and receptor status. Information gained from surgical excision influenced receipt of adjuvant radiation and endocrine therapy in most patients, and indicated benefit from chemotherapy in 18 % of patients. Surgical excision is warranted until additional risk stratification is available to identify a cohort of DCIS patients at lower risk for clinically significant synchronous invasive carcinoma.

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Neoadjuvant Systemic Therapy for Breast Cancer: Factors Influencing Surgeons’ Referrals

Abstract

Background

This study aimed to assess the influence of disease- and patient-related factors on surgeons' decisions to refer patients with early-stage breast cancer (EBC) for neoadjuvant systemic therapy (NST).

Methods

An online survey of United States surgeons evaluated the influence of selected disease- and patient-related factors on surgeons' decisions, rated their influence (individually and in combination), and provided a relative ranking of jointly considered factors using best–worst scaling.

Results

The participants in this study were 100 licensed surgeons. The surgeons referred approximately 25 % of EBC patients for NST to improve surgical management. Approximately 75 % of the surgeons agreed that NST is important for EBC, if only to improve surgical management. More than half were "very likely" to refer EBC patients for NST based on anatomicopathologic factors. Less than 50 % were "very likely" to do so when considering tumor phenotype factors. Tumor size and lymph node status were ranked highest in hypothetical patient scenarios. Regarding combinations of factors, the importance of any single factor varied according to the combinations presented. Less than half of the respondents were "very familiar," and half were "somewhat familiar" with NST guidelines for breast cancer. More than half of the respondents were unaware that findings have shown achievement of pathologic complete response (pCR) after NST to be associated with improved survival.

Conclusions

Surgeons' decision to refer for NST is strongly driven by surgical management goals. Anatomicopathologic factors are more influential than tumor phenotype. However, no single disease or patient factor consistently drives the decision to refer for NST. Surgeons' awareness of the association between pCR achievement and longer survival could be improved.

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Targeting proprotein convertases in furin-rich lung cancer cells results in decreased in vitro and in vivo growth

ABSTRACT

Proprotein convertases (PCs) are serine proteases with an active role in the post-translational processing of numerous inactive proteins to active proteins including many substrates of paramount importance in cancer development and progression. Furin (PCSKC3), a well-studied member of this family, is overexpressed in numerous human and experimental malignancies. In the present communication we treated two furin-overexpressing non-small cell carcinoma (NSCLC) cell lines (Calu-6 andHOP-62) with the PC inhibitor CMK (Decanoyl-Arg-Val-Lys-Arg-chloromethylketone). This resulted in a diminished IGF-1R processing and a simultaneous decrease in cell proliferation of two NSCLC lines. Similarly, growth and proliferation of subcutaneous xenografts of both cell lines, were partially inhibited by an in vivo treatment with the same drug. These observations point to a potential role of PC inhibitors in cancer therapy. This article is protected by copyright. All rights reserved

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Protective effect of metformin in an aberrant crypt foci model induced by 1,2-dimethylhydrazine: Modulation of oxidative stress and inflammatory process

Abstract

Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET - an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2-dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. This article is protected by copyright. All rights reserved

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