Margins for cervical and vulvar cancer

Khanna, Namita; Rauh, Lisa A.; Lachiewicz, Mark; Horowitz, Ira

doi:10.1002/jso.24108

Cited by 27 publications

(20 citation statements)

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“…Margin clearance of at least 5 mm from invasive tumor site has been associated with improved oncological outcomes in cervical cancer surgery (13,29). When this is not achieved, adjuvant radiotherapy has been found to improve overall survival (13,(29)(30)(31) at the cost of substantial morbidity. Radiotherapy can adversely affect quality of life and lead to vaginal stenosis, sexual dysfunction, and bowel and bladder symptoms (32,33).…”

Section: Discussionmentioning

confidence: 99%

“…In this study the iKnife had accuracy that was better than that reported for frozen section when compared to gold-standard histology between malignant and healthy tissue. Frozen section requires infrastructure (39) and prolongs operating time (29,39), while the iKnife can give nearly real-time (3 s) diagnosis without any tissue preparation, allowing immediate excision of further tissue if deemed necessary by the surgeon. A future surgical model may include sentinel lymph node dissection, which is currently tested in clinical trials (40), with on-the-spot iKnife diagnosis of presence of disease.…”

Section: Discussionmentioning

confidence: 99%

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The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

Tzafetas

Mitra

Paraskevaidi

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.REIMS | cervical cancer | mass spectrometry | iKnife | fertility preservation

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

Tzafetas

Mitra

Paraskevaidi

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…A positive surgical margin is widely recognized as a significant risk factor for the recurrence of cervical cancer [61,62] . In the present study, the existence of cancer tissue within the area of surgical incision was confirmed in only 13 patients (12.7%), comparable to previously reported results [40,43] .…”

Section: Discussionmentioning

confidence: 99%

Prognostic Parameters for Patients with Cervical Cancer FIGO Stages IA2-IIB: A Long-Term Follow-Up

Obrzut¹,

Semczuk

Naróg

et al. 2017

Oncology

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Objective: We assessed the prognostic factors related to 10-year overall survival and disease-free survival in cervical cancer patients that underwent primary surgical protocols in 1 institution. Materials and Methods: A total of 102 patients with uterine cervical cancer at FIGO stages IA2-IIB that underwent a Piver type III radical hysterectomy and pelvic lymphadenectomy between 1998 and 2001 were included. Univariate and multivariate analyses of 10-year overall survival and 10-year disease-free survival were performed. Results: Univariate analysis revealed that only lymphovascular space invasion significantly affected 10-year overall survival (p = 0.04), but it had no effect on the 10-year disease-free survival rate. Multivariate analysis demonstrated that survival rates were significantly affected by FIGO stage (p = 0.02, 95% CI: 1.18-5.55, for 10-year overall survival; p = 0.03, 95% CI: 1.07-6.12, for 10-year disease-free survival) and metastases to the pelvic lymph nodes (p = 0.0005, 95% CI: 1.81-8.53, for 10-year overall survival; p = 0.01, 95% CI: 1.26-7.24, for 10-year disease-free survival). Conclusions: The only independent prognostic factors for 10-year survival rates in patients with cervical cancer at FIGO stages IA2-IIB were clinical stage and presence of metastases to the pelvic lymph nodes. The presence of lymphovascular space invasion adversely affected 10-year overall survival.

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“…CK5 is known to have high levels of expression in squamous cell carcinomas and can be used as a marker of differentiation, with weaker to no expression in adenocarcinomas [ 22 ]. Given squamous cell carcinomas account for over 90% of all vulvar cancers and that CK5 is a structural protein of basal epithelial cells [ 23 ], the detection of CK5 by both MALDI-MSI was to be expected. A study characterizing the expression of CK5 in serous gynecological carcinomas of the ovaries, endometrium, fallopian tube, primary peritoneum, and cervix observed the highest level of CK5 expression in the cervical and ovarian serous carcinomas, with little to no reactivity in the endometrial, fallopian tube, or primary peritoneum serous carcinomas [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, tissues were sectioned 8 μm thick and mounted on the Indium-Tin-Oxide (ITO) coated glass slides (Bruker Daltonics, Bremen, Germany) by heating at 60 °C for 1 h. Tissues were deparaffinised in xylene for 5 min, following by two 2 min incubations in 100% ethanol, and two 5 min incubations in 100 mM NH 4 HCO 3 . The tissues were then subjected to heat induced citric acid antigen retrieval (CAAR) (10 mM citric acid, pH = 6) [ 26 ] followed by digestion with trypsin gold (Promega, Madison, WI, USA) using an ImagePrep station (Bruker Daltonics, Bremen, Germany) at 37 °C for 2 h. Peptide Internal calibrants (Angiotensin I, [Glu1]-Fibrinopeptide B, Dynorphin A and ACTH fragment [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]) and α-cyano-4-hydroxycinnamic acid (CHCA) matrix was overlaid onto the tissue sections using an ImagePrep station (Bruker Daltonics, Bremen, Germany) [ 27 ]. An ultrafleXtreme MALDI-TOF/TOF MS system (Bruker Daltonics, Bremen, Germany) was used for data acquisition in positive reflectron mode as monitored by flexControl (V3.0.1 Bruker Daltonics, Bremen, Germany) using following settings: 2 kHz, m / z 800–4000, with 100 μm spatial resolution.…”

Section: Methodsmentioning

confidence: 99%

MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia

Zhang

Arentz

Winderbaum

et al. 2016

IJMS

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Vulvar cancer is the fourth most common gynecological cancer worldwide. However, limited studies have been completed on the molecular characterization of vulvar squamous cell carcinoma resulting in a poor understanding of the disease initiation and progression. Analysis and early detection of the precursor lesion of HPV-independent vulvar squamous cell carcinoma (VSCC), differentiated vulvar intraepithelial neoplasia (dVIN), is of great importance given dVIN lesions have a high level of malignant potential. Here we present an examination of adjacent normal vulvar epithelium, dVIN, and VSCC from six patients by peptide Matrix-assisted laser desorption/ionization Mass Spectrometry Imaging (MALDI-MSI). The results reveal the differential expression of multiple peptides from the protein cytokeratin 5 (CK5) across the three vulvar tissue types. The difference observed in the relative abundance of CK5 by MALDI-MSI between the healthy epithelium, dVIN, and VSCC was further analyzed by immunohistochemistry (IHC) in tissue from eight VSCC patients. A decrease in CK5 immunostaining was observed in the VSCC compared to the healthy epithelium and dVIN. These results provide an insight into the molecular fingerprint of the vulvar intraepithelial neoplasia that appears to be more closely related to the healthy epithelium than the VSCC.

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Margins for cervical and vulvar cancer

Cited by 27 publications

References 50 publications

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

Prognostic Parameters for Patients with Cervical Cancer FIGO Stages IA2-IIB: A Long-Term Follow-Up

MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia

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