STUDY DESIGN: A case report. OBJECTIVES: To report a case of indirect repair of cerebrospinal fluid (CSF) leakage after cervical anterior foraminotomy using Surgicel® and fibrin glue. SUMMARY OF LITERATURE REVIEW: There is no single modality that is best practice for this type of case because it is difficult to apply primary repair for a case of CSF leakage after cervical anterior decompression. MATERIALS AND METHODS: A 49-year-old female patient was diagnosed with CSF leakage on the second day after cervical anterior foraminotomy. We performed coverage with Surgicel® and fibrin glue at the CSF leak site. RESULTS: The patient was treated with indirect repair of CSF leakage without any complications. The clinical and radiological outcomes were excellent upon follow-up 1 year postoperatively. CONCLUSIONS: Indirect repair using Surgicel® and fibrin glue is an effective treatment for postoperative CSF leakage after cervical anterior foraminotomy.
Cerebrospinal Fluid Leak* ; Cerebrospinal Fluid* ; Decompression ; Female ; Fibrin Tissue Adhesive* ; Fibrin* ; Follow-Up Studies ; Foraminotomy* ; Humans ; Middle Aged ; Practice Guidelines as Topic

Objective: Unlike cervical squamous cell carcinoma, there are no consensus criteria for serum tumor markers in cervical adenocarcinoma. This study aimed to identify the prognostic value of preoperative carbohydrate antigen 125 (CA125) levels in cervical adenocarcinoma patients with adverse pathologic features. Methods: A total of 105 patients who underwent radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiation therapy were included. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Cox proportional hazard regression model. Results: Using a cutoff value of 50 U/mL, 83 and 22 patients had low- and high-CA125, respectively. Patients with high-CA125 had a larger tumor size, more frequent parametrial extension, and more frequent lymph node metastasis than those with low-CA125. During a median follow-up of 59.3 (interquartile range, 32.7–97.8) months, patients with high-CA125 showed inferior 5-year LRFS, DMFS, and OS rates compared to those with low-CA125 (38.5% vs. 70.0%; 37.0% vs. 69.4%; 43.6% vs. 78.1%, respectively, all p<0.05). In multivariable analysis, the high-CA125 remained significant prognostic factor for LRFS, DMFS, and OS (all p<0.05). Furthermore, 12 patients with high-CA125 at recurrence exhibited lower 5-year OS rates than 21 patients with low-CA125 at recurrence (0.0% vs. 51.3%, p=0.003). Conclusion In this retrospective analysis, the serum CA125 level at diagnosis and recurrence was related to the extent of disease and prognosis of cervical adenocarcinoma with adverse pathologic features. A CA125 level of ≥50 U/mL may be a prognostic surrogate marker for cervical adenocarcinoma in patients with the presence of adverse factors.

Purpose: This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer. Materials and Methods: We identified 116 patients treated with definitive RT, including FDG-PET/CT–guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed. Results: We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax < 50% (n=29) (DFS, 76% vs. 35%, p < 0.001; OS, 90% vs. 41%, p < 0.001, respectively). Adenocarcinoma was frequently observed in ΔSUVmax < 50% compared to ΔSUVmax ≥ 50% (27.6% vs. 10.3%, p=0.003). In addition, models incorporating metabolic parameters showed improved accuracy for predicting DFS (p=0.012) and OS (p=0.004) than models with clinicopathologic factors. Conclusion Changes in metabolic parameters, especially those in SUVmax by > 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT.

Purpose: This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer. Materials and Methods: We identified 116 patients treated with definitive RT, including FDG-PET/CT–guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed. Results: We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax < 50% (n=29) (DFS, 76% vs. 35%, p < 0.001; OS, 90% vs. 41%, p < 0.001, respectively). Adenocarcinoma was frequently observed in ΔSUVmax < 50% compared to ΔSUVmax ≥ 50% (27.6% vs. 10.3%, p=0.003). In addition, models incorporating metabolic parameters showed improved accuracy for predicting DFS (p=0.012) and OS (p=0.004) than models with clinicopathologic factors. Conclusion Changes in metabolic parameters, especially those in SUVmax by > 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT.

Objective: The recently updated World Health Organization classification divides endocervical adenocarcinomas (ADCs) into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) ADCs. This study aimed to investigate the differences in the clinical features and treatment outcomes between patients with HPVA and HPVI. Methods: We retrospectively reviewed the electronic medical records and pathology slides of 123 patients with endocervical ADC who underwent radical hysterectomy and adjuvant radiation therapy. Tumor characteristics, patterns of failure, and survival outcomes were compared between HPVA and HPVI ADCs. Results: Eighty-one (65.9%) and 42 (34.1%) patients were diagnosed with HPVA and HPVI ADCs, respectively. HPVI ADC showed more frequent positive vaginal resection margin (VRM) and peritoneal seeding than HPVA ADC. After a median follow-up of 58.1 months, local recurrence and distant metastasis were more frequently observed in HPVI ADC than in HPVA ADC. Both local recurrence-free survival (77.3% vs. 91.8%) and distant metastasis-free survival (50.1% vs. 73.7%) rates of HPVI ADC were lower than those of HPVA ADC. Disease-free survival was not significantly different between HPVI and HPVA ADCs. Conclusion We demonstrated that HPVI ADC exhibited higher rates of VRM involvement and peritoneal seeding than those of HPVA ADC, resulting in higher rates of local recurrence and distant metastasis. Further studies with larger populations are warranted to explore optimal treatment strategies based on the histological subtypes of endocervical ADC.

OBJECTIVE: Tissue inhibitors of metalloproteinases (TIMPs) play a key role in maintaining homeostasis of the extracellular matrix (ECM) by controlling matrix metalloproteinases (MMPs). In addition to their role in regulating MMPs, TIMPs have also been shown to have pluripotential effects on cell growth, apoptosis and differentiation. The aim of this study was to examine TIMP-2 level in serous ovarian tumor tissues and to understand further the role of TIMP-2 protein in ovarian tumorigenesis. METHODS: Expression of TIMP-2 was assessed by immunohistochemistry in a total of 57 ovarian specimens including five normal ovaries, 12 benign serous cystadenomas, 20 serous borderline tumors and 20 serous carcinomas. RESULTS: The present study found that TIMP-2 immunostaining was significantly more frequent in serous carcinomas, mainly in tumor epithelium, compared with cells of the other tissues studied. CONCLUSION: TIMP-2 in serous ovarian carcinoma may function to favor tumor growth in serous ovarian tumorigenesis. Additional research is now needed to elucidate further the role of TIMP-2 in the biological behavior of ovarian serous tumors.
Apoptosis ; Carcinogenesis ; Cystadenoma, Serous ; Epithelium ; Extracellular Matrix ; Female ; Homeostasis ; Immunohistochemistry ; Matrix Metalloproteinases ; Metalloproteases ; Ovarian Neoplasms ; Ovary ; Tissue Inhibitor of Metalloproteinase-2

OBJECTIVE: The aim of this study was to investigate the association of phosphorylated AKT (pAKT) expression and radiation resistance in cervical cancer. METHODS: A retrospective review was made of the records of 25 women who received primary radiation therapy due to locally advanced cervical cancer (LACC) with FIGO stage IIB-IVA. Nine patients regarded as radiation resistant developed local recurrences with a median progression free interval of 10 months. Sixteen patients did not show local recurrences, and were regarded as a radiation sensitive group. Using pretreatment paraffin-embedded tissues, we evaluated pAKT expression by immunohistochemistry. RESULTS: A significant association was found between the level of pAKT expression and local recurrence. Immunohistochemical staining for pAKT was significantly more frequent in the radiation resistant than in the radiation sensitive group (p=0.007). The mean progression free survival (PFS) was 84 months for patients with pAKT negative staining (17 cases) and 44 months for patients with pAKT positive expression (8 cases)(p=0.015). CONCLUSION: These results suggest that signaling from PI3K/pAKT can lead to radiation resistance in LACC.
Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Negative Staining ; Recurrence ; Retrospective Studies ; Uterine Cervical Neoplasms*

OBJECTIVE: This study was to determine the expression of Toll-like receptor 4 (TLR-4) in ovarian serous adenocarcinoma tissues. METHODS: TLR-4 expression was evaluated at the RNA level by real-time quantitative RT-PCR, in 24 fresh frozen ovarian serous adenocarcinoma tissues and 9 normal ovarian tissues. TLR-4 expression was also evaluated by immunohistochemistry (IHC) in each three ovarian carcinoma tissues and normal ovarian tissues. RESULTS: Positive immunoreactivity for TLR-4 was observed in the normal ovarian tissues but not in the ovarian carcinoma tissues. The staining was localized in the cytoplasm as well as on the cell surface. Real-time quantitative RT-PCR revealed that TLR-4 expression was significantly lower in tumors than in normal ovarian tissues (p=0.0003). There were no significant correlations between clinical parameters and the expression level of TLR-4 mRNA in ovarian serous adenocarcinomas. However, tumors without LN metastasis (p=0.068) and lower grade (p=0.075) showed trends of higher TLR-4 mRNA expression. CONCLUSION: TLR-4 expression was significantly lower in ovarian serous adenocarcinoma tissues than in normal ovarian tissues, and further studies on TLR-4 signaling pathway in ovarian carcinoma are needed.
Adenocarcinoma ; Cytoplasm ; Immunohistochemistry ; Neoplasm Metastasis ; Ovarian Neoplasms* ; RNA ; RNA, Messenger ; Toll-Like Receptor 4

OBJECTIVE: Galectin-3, a member of the beta-galactoside-binding proteins, is an intracellular and extracellular lectin that interacts with intracellular glycoproteins, cell surface molecules and extracellular matrix proteins. Galectin-3 is expressed widely in epithelial and immune cells and the level of expression varies in many cancer cells relative to the normal tissues from which they arise. We investigated whether the expression of galectin-3 is associated with the progression of cervical neoplasia. METHODS: The galectin-3 expression was evaluated by immunohistochemistry in 90 formalin-fixed paraffin-embedded cervical tissues: 10 normal cervical specimens, 20 low-grade squamous intraepithelial lesions (LSILs), 20 high-grade squamous intraepithelial lesions (HSILs), and 40 invasive squamous cell carcinomas (ISCCs). RESULTS: The immunohistochemical staining showed that the expression of galectin-3 was strong in all normal cervical squamous epithelia. Staining gradually decreased in accordance with the histopathologic grades from an LSIL to an HSIL and an ISCC (P<0.001). In particular, the expression of galectin-3 was significantly decreased in HSILs (P=0.001) and this down-regulation was more pronounced in ISCCs than normal tissues (P<0.001). CONCLUSION: These data constitute the first observation that the expression of galectin-3 is down-regulated in cervical cancer tissues and suggest the decreased expression of this galactoside-binding lectin is associated with the progression of cervical neoplasia.
Carcinoma, Squamous Cell ; Cervical Intraepithelial Neoplasia ; Down-Regulation ; Extracellular Matrix Proteins ; Galectin 3* ; Immunohistochemistry ; Membrane Glycoproteins ; Uterine Cervical Neoplasms

PURPOSE: This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H⁺ ATPase (V-ATPase) in cervical cancer. MATERIALS AND METHODS: The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively. RESULTS: Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co-treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05). CONCLUSION: V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V-ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells.
Adenocarcinoma ; Adenosine Triphosphatases ; Antineoplastic Agents ; Apoptosis ; Caspase 3 ; Cell Line ; Cell Proliferation ; Disease-Free Survival ; Enzyme-Linked Immunosorbent Assay ; Esomeprazole ; Humans ; Immunohistochemistry ; Paclitaxel* ; Prognosis ; Proton Pump Inhibitors ; Proton Pumps* ; Protons* ; Risk Factors ; RNA, Small Interfering ; Transfection ; Uterine Cervical Neoplasms* ; Vacuolar Proton-Translocating ATPases