Treatment of vulvar cancer recurrence with electrochemotherapy: a case-control study.

BACKGROUND: Electrochemotherapy (ECT) is a combined treatment method based on electroporation and simultaneous chemotherapy. In cases where radiotherapy has previously been used, surgery is often the only treatment option for vulvar cancer recurrence with potential resection of clitoris, vagina, urethra or anal sphincter. The unique advantage of ECT is its selectivity for cancer cells while sparing the surrounding healthy tissue. The aim of the study was to compare the ECT treatment of vulvar cancer recurrence for non-palliative purposes with surgical treatment. MATERIALS AND METHODS: Eleven patients with single vulvar cancer recurrence were treated with ECT and followed up for 12 months. As a control group, 15 patients with single vulvar cancer recurrence were treated with wide local excision. The following data were collected, analyzed and compared: Age, body mass index, comorbidities, histological type, location and size of vulvar cancer recurrence, treatment history, details of procedures and hospital stay. RESULTS: The probability curves for local tumor control did not differ between the ECT group and the surgical group (p = 0.694). The mean hospital stay and the mean duration of procedure were statistically significantly shorter in the ECT group (p < 0.001). There were no statistically significant differences between the ECT and surgical groups in terms of mean body mass index, associated diseases, previous treatments, presence of lichen sclerosus, p16 status, gradus, anatomical site of the tumor, and type of anesthesia. CONCLUSION: In this case-control study, treatment of vulvar cancer recurrence with ECT for non-palliative purposes was comparable to surgical treatment in terms of effectiveness. The results need to be confirmed in larger randomized trials.

High-Grade Serous Ovarian Cancer during Pregnancy: From Diagnosis to Treatment.

BACKGROUND: Due to the rarity of ovarian cancer diagnosed during pregnancy, the literature on the treatment of subtypes of epithelial ovarian cancer in pregnancy is sparse. The aim of our review was to analyze cases of high-grade serous ovarian cancer in pregnancy. METHODS: The PubMed and Scopus databases were searched for relevant articles published in English between January 2000 and December 2023. The references of all the relevant reviews found were also checked to avoid omitting eligible studies. Information on the all retrieved cases was extracted and reviewed in detail. The most important detail was the subtype of high-grade serous ovarian cancer, which was referred to as serous adenocarcinoma (grade 2 or grade 3) in older cases. RESULTS: We found eleven cases with relevant details of high-grade serous ovarian cancer diagnosed in pregnancy. Despite the small number of cases we found, our study demonstrated the importance of an accurate initial vaginal ultrasound at the first examination in pregnancy and the safety of diagnostic surgery and chemotherapy in pregnancy. CONCLUSIONS: There have not been long-term follow-ups of patients' oncologic and obstetric outcomes. As patients should be comprehensively informed, more detailed case reports or series with longer follow-up periods are needed.

A Population-Based Study of Patients With Small Cell Carcinoma of the Ovary, Hypercalcemic Type, Encompassing a 30-Year Period.

CONTEXT.­: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor, characterized by hypercalcemia and early onset and associated with germline and somatic SMARCA4 variants. OBJECTIVE.­: To identify all known cases of SCCOHT in the Slovenian population from 1991 to 2021 and present genetic testing results, histopathologic findings, and clinical data for these patients. We also estimate the incidence of SCCOHT. DESIGN.­: We conducted a retrospective analysis of hospital medical records and data from the Slovenian Cancer Registry in order to identify cases of SCCOHT and obtain relevant clinical data. Histopathologic review of tumor samples with assessment of immunohistochemical staining for SMARCA4/BRG1 was undertaken to confirm the diagnosis of SCCOHT. Germline and somatic genetic analyses were performed using targeted next-generation sequencing. RESULTS.­: Between 1991 and 2021, we identified 7 cases of SCCOHT in a population of 2 million. Genetic causes were determined in all cases. Two novel germline loss-of-function variants in SMARCA4 LRG_878t1:c.1423_1429delTACCTCA p.(Tyr475Ilefs*24) and LRG_878t1:c.3216-1G>T were identified. At diagnosis, patients were ages 21 to 41 and had International Federation of Gynecology and Obstetrics, or FIGO, stage IA-III disease. Outcomes were poor, with 6 of 7 patients dying of disease-related complications within 27 months from diagnosis. One patient had stable disease for 12 months while receiving immunotherapy. CONCLUSIONS.­: We present genetic, histopathologic, and clinical characteristics for all cases of SCCOHT identified in the Slovenian population during a 30-year period. We report 2 novel germline SMARCA4 variants, possibly associated with high penetrance. We estimate the minimal incidence of SCCOHT to be 0.12 per 1 million per year.

Vascular and Urinary Tract Anatomic Variants Relevant to Para-Aortic Lymphadenectomy in Women with Gynecological Cancers.

BACKGROUND: Para-aortic lymphadenectomy is an essential part of gynecologic oncologic surgical treatment. The surgeon should be aware of the complex usual anatomy and its common variants. METHODS: Between January 2021 and May 2023, 58 women underwent para-aortic lymphadenectomy for gynecologic malignancies. RESULTS: Vascular and urinary tract anatomic variants were retrospectively reviewed from the prospective institutional database and results were compared with preoperative contrast-enhanced abdominal CT. Of these 58 women, 47 women had no vascular or urinary tract variants. One woman had a double inferior vena cava, two patients were found to have a retro-aortic left renal vein, four had accessory renal arteries, two had a double left ureter, one had a ptotic kidney in the iliac fossa, and one patient had bilateral kidney malrotation. Anatomic variants in the preoperative CT were described by a radiologist in only two patients, and additional vascular and urinary tract variants were found incidentally at the time of surgery. CONCLUSIONS: Acknowledgment of vascular and urinary tract variants is helpful for the surgeon to establish an appropriate surgical plan and to avoid iatrogenic surgical trauma.

Modern approach to the management of genitourinary syndrome in women with gynecological malignancies.

BACKGROUND: The term genitourinary syndrome of menopause was first used in 2014 by the North American Menopause Society and the International Society for the Study of Women's Sexual Health to describe conditions previously known as atrophic vaginitis, urogenital atrophy, or vulvovaginal atrophy. It is a complex, chronic, progressive condition characterized by a wide range of signs and symptoms affecting sexual function and the tissues of the urinary and genital tracts. The main cause of genitourinary syndrome of menopause is estrogen deficiency caused by ovarian removal or dysfunction. The most bothersome symptoms are vaginal dryness, decreased vaginal lubrication, and pain during penetration and intercourse. They all have a negative impact on the quality of life. CONCLUSIONS: The main goal of treatment is to relieve the symptoms. Treatment modalities are pharmacological or non-pharmacological. The first-line treatment for mild to moderate symptoms is the use of personal lubricants and moisturizers, but the gold standard is estrogen replacement therapy. Hormone therapy may not be an option for women with hormone-dependent cancer.

Safety and Feasibility of Vulvar Cancer Treatment with Electrochemotherapy.

Electrochemotherapy is a local ablative therapy used for the treatment of various superficial and deep-seated tumors. Electrochemotherapy involves the application of electric pulses locally to tumors to destabilize cell membranes and facilitate the entry of cytotoxic drugs, thereby enhancing their cytotoxicity locally. The aim of our study is to investigate the safety and feasibility of electrochemotherapy in patients with vulvar cancer recurrence used for nonpalliative purposes. Ten patients with single local vulvar cancer recurrence were treated with intravenous bleomycin, followed by a local application of electric pulses (electrochemotherapy) to the tumor. Adverse events were determined using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The feasibility of treating vulvar cancer with electrochemotherapy was determined by an appropriate selection of electrodes based on the size and location of the tumor with safety margins included. Electrochemotherapy was feasible in all patients. No electrochemotherapy-related or other serious adverse events occurred. Our data suggest that electrochemotherapy is a feasible and safe technique for the treatment of vulvar cancer recurrence for nonpalliative purposes. Based on our results, electrochemotherapy might be a viable therapeutic tool for patients who would otherwise undergo surgery involving a mutilation of the external genitalia.

Treatment of vulvar cancer recurrences with electrochemotherapy - a detailed analysis of possible causes for unsuccessful treatment.

BACKGROUND: Electrochemotherapy has good local effectiveness in the treatment of vulvar cancer. Most studies have reported the safety and effectiveness of electrochemotherapy for palliative treatment of gynecological cancers and mostly vulvar squamous cell carcinoma. Some tumors, however, fail to respond to electrochemotherapy. The biological features/determinants for the nonresponsiveness are not determined yet. PATIENT AND METHODS: A recurrence of vulvar squamous cell carcinoma was treated by electrochemotherapy using intravenous administration of bleomycin. The treatment was performed by hexagonal electrodes according to standard operating procedures. We analyzed the factors that could determine nonresponsiveness to electrochemotherapy. RESULTS: Based on the presented case of nonresponsive vulvar recurrence to electrochemotherapy, we hypothesize that the vasculature of the tumors prior to treatment may predict the response to electrochemotherapy. The histological analysis showed minimal presence of blood vessels in the tumor. Thus, low perfusion may reduce drug delivery and lead to a lower response rate because of the minor antitumor effectiveness of vascular disruption. In this case, no immune response in the tumor was elicited by electrochemotherapy. CONCLUSIONS: In this case, of nonresponsive vulvar recurrence treated by electrochemotherapy, we analyzed possible factors that could predict treatment failure. Based on histological analysis, low vascularization of the tumor was observed, which hampered drug delivery and distribution and resulted in no vascular disrupting action of electro-chemotherapy. All these factors could contribute to ineffective treatment with electrochemotherapy.

Electrochemotherapy as an Alternative Treatment Option to Pelvic Exenteration for Recurrent Vulvar Cancer of the Perineum Region.

Objective: Pelvic exenteration in women with recurrent vulvar carcinoma is associated with high morbidity and mortality and substantial treatment costs. Because pelvic exenteration severely affects the quality of life and can lead to significant complications, other treatment modalities, such as electrochemotherapy, have been proposed. The aim of this study was to evaluate the feasibility and suitability of electrochemotherapy in the treatment of recurrent vulvar cancer. We aimed to analyze the treatment options, treatment outcomes, and complications in patients with recurrent vulvar cancer of the perineum. Methods: A retrospective analysis of patients who had undergone pelvic exenteration for vulvar cancer at the Institute of Oncology Ljubljana over a 16-year period was performed. As an experimental, less mutilating treatment, electrochemotherapy was performed on one patient with recurrent vulvar cancer involving the perineum. Comparative data analysis was performed between the group with pelvic exenteration and the patient with electrochemotherapy, comparing hospital stay, disease recurrence after treatment, survival after treatment in months, and quality of life after treatment. Results: We observed recurrence of disease in 2 patients with initial FIGO stage IIIC disease 3 months and 32 months after pelvic exenteration, and they died of the disease 15 and 38 months after pelvic exenteration. Two patients with FIGO stage IB were alive at 74 and 88 months after pelvic exenteration. One patient with initial FIGO stage IIIC was alive 12 months after treatment with electrochemotherapy with no visible signs of disease progression in the vulvar region, and the lesions had a complete response. The patient treated with electrochemotherapy was hospitalized for 4 days compared with the patients with pelvic exenteration, in whom the average hospital stay was 19.75 (± 1.68) days. Conclusion: Our experience has shown that electrochemotherapy might be a less radical alternative to pelvic exenteration, especially for patients with initially higher FIGO stages.

Literature Review and Our Experience With Bleomycin-Based Electrochemotherapy for Cutaneous Vulvar Metastases From Endometrial Cancer.

Endometrial carcinoma is the most common gynecological malignancy and the fifth most common malignancy in women. The worldwide incidence is 15.9 new cases per 100,000 women per year, and the incidence in Europe is 22.7 new cases. Minority of cases are diagnosed at an advanced stage of the disease. Cutaneous metastases are very rare with a prevalence of 0.8%. If cutaneous metastases are present, the prognosis is poor with an overall survival of up to 12 months. In this review, we presented clinical data on treatment of gynecological cancers with electrochemotherapy, with focus on treatment of cutaneous vulvar metastases from endometrial cancer. Further, we present our data on the case of a 64-year-old woman with recurrent endometrial adenocarcinoma with vulvar skin metastases. Treatment of endometrial carcinoma metastases is multimodal with surgery, chemotherapy, radiotherapy and hormone treatment. There is still no consensus about the specific treatment of cutaneous metastases from endometrial cancer, in particular in order to release symptoms. Electrochemotherapy may be a treatment option to reduce pain and bleeding and a safe option to treat multiple skin metastases.

Preoperative serum CA-125 level as a predictor for the extent of cytoreduction in patients with advanced stage epithelial ovarian cancer.

BACKGROUND: Ovarian cancer is the seventh most common cancer in women worldwide and the eighth most common cause of cancer death. Due to the lack of effective early detection strategies and the unspecific onset of symptoms, it is diagnosed at an advanced stage in 75% of cases. The cancer antigen (CA) 125 is used as a prognostic marker and its level is elevated in more than 85% of women with advanced stages of epithelial ovarian cancer (EOC). The standard treatment is primary debulking surgery (PDS) followed by adjuvant chemotherapy (ACT), but the later approach is neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Several studies have been conducted to find out whether preoperative CA-125 serum levels influence treatment choice, surgical resection and survival outcome. The aim of our study was to analyse experience of single institution as Cancer comprehensive center with preoperative usefulness of CA-125. PATIENTS AND METHODS: At the Institute of Oncology Ljubljana a retrospective analysis of 253 women with stage FIGO IIIC and IV ovarian cancer was conducted. Women were divided into two groups based on their primary treatment. The first group was the NACT group (215 women) and the second the PDS group (38 women). The differences in patient characteristics were compared using the Chi-square test and ANOVA and the Kaplan-Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). RESULTS: The median serum CA-125 level was higher in the NACT group than in the PDS group, 972 IU/ml and 499 IU/ ml, respectively. The PFS in the NACT group was 8 months (95% CI 6.4-9.5) and 18 months (95% CI 12.5-23.4) in the PDS group. The median OS was lower in the NACT group than in the PDS group, 25 months (95% CI 20.6-29.5) and 46 months (95% CI 32.9-62.1), respectively. CONCLUSIONS: Preoperative CA-125 cut off value of 500 IU/ml is a promising threshold to predict a successful PDS.

Hypercalcemia and Unilateral Ovarian Mass in a Young Adult: A Case Report of Small Cell Ovarian Carcinoma.

BACKGROUND Small cell ovarian carcinoma, hypercalcemic type is an uncommon malignant ovarian tumor entity with an unfavorable prognosis and a short overall survival rate. It mainly affects women of childbearing age. CASE REPORT We report a case in which a 31-year-old woman with small cell ovarian carcinoma, hypercalcemic type presented with unspecific symptoms. We emphasize the importance of treatment planning and address fertility-sparing surgical procedures, which remain a therapeutic dilemma. CONCLUSIONS The occurrence of unspecific abdominal symptoms, unilateral tumor masses, and hypercalcemia may indicate the presence of malignant ovarian neoplasm in young adults. Histopathological examination of the mass should be performed by an experienced gynecological pathologist. A misdiagnosis can lead to inadequate surgical and adjuvant treatment. Adjuvant multi-agent chemotherapy and high-dose chemotherapy with autologous stem cell rescue may prolong the progression-free interval and overall survival.

Modern treatment of vulvar cancer.

Background Vulvar cancer accounts for 3-5% of malignant diseases of the female genital tract. The Slovenian incidence rate is 5.5/100,000, which means 57 new cases per year. The most common histological type (90%) is squamous cell carcinoma. Based on etiology, it can be classified into the first type which correlates with human papillomavirus (HPV) infection and the second type which is not associated with HPV. The most common and long-lasting symptom of vulvar cancer is pruritus. The preferred diagnostic procedure to confirm the diagnosis is a punch or incision biopsy. Surgery in combination with radiotherapy is the standard treatment for vulvar cancer. Sentinel lymph node biopsy with lymphoscintigraphy is now a standard part of surgical treatment. Chemotherapy is a palliative treatment option. Conclusions Vulvar cancer is a rare disease. Because of the pathogenesis, surgery and radiotherapy are the main treatment modalities. The sentinel node biopsy (SNB) represents a contemporary approach to the vulvar cancer treatment and significantly reduces morbidity. Improvements in treatment of vulvar cancer contributed to the decrease of mortality among Slovenian women.

The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer.

BACKGROUND: Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. METHODS: We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005-2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. RESULTS: Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. CONCLUSIONS: Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery.

Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM.