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.

Evaluation of an Early Individualized Integrated Rehabilitation Program versus Standard Rehabilitation Program for Smoking Cessation in 115 Smokers Among 467 Female Breast Cancer Patients 2019-2021 in Slovenia.

BACKGROUND Cigarette smoking affects cancer risk and cardiovascular risk. Smoking cessation is very beneficial for health. This study aimed to evaluate an early individualized integrated rehabilitation program and standard rehabilitation program for smoking cessation in breast cancer patients. MATERIAL AND METHODS This prospective study included 467 breast cancer patients (29-65 (mean 52) years of age) treated at the Institute of Oncology Ljubljana from 2019 to 2021 and were followed longer than 1 year. The control group and intervention group included 282 and 185 patients, respectively. Three questionnaires were completed by patients before and 1 year after the beginning of oncological treatment. The intervention group received interventions according to the patient's needs, while the control group underwent standard rehabilitation. The data obtained from the survey were analyzed using the chi-square test and analysis of variance. RESULTS In total, 115 patients were tobacco smokers before the beginning of cancer treatment. There were no differences between the intervention and control group in the prevalence of smoking before the treatment. Before the cancer treatment, smoking was present in the intervention group in 22% and in control group in 27% (P=0.27). One year after the beginning of cancer treatment, smoking was present in the intervention group in only 10% of cases, while it was present in control group in 20% of cases. Smoking was significantly less common in the intervention group than in the control group (P=0.004). CONCLUSIONS Smoking cessation was more common after early integrated rehabilitation than after standard rehabilitation.

Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists.

BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.

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.

Impact of early integrated rehabilitation on fatigue in 600 patients with breast cancer - a prospective study.

BACKGROUND: Fatigue after breast cancer treatment is a common burden that is challenging to treat. The aim of this study was to explore if such integrated rehabilitation program reduces the prevalence of chronic fatigue compared to simple, non-integrated rehabilitation. PATIENTS AND METHODS: The subjects of our prospective study were 600 female breast cancer patients (29-65 [mean 52 years] of age), who participated in the pilot study on the individualized integrated rehabilitation of breast cancer patients in 2019-2021 and were monitored for one year. The control group included 301 patients and the intervention group numbered 299 patients. The patients completed three questionnaires (EORTC QLQ-C30, -BR23 and NCCN): before cancer treatment, and then six and twelve months after the beginning of cancer treatment. The control group obtained the standard rehabilitation program, while the intervention group was part of the early, individualized multidisciplinary and integrated approach of rehabilitation. The rehabilitation coordinator referred patients for additional interventions (e.g., psychologist, gynecologist, pain management team, physiotherapy, clinical nutrition team, kinesiologist-guided online training, vocational rehabilitation, general practitioner). Data on the patients' demographics, disease extent, cancer treatment and complaints reported in questionnaires were collected and analyzed. RESULTS: There were no differences between the control and the intervention group of patients in terms of age, education, disease extent, surgical procedures, systemic cancer treatment, or radiotherapy, and also no differences in the fatigue before the beginning of treatment. However, patients from the control group had a greater level of constant fatigue than patients from the intervention group half a year (p = 0.018) and a year (p = 0.001) after the beginning of treatment. Furthermore, a greater proportion of patients from the control group experienced significant interference with their usual activities from fatigue than from the intervention group, half a year (p = 0.042) and a year (p = 0.001) after the beginning of treatment. A multivariate logistic regression showed that one year after the beginning of treatment, the only independent factor correlated to fatigue was inclusion into the intervention group (p = 0.044). Inclusion in the intervention group was beneficial-patients from the control group were 1.5 times more likely to be fatigued. CONCLUSIONS: Early individualized integrated rehabilitation is associated with a lower prevalence of chronic fatigue or fatigue interfering with usual activities in breast cancer patients in comparison to the control group of patients.

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.

Association of Maternal Antenatal Education with Quality of Life after Childbirth in the Slovenian Population before and during the COVID-19 Pandemic.

Pregnancy and childbirth have a crucial impact on a woman's quality of life. In Slovenia, antenatal classes are the main educational tool used to prepare expectant mothers for their new role. The aim of our study was to assess the relationship between the duration of antenatal classes and the mothers' quality of life after childbirth. A self-administered, previously validated and tested questionnaire regarding the quality of life after childbirth was completed by Slovenian women. Based on an online survey, data were collected for two groups of mothers. The first group (n = 1091) gave birth before the COVID-19 pandemic, and the second group (n = 1163) gave birth during the pandemic. Group differences were analyzed using the Mann-Whitney U test. Linear regression and correlation coefficients were calculated for the association between quality of life and the duration of antenatal classes. Our study showed a significant decrease in the duration of antenatal classes and a decrease in quality of life after birth during the COVID-19 pandemic. We also showed that more antenatal education was associated with a higher quality of life. Despite the influence of multiple factors during the COVID-19 pandemic, we defined the correlation between the duration of antenatal classes and postpartum quality of life in a sample of Slovenian mothers. The duration of the antenatal classes is an important factor influencing the quality of life after childbirth.

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.

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.

Surgical treatment and fertility perservation in endometrial cancer.

BACKGROUND: Endometrial cancer (EC) represents a high health burden in Slovenia and worldwide. The incidence is increasing due to lifestyle and behavioural risk factors such as obesity, smoking, oestrogen exposure and aging of the population. In many cases, endometrial cancer is diagnosed at an early stage due to obvious signs and symptoms. The standard treatment is surgery with or without adjuvant therapy, depending on the stage of the disease and the risk of recurrence. However, treatment modalities have changed in the last decades, considerably in the extent of lymphadenectomy. CONCLUSIONS: The gold standard of treatment for is surgery, which may be the only treatment modality in the early stages of low-grade tumours. In recent years, a minimally invasive approach with sentinel node biopsy (SNB) has been proposed. A conservative approach with hormonal treatment is used if fertility preservation is desired. If EC is in advance stage, high-risk histology, or high grade, radiotherapy, chemotherapy, or a combination of both is recommended.

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.

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.

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.