Safety, feasibility, and short-term-outcome of anal endoscopic submucosal dissection for anal intraepithelial neoplasia: an option for focal lesions?

BACKGROUND: Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3. METHODS: We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed. RESULTS: Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm2. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period. CONCLUSIONS: Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear. TRIAL REGISTRATION: Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.

Coincidence of giant uterine myomatosis and detection of two advanced malignancies in 77-year-old female patient.

OBJECTIVE: Our aim is to emphasize the importance of patient participation in screening programs available in the Czech Republic and in preventive gynaecological examinations. As an example, we present a case report of a 77-year-old female patient with the accumulation of serious gynaecological diseases (extreme uterine myomatosis, breast cancer) and non-Hodgkin´s B-lymphoma. DESIGN: Case report. SETTING: Department of Obstetrics and Gynaecology, Faculty Hospital in Pilsen, Charles University Medical Faculty in Pilsen. CASE REPORT: Our case report of a 77-year-old patient is a rare case of the simultaneous detection of giant uterine myomatosis causing voluminous ventral hernia, invasive ductal breast cancer, and non-Hodgkin´s B-lymphoma. The patient was not gynecologically examined for last 20 years and did not undergo any screening examinations. In the postoperative period, the patient was diagnosed with invasive ductal breast cancer and follicular lymphoma. All the diseases were diagnosed in advanced stage. CONCLUSION: The occurrence of bulky fibroids is very rare in postmenopause. Long-term neglect of clinical symptoms and adverse health signals allows their gradual progression. Especially in older patients, other serious illnesses may complicate the situation.

[One-Step Nucleic Acid Amplification method - what is the future of sentinel lymph node management?] / Metoda One-Step Nucleic Acid Amplification - jaká je budoucnost zpracování sentinelových uzlin?

OBJECTIVE: The article summarizes current possibilities of usage of the One-Step Nucleic Acid Amplification method (OSNA) in the perioperative management of sentinel lymph nodes in oncologic surgery. The principle of this method is the detection of cytokeratin 19 (CK19) in the lymphatic tissue as a marker of the metastatic spread. DESIGN: Review article. SETTINGS: Department of Obstetrics and Gynaecology, University Hospital Pilsen, Faculty of Medicine in Pilsen, Charles University, Prague; Department of Biology, Faculty of Medicine in Pilsen, Charles University, Prague; Department of Immunochemistry, University Hospital Pilsen, Faculty of Medicine in Pilsen, Charles University, Prague; Sikl´s Department of Pathology, University Hospital Pilsen, Faculty of Medicine in Pilsen, Charles University, Prague. METHODS: The review of the literature published until the end of April 2017 available on the PubMed database was performed. The official abbreviation OSNA and the full name of the method One-Step Nucleic Acid Amplification was used for search in this database. CONCLUSION: The usage of the OSNA method with the detection of CK 19 in the sentinel lymph nodes as a marker of metastatic spread to the lymphatic tissue currently represents an acceptable form of perioperative sentinel lymph node management in patients with breast and colorectal cancer. Until now published data are pointing towards possible successful application of this method in sentinel lymph node management in patients with some other malignancies, such as thyroid carcinoma, gastric cancer, uterus cancer and head and neck cancer. More data is needed to establish this method also in those neoplasms.

[Carcinosarcoma of the endometrium with melanocytic differentiation, case report]. / Karcinosarkom endometria s melanomovou diferenciací, kazuistika.

OBJECTIVE: The case report presents a case of 60-year old woman with a rare malignant mixed Müllerian tumor with melanomatous differentiation diagnosed from a histology after cervical polyp ablation and curettage. DESIGN: Case report. SETTING: Department of gynecology and obstetrics, University Hospital in Pilsen. CONCLUSION: Carcinosarcoma, previously malignant mixed Müllerian tumor, is a very rare aggressive endometrial carcinoma with low incidence, which typically occurs among older women and commonly affects the uterine body and cervix. Clinically, the carcinosarcoma is impossible to be distinguished from endometrial carcinoma or uterine sarcoma and the definitive diagnosis can only be made based on histological examination.

Incidence of uterine sarcomas in West Bohemia, at the Department of Gynaecology and Obstetrics, University Hospital in Pilsen, Czech Republic.

OBJECTIVE AND SETTING: A retrospective review of women of the West Bohemian population was performed at the Department of Gynaecology and Obstetrics, University Hospital in Pilsen, Czech Republic from 1/2005 - 1/2017. METHODS: The following data was analysed: patients age, histological type, tumour size, FIGO stage, body mass index, previous irradiation, Tamoxifen usage, and other possible risk factors. A total number of 20 uterine sarcoma patients were detected in the period from 1/2005 to 1/2015, and these cases were followed until 1/2017. RESULTS: The histological types identified were: leiomyosarcoma in 12 cases, endometrial stromal sarcoma in 7 cases and one case of high-grade undifferentiated uterine sarcoma. This only patient diagnosed with high-grade undifferentiated uterine sarcoma showed distant metastases 12 months after the surgical treat-ment and died one month later. The whole group of uterine sarcoma patients regardless histological subtype reached two years in 50% of cases, with the median disease-free interval 18 months and the median follow up of 38 months. The diagnosis of sarcoma was already known in 25% of cases from dilatation and curettage histology. There were suspicious sonographic findings suggestive of sarcoma in 10% of cases. Multiparity was associated with 48.2% of endometrial stromal sarcoma cases. The leading clinical symptom was postmenopausal bleeding in 55% of patients. CONCLUSION: We confirmed uterine sarcomas to be rare malignancies, even in the Czech population with high uterine malignancy incidence. Uterine cold knife morcellation during the vaginal part of laparoscopically assisted vaginal hysterectomy didnt worsen the prognosis of our patients.

[Agressive small cell carcinoma of the ovary, hypercalcemic type, surgery and oncological treatment: case report]. / Agresivní malobunecný karcinom ovaria hyperkalcemického typu, chirurgická a onkologická lécba: kazuistika.

Small cell carcinoma of the ovary (SCCOHT) is a rare tumor typically affecting young women. It is a highly malignant tumor accompanied with poor prognosis, early relapse and low survival rates. The most significant prognostic factor is stage of the disease. Due to above mentioned factors there are no guidelines for therapy of this rare tumor. We present a case of 22-years-old patient initially treated with antibiotics under diagnosis of pelvic inflammatory disease. Due to persistent mass at left adnexa, she was indicated for diagnostic laparoscopy, converted to laparotomy and left adnexectomy with frozen section revealing unspecified malignant tumor of left ovary. A conservative operation was performed and, after diagnosis of SCCOHT was established, the patient was indicated for adjuvant chemotherapy.

The guidelines for clinical practice for carriers of germline mutations in hereditary breast, ovarian, prostate, and pancreatic cancer predisposition genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 (4.2024).

The Guidelines for Clinical Practice for carriers of pathogenic variants in clinically relevant cancer predisposition genes define the steps of primary and secondary prevention that should be provided to these individuals at high risk of developing hereditary cancer in the Czech Republic. The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyne Czech Medical Society (SLG CLS JEP) in cooperation with the representatives of oncology and oncogynecology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.

[HE4 a biomarker of ovarian cancer]. / HE4 - biomarker ovariálního karcinomu.

OBJECTIVE: Verification of the importance of determination of HE4 and calculation of ROMA index for increasing the efficiency of diagnosis of ovarian cancer in a population of Czech women. DESIGN: Prospective study. SETTING: Department of Gynaecology and Obstetrics, Faculty Hospital in Pilsen. METHODS: In the period from 06/24/2010 to 12/01/2011 was at the Department of Gynaecology and Obstetrics, University Hospital Pilsen examined 552 patients with abnormalities in the pelvis. Patients were divided into two groups. There were 30 women with histologically confirmed malignant ovarian tumors. Another 522 women had benign findings. According to the levels of FSH were women in both groups divided into premenopausal and postmenopausal. At all women were measured CA 125, HE4 and FSH. HE4 and CA125 were determined using the chemiluminescent device Architect 1000 (Abbott, USA), FSH chemiluminescent method on the device DXI 800 (Beckman Coulter, USA). At all premenopausal women was calculated ROMA1 index and at all postmenopausal women ROMA2 index. SAS statistical software 9.2 were used for all statistical calculations. RESULTS: The highest diagnostic efficiency was achieved by a combination of HE4 and CA125 markers with the calculation ROMA2 index for postmenopausal women. In determining of menopausal status according to the values of FSH cut-off for menopause 40 IU/L and cut-off at 26.4% for ROMA2 reaches ROMA2 sensitivity of 92.3%, specificity of 88.5% and PV- of 99.3%. If we reduce the cut-off for laboratory diagnosis of menopause using FSH at 22 IU/L, and cut-off for ROMA2 was 26.3% reaches ROMA2 sensitivity of 95.2%, specificity of 87.8% and PV- of 99.5%. CONCLUSION: HE4 in combination with CA125 and current ROMA index calculation is a suitable methodology to improve the detection of ovarian cancer.

Melatonin rhythm in human milk.

The pineal hormone melatonin exhibits a circadian rhythm in body fluids. No data are available on melatonin in human milk. The present study was undertaken to determine whether melatonin is detectable in human milk and, if so, whether it exhibits a daily rhythm. Blood and milk were sampled between 1400-1700 h and again between 0200-0400 h from 10 mothers 3-4 days after delivery. Melatonin in both fluids was beyond the limit of detection during the day, whereas during the night, its concentration was 280 +/- 34 pmol/L in serum and 99 +/- 26 pmol/L in milk. Six mothers collected milk after each feeding throughout 1 24-h period within 3 months after delivery. Melatonin in the milk of all subjects exhibited a pronounced daily rhythm, with high levels during the night and undetectable levels during the day. The presence of the rhythm in milk suggests that melatonin fluctuations in milk might communicate time of day information to breast-fed infants.

Serum osteocalcin levels and bone alkaline phosphatase isoenzyme after oophorectomy and in primary hyperparathyroidism.

Serum osteocalcin levels peaked 1 yr after oophorectomy in a prospective study of 12 women. Estrogen treatment restored serum osteocalcin to the normal range within 4 months of therapy. The changes in serum osteocalcin preceded those in bone alkaline phosphatase activity by 1-2 months, in these oophorectomized patients and during estrogen treatment. The changes in these two markers of bone formation over time were significantly different from those in urinary hydroxyproline excretion. A significant positive correlation was found between bone alkaline phosphatase and serum osteocalcin levels in patients after oophorectomy and in 18 patients with primary hyperparathyroidism. Significant positive correlations also were found between the biochemical indices of osteoblastic function and urinary hydroxyproline excretion and/or nephrogenous cAMP in primary hyperparathyroidism. In most of the patients with primary hyperparathyroidism, however, the elevation in bone alkaline phosphatase was more marked than that in osteocalcin. These data indicate that the clinical utility of serum osteocalcin as a marker of bone formation is similar but not identical to that of bone alkaline phosphatase.

Prospective trial of ossein-hydroxyapatite compound in surgically induced postmenopausal women.

Women with increased bone resorption induced by bilateral oophorectomy 1-5 years previously (of a total of 48 women in the study, 20 were controls, and 28 were the treatment group) were studied during a 3 year follow-up. The ossein-hydroxyapatite compound (OHC) treatment provided 1.6 g calcium, 0.74 g phosphorus and 1.94 g noncollagen peptides a day. Biochemical indices of bone remodeling (urinary hydroxyproline/creatinine and calcium/creatinine ratios, bone alkaline phosphatase isoenzyme in serum and plasma tartrate resistant acid phosphatase) decreased significantly in both treatment and control groups compared with their baseline values. Biochemical indices were significantly lower in the treatment group compared to the controls after the first year, but in only half the patients after three years. By the third year these responders had significantly higher cortical area than controls. In an additional 13 women a transient response to OHC was followed by an accelerated bone loss and a return to the control values of the biochemical indices of bone resorption. In the poor responders an estrogen/progesterone substitution resulted within 6 months in a complete normalization in the biochemical parameters and in no further cortical bone loss. The results confirm a heterogeneous pattern of bone mass loss in menopause and indicate that OHC treatment is of value in preventing cortical bone loss in a portion of at-risk postmenopausal women, provided that the efficacy of the treatment is monitored.

Bone loss and biochemical indices of bone remodeling in surgically induced postmenopausal women.

In a cross-sectional study in 214 women who had undergone bilateral oophorectomy up to 12 years previously, the maximal rate of bone loss, as judged by radiogrammetry of the metacarpals and by dual-photon absorptiometry of the lumbar spine, coincided with the peak of the dissociation between urinary hydroxyproline excretion and/or plasma tartrate resistant acid phosphatase activity and the activity of bone isoenzyme of serum alkaline phosphatase. A significant negative correlation was found between the prevalence of the biochemical indices of bone resorption relative to bone formation and/or biochemical indices of bone resorption and the change in the metacarpal cortical area per year. The prevalence of bone resorption relative to bone formation was evident even 12 years after oophorectomy, indicating continuous imbalance of bone remodeling in the patients. Accordingly, the rates of 2.8% cortical and 8% trabecular bone loss per year on the first year after oophorectomy decreased exponentially but did not become asymptotic with the slow phase of bone loss in healthy women up to 12 years after oophorectomy.

Transport of novel ovum surrogates in the human fallopian tube: a clinical study.

Functional inadequacy of the fallopian tube cannot be adequately diagnosed by classical tubal patency tests. A new method using novel ova surrogates, microspheres transport test, is designed to diagnose dysfunctional tubal sterility. Biodegradable test microspheres with diameters matching that of the native ovum were used. According to the optimum procedure, the suspension of test microspheres was applied through the vaginal wall into the Douglas' space under local anesthesia, and the transported microspheres were collected in a modified cervical cap. The microspheres were readily identified in the sediment of cervical secretion by their fluorescence. The method was tested in 139 long-term infertility patients. Transport was observed in 100% of the control group, and positive correlation between the transport findings and the anticipated frequencies of dysfunctional tubal sterility cases in other groups was found. Optimum diameter of test microspheres was estimated at about 175 microns. The test appears to be useful for examination of functional disorders of the ovum transport in human practice.

Control of ovarian function by the immune system: commentary on the criticisms of Schenzle.

Recent hypothesis on the participation of the immune system in the control of ovarian function is supported by new experimental data. Schenzle's oversimplified endocrine explanation of problems of ovarian function control was critically examined. It is questionable whether the neuroendocrine paradigm should not be revised in the light of the modulating role of the immune system in the ovarian function control.

Allosensitization in tumor therapy and prophylaxis, and in female contraception--a prospect for clinical use.

A hypothesis is presented on the possible role of allosensitization in therapy and prophylaxis of human tumors, and in human female contraception. The essence of the proposed treatment of human malignancies is allosensitization with allogeneic white blood cells by means of application of two blood transfusions from normal healthy donors within a certain time interval to patients with invasive or metastasizing cancer. The therapy should be accompanied by immunoglobulins, bacterial toxins and a single dose of cytostatics. In the case of a successful tumor regression a prophylaxis of recurrence should be made with two doses of intradermally injected allogeneic lympho-leucocytic concentrates mixed with bacterial toxins; such treatment might also be effective in tumor prophylaxis, or in long-lasting contraception in women. The hypothesis is supported by recent literature as well as by our recent results in the area of cell-mediated control of tissue proliferation, fetal allograft survival or tumor development. It is concluded that tumor rejection can be mediated not only by the direct effect of anti-tumor drugs but more effectively by the organisms mechanisms responsible for removal of undesirable tissue.

Ovarian function and the immune system.

A hypothesis is presented on the interaction between the immune system and ovary in the regulation of the reproductive system and in the origin of some of its disorders. It has been suggested that the beginning, duration and age dependent failure of ovarian ovulatory function depends among other things on the adequate relationship between the immune system and approriate ovarian target structures. The cyclicity of ovarian function is considered to be primarily dependent on the induction of a specific cyclic immune response to the ovary. Similarly, the selection of a species-specific number of ovulating follicles during sexual maturity is thought to be ensured by immune mechanisms. This hypothesis, on the role of the immune system in regulation of ovulatory ovarian function respects the physiological effect of gonadotropins and steroids on the ovarian structures. The interaction between the ovary and the hypothalamus-pituitary system appears to be modulated by the relationship between the ovary and the immune system.

Cell-mediated and neural control of morphostasis.

Morphostasis refers to the maintenance of the differentiated state of tissues in an adult individual and it represents a basal event of homeostasis and the organism's existence. Most of the cells in the body are arrested in their differentiation at a certain point related to their optimal function. Evidence is rapidly accumulating on the general role of immunoglobulin-gene superfamily (IGSF) domains in the non-immune control of behavior of cells in various tissues. A novel 'tissue control system' (TCS) has been suggested, supporting the differentiation of tissue cells in an adult organism and functioning via the IGSF domains and cell-mediated control of morphostasis. We assume here that the morphostasis is established epigenetically during the early adaptive period. With its termination, coinciding with the attainment of an organism's immunocompetence, the combination of cell surface markers of the most mature cells in tissues are encoded in the TCS as the stop-signal (SS). This stage of tissue differentiation is maintained during further life: upon recognition of SS the committed TCS element does not stimulate further differentiation of the cell, i.e. it exhibits a stop-effect (SE). Each tissue-specific cell line has only one or no SE established depending on its presence or absence during development, respectively. The only way to escape an established SE and continue in differentiation is to change at least a portion of the SS. Hormones might act here directly, by conformation of their cell surface receptors recognized as a portion of SS, or indirectly, by influencing proteosynthesis of cell surface markers.(ABSTRACT TRUNCATED AT 250 WORDS)