Utility of expression of 4-hydroxynonenal tested by immunohistochemistry for cervical cancer.

Introduction: Cervical cancer (CC) is a leading cause of mortality in women around the world, with the highest incidence rate still being in developing countries. The most common aetiological factor is infection with high-risk human papilloma virus viral strains. Oxidative stress through generation of reactive oxygen species leads to lipid peroxidation and DNA damage. Studies show that reactive lipid electrophiles such as 4-hydroxynonenal (4-HNE) produced in the process play an important role in cancer signalling pathways and are a good biomarker for oxidative stress. We aim to investigate the prognostic role of 4-HNE as a biomarker for oxidative stress in patients in early and advanced stages of CC measured by immunohistochemistry. Material and methods: This is a retrospective study of 69 patients treated at our Department of Oncogynaecology. Paraffin embedded tumour tissues were immunohistochemically tested for the levels of expression of 4-HNE. The results for H-score, Allred score, and combined score were investigated for association with tumour size, lymph node status, andInternational Federation of Gynaecology and Obstetrics stage. Results: 4-hydroxynonenal showed higher expression in more advanced stages of CC and in cases with involved lymph nodes. Tumour size was not associated with the levels of 4-HNE. Conclusions: To best of our knowledge, this is the first study to use immunohistochemistry to examine the expression of 4-HNE as a prognostic factor in CC. The 3 score systems showed similar results. The pattern of 4-HNE histological appearance is dependent on the histological origin of cancer and is not universal.

Primary Vaginal Mucinous Adenocarcinoma of Intestinal Type-Clinical, Radiological and Morphological Aspects.

Background and Objectives: Neoplasms of the vagina are rare and account for 1-2% of all tumors of the female reproductive system. Primary neoplasms of the vagina are most often carcinomas originating from squamous or glandular epithelium. Of the primary glandular tumors, clear cell, endometrioid, and serous adenocarcinomas are the most common types, while mucinous and mesonephric types are very rare. Mucinous adenocarcinoma is histologically subclassified into endocervical and intestinal types. We add to the existing literature another case of an extremely rare gynecological neoplasm-primary vaginal mucinous adenocarcinoma (PVMAC) intestinal type associated with vaginal villous adenoma with high-grade dysplasia. We discuss the clinical, radiological and morphological features of this rare entity. Materials and Methods: We report a case of a 59-year-old woman with PVMAC intestinal type associated with vaginal villous adenoma with high-grade dysplasia. The patient was evaluated with a gynecological exam, and biopsy, curettage and tumor excision were performed. The positron emission tomography-computed tomography (PET/CT) scan, at the level of the pelvis, supported the primary location of the disease. Histological and immunohistochemical methods were applied. Results: The gynecological examination of the vagina revealed an exophytic polypoid mass with a diameter of 3 cm, located on the posterior wall, in the area of introitus vaginae. The PET/CT scan revealed a hypermetabolic malignant formation involving the vagina and anal canal, without evidence of pelvic and inguinal lymphadenopathy, and also, it excluded disease at sites other than the vagina. The histological and immunohistochemical investigations, as well as the clinical and radiological data, lent support to the diagnosis "primary vaginal mucinous adenocarcinoma intestinal type". Conclusions: PVMAC intestinal type is a rare gynecological pathology, which presents a serious challenge for oncogynecologists, radiologists and pathologists.

Neglected Anatomical Areas in Ovarian Cancer: Significance for Optimal Debulking Surgery.

Ovarian cancer (OC), the most lethal gynecological malignancy, usually presents in advanced stages. Characterized by peritoneal and lymphatic dissemination, OC necessitates a complex surgical approach usually involving the upper abdomen with the aim of achieving optimal cytoreduction without visible macroscopic disease (R0). Failures in optimal cytoreduction, essential for prognosis, often stem from overlooking anatomical neglected sites that harbor residual tumor. Concealed OC metastases may be found in anatomical locations such as the omental bursa; Morison's pouch; the base of the round ligament and hepatic bridge; the splenic hilum; and suprarenal, retrocrural, cardiophrenic and inguinal lymph nodes. Hence, mastery of anatomy is crucial, given the necessity for maneuvers like liver mobilization, diaphragmatic peritonectomy and splenectomy, as well as dissection of suprarenal, celiac, and cardiophrenic lymph nodes in most cases. This article provides a meticulous anatomical description of neglected anatomical areas during OC surgery and describes surgical steps essential for the dissection of these "neglected" areas. This knowledge should equip clinicians with the tools needed for safe and complete cytoreduction in OC patients.

Radical Hysterectomy or Total Mesometrial Resection-Two Anatomical Concepts for Surgical Treatment of Cancer of the Uterine Cervix.

A radical hysterectomy is the standard method of surgical treatment for patients with early-stage cancer of the uterine cervix. It was first introduced more than 100 years ago. Since then, various and many different radical procedures, which diverge in terms of radicality, have been described. Inconsistencies are clearly seen in practical anatomy, which were defined as surgically created artifacts. Moreover, the disparity of the procedure is most notable regarding the terminology of pelvic connective tissues and spaces. Despite these controversies, the procedure is widely performed and implemented in the majority of guidelines for the surgical treatment of cancer of the uterine cervix. However, a different and unique concept of surgical treatment of cervical cancer has been reported. It is based on ontogenetic anatomy and maps any tissue in the mature organism according to its embryologic development. The clinical implementation of this theory in the context of early cervical cancer is total mesometrial resection. The present article aims to describe and compare the anatomical and surgical basics of a radical hysterectomy (type C1/C2) and total mesometrial resection. Discrepancies regarding the terminology, resection lines, and surgical planes of both procedures are highlighted in detail. The surgical anatomy of the pelvic autonomic nerves and its surgical dissection is also delineated. This is the first article that compares the discrepancy of classic anatomy and ontogenic anatomy regarding surgical treatment of cancer of the uterine cervix. Clinical data, oncological outcome, and neoadjuvant and adjuvant treatment regarding both procedures are not the topic of the present article.

A rare case of angiomyomatous hamartoma in the pelvic and paraaortic lymph nodes.

Angiomyomatous hamartoma (AMH) of the lymph node is an extremely rare, benign vascular disease of unknown etiology. It is characterized by partial or complete replacement of the lymph node parenchyma by irregularly distributed, thick-walled blood vessels, smooth muscle bundles and adipose tissue in a fibrotic stroma. Angiomyomatous hamartoma occurs mainly in inguinal and femoral nodal regions, but there are a few reports of some other locations - submandibular, cervical, popliteal and paraaortic lymph nodes. We present a case of a 37-old female patient with AMH in the pelvic and paraaortic lymph nodes who presented with weight loss - 7 kg in 7 months. The differential diagnosis of AMH includes lymphangiomyomatosis, which, unlike AMH, involves primarily thoracic and intra-abdominal lymph nodes: nodal leiomyomatosis with less pronounced vascular proliferation and angiomyolipoma of the lymph node. The latter is composed of the same tissues as in AMH, but the smooth muscle component shows increased cellularity, polymorphism and increased mitotic activity, as well as a typical immune profile with coexpression of melanocyte markers and estrogen, which were negative in our case. The world literature references show that this is the first reported case in which the disease manifested itself with weight loss and affected paraaortic lymph nodes in a female patient.

Surgical Anatomy of the Liver-Significance in Ovarian Cancer Surgery.

INTRODUCTION: Ovarian cancer is the leading cause of death among all gynecological malignancies. Most patients present with an advanced stage of the disease. The routes of spread in ovarian cancer include peritoneal dissemination, direct invasion, and lymphatic or hematogenous spread, with peritoneal and lymphatic spread being the most common among them. The flow direction of the peritoneal fluid makes the right subphrenic space a target site for peritoneal metastases, and the most frequently affected anatomical area in advanced cases is the right upper quadrant. Complete cytoreduction with no macroscopically visible disease is the most important prognostic factor. METHODS: We reviewed published clinical anatomy reports associated with surgery of the liver in cases of advanced ovarian cancer. RESULTS: The disease could disseminate anatomical areas, where complex surgery is required-Morrison's pouch, the liver surface, or porta hepatis. The aim of the present article is to emphasize and delineate the gross anatomy of the liver and its surgical application for oncogynecologists. Moreover, the association between the gross and microscopic anatomy of the liver is discussed. Additionally, the vascular supply and variations of the liver are clearly described. CONCLUSIONS: Oncogynecologists performing liver mobilization, diaphragmatic stripping, and porta hepatis dissection must have a thorough knowledge of liver anatomy, including morphology, variations, functional status, potential diagnostic imaging mistakes, and anatomical limits of dissection.

Endometrial carcinoma in patients under 40 years of age: insights from the Bulgarian Cancer Registry.

OBJECTIVES: We aimed to investigate the overall survival (OS) of young women with endometrial cancer (EC) in Bulgaria and the impact of histological type on survival. MATERIAL AND METHODS: This is a population-wide retrospective study of patients with EC (≤ 40 years at diagnosis) registered at Bulgarian National Cancer Registry (BNCR) between 1993 and 2020. Patients were re-classified according to the 8th edition of the TNM classification. RESULTS: In total, 30 597 patients were registered and histologically confirmed with malignant tumors of the uterine body. From that, 29 065 of them (95%) had ECs, and the rest had sarcomas. Around 1.64% of all malignant tumors of the uterine body are diagnosed in women under the age of 40. Most of them are diagnosed in the early stage. There was no significant difference in median OS for patients diagnosed before or after 2003. In recent years there was a slight improvement in survival and patients from the last cohort of this study had a 5-year survival rate of 92.5%. Patients with favorable pathology (T1, G1/2) had no lymph node involvement at the time of diagnosis and their 10-year survival rate was 94%. CONCLUSIONS: EC in young women is a rare disease. In most cases, patients are diagnosed in early stageT1, G1/2, N0 and their prognosis is excellent. However, the lack of improvement of OS of young patients with EC in the last three decades shows the need for treatment optimization.

Vascular Anatomy and Variations of the Anterior Abdominal Wall - Significance in Abdominal Surgery.

Detailed knowledge of the human anatomy is an integral part of every surgical procedure. The majority of surgery related complications are due to a failure to possess appropriate knowledge of human anatomy. However, surgeons pay less attention of the anatomy of the anterior abdominal wall. It is composed of nine abdominal layers, which are composed of fascias, muscles, nerves, and vessels. Many superficial and deep vessels and their anastomoses supply the anterior abdominal wall. Moreover, anatomical variations of these vessels are often presented. Intraoperative and postoperative complications associated with entry and closure of the anterior abdominal wall could compromise the best surgical procedure. Therefore, sound knowledge of the vascular anatomy of the anterior abdominal wall is fundamental and a prerequisite to having a favourable quality of patient care. The purpose of the present article is to describe and delineate the vascular anatomy and variations of the anterior abdominal wall and its application in abdominal surgery. Consequently, the most types of abdominal incisions and laparoscopic accesses will be discussed. Furthermore, the possibility of vessels injury related to different types of incisions and accesses will be outlined in detail. Morphological characteristics and distribution pattern of the vascular system of the anterior abdominal wall is illustrated by using figures either from open surgery, different types of imaging modalities or embalmed cadaveric dissections. Oblique skin incisions in the upper or lower abdomen such as McBurney, Chevron and Kocher are not the topic of the present article.

Surgical and Anatomical Basics of Pelvic Debulking Surgery for Advanced Ovarian Cancer - the "Hudson Procedure" as a Cornerstone of Complete Cytoreduction.

Ovarian cancer (OC) is the fifth most common cause of death in women and accounts for more deaths than any other cancer of the female reproductive tract. OC usually spreads through peritoneal dissemination and direct invasion. Optimal cytoreduction (no macroscopic residual disease) and adjuvant platinum-based chemotherapy are the fundaments of OC treatment. OC is usually diagnosed at advanced stages, hence the obliteration of the Douglas pouch by the tumor as well as disseminated pelvic peritoneal carcinomatosis are commonly seen. Radical surgical cytoreduction typically requires a retroperitoneal approach to the pelvic masses and multivisceral resections in the upper abdomen. In 1968, Christopher Hudson introduced a new retroperitoneal surgical technique ("radical oophorectomy") for fixed ovarian tumors. Since then, numerous modifications have been described, including visceral peritonectomy, the "cocoon" technique, Bat-shaped en-bloc total peritonectomy (Sarta-Bat approach), or en-bloc resection of the pelvis. Although these modifications expanded the classical description in many ways, the concepts and key surgical steps are derived from the Hudson procedure. However, there are some gaps or disagreements regarding the anatomical or practical rationale for certain surgical steps. The purpose of this article is to outline the critical steps of radical pelvic cytoreduction ("Hudson procedure"), and to delineate the anatomical basis for the procedure in the proposed form. In addition, we discuss the controversies and address the perioperative morbidity associated with the procedure.

Surgical Anatomy and Dissection of the Hypogastric Plexus in Nerve-Sparing Radical Hysterectomy.

Radical hysterectomy is a central surgical procedure in gynecological oncology. A nerve-sparing approach is essential to minimize complications from iatrogenic injury to the pelvic nerves, resulting in postoperative urinary, anorectal, and sexual dysfunction. The hypogastric plexus (HP), a complex network of sympathetic and parasympathetic nerves, plays a critical role in pelvic autonomic innervation. This article offers a comprehensive overview of the surgical anatomy of the HP and provides a step-by-step description of HP dissection, with a particular emphasis on preserving the bladder nerve branches of the inferior HP. A thorough understanding and mastery of the anatomical and surgical nuances of HP dissection are crucial for optimizing outcomes in nerve-sparing gynecologic-oncological procedures.

A very rare case of echinococcus granulosus arising in the ovary and the uterus.

Hydatidosis is a zoonosis caused by the larval form of a cestode of the species Echinococcus granulosus, the canine tapeworm. It can affect any organ of the human body except nails, hair, and cornea. It most often involves the liver, lungs, muscles, and bones. Involvement of organs in the small pelvis is extremely rare, mainly secondary to dissemination of hydatidosis from another organ, and the ovaries are most often involved, followed by the uterus. We present a 41-year-old Caucasian woman with complaints of mild pain, heaviness in the small pelvis, and a fibroid detected by ultrasound examination. She had reported for 2 previous operations for echinococcus cysts, and we found cystic formations in the liver and pelvis by computed tomography. It was decided that it is a recurrence of echinococcosis with a new cyst both in ovary and uterus. A hysterectomy with adnexectomy was performed, and one year later there is no evidence of recurrence of echinococcosis. In the presence of a formation in the small pelvis, one should always think about echinococcosis, especially if there is evidence of previous manifestations of the disease. Diagnosing this disease is extremely important for proper treatment. As rare as uterine involvement is, this possibility should not be overlooked.

Internal Iliac Artery Ligation in Obstetrics and Gynecology: Surgical Anatomy and Surgical Considerations.

The internal iliac artery (IIA) is the main arterial vessel of the pelvis. It supplies the pelvic viscera, pelvic walls, perineum, and gluteal region. In cases of severe obstetrical or gynecologic hemorrhage, IIA ligation can be a lifesaving procedure. Regrettably, IIA ligation has not gained widespread popularity, primarily due to limited surgical training and concerns regarding possible complications, including buttock claudication, impotence, and urinary bladder and rectum necroses. Nowadays, selective arterial embolization or temporary balloon occlusion are increasingly utilized alternatives, which can be applied preoperatively or intraoperatively for threatening severe genital or pelvic bleeding. However, IIA ligation retains its relevance, as the previously described procedures are not always available and have limitations. This article provides a step-by-step guide to the IIA ligation procedure and its possible complications. It also includes a detailed description of the anatomy of the IIA and pelvic arterial anastomoses. This review highlights the importance of a thorough understanding of pelvic anatomy as a prerequisite for safe IIA ligation and posits that training in this procedure should be an integral part of obstetrics and gynecology curricula.

Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix with Atypical Presentation: A Case Report with a Literature Review.

Introduction: Cervical cancer is the fourth most prevalent malignancy and the fourth leading cause of cancer-related death in women around the world. Histologically, squamous cell carcinoma (SCC) is the most common form of cervical cancer. SCC has several subtypes, and one of the rarest is papillary squamotransitional cell carcinoma (PSCC). In general, PSCC is believed to have a similar course and prognosis to typical SCC, with a high risk of late metastasis and recurrence. Case report: We discuss the case of a 45-year-old patient diagnosed with PSCC who was admitted to our department in December 2021. The clinical manifestations were pelvic discomfort and lymphadenopathy throughout the body. On admission, all laboratory values, with the exception of C-Reactive Protein (CRP) at 22.35 mg/L and hemoglobin (HGB) at 87.0 g/L, were normal. The clinical and ultrasound examination revealed a painful formation with indistinct borders in the right portion of the small pelvis. Following dilation and curettage, a Tru-Cut biopsy of the inguinal lymph nodes was performed. The investigation histologically indicated PSCC. MRI of the small pelvis showed an endophytic tumor in the cervix with dimensions of 35/26 mm and provided data for bilateral parametrial infiltration; a hetero-intensive tumor originating from the right ovary and involving small intestinal loops measuring 90/58 mm; and generalized lymphadenopathy and peritoneal metastases in the pouch of Douglass. The FIGO classification for the tumor was IVB. The patient was subsequently referred for chemotherapy by the tumor board's decision. Discussion: Despite the generally good prognosis of SCC, PSCC is a rare and aggressive subtype. It is usually diagnosed at an advanced stage and has a poor prognosis. Conclusions: PSCC is a rare subtype of SCC, and its diagnosis and treatment are challenging.

Placental site trophoblastic tumour mimicking an intramural pregnancy: a case report and review of the literature.

Gestational trophoblastic disease (GTD) covers a range of proliferative disorders from non-neoplastic hydatid moles to malignant neoplastic conditions such as choriocarcinoma. The incidence of these diseases is low and often challenging to diagnose. Placental site trophoblastic tumour (PSTT) is the rarest form of GTD, accounting for up to 3% of all cases. We present a case of a 35-year-old patient diagnosed with PSTT mimicking an intramural pregnancy. Placental site trophoblastic tumour occurred after pregnancy, which ended as a blighted ovum. ß-hCG was not very high, and the patient had no complaints. The diagnosis was made after resection of formation which was accepted for intramural pregnancy. To our knowledge, this is the first such case described in the literature. A hysterectomy performed later confirmed the absence of a residual tumour after conservative intervention. The lack of distant metastases, confirmed by positron emission tomography-computed tomography scan, allowed for only hysterectomy with bilateral salpingo-oophorectomy to be performed. The patient was classified as low risk according to the World Health Organization (WHO) scoring system. Placental site trophoblastic tumour is a rare malignant tumour (despite its WHO coding) from the group of GTDs. It is not presented with a classic clinical picture, and its clinical diagnosis is challenging. However, clinicians should consider it in the case of unclear events after any type of pregnancy.

TREATMENT WITH THERESIENöL OF SURGICAL DISEASES OF THE SKIN.

Theresienöl is a 100 % natural product representing a mixture of animal and vegetable raw materials from Tyrol. Its exact recipe has been preserved untouched and in deep secret for more than six centuries yet, and has been passed down from generation to generation. Six patients were included in this case series one patient with malignant melanoma of the skin after re-excision with subsequent non-free skin surgical plastic, two patients with III degree skin burning and three patients with infected wound successfully treated with Theresienöl. All of them - before the application of Theresienöl - were treated with different operative methods. The treatment of scars from operative interventions with Theresienöl is very effective. That is why it must start directly after the operative intervention. The therapeutic effect of Theresienöl for postoperative scars is commensurable with and even better than the one of all applied until now local medicines, which makes it an agent of choice in those cases. Theresienöl represents a good alternative to the free skin surgical plastic for small burns of III degree. The local treatment of infected wounds with Theresienoil is more effective and economically sound than the treatment with all the rest types of dressings. The effects from the treatment of different surgical diseases with Theresienöl occur very rapidly, while there is a very good response to local hematomas, pain, and itchiness by the medicine, and there are no side effects from its administration.

Warty carcinoma of the uterine cervix: a virus-induced disease?

Introduction: Warty carcinoma (WC) of the uterine cervix is a rare subtype of squamous-cell carcinoma (SCC), and its frequency, clinical behaviour, and aetiology are obscure. It originates from condylomas, and a viral carcinogenesis seems logical. Material and methods: Retrospective analysis was performed of all cervical carcinomas (CC), diagnosed at a single institution for a 10-year period. Analysed patients had stage I carcinoma. Patients with WC were identified, and their tumour samples were tested for high-risk HPV (hr-HPV) and EBV, using PCR and ISH. Clinical characteristics and WC rates across all stage I CC patients were assessed. All patients had minimum 3-year follow-up, and overall survival (OS) and 5-year survival rates were calculated. Results: WC comprised 2.2% of all stage I CC (n = 630). The mean age of the patients was 48 years (range: 29-72). The primary tumour size was 2 cm in 4 (28.6%) patients, 2-4 cm in 2 (14.3%) patients, and 4 cm in 8 (57.1%) patients. Lymph node metastasis was found in 1 (7.1%) patient. EBV or hr-HPV were detected in 2 (18.2%) patients using ISH, with no coinfection reported. Hr-HPV was detected in 2 (18.2%) patients; EBV in 4 (36.4%) cases, and in 2 of them (18.2%) there was a co-infection. Thirteen patients had a follow-up of ≥ 5 years and their 5-year OS was 100%. Conclusions: WC is a rare subtype of SCC with good prognosis, regardless of viral status. In contrast to SCC, its aetiology is not related to hr-HPV. The role of EBV remains unclear and cannot currently be denied.

Long-term quality of life assessment after excisional treatment for cervical dysplasia.

We evaluated factors influencing long-term health-related quality of life (HRQoL) after excisional treatments of low- and high grade squamous intraepithelial cervical lesions (SIL) in three groups of women (n = 160): nulliparas interested in reproduction (A), parous women interested in reproduction (B) and women without pregnancy desire (C). The HRQoL was assessed using the disease-specific FACIT-CD and the generic SF36v2 questionnaires. Anxiety and depression were evaluated by Beck's inventories. After median follow-up of 5 (2-18) years, FACIT-CD total score and the score for Emotional Well-Being (EWB) were significantly lower in group A. The total, EWB and REL (Relationships) scores of FACIT-CD were the highest in group B. Women operated for HSIL demonstrated lower REL quality in comparison to those with LSIL. Neither SF36v2 nor FACIT-CD total scores differed in relation to SIL grade or type of excision. 'SF36v2 Mental Component Summary Score' and 'being parous and interested in fertility' were independent predictors of disease-specific FACIT-CD score.Impact StatementWhat is already known on this subject? Long-term consequences of excisional treatments for cervical dysplasia on health-related quality of life (HRQoL) are not well reported.What do the results of this study add? Our study provides data on HRQoL in women treated with large loop excision of the transformation zone (LLETZ) or cold knife conization (CKC) obtained during the longest (median 5 years) follow-up as reported to date. We were able to show that having children and planning further pregnancies positively influenced HRQoL in these patients. In addition, we identified nulliparas with pregnancy desire as psychologically the most vulnerable group within the studied cohort.What are the implications of these findings for clinical practice and/or further research? Even several years after LLETZ or CKC, women may suffer from impaired Emotional Well-Being and reduced HRQoL. Awareness and assessment of these long-term consequences should be part of surveillance after excisional treatments for cervical dysplasia.

Hereditary Gynecologic Cancer Syndromes - A Narrative Review.

Hereditary cancer syndromes are defined as syndromes, where the genetics of cancer are the result of low penetrant polymorphisms or of a single gene disorder inherited in a mendelian fashion. During the last decade, compelling evidence has accumulated that approximately 5-10% of all cancers could be attributed to hereditary cancer syndromes. A tremendous progress has been made over the last decade in the evaluation and management of these syndromes. However, hereditary syndromes associated with gynecologic malignancies still present significant challenge for oncogynecologists. Oncogynecologists tend to pay more attention to staging, histological type and treatment options of gynecological cancers than thinking of inherited cancers and taking a detailed family history. Moreover, physicians should also be familiar with screening strategies in patients with inherited gynecological cancers. Lynch syndrome and hereditary breast-ovarian cancer syndrome are the most common and widely discussed syndromes in medical literature. The aim of the present review article is to delineate and emphasize the majority of hereditary gynecological cancer syndromes, even these, which are rarely reported in oncogynecology. The following inherited cancers are briefly discussed: Lynch syndrome; "site-specific" ovarian cancer and hereditary breast-ovarian cancer syndrome; Cowden syndrome; Li-Fraumeni syndrome; Peutz-Jeghers syndrome; ataxia-telangiectasia; DICER1- syndrome; gonadal dysgenesis; tuberous sclerosis; multiple endocrine neoplasia type I, II; hereditary small cell carcinoma of the ovary, hypercalcemic type and hereditary undifferentiated uterine sarcoma; hereditary diffuse gastric cancer and MUTYH-associated polyposis. Epidemiology, pathogenesis, diagnosis, pathology and screening of these syndromes are discussed. General treatment recommendations are beyond the scope of this review.