Porta-caval fibrous connections - the lesser-known structure of intrahepatic connective-tissue framework: A unified view of liver extracellular matrix.

Knowledge about the connective-tissue framework of the liver is not systematized, the terminology is inconsistent and some perspectives on the construction of the hepatic matrix components are contradictory. In addition, until the last two decades of the 20th century, the connective-tissue sheaths of the portal tracts and the hepatic veins were considered to be independent from each other in the liver and that they do not make contact with each other. The results of the research carried out by Professor Shalva Toidze and his colleagues started in the 1970s in the Department of Operative Surgery and Topographic Anatomy at the Tbilisi State Medical Institute have changed this perception. In particular, Chanukvadze I showed that in some regions where they intersect with each other, the connective tissue sheaths of the large portal complexes and hepatic veins fuse. The areas of such fusion are called porta-caval fibrous connections (PCFCs). This opinion review aims to promote a systematic understanding of the hepatic connective-tissue skeleton and to demonstrate the hitherto underappreciated PCFC as a genuine structure with high biological and clinical significance. The components of the liver connective-tissue framework - the capsules, plates, sheaths, covers - are described, and their intercommunication is discussed. The analysis of the essence of the PCFC and a description of its various forms are provided. It is also mentioned that analogs of different forms of PCFC are found in different mammals.

Spatial architecture of biliary tree in mammals: Fractal and Euclidean geometric features.

The study of the fractal architecture of various organs and structures expanded the possibilities for determining the ranges of their functioning and structural arrangement, which, as a result, was reflected in the development of new approaches to diagnostics and therapeutic impacts. The architecture of the excretory duct systems, similar to the hemo- and lymph- circulatory beds and the bronchial tree, is considered fractal. At the same time, information about hitherto unknown structures of the biliary tree continues to appear in the literature. We aimed to study the features of the spatial geometry of the biliary tree and assess the significance of both its fractal and Euclidean characteristics for the development of approaches that facilitate comprehensive description of intrahepatic biliary tract architecture. We investigated the architecture of the biliary trees of six men, seven male canines, and seven male Wistar rats using the corrosion casting method. Corrosion casts were prepared by injecting solidifying latexes into the bile ducts. The preparations were studied using a light stereomicroscope and a scanning electron microscope. Biliary tree branching is of various types. In addition, the correlation between variations in the caliber and length of the bile ducts and their order is not significant. Therefore, the biliary tree should not be considered as a classical fractal and it consists of the main modules, represented by the network of the bile canaliculi (first nonfractal module) and a biliary tree with a fractal branching (second module) that drains the bile canaliculi mesh and the additional modules represented by the mucosal biliary glands (in mammals with the gallbladder) or the periportal biliary plexus (in mammals without a gallbladder) and the aberrant biliary ducts. Such a configuration of the biliary bed should optimally ensure the smooth implementation of the physiological function of the liver, as well as its adaptation to different pathologies accompanied by biliary hypertension. It also might be considered in the diagnosis and assessment of ductular reaction, biliary regeneration, and/or carcinogenesis.

Challenges and perspectives of surgical treatment of liver failure. Current status and last achievements in Georgia.

Liver transplantation is considered to be the last hope of treatment for irreversible liver failure caused by different diffuse and/or space-occupying lesions of this organ. The strict limitation of the donor organs stipulates for development of alternative approaches for the solving this problem. The presented review of literature and our experience aims to discuss the modern aspects of management of different hepatic pathologies causing liver failure with the view of creation of the auxiliary, bioengineer-based functional tissues and/or organs and innovative surgical interventions allowing to conduct the operations in cases, which were up to date considered as inoperable. There are highlighted the last achievements of the experimental and translational studies performed in four University research centers of Georgia, which, on the one hand, provoke the specific professional interest, and on the other hand, require the international cooperation and collaboration for further progress and advances in this field of surgery. KEY WORDS: Artificial liver, Bio-Artificial organs, Liver failure, Innovative surgery, Tissue engineering.

Liver structural transformation after partial hepatectomy and repeated partial hepatectomy in rats: A renewed view on liver regeneration.

BACKGROUND: The phenomenon of liver regeneration after partial hepatectomy (PH) is still a subject of considerable interest due to the increasing frequency of half liver transplantation on the one hand, and on the other hand, new surgical approaches which allow removal of massive space-occupying hepatic tumors, which earlier was considered as inoperable. Interestingly, the mechanisms of liver regeneration are extensively studied after PH but less attention is paid to the architectonics of the regenerated organ. Because of this, the question "How does the structure of regenerated liver differ from normal, regular liver?" has not been fully answered yet. Furthermore, almost without any attention is left the liver's structural transformation after repeated hepatectomy (of the re-regenereted liver). AIM: To compare the architectonics of the lobules and circulatory bed of normal, re-generated and re-regenerated livers. METHODS: The livers of 40 adult, male, albino Wistar rats were studied. 14 rats were subjected to PH - the 1st study group (SG1); 10 rats underwent repeated PH - the 2nd study group (SG2); 16 rats were subjected to sham operation - control group (CG); The livers were studied after 9 months from PH, and after 6 months from repeated PH. Cytological (Schiff reaction for the determination of DNA concen-tration), histological (H&E, Masson trichrome, CK8 Immunohistochemical marker, transparent slides after Indian Ink injection, ), morphometrical (hepatocytes areas, perimeters and ploidy) and Electron Microscopical (Scanning Electron Microscopy of corrosion casts) methods were used. RESULTS: In the SG1 and SG2, the area of hepatocytes and their perimeter are increased compared to the CG (P < 0.05). However, the areas and perimeters of the hepatocytes of the SG1 and SG2 groups reveal a lesser difference. In regenerated (SG1) and re-regenerated (SG2) livers, the hepatocytes form the remodeled lobules, which size (300-1200 µm) exceeds the sizes of the lobules from CG (300-600 µm). The remodeled lobules (especially the "mega-lobules" with the sizes 1000-1200 µm) contain the transformed meshworks of the sinusoids, the part of which is dilated asymmetrically. This meshwork might have originated from the several portal venules (interlobular and/or inlet). The boundaries between the adjacent lobules (including mega-lobules) are widened and filled by connective tissue fibers, which gives the liver parenchyma a nodular look. In SG2 the unevenness of sinusoid diameters, as well as the boundaries between the lobules (including the mega-lobules) are more vividly expressed in comparison with SG1. The liver tissue of both SG1 and SG2 is featured by the slightly expressed ductular reaction. CONCLUSION: Regenerated and re-regenerated livers in comparison with normal liver contain hypertrophied hepatocytes with increased ploidy which together with transformed sinusoidal and biliary meshworks form the remodeled lobulli.

New corrosion cast media and its ability for SEM and light microscope investigation.

SEM of corrosion casts (CC) provides the opportunities to study the vessels and ducts in the phyllogenetic and ontogenetic (age-related) settings, as well as the pathogenesis, compensation, and sanogenesis in different diseases and experimental models. Along with the refinement of SEM CC, the requirements toward casting media (CM) as nontoxicity, low viscosity, quick polymerization, resistance to corrosion solutions, availability, and so on, gradually has developed. We aimed to adapt the sets widely used in dental practice toward the modern requirements to the CC. The following ratio of the components of Protacryl-M and Aycryl-C sets were used for the preparation CM-0.25 g MAYCRYL Powder +0.08 g Benzoyl Peroxide +5.0 ml Protacryl-M liquid component +0.2 Redont Colour (dye concentrate). The obtained solidifying mass was injected in the blood vessels and biliary ducts of the adult Wistar white rats. The SEM of CC of different organs' vascular networks, as well as a biliary tract, reveals that offered CM excellently replicates the forms and branching features of studied tubular structures of all sizes and gives the adequate imprinting of their luminal surfaces. Besides, CM may provide the replication of perivascular spaces and give the casts having no analogous in the appropriate literature. The CM prepared by us perfectly reproduces all possibilities of famous rubbers widely used for the casting of different vascular-ductular structures. Besides, it presents the new implications, which should be implemented in the profound research of the connective-tissue skeleton of different organs.

Papillary thyroid carcinoma in Struma Ovarii.

Struma Ovarii is one of the types of mature teratoma, with predominant thyroid tissue (>50%). It occurs in 1% of all cases of ovarian tumors and in 2.7% of dermoid tumors. There are no specific clinical, radiological or serum markers for this rare pathology. Rarely it may be accompanied by ascites and the increased level of CA-125. In general Stuma Ovarii is clinically defined as an ovarian malignancy. It is diagnosed only by histopathological examination of the surgical material. Diagnosis of Struma Ovarii dictates the need for advanced research of the thyroid. Struma Ovarii is mostly benign. Its malignant transformation occurs in only 5% of all cases, That leads to further management planning analogous to the treatment of thyroid cancer. The case of malignant Struma Ovarii of the 50-year-old woman, which led to total thyroidectomy and radioactive iodine therapy - is described.

The Attitudes, Needs, and Requirements at End of Life in the Republic of Georgia (Comparative Analysis of Groups of Patients With Cancer and Elders).

INTRODUCTION: In developing a model of palliative care, the attitudes, needs, and requirements of its beneficiaries recognizing the limited remaining life expectancy need to be met. We aimed to map and compare these issues at the end of life in the groups of patients with advanced cancer and elderly individuals. MATERIALS AND METHODS: The prospective study based on the analysis of semistructured interviews was conducted. Fifty individuals aged older than 85 and 50 incurable patients with advanced cancer were studied. Transcripts of interviews were analyzed qualitatively (the interviews were divided into logically completed themes, and the compliance of each with one of the levels of Abraham Maslow pyramid was determined) and quantitatively (data comparisons of 2 groups were tested in bivariate analysis using Pearson χ2 or Fisher exact test. Two-sided significance tests were used; P value of <.05 was deemed significant). RESULTS: It was assumed that 120 themes were relevant to a certain level of Maslow pyramid. Their comparison showed small differences in the narratives of the patients with advanced cancer and elderly individuals aged 85 and older-concerning the past, present, and future terms of lives. In studied themes explicitly prevail the stories that are consistent with satisfaction of the upper levels of the hierarchy of needs and demands of Maslow: social relation (belonging), love, esteem, and transcendence. CONCLUSION: The attitudes, needs, and requirements at the end of life of the people are basically similar, regardless of what determined the sense of limitation of the remaining life-incurable disease or advanced age.

Impact of Ambiguous and Restrictive Regulations on Opioid-Prescribing Practice in Georgia.

CONTEXT: Chronic pain management with opioids in incurable patients remains a challenge of modern medicine regardless of the evidence-based effectiveness of opioids and recommendations of authorities such as the World Health Organization and International Narcotics Control Board. Many countries, including Georgia, maintain overly restrictive regulations that contribute to inadequate pain management. OBJECTIVE: To identify barriers to pain management in Georgia caused by legislation, administrative issues, and physicians' lack of knowledge and understanding of legislative aspects governing opioid use, and their impact on opioid-prescribing practice. METHODS: We conducted a survey among 550 primary health care physicians. In total, 302 physicians completed the questionnaire. Overall, 289 questionnaires were analyzed statistically with SPSS version 20 (Armonk, NY: IBM Corp.). RESULTS: We found that 38% of the physicians avoid prescribing opioids and only one-third of the physicians make an independent decision to treat the patients with opioids. About one-third of the physicians know the updated liberalized legislation and even fewer follow it. Those who apply more liberal legislation and have better medical practice are investigated three to five times more by legal authorities for prescribing morphine to incurable patients than those who do not. CONCLUSION: Ambiguous legislation negatively influences opioid-prescribing practice. Most of the physicians believe that the legislation is restrictive. Physicians who have better medical and legal knowledge and understanding are controlled and investigated more because of their opioid-prescribing practice. Physicians who are concerned that they might be investigated are less inclined to prescribe opioids or use liberalized regulations.

The Contribution of the International Pain Policy Fellowship in Improving Opioid Availability in Georgia.

In the Republic of Georgia, the incidence and prevalence of cancer are increasing, signifying a growing need for palliative care and pain relief, including with controlled opioid medicines. As a signatory to the Single Convention, the Georgian government has a responsibility to ensure the adequate availability of controlled medicines for medical purposes; however, the consumption of morphine is very low, suggesting a high occurrence of unrelieved pain. In Georgia, palliative care development began in the 2000s including the adoption of a policy document in 2005, the creation of the National Palliative Care Coordinator in 2006, and important changes in Georgian legislation in 2007 and 2008, which served to lay a foundation for improving opioid availability. In 2008, a neurologist from the Sarajishvili Institute of Neurology and Neurosurgery in Tbilisi, and member of the Georgia National Association for Palliative Care, was selected to be an International Pain Policy Fellow to focus on improving opioid availability. Working with colleagues, government officials, and international experts, the Fellow contributed to several improvements to opioid availability, such as 1) positive changes to opioid prescribing legislation, 2) clarification of legislative terminology regarding dependence syndrome, 3) initiating the importation of both sustained-release and immediate-release oral morphine, and 4) improvements in the availability of sustained-release morphine. Despite these varied achievements, morphine consumption remains low in Georgia relative to the estimated amounts needed. The Fellow is continuing to study and understand the barriers that are impeding physician's prescription of opioids and patient's acceptance of them.

Hepatitis C virus seroprevalence in the general female population of 9 countries in Europe, Asia and Africa.

BACKGROUND: New oral treatments with very high cure rates have the potential to revolutionize global management of hepatitis C virus (HCV), but population-based data on HCV infection are missing in many low and middle-income countries (LMIC). METHODS: Between 2004 and 2009, dried blood spots were collected from age-stratified female population samples of 9 countries: China, Mongolia, Poland, Guinea, Nepal, Pakistan, Algeria, Georgia and Iran. HCV antibodies were detected by a multiplex serology assay using bead-based technology. RESULTS: Crude HCV prevalence ranged from 17.4% in Mongolia to 0.0% in Iran. In a pooled model adjusted by age and country, in which associations with risk factors were not statistically heterogeneous across countries, the only significant determinants of HCV positivity were age (prevalence ratio for ≥45 versus <35 years = 2.84, 95%CI 2.18-3.71) and parity (parous versus nulliparous = 1.73, 95%CI 1.02-2.93). Statistically significant increases in HCV positivity by age, but not parity, were seen in each of the three countries with the highest number of HCV infections: Mongolia, Pakistan, China. There were no associations with sexual partners nor HPV infection. HCV prevalence in women aged ≥45 years correlated well with recent estimates of female HCV-related liver cancer incidence, with the slight exception of Pakistan, which showed a higher HCV prevalence (5.2%) than expected. CONCLUSIONS: HCV prevalence varies enormously in women worldwide. Medical interventions/hospitalizations linked to childbirth may have represented a route of HCV transmission, but not sexual intercourse. Combining dried blood spot collection with high-throughput HCV assays can facilitate seroepidemiological studies in LMIC where data is otherwise scarce.

Mismatch between physicians and family members views on communications about patients with chronic incurable diseases receiving care in critical and intensive care settings in Georgia: a quantitative observational survey.

BACKGROUND: Physicians working in critical and intensive care settings encounter death of chronic incurable patients on a daily basis; however they have scant skills on how to communicate with the patients and their family members. The aim of the present survey is to examine communication of critical and intensive care physicians with patients' family members receiving treatment due to chronic incurable diseases/conditions and to compare the views of families with physicians working in critical and intensive care settings. METHODS: The survey was conducted in four cities of Georgia (Tbilisi, Kutaisi, Batumi and Telavi) in 2014. Physicians working in critical and intensive care settings and family members were asked to fill in separate questionnaires, covering various aspects of communication including patients' prognosis, ways of death occurrence, treatment plans and religion. Participants ranked their responses on a scale ranging from "0" to "10", where "0" represented "never" and "10"-"always". After data collection, responses were recoded into three categories: 0-3 = never/rarely, 4-7 = somewhat and 8-10 = often/always. Differences were tested using Pearson's chi-square or Fisher's exact test as appropriate. P value of < 0.05 was considered as significant. RESULTS: Sixty-five physicians and 59 patients' family members participated in this cross-sectional study. Majority of their responses was statistically significantly different. Only one quarter (23.7 %) of family members of patients receiving medical aid in critical and intensive care settings were satisfied with the communication level. In contrast, 78.5 % of physicians considered their communication with families as positive (p < 0.0001). CONCLUSIONS: The survey revealed the mismatch between the views on communication of critical and intensive care settings physicians and family members of the patients with chronic incurable diseases receiving care in critical and intensive care settings. In order to provide the best care for chronic incurable patients and their family members, physicians working in critical and intensive care settings must have relevant clinical knowledge and ability to provide effective communication. Present results reflect important potential targets for educational interventions including critical and intensive care physicians training through online modules.

Traditional risk factors for Helicobacter pylori infection not found among patients undergoing diagnostic upper endoscopy-Republic of Georgia, 2007-2008.

OBJECTIVES: Helicobacter pylori causes gastritis, duodenal ulcers, and gastric cancer. Although household crowding, low socioeconomic status (SES), and poor sanitation are associated with infection elsewhere, risk factors of infection in the Republic of Georgia (ROG), a country with a high prevalence rate (>70%), remain unknown. In this study we explored potential risk factors of infection among symptomatic patients in ROG. METHODS: During 2007-2008, we prospectively recruited 390 subjects with gastrointestinal symptoms referred to five tertiary care centers for diagnostic upper endoscopy. We administered a questionnaire on potential risk factors and tested patients using three diagnostic tests: gastric biopsies underwent histological evaluation and rapid urease test (CLO test), and an ELISA was used to detect IgG against H. pylori in serum. We defined a case as having two or more positive results from the three available tests. Univariate and multivariate logistic regression analyses were performed. RESULTS: Overall, 217 (56%) patients met the study case definition. Subjects diagnosed with cancer had the highest rate of H. pylori infection (62%), followed by those with gastritis (55%), and ulcer (54%). Age >30 years (adjusted odds ratio (aOR 2.6, 95% confidence interval (CI) 1.6-4.3) and residing in the capital city (aOR 0.6, 95% CI 0.4-0.9) were significantly associated with infection. CONCLUSIONS: In this large cohort with gastrointestinal symptoms, only age >30 years and living in the capital were significant factors associated with infection. Lower SES, less education, and crowding did not confer an increased risk, in contrast to the findings of previous studies. Population-based studies are needed to identify potential routes and risk factors of H. pylori infection in ROG.

Perspective in supportive care--practical experiences in Georgia.

Authors describe the first steps of Palliative Care development in Georgia, including policy, educational issues, drug availability and services. It is underlined the importance and effectiveness of collaboration of Governmental institutions, NGOs and international organizations and experts to create the basis for Palliative care system in the Country. Georgian experience on revealing of problems of adequate pain control gained by survey with participation of advanced patients and their family members is also discussed. All current activities in the sphere of Palliative Care as well as the future models of Palliative Care provision in the capital and regions of Georgia is shown.

Human papillomavirus infection in women with and without cervical cancer in Tbilisi, Georgia.

BACKGROUND: No accurate estimates of cervical cancer incidence or mortality currently exist in Georgia. Nor are there any data on the population-based prevalence of high-risk (HR) human papillomavirus (HPV) infection, which, in the absence of good-quality screening, is known to correlate with cervical cancer incidence. METHODS: We obtained cervical cell specimens from 1309 women aged 18-59 years from the general population of Tbilisi, and also from 91 locally diagnosed invasive cervical cancers (ICC). DNA of 44 HPV types was tested for using a GP5+/6+-based PCR assay. RESULTS: In the general population (of whom 2% reported a previous Pap smear) HPV prevalence was 13.5% (95% CI: 11.6-15.9), being highest in women aged 25-34 years (18.7%) and falling to between 8.6% and 9.5% for all age groups above 34 years. HR HPV prevalence was 8.6% overall, being 6.8% and 38.9% among women with normal and abnormal cytology, respectively. HPV45 (1.6%) was the most common type in women with normal cytology, whereas HPV16 predominated among women with cervical abnormalities (including 7 of 10 histologically confirmed cervical intraepithelial neoplasia 2/3) and among ICC (57.6%). The next most common types in ICC in Georgia were HPV45 and 18 (13.2 and 11.0%, respectively). CONCLUSIONS: We report a relatively high burden of HPV infection in Tbilisi, Georgia. Improving cervical cancer prevention, through screening and/or HPV vaccination, is an important public health issue in Georgia, where 70% of ICC are theoretically preventable by HPV16/18 vaccines.