Impact of Glissonean Pedicle Approach for Centrally Located Hepatocellular Carcinoma in Mongolia

Approaches to surgical resection of centrally located HCC remain controversial. Traditionally, hemi- or extended hepatectomy is suggested. However, it carries a high risk of postoperative complications in patients with cirrhosis. An alternative approach is Glissonean pedicle transection method. This study was conducted to assess the surgical and survival outcomes associated with central liver resection using the Glissonean pedicle transection. Sixty-nine patients with centrally located HCC were studied retrospectively. They were divided into conventional approach group with hemi- or extended hepatectomy, and Glissonean approach group with multisegmental central liver resection using the Glissonean pedicle transection. Glissonean pedicle transection method has comparable or superior surgical and survival outcomes to conventional hemi- or extended hepatectomy with regard to intraoperative bleeding, complications, hospital stay, and postoperative mortality and survival outcomes in patients with centrally located HCC. The 1-, 3-, and 5-year overall survival rates of the conventional approach group were 74%, 64%, and 55% respectively. For the Glissonean approach group, the 1 and 3-year overall survival rates were 86% and 61%, respectively. Glissonean pedicle transection method is a safe and effective surgical procedure in patients with centrally located HCC.Key words: Centrally located HCC, Glissonean approach, Glissonean pedicle transection, Central hepatectomyHepatocellular carcinoma (HCC) is the first leading cause of cancer-related mortality in both men and women in Mongolia, and its incidence is among the highest worldwide.¹ Surgical resection remains the first-line therapeutic strategy for HCC despite recent advancements in treatment modalities.^2-4 However, underlying liver diseases significantly limit the number of HCC patients eligible for surgical resection. This is especially problematic, where the prevalence of chronic hepatitis B and C is over 10% in the general population, and 86.8% of HCC patients have cirrhosis.⁵ Therefore, refining surgical techniques to preserve as much liver parenchyma as possible could potentially improve treatment prospects for cirrhotic HCC patients, particularly in cases when the tumor is centrally located.Traditionally, hemi- or extended hepatectomy is suggested for the treatment of centrally located HCC.⁶ However, such a major hepatic resection sacrifices a large volume of noncancerous liver parenchyma, which carries a high risk of postoperative liver failure in patients with cirrhotic background.^6-8 Preservation of functioning liver parenchyma to a maximum extent possible is crucial to avoid postoperative liver failure in cirrhotic patients. Therefore, Glissonean pedicle transection method is increasingly considered as an effective alternative to hemi- or extended hepatectomies in such cases.^9-16 Nonetheless, multisegmental central liver resection has not been widely used since its introduction for gallbladder cancer in 1972.^17,18 Conventional central liver resection method is technically demanding, and may require prolonged surgical time in order to dissect and confirm each branch of hepatic artery, portal vein, and bile duct to the anterior section.^19,20 This often results in increased risk of bleeding, bile leakage or parenchymal necrosis, and therefore, central liver resection particularly in cirrhotic patients remains controversial.^21,22 The answer to the dilemma could lie with the Glissonean pedicle transection method, which was introduced in the mid-1980s owing to a better understanding of the surgical anatomy of the liver.^20,23 When using this resection method, Glissonean pedicle supplying the target area is ligated and divided at the hepatic hilum prior to resection without exposing the vessels individually.²³ This simplifies hepatic resection, shortens operation time and reduces intraoperative bleeding.²³⁻²⁵ Our previous experience with using this method for hemihepatectomy has resulted in considerable reduction of blood loss during resection, a major determinant of patient outcome.This approach has allowed the ability to adapt the size of resection to the extent of the tumor and to preserve the maximum amount of liver parenchyma, which is crucial for the prevention of postoperative liver failure especially in patients with cirrhotic background. However, it remains unclear whether central liver resection using the Glissonean pedicle transection improves long-term survival. Therefore, the current retrospective study of patients with centrally located HCC, who underwent either hemi- or extended hepatectomy or multisegmental central liver resection, was conducted to assess the perioperative and long-term outcomes associated with central liver resection using the Glissonean pedicle transection.     

Association between HRAS rs12628 and rs112587690 polymorphisms with the risk of melanoma in the North American population

HRAS belongs to the RAS genes superfamily. RAS genes are important players in several human tumors and the single-nucleotide polymorphism rs12628 has been shown to contribute to the risk of bladder, colon, gastrointestinal, oral, and thyroid carcinoma. We hypothesized that this SNP may affect the risk of cutaneous melanoma as well. HRAS gene contains a polymorphic region (rs112587690), a repeated hexanucleotide -GGGCCT- located in intron 1. Three alleles of this region, P1, P2, and P3, have been identified that contain two, three, and four repeats of the hexanucleotide, respectively. We investigated the clinical impact of these polymorphisms in a case?Ccontrol study. A total of 141 melanoma patients and 118 healthy donors from the North America Caucasian population were screened for rs12628 and rs112587690 polymorphisms. Genotypes were assessed by capillary sequencing or fragment analysis, respectively, and rs12628 CC and rs112587690 P1P1 genotypes significantly associated with increased melanoma risk (OR?=?3.83, p?=?0.003; OR?=?11.3, p?=?0.033, respectively), while rs112587690 P1P3 frequency resulted significantly higher in the control group (OR?=?0.5, p?=?0.017). These results suggest that rs12628 C homozygosis may be considered a potential risk factor for melanoma development in the North American population possibly through the linkage to rs112587690.     

Attitudes of Healthcare Providers towards Non-initiation and Withdrawal of Neonatal Resuscitation for Preterm Infants in Mongolia

Antenatal parental counselling by healthcare providers is recommended to inform parents and assist with decision-making before the birth of a child with anticipated poor prognosis. In the setting of a low-income country, like Mongolia, attitudes of healthcare providers towards resuscitation of high-risk newborns are unknown. The purpose of this study was to examine the attitudes of healthcare providers regarding ethical decisions pertaining to non-initiation and withdrawal of neonatal resuscitation in Mongolia. A questionnaire on attitudes towards decision-making for non-initiation and withdrawal of neonatal resuscitation was administered to 113 healthcare providers attending neonatal resuscitation training courses in 2009 in Ulaanbaatar, the capital and the largest city of Mongolia where ~40% of deliveries in the country occur. The questionnaire was developed in English and translated into Mongolian and included multiple choices and free-text responses. Participation was voluntary, and anonymity of the participants was strictly maintained. In total, 113 sets of questionnaire were completed by Mongolian healthcare providers, including neonatologists, paediatricians, neonatal and obstetrical nurses, and midwives, with 100% response rate. Ninety-six percent of respondents were women, with 73% of participants from Ulaanbaatar and 27% (all midwives) from the countryside. The majority (96%) of healthcare providers stated they attempt pre-delivery counselling to discuss potential poor outcomes when mothers present with preterm labour. However, most (90%) healthcare providers stated they feel uncomfortable discussing not initiating or withdrawing neonatal resuscitation for a baby born alive with little chance of survival. Religious beliefs and concerns about long-term pain for the baby were the most common reasons for not initiating neonatal resuscitation or withdrawing care for a baby born too premature or with congenital birth-defects. Most Mongolian healthcare providers provide antenatal counselling to parents regarding neonatal resuscitation. Additional research is needed to determine if the above-said difficulty with counselling stems from deficiencies in communication training and whether these same counselling-related issues exist in other countries. Future educational efforts in teaching neonatal resuscitation in Mongolia should incorporate culturally-sensitive training on antenatal counselling.Key words: Antenatal counselling, Ethics, Low-income country, Neonates, Resuscitation, Mongolia     

Genetic variants in potassium channels are associated with type 2 diabetes in a Mongolian population

Background: Recent genome‐wide association studies (GWAS) have identified more than 40 common sequence variants associated with type 2 diabetes (T2D). However, the results are not always the same in populations with differing genetic backgrounds. In the present study, we evaluated a hypothesis that a North Asian population living in a geographic area with unusually harsh environmental conditions would develop unique genetic risks. Methods: A population‐based association study was performed with 21 single‐nucleotide polymorphisms (SNPs) in nine genes selected according to the results of GWAS conducted in other populations. The study participants included 393 full‐heritage Mongolian individuals (177 diagnosed with T2D and 216 matched controls). Genotyping was performed by TaqMan methodology. Results: The strongest association was detected with SNPs located within the potassium channel‐coding genes KCNQ1 (highest odds ratio [OR] = 1.92; P = 3.4 × 10^?5) and ABCC8 (OR = 1.79; P = 5 × 10^?4). Genetic variants identified as strongly influencing the risk of T2D in other populations (e.g. KCNJ11 or TCF7L2) did not show significant association in Mongolia. Conclusions: The strongest T2D risk‐associated SNPs in Mongolians are located within two of three tested potassium channel‐coding genes. Accumulated variations in these genes may be related to the exposure to harsh environmental conditions.     

CCL2, but not its receptor,is essential to restrict immune privileged central nervous system‐invasion of Japanese encephalitis virus via regulating accumulation of CD11b+ Ly‐6Chi monocytes

Japanese encephalitis virus (JEV) is a re‐emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2–CCL2 axis plays an important role in trafficking CD11b⁺ Ly‐6C^hi monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2‐ and CCL2‐ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly‐6C^hi monocytes and Ly‐6G^hi granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2‐ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2‐ and CCL2‐ablated mice was unlikely to be mediated by innate natural killer and adaptive T‐cell responses. Furthermore, CCL2 produced by haematopoietic stem cell‐derived leucocytes played a dominant role in CNS accumulation of Ly‐6C^hi monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE.     

Hypertension,knowledge, attitudes,and practices of primary care physicians in Ulaanbaatar,Mongolia

We examined the knowledge, attitudes, and practices of primary care doctors in Ulaanbaatar, Mongolia using a recently developed World Hypertension League survey. The survey was administered as part of a quality assurance initiative to enhance hypertension control. A total of 577 surveys were distributed and 467 were completed (81% response rate). The respondents had an average age of 35 years and 90.1% were female. Knowledge of hypertension epidemiology was low (13.5% of questions answered correctly); 31% of clinical practice questions had correct answers and confidence in performing specific tasks to improve hypertension control had 63.2% “desirable/correct” answers. Primary care doctors mostly had a positive attitude toward hypertension management (76.5% desirable/correct answers) and highly prioritized hypertension management activities (85.7% desirable/correct answers). Some important highlights included the majority (> 80%) overestimating hypertension awareness, treatment, and control rates; 78.2% used aneroid blood pressure manometers; 15% systematically screened adults for hypertension in their clinics; 21.8% reported 2 or more drugs were required to control hypertension in most people; and 16.1% reported most people could be controlled by lifestyle changes alone. 55% of respondents were not comfortable prescribing more than 1 or 2 antihypertensive drugs in a patient and the percentage of desirable/correct responses to treating various high‐risk patients was low. Most (53%‐74%) supported task shifting to nonphysician health care providers except for drug prescribing, which only 13.9% supported. A hypertension clinical education program is currently being designed based on the specific needs identified in the survey.     

Live attenuated Salmonella enterica serovar Typhimurium expressing swine interferon-α has antiviral activity and alleviates clinical signs induced by infection with transmissible gastroenteritis virus in piglets

Enhancing innate and acquired immunity by cytokines such as IFN-α appears to be useful as a first line of defense against viral infection. However, the practical use of cytokines in livestock is not evident due to cost and production issues associated with mass administration. In this study, we tested the efficacy of live attenuated Salmonella enterica serovar Typhimurium designed to secrete swine IFN-α (swIFN-α) protein for preventing the clinical signs caused by infection with transmissible gastroenteritis virus (TGEV), one of the diarrhea-causing viruses in the swine industry. Attenuated Salmonella vaccine (χ8501) containing swIFN-α-encoding pYA3560 vector (χ8501/swIFN-α) successfully induced the secretion of swIFN-α protein into the culture supernatants, as confirmed by SDS-PAGE and Western blot. The culture supernatants of χ8501/swIFN-α had antiviral activity against TGEV with 50% effective dose (ED₅₀) of 320 per mg of supernatant protein. In addition, oral administration of χ8501/swIFN-α reduced the severity of clinical signs caused by TGEV infection with the effect more apparent at 6–8 days post-infection, and reduced excretion of TGEV in feces. Similarly, the amount of TGEV in intestinal tissues and mesenteric lymph node of χ8501/swIFN-α-administered piglets was lower than in piglets that were treated with control bacteria. These results indicate the value of attenuated Salmonella vaccines as delivery systems of cytokines that can be used for mass administration, thereby overcoming cost and production issues.