Xenobiotic metabolism and its physiological consequences in high-Antarctic Notothenioid fishes

The Antarctic ecosystem is progressively exposed to anthropogenic contaminants, such as polycyclic aromatic hydrocarbons (PAHs). So far, it is largely unknown if PAHs leave a mark in the physiology of high-Antarctic fish. We approached this issue via two avenues: first, we examined the functional response of the aryl hydrocarbon receptor (Ahr), which is a molecular initiating event of many toxic effects of PAHs in biota. Chionodraco hamatus and Trematomus loennbergii served as representatives for high-Antarctic Notothenioids, and Atlantic cod, Gadus morhua as non-polar reference species. We sequenced and cloned the Ahr ligand binding domain (LBD) of the Notothenioids and deployed a GAL4-based luciferase reporter gene assay expressing the Ahr LBD. Benzo[a]pyrene (BaP), beta-naphthoflavone and chrysene were used as ligands for the reporter gene assay. Second, we investigated the energetic costs of Ahr activation in isolated liver cells of the Notothenioids during acute, non-cytotoxic BaP exposure. In the reporter assay, the Ahr LBD of Atlantic cod and the Antarctic Notothenioids were activated by the ligands tested herein. In the in vitro assays with isolated liver cells of high-Antarctic Notothenioids, BaP exposure had no effect on overall respiration, but caused shifts in the respiration dedicated to protein synthesis. Thus, our study demonstrated that high-Antarctic fish possess a functional Ahr that can be ligand-activated in a concentration-dependent manner by environmental contaminants. This is associated with altered cost for cellular protein synthesis. Future studies have to show if the toxicant-induced activation of the Ahr pathway may lead to altered organism performance of Antarctic fish.

Prognostic Analysis of Different Metastatic Patterns in Invasive Intraductal Papillary Mucinous Neoplasm: A Surveillance, Epidemiology, and End Results Database Analysis

Objective. To evaluate the impacts of different metastatic patterns on the prognosis of patients with invasive intraductal papillary mucinous neoplasm (IPMN). Materials and Methods. All patients who were diagnosed with invasive IPMN in the Surveillance, Epidemiology, and End Results SEER database (2010–2015) were included in this study. They were grouped according to different metastatic patterns. Kaplan–Meier analysis and log-rank test were used for the comparison of their survival rates. The hazard ratio (HR) with 95% confidence interval (CI) was analyzed using the Cox proportional-hazards model. Results. A total of 2264 cases were included in this study. The most common metastatic site was the liver. The patients with the nonorgan metastasis demonstrated the best survival outcomes, while those with multiple metastases showed the worst survival outcomes. As compared to the patients with isolated liver metastasis, those with isolated lung and other organ metastases showed better overall survival rates and tumor-specific survival rates. The patients with liver, lung, multiple, and other organ metastases or of age >60 years were the independent predictors of poor prognosis. Conclusions. The patients with isolated lung and other organ metastases demonstrated better survival outcomes as compared to those with isolated liver metastasis. The patients with nonorgan metastasis demonstrated the best survival outcomes, while those with multiple metastases showed the worst survival outcomes. Further studies are needed to determine a highly selected subset of patients, who might benefit from surgery or chemotherapy.

Immediate results of treatment of patients with metastatic uveal melanoma using isolated liver chemoperfusion. The first domestic experience

Introduction. Uveal melanoma is the most common primary intraocular tumor in adults. Despite some achievements in primary tumor treatment, 50% of patients develop distant metastases in various times (3 years to decades). Hematogenous spread is typical for uveal melanoma, and in 90% of the cases liver is the target. Median survival of patients with liver metastases is 4 to 9 months according to various researchers. And the result of treatment is extremely poor, unlike the results of skin melanoma treatment.The aim is to evaluate the immediate results of treatment of patients with uveal melanoma metastatic to the liver using isolated hepatic perfusion technique.Materials and methods. Considering a high risk of developing a metastatic liver disease in patients with uveal melanoma, local therapy is particularly interesting. This article describes the results of 10 metastatic uveal melanoma patients’ Isolated Hepatic Perfusion (IHP) Treatment. IHP was conducted using the standard methods with 100 mg of Melphalan for 60 min.Results and discussion. IHP treatment shows low complication rate. The data for response assessment is available on 9 out of 10 patients, because 10th patient received this treatment less than a month ago. Follow-ups a month after 9 patients underwent IHP showed an objective response to treatment in 6 patients (complete response in 1, partial response in 5 patients).Conclusion. The use of isolated liver chemoperfusion in a small group of patients according to the standard procedure allowed achieving an immediate response in 67% of cases.

Isolated chemohyperthermal perfusion of the liver with melphalan in the treatment of unresectable liver metastases with uveal melanoma

Uveal melanoma belongs to rare malignant neoplasms, and the biological peculiarity of this tumor determines the high rate of distant metastasis, which reaches 60 %. Most frequently, uveal melanoma metastases are localized in the liver and have an isolated character. At the same time, despite the achievements of modern drug therapy, the treatment results of this category of patients remain unsatisfactory. Among the regional methods of treatment of metastatic uveal melanoma, surgical treatment is considered to be the most effective. Median survival rate in the group of radically operated patients (R0) is 27 months. At present, in the vast majority of cases, surgical treatment is impossible because of multiple bilobar metastasis and advanced cancer process. Median life expectancy of patients with liver metastases is only 9 months. A promising method of regional treatment of inoperable metastatic uveal melanoma is isolated liver chemoperfusion. Multidisciplinary team of Radiology Scientific Research Center and Kostroma Oncologic Dispensary for the first time in Russia presents a clinical case of a patient with isolated inoperable uveal melanoma liver metastases using an innovative method - isolated high-dose chemo hyperthermic liver perfusion with melphalan. The article describes in detail the method of the procedure, estimates immediate (partial response in 1 month after the procedure) and long-term results of the method (stabilization of the condition against the background of immunotherapy in 9 months after surgery). Based on the presented clinical observation, isolated liver chemoperfusion with melphalan for this category of patients is reasonable. However, despite the encouraging immediate results, clinical experience needs to be accumulated in order to be further evaluated in clinical trials.

Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist

For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.

Highlighting the Place of Metastasis-Directed Therapy in Isolated Liver Metastases in Prostate Cancer: A Case Report

Metastatic prostate cancer remains a challenge for clinicians. Metastases involve mainly the bone compartment and can manifest as oligometastatic disease. In this setting, the role of metastasis-directed therapies (MDT) including surgery and/or stereotactic body radiotherapy is currently evaluated. Visceral metastases are less common and have very poor prognosis in mPC. Whether treating isolated visceral metastases such as liver metastases with MDT could increase the prognosis remains unknown. We report the management of a prostate cancer patient who progressed on androgen deprivation therapy with apparition of two liver metastases. We describe the feasibility of combining MDT with abiraterone acetate and prednisone in a patient with metastatic castration-resistant prostate cancer. MDT allowed the interruption of abiraterone acetate, preventing cumulative toxicity of this agent.

STUDY ON SOME ASPECTS OF PATHOGENESIS OF RHODOCOCCUS EQUI IN MICE

In order to study some aspects of pathogenesis of Rhodococcus equi, 60 white Swiss mice were used. They were randomly divided into 2 groups. The 1s' group (40 animals) was inoculated subcutaneously with a dose of 4x10° CFU .of R.equi while the 2nd group was kept as a control. Four animals from the 1st group and 2 animals from the 2nd group were sacrified at day, 1,2,4,8,12,16,20,24,28 and 30 postinoculation (P.I) Six animals of 1stgroup were died during the first and second days P.I. Microscopical examination showed acute to subacute suppurative inflammation in the liver, lung and spleen at I to 4 days PI. While pyogranulomatous lesions and epithelioid granuloma were seen in liver, lungs and spleen at 4 to 24 days PI R.equi was isolated liver, lungs, spleen, kidney and brain in the first day PI. The bacteria persisted in the spleen from and brain up to 20th day, in the liver up to 24" day while in the lungs, and kidney bacterial isolation continuous till 28th day PI.

“Complex” hepatic echinococcosis

Aim. To study the long-term results of surgical treatment in patients with “complex” hepatic echinococcosis.Materials and methods. The results of surgical treatment of 118 patients with hepatic echinococcosis from 2015 to 2020 at the A.V. Vishnevsky National Medical Research Center of Surgery were analyzed. The term “complex” hepatic echinococcosis has been proposed. A comparative analysis of the number and type of complications and surgical interferences 2 groups of patients was carried out: 66 patients with hepatic echinococcosis, 52 patients with complex hepatic echinococcosis.Results. During the observation period, no any recurrence was recorded. 55 (44%) of 118 patients had complex hepatic echinococcosis. Isolated liver damage was found in 74% of cases, combined liver and lung damage in 20% cases and with other organs – in 6%. In most cases, pericystectomy was performed (82%), 8% of patients underwent atypical hepatectomy, 4% – segmental resection, 3% – laparoscopic intervention, 3% – hemihepatectomy. Postoperative complications were recorded in 22 (18,6%) of cases. Accumulations of bile and biliary fistulas formed in 45% of cases, pneumotothorax or hydrothorax – in 23%, wound abscess – in 18%, hematomas in the hepatectomy zone – in 14% of the cases.Conclusion. Surgical treatment of complex hepatic echinococcosis requires an individual approach to the choice of the operation option. Preference should be given to parenchyma-preserving radical operations. When the liver lobe is totally replaced with a hydatid cyst and in case of cystobiliary fistulas hemihepatectomy should be performed, and it is acceptable to leave the fibrous capsule on large tubular structures.