The Effect of Enhanced Recovery After Surgery Protocol on Surgical Site Infections in Liver Transplantation.

Background: Liver surgeries are treatment modalities that require careful pre- and postoperative follow-up for both the surgeon and the patient. Infections are the leading causes of morbidity and mortality after liver transplantation. Infections are the most frequent cause of death between 30 and 180 days after liver transplantation. We aimed to investigate the effect of the Enhanced Recovery After Surgery (ERAS) protocol on the prevention of infections in liver transplant patients. Patients and Methods: The study included patients who underwent liver transplantation in Ataturk University Organ Transplantation Center between 2017 and 2022. Two patient groups with and without ERAS were formed. Blood and urine cultures were collected retrospectively, and those with positive blood cultures for bacteremia were recorded as infection development. The development of infection between the two groups was statistically compared. Also, all patients' length of intensive care stay, length of hospital stay, and duration of antibiotic use were recorded. These parameters were compared between both groups. Results: There was a statistically significant difference between the two groups in terms of infection development (p: 0.01). There was a statistically significant difference between the two groups in terms of duration of antibiotic use and length of hospital stay (Mann-Whitney U test; p: 0.00, p: 0.04, respectively). There was no statistically significant difference between the two groups in terms of length of intensive care stay. Conclusion: We concluded that the introduction of an ERAS protocol was associated with fewer infections, thus shortening the duration of antibiotic therapy and length of hospital stay, although the standardization of the protocols is difficult, especially in liver transplants.

Relationship of vascular variations with liver remnant volume in living liver transplant donors.

BACKGROUND: In this study, we investigated the relationship between the portal vein and hepatic artery variations and the remaining liver volume in living donors in liver transplantation. MATERIALS AND METHODS: In the study, triphasic abdominal computed tomography images of 180 live liver donor candidates were analysed retrospectively. Portal veins were divided into four groups according to the Nakamura classification and seven groups according to the Michels classification. The relationship between vascular variations and remnant liver volume was compared statistically. RESULTS: According to the Nakamura classification, there were 143 (79.4%) type A, 23 (12.7%) type B, 7 (3.9%) type C and 7 (3.9%) type D cases. Using the Michels classification, 129 (71%) type 1, 12 (6.7%) type 2, 24 (13%) type 3, 2 (2.2%) type 4, 10 (5.6%) type 5, 1 (0.6%) type 6, and 2 (1.1%) type 7 cases were detected. There was no significant difference in the percentage of the remaining volume of the left liver lobe between the groups (p = 0.055, p = 0.207, respectively). CONCLUSIONS: Variations in the hepatic artery and portal vein do not affect the remaining liver volume in liver transplantation donors.

Parvovirus B19 Infection as a Rare Cause of Fulminant Liver Failure: A Case Report.

Parvovirus B19 infection is common in childhood. The clinical presentations range from benign to life threatening. The literature shows that the clinical presentation is influenced by the patient's age and the presence of chronic disease such as chronic hemolytic disorders and immunosuppressed conditions. As the majority of patients with liver failure are diagnosed as indeterminate, knowledge about parvovirus B19 associated liver disease is limited. We examined 3 children with parvovirus B19-induced fulminant liver failure, 2 of whom underwent liver transplantation. Although the presented patients received standard corticosteroid and tacrolimus therapy as an immunosuppressive regimen, acute rejection, parvovirus B19 persistence, or any other complications due to parvovirus B19 were not observed. Physicians should be aware of the parvovirus B19 infection in association to acute liver diseases.

Effect of different modes of erbium:yttrium aluminum garnet laser on shear bond strength to dentin.

OBJECTIVES: The aim of this study was to evaluate the effect of different surface treatments on the shear bond strength (SBS) of resin composites to dentin using total etch dentin bonding adhesives. MATERIALS AND METHODS: Sixty extracted human molars were flattened to obtain dentin surfaces. The samples were divided into three groups (n = 20): Group I: 37% phosphoric acid + optibond FL + resin composite; Group II: Erbium:yttrium aluminum garnet (Er:YAG) laser (medium short pulse [MSP] mode, 120 mJ/10 Hz) + optibond FL + resin composite; Group III: Er:YAG laser (quantum square pulse [QSP] mode, 120 mJ/10 Hz) + optibond FL + resin composite. After the specimens were prepared, the SBS test was performed at a crosshead speed of 0.5 mm/min. The fractured specimens were examined under a stereomicroscope to evaluate the fracture pattern. Statistical analyses were performed with one-way ANOVA and Tukey's honestly significant difference tests. One sample of treated dentin surface from each group was sputter-coated with gold, and scanning electron microscope (SEM) images were captured. RESULTS: Acid etching showed significantly higher SBS than the other groups (P < 0.05). However, the difference between Er:YAG MSP and QSP mode groups was not statistically significant (P > 0.05). SEM images of the acid-etched dentin surface showed opened dentinal tubule with a regular surface, but Er:YAG MSP mode treated surface was irregular. The surface treated with Er:YAG QSP mode represented wide dentinal tubules with a clean and flat surface. CONCLUSION: Using different modes (MSP and QSP) of Er:YAG laser for dentin surface treatment before application of total etch adhesives is still not an sufficient alternative compared to acid etching.

Inhibition of growth of MCF-7 MIII human breast carcinoma in nude mice by treatment with agonists or antagonists of LH-RH.

Human breast carcinoma (MCF-7 MIII), which exhibits an estrogen-independent but estrogen-responsive phenotype, was xenografted in 8-9-week-old intact female athymic nude mice without estrogen supplementation. In this model, we investigated inhibitory effects of the modern luteinizing hormone-releasing hormone (LH-RH) antagonist SB-75 and the agonist D-Trp6-LH-RH. The analogs were administered in the form of sustained delivery systems (microcapsules and microgranules). In the first experiment, treatment lasted 10 weeks. After 9 weeks of treatment, a significant inhibition of tumor volume was first found only in the group treated with SB-75, but the final tumor volume was significantly suppressed both by D-Trp6-LH-RH and SB-75. In the second experiment, treatment was started 70 days after tumor transplantation and was continued for 6 weeks. Chronic treatment with SB-75 or D-Trp6-LH-RH appeared to completely arrest tumor growth as measured by tumor volume, percentage change in tumor volume, and tumor weight. Serum estradiol was suppressed to undetectable levels and LH levels were also diminished. Histologically, the regressive changes in the treated tumors were due to the enhancement of apoptosis (programmed cell death) of tumor cells. Membrane receptor assays showed that LH-RH binding sites were down-regulated in tumor cells after treatment with SB-75 or D-Trp6-LH-RH. The results indicate that the antagonist SB-75, released from sustained delivery systems, can inhibit the growth of MCF-7 MIII tumors as effectively as the agonist D-Trp6-LH-RH, but more rapidly. In view of its immediate blockade of the pituitary-gonadal axis and the absence of side effects, the LH-RH antagonist SB-75 might be considered as a possible new hormonal agent for the treatment of breast cancer.

Decrease in the AgNOR number in Dunning R3327 prostate cancers after treatment with an agonist and antagonist of luteinizing hormone-releasing hormone.

The argyrophilic staining of the nucleolar organizer region (AgNOR) in cells of Dunning R3327 rat prostate tumors was studied and the effect of hormonal treatments on their appearance was analyzed. The nuclei of the control tumor cells contained 4.1 +/- 0.17 AgNOR granules. Treatment of rats for 8 weeks with luteinizing hormone-releasing hormone (LH-RH) agonist (D-Trp-6-LH-RH) and antagonist SB-75 induced a marked inhibition of tumor growth and decreased significantly (P less than 0.01) the number of Ag-NORs in the tumors to 2.89 +/- 0.10 AgNOR granules/cell in the group given the agonist and to 2.82 +/- 0.10 after therapy with the highest dose of the antagonist. A reduced AgNOR number (3.14 +/- 0.16) also was found after 3 days of treatment with SB-75 (P less than 0.05), but the AgNORs returned to near control values 1 week after the short-term therapy, showing the reversibility of these changes. These results suggest that the AgNOR method, which was widely tested on human tumors in the past few years, can be a valuable technique in experimental tumor pathology and useful in the evaluation of the effects of various treatments.

Inhibition of growth of experimental prostate cancer with sustained delivery systems (microcapsules and microgranules) of the luteinizing hormone-releasing hormone antagonist SB-75.

Inhibitory effects of the sustained delivery systems (microcapsules and microgranules) of a potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1, 4-chloro-D-phenylalanine2, 3-(3-pyridyl)-D-alanine3, D-citrulline6, D-alanine10]LH-RH (SB-75) on the growth of experimental prostate cancers were investigated. In the first experiment, three doses of a microcapsule preparation releasing 23.8, 47.6, and 71.4 micrograms of antagonist SB-75 per day were compared with microcapsules of agonist [D-Trp6]LH-RH liberating 25 micrograms/day in rats bearing Dunning R3327H transplantable prostate carcinoma. During 8 weeks of treatment, tumor growth was decreased by [D-Trp6]LH-RH and all three doses of SB-75 as compared to untreated controls. The highest dose of SB-75 (71.4 micrograms/day) caused a greater inhibition of prostate cancer growth than [D-Trp6]LH-RH as based on measurement of tumor volume and percentage change in tumor volume. Doses of 23.8 and 47.6 micrograms of SB-75 per day induced a partial and submaximal decrease, respectively, in tumor weight and volume. Tumor doubling time was the longest (50 days) with the high dose of SB-75 vs. 15 days for controls. The body weights were unchanged. The weights of testes, seminal vesicles, and ventral prostate were greatly reduced in all three groups that received SB-75, and testosterone levels were decreased to nondetectable values in the case of the two higher doses of SB-75. LH levels were also diminished. Similar results were obtained in the second experiment, in which the animals were treated for a period of 8 weeks with microgranules of SB-75. Therapy with microgranules of SB-75 significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The results indicate that antagonist SB-75, released from sustained delivery systems, can produce a state of chemical castration and effectively inhibit the growth of experimental prostate cancers. The efficacy of the antagonist SB-75 in inhibiting androgen-dependent Dunning prostatic carcinoma and the absence of side effects suggest its possible usefulness for the treatment of hormone-sensitive tumors.

Histological changes in Dunning prostate tumors and testes of rats treated with LH-RH antagonist SB-75.

Rats bearing Dunning R-3327 hormone-dependent prostate tumors were treated with LH-RH antagonist SB-75 in the form of microcapsules for sustained delivery administered every 3 weeks and which released 24, 48, 72 micrograms/day respectively. The effects were compared with those of microcapsules of the agonist D-Trp-6-LH-RH releasing 25 micrograms/day. Both types of LH-RH analogs significantly inhibited tumor growth over a period of treatment lasting 8 weeks. The effect of SB-75 was dose-dependent. The total inhibition of spermatogenesis, as well as atrophic signs in the prostate and seminal vesicles, demonstrated a marked suppression of the pituitary-gonadal system by these analogs. The histological signs of tumor regression were analyzed. The vascular content of tumors did not change after the treatments, but an increased amount of connective tissue was found in the treated tumors, especially after administration of SB-75. Both the agonist and the antagonist caused a moderate decrease of the number of mitotic cells and a marked increase of apoptosis in the tumors. The apoptotic index, i.e. the percentage of tumorous glands showing signs of apoptosis, reached 40-50% in treated groups, compared to only 15% in controls. An apoptotic index of 60% was noted in a separate group of rats treated with 200 micrograms SB-75/animal/day for 3 days. The signs of enhanced apoptosis disappeared 1 week after the short-term treatment. The induction of apoptosis by LH-RH analogs seemed to be of greater importance in tumor growth inhibition than their antimitotic effect. These results extend our previous observations on the efficacy of LH-RH antagonists in inhibition of various cancers. This histopathologic evaluation clearly supports our contention that modern antagonists of LH-RH, free of edematogenic effects, inhibit the growth of Dunning prostate tumors. Because of the immediate inhibitory effects, the use of LH-RH antagonists might lead to an improvement in the clinical response in patients with prostate cancer.

Receptors for luteinizing hormone-releasing hormone (LHRH) in Dunning R3327 prostate cancers and rat anterior pituitaries after treatment with a sustained delivery system of LHRH antagonist SB-75.

Membrane receptors for LHRH were evaluated in Dunning R3327 prostate cancers and rat anterior pituitaries. The receptors were characterized both in untreated animals and after in vivo treatment with microcapsules of the agonist D-Trp6-LHRH and a sustained delivery system releasing different doses (23.8, 47.6, 71.4 micrograms/day) of LHRH antagonist [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6, D-Ala10]-LHRH (SB-75). The therapy, which lasted 8 weeks, strongly inhibited tumor growth. A group of normal Sprague-Dawley male rats was also treated for 6 weeks with microcapsules of SB-75 releasing 25 micrograms/day. In the Dunning tumors from the control group, ligand [125I, D-Trp6]-LHRH was bound to two classes of binding sites [dissociation constant, class a (Kda) = 1.01 +/- 0.30 x 10(-9) M; Kdb = 1.71 +/- 0.41 x 10(-6) M; maximal binding capacity of receptors, class a (Bmaxa) = 48.66 +/- 22.13 fmol/mg of protein; Bmaxb = 92.10 +/- 29.40 pmol/mg of protein] in both kinetic and equilibrium studies. Treatment with D-Trp6-LHRH produced down-regulation of membrane receptors for LHRH in Dunning tumors. Microcapsules of SB-75 resulted in dose-dependent up-regulation of binding sites for LHRH in Dunning tumors. Analysis of the binding data showed that interaction of labeled D-Trp6-LHRH with binding sites in anterior pituitaries was consistent with the presence of a single class of noncooperative receptors (Kd = 43.75 x 10(-9) M; Bmax = 5.25 pmol/mg membrane proteins). Prolonged treatment with microcapsules of D-Trp6-LHRH reduced both Bmax and Kd. Lower doses of SB-75 (23.8 and 47.6 micrograms/day) produced up-regulation, whereas the highest dose (71.4 micrograms/day) resulted in down-regulation of binding sites for LHRH in rat pituitaries. In normal Sprague-Dawley rats, treatment with microcapsules of SB-75 (25 micrograms/day) for 6 weeks produced a slight increase in the number of available binding sites (Bmax = 2.35 +/- 0.82 pmol/mg membrane protein) and a moderate decrease in affinity (Kd = 35.10 +/- 15.19 x 10(-9) M) of pituitary membrane receptors for LHRH. The findings provide additional support for the view that LHRH analogs exert direct effects on tumor cells. Our findings indicate that prolonged treatment with high doses of modern LHRH antagonists produces down-regulation of pituitary receptors. Our work in tumors also implies that some differences may exist between LHRH receptors, even in the same tissue, leading to the concept of subclassification of LHRH receptors.

Antitumor effects of analogs of LH-RH and somatostatin: experimental and clinical studies.

Many clinical approaches for the treatment of hormone-sensitive tumors are being developed based on analogs of LH-RH and somatostatin. Inhibition of the pituitary-gonadal axis forms the basis for oncological applications of LH-RH agonists like [D-Trp6]-LH-RH and new LH-RH antagonists free of edematogenic effects such as [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6,D-Ala10]-LH -RH (SB-75). Agonists and antagonists of LH-RH have been used in patients with prostate cancer and might be also beneficial for the treatment of breast cancer and ovarian, endometrial and pancreatic carcinomas. Some of the effects of LH-RH analogs can be due to direct action since LH-RH receptors have been found in these cancers. The use of sustained delivery systems based on microcapsules of PLG, makes the treatment more efficacious. Octapeptide analogs of somatostatin such as D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and related analogs were designed specifically for antitumor activity. These somatostatin analogs, by virtue of having a wide spectrum of activities appear to inhibit various tumors through multiple mechanisms. Direct antiproliferative actions of somatostatin analogs appear to be mediated by specific receptors located on tumor cells. High affinity binding sites for RC-160 and related analogs have been found in human pancreatic, prostate, breast and ovarian cancers and brain tumors such as meningiomas. In vivo administration of analog RC-160 inhibits the growth of Dunning R-3327 prostate cancers in rats, MXT mammary tumors in mice and BOP-induced ductal pancreatic cancers in hamsters. Combination of microcapsules of RC-160 with [D-Trp6]-LH-RH results in synergistic potentiation of the inhibition of these cancers. Somatostatin analog RC-160 and LH-RH antagonist SB-75 are the object of further experimental studies and clinical trials aimed at the exploration of their inhibitory effects on the processes of malignant growth.

[Direct arterial administration of cytostatics]. / Direktna arterijska primjena citostatika.

Since 1984, intraarterial infusion chemotherapy (IAC) has been practised at our Institute. Patients with irresectable, previously untreated abdominal neoplasms were treated with intraarterial regional chemotherapy and radiation therapy after that. The objective remission rate was 40%, and a subjective response was observed in 90% of all cases.