Can intraoperative endoscopy prevent esophagojejunal anastomotic leakage after total gastrectomy?

BACKGROUND: Esophagojejunostomy (EJ) is frequently performed after total gastrectomy for proximal gastric tumors. Despite evolving surgical techniques and improving perioperative care, the EJ leak is one of the most severe life-threatening complications. This study investigated the preventability of postoperative anastomotic complications by performing intraoperative endoscopy. METHODS: We included 86 patients who underwent total gastrectomy and Roux-en-Y esophagojejunostomy anastomosis in the study. Patients were divided into two groups and analyzed retrospectively. Group 1 consisted of 43 patients who did not undergo intraoperative endoscopy between 2017 and 2019, and Group 2 included 43 patients who underwent intraoperative endoscopy between 2019 and 2020. RESULTS: Esophagojejunostomy anastomotic leak (EAL) was observed in 2.3 % of patients in Group 1 but not in Group 2. Anastomosis-related abnormal findings (anastomotic defect, bleeding, air leak, mucosal separation) were recorded in seven patients of Group 2 during endoscopy. When such findings were observed, additional full-thickness sutures were placed on the anastomosis line and strengthened. Complication related to anastomosis was not observed in the postoperative period in Group 2. DISCUSSION: After a total gastrectomy, the most severe complication affecting mortality, morbidity, and consequently the cost of the disease is esophagojejunal anastomotic leakage. Most of these complications are induced by technical errors not noticed during surgery. The crucial advantage of performing intraoperative endoscopy is the technically detailed evaluation of anastomosis. CONCLUSION: Intraoperative endoscopy is a safe method to evaluate the strength of anastomosis. This procedure provides detailed information regarding anastomotic integrity. HIPPOKRATIA 2021, 25 (3):108-112.

Association of PALB2 sequence variants with the risk of early-onset breast cancer in patients from Turkey.

The PALB2 gene, has been accepted as a moderate-penetrance gene associated with breast cancer susceptibility and this gene product is involved in the DNA damage repair pathway via co-localization with BRCA2. Germline PALB2 mutations are associated with an increased breast cancer risk. However, the prevalence of the diverse types of PALB2 variants depend on the population. Thus, the aim of the present study was to determine, for the first time, the prevalence of PALB2 variants in a Turkish population of BRCA1/BRCA2-negative early-onset patients with breast cancer. In total, 223 Turkish patients with BRCA1/BRCA2 negative early-onset breast cancer and 60 unaffected women were included in the study. All the coding exons and intron/exon boundaries of PALB2 were subjected to mutational analysis by heteroduplex analysis (HDA)and DNA sequencing. Eighteen PALB2 variants were found in breast cancer patients within the Turkish population. Three variants (c.271G>A, c.404C>A and c.2981T>A) have not been previously reported. In addition, nine intronic variants were described, and this study is the first to describe the c.1685-44T>A intronic variant. The prevalence of possible pathogenic PALB2 variants was found to be 4.03 % in BRCA1/2-negative Turkish patients with early-onset breast cancer. Different variants of PALB2 have been reported in the literature, and the prevalence of these variants could different for each population. This is the first study to investigate the prevalence of PALB2 variants in Turkish patients with early-onset breast cancer.

Intracerebral co-transplantation of liposomal tacrolimus improves xenograft survival and reduces graft rejection in the hemiparkinsonian rat.

Immunosuppression remains a key issue in neural transplantation. Systemic administration of cyclosporin-A is currently widely used but has many severe adverse side effects. Newer immunosuppressive agents, such as tacrolimus (TAC) and rapamycin (RAPA), have been investigated for their neuroprotective properties on dopaminergic neurons. These drugs have been formulated into liposomal preparations [liposomal tacrolimus (LTAC) and liposomal rapamycin (LRAPA)] which retain these neuroprotective properties. Due to the slower release of the drugs from the liposomes, we hypothesized that co-transplantation of either LTAC or LRAPA within a xenogeneic cell suspension would increase cell survival and decrease graft rejection in the hemiparkinsonian rat, and that a combination of the two drugs may have a synergistic effect. 6-hydroxydopamine-lesioned rats were divided to four groups which received intra-striatal transplants of the following: 1) a cell suspension containing 400,000 fetal mouse ventral mesencephalic cells; 2) the cell suspension containing 0.63 microM LRAPA; 3) the cell suspension containing a dose of 2.0 microM LTAC; 4) the cell suspension containing 2.0 microM LTAC and 0.63 microM LRAPA. Functional recovery was assessed by amphetamine-induced rotational behavior. Animals were killed at 4 days or 6 weeks post-transplantation, and immunohistochemistry was performed to look at the expression of tyrosine hydroxylase and major histocompatibility complex classes I and II. Only the group receiving LTAC had a decrease in rotational behavior. This observation correlated well with significantly more surviving tyrosine hydroxylase immunoreactive cells compared with the other groups and significantly lower levels of immunorejection as assessed by major histocompatibility complex class I and II staining. This study has shown the feasibility of using local immunosuppression in xenotransplantation. These findings may be useful in optimizing immunosuppression in experimental neural transplantation in the laboratory and its translation into the clinical setting.

Liposomal tacrolimus administered systemically and within the donor cell suspension improves xenograft survival in hemiparkinsonian rats.

The most widely used immunosuppressant in neural transplantation is cyclosporine- A (CsA). However, CsA has significant toxic effects when administered systemically. Tacrolimus (FK506), is a more potent immunosuppressant than CsA and can be prepared in lipid micelles (LTAC). This liposomal preparation allows for the administration of tacrolimus to the site of transplantation, possibly reducing the systemic side effects of immunosuppression. In this study we investigated the ability of LTAC to promote graft survival in hemiparkinsonian rats implanted with fetal mouse xenografts when LTAC is administered systemically to the host, when added to the donor cell suspension, or in combination. Rats with unilateral 6-hydroxydopamine lesions were transplanted with 800,000 fetal mouse ventral mesencephalic (VM) cells and were randomly divided into four groups. Group 1 was not immunosuppressed; Group 2 received daily systemic injections of LTAC; Group 3 received LTAC within the cell suspensions of mouse VM cells; and Group 4 received LTAC in the cell suspensions along with daily systemic administration of LTAC. Transplanted rats were assessed for rotational behavior 3 and 6 weeks posttransplantation. Cell survival was assessed using tyrosine hydroxylase (TH) immunohistochemistry. A significant reduction in rotational scores was observed only in the group of animals receiving the combination of LTAC-treated donor cells and systemic LTAC administration. This functional improvement correlated with a significantly greater survival of TH-immunoreactive cells in this group of animals. The other groups had poor cell survival and no significant functional improvement. We conclude that a combination of systemic immunosuppression and treatment of the cell suspension with LTAC may be a superior strategy to optimize xenograft survival. This strategy may have important implications for clinical neural transplantation.

Comparison between semiquantitative interictal Tc-99m HMPAO SPECT and clinical parameters in children with partial seizures.

The aim of the present study was to correlate between clinical parameters (age, age of onset, frequency and duration of seizures) and semiquantitative interictal SPECT parameters in children with partial seizures. We obtained 30 patients who had hypoperfusion in interictal SPECT, retrospectively. All patients underwent a detailed clinical examination, electroencephalography (EEG) investigation and brain computerized tomography (CT) and/or magnetic resonance imaging (MRI). Single photon emission computerized tomography (SPECT) studies were evaluated visually and by calculating semiquantitative parameters (the degree (asymmetry index, AI) and extent (number of ROI) of hypoperfusion). Visual analysis detected ipsilateral hypoperfusion in 23 (76%) patients with a unilateral focus and contralateral hypoperfusion in seven patients. We found an inverse correlation between the age at onset of seizure (r = -0.40, P = 0.025), frequency of seizures(but positive correlation; r = 0.77, P = 0.000) and AI. Number of ROIs showed a moderate correlation with the frequency of seizures (r = 0.67, P = 0.000), while correlation of the age at onset of seizures was not significant. This study performed in pediatric patients also suggested that either SPECT parameters may be used for correlating with clinical parameters.