Segment 4 Research Articles

Recognition of novel proteins encoded by an aquareovirus using mass spectrometry

Aquareovirusa genus of within the family Spinareoviridae, order Reovirales, infects aquatic animals. Their genomes comprise 11 segments of double-stranded RNA, which function directly as mRNAs upon release into the cytoplasm of infected cells. Here, liquid chromatography-tandem mass spectrometry was employed to annotate small coding ORFs in the Aquareovirus-C genome. Its plus-strand RNA of segment 8 (S8) contains a novel protein-coding frame (NS15), and S5 seems to has an additional reading frame (NS18) with a putative non-AUG initiation codon. Among them, NS15 polypeptide has been proved by immunoblotting assay. Remarkably, the S4 and S11 minus-strand mRNAs may encode polypeptides, suggesting ambisense polarity of the two segmented RNAs. And the newly discovered NS12 ORF in 2019, from viral tricistronic S7 mRNA, was also confirmed by this mass-spectrometry data. Taken together, these identified new ORFs reveal the genome-coding complexity of Aquareovirus-C.

Reproducibility of ultrasound-derived fat fraction in measuring hepatic steatosis

PurposeSteatotic liver disease (SLD) has become the most common cause of chronic liver disease. Nevertheless, the non-invasive quantitative diagnosis of steatosis is still lacking in clinical practice. This study aimed to evaluate the reproducibility of the new parameter for steatosis quantification named ultrasound-derived fat fraction (UDFF).Materials and methodsThe UDFF values were independently executed by two operators in two periods. In the process, repeated measurements of the same patient were performed by the same operator under different conditions (liver segments, respiration, positions, and dietary). Finally, the results of some subjects (28) were compared with the MRI-derived proton density fat fraction (PDFF). The concordance analysis was mainly achieved by the intraclass correlation coefficient (ICC) and Bland–Altman.ResultsOne hundred-five participants were included in the study. UDFF had good reliability in measuring the adult liver (ICCintra-observer = 0.96, ICCinter-observer = 0.94). Meanwhile, the ICC of the two operators increased over time. The variable measurement states did not influence the UDFF values on the surface, but they affected the coefficient of variation (Cov) of the results. Segment 8 (S8), end-expiratory, supine, and fasting images had the most minor variability. On the other hand, the UDFF value of S8 displayed satisfied consistency with PDFF (mean difference, −0.24 ± 1.44), and the results of both S5 (mean difference: −0.56 ± 3.95) and S8 (mean difference: 0.73 ± 1.87) agreed well with the whole-liver PDFF.ConclusionUDFF measurements had good reproducibility. Furthermore, the state of S8, end-expiration, supine, and fasting might be the more stable measurement approach.Critical relevance statementUDFF is the quantitative ultrasound parameter of hepatic steatosis and has good reproducibility. It can show more robust performance under specific measurement conditions (S8, end-expiratory, supine, and fasting).Trial registrationThe research protocol was registered at the Chinese Clinical Trial Registry on October 9, 2023 (http://www.chictr.org.cn/). The registration number is ChiCTR 2300076457.Key PointsThere is a lack of non-invasive quantitative measurement options for hepatic steatosis.UDFF demonstrated excellent reproducibility in measuring hepatic steatosis.S8, end-expiratory, supine, and fasting may be the more stable measuring condition.Training could improve the operators’ measurement stability.Variable measurement state affects the repeatability of the UDFF values (Cov).Graphical

Liver anatomy for totally laparoscopic segment 7 resection from a caudal magnified view-a 3-dimensional computed tomographic analysis.

Laparoscopic resection of hepatic segment 7 is considered particularly difficult. We analyzed anatomic variation of this segment in caudally oriented 3-dimensional (3D) magnified computed tomographic (CT) images obtained prior to liver resection. Analysis included 105 patients with preoperative 3D CT evaluation preceding liver resection for hepatobiliary malignancies between April 2021 and April 2024. Five ramification patterns were evident from a caudal magnified view. Some patients who had multiple segment 7 (S7) portal pedicles and an S7 pedicle branching ventrally posed difficulty in performing segmentectomy for the exact extent of S7. Distance from the point where a perpendicular line from the right rim of the inferior vena cava (IVC) intersected the right posterior portal pedicle to the point of bifurcation of the S6 and 7 pedicles was 34.6mm (range, 3.9-78.8; mean ± standard deviation, 35.2 ± 14.8mm). The median angle between the perpendicular line from the right rim of the IVC and the line from the root of the S7 pedicle to the right rim of the IVC was 77° (10-140); the mean ± standard deviation was 75.3° ± 28.1. Differences among ramification patterns also were evident. The angle between the right posterior portal pedicle and the S7 pedicle was 143° (79-215) or 143.3 ± 26.7, and that between S7 and S6 pedicles was 71°(15-123) or 75.5 ± 21.7°, representing relatively little variation. Understanding these details of caudal-view anatomy may resolve difficulties and clarify access required for exposing S7 portal pedicles.

Comparative Analysis of the Safety and Feasibility of Laparoscopic Versus Open Segment 7 Hepatectomy.

Laparoscopic hepatectomy has been widely accepted owing to its advantages as a minimally invasive surgery; however, laparoscopic segment 7 (S7) hepatectomy (LSH) has been rarely reported. We aimed to explore the safety and feasibility of LSH by comparing it with open surgical approaches. Twenty-nine patients who underwent S7 hepatectomy between January 2016 and January 2023 were enrolled in this study. The patients' characteristics, intraoperative details, and postoperative outcomes were compared between the 2 groups. No significant differences were observed in the preoperative data. The patients who underwent LSH had significantly shorter hospital stays (P=0.016) but longer operative times (P=0.034) than those who underwent open S7 hepatectomy. No significant differences in blood loss (P=0.614), transfusion (P=0.316), hospital expenses (P=0.391), surgical margin (P=0.442), rate of other complications, postoperative white blood cell count, and alanine aminotransferase and aspartate aminotransferase levels were noted between the 2 groups (P>0.05). For hepatocellular carcinoma, the results showed no differences in either disease-free survival (P=0.432) or overall survival (P=0.923) between the 2 groups. LSH is a safe and feasible surgical procedure that is efficient from an oncological point of view. It may be the preferred technique for lesions in the S7 of the liver.

A novel loss-of-function KCNB1 gene variant in a twin with global developmental delay and seizures.

Human voltage-gated potassium (Kv) channels are expressed by a 40-member gene family that is essential for normal electrical activity and is closely linked to various excitability disorders. Function-altering sequence variants in the KCNB1 gene, which encodes the neuronally expressed Kv2.1 channel, are associated with neurodevelopmental disorders including developmental delay with or without epileptic activity. In this study, we describe a 40-month-old fraternal twin who presented with severe neurodevelopmental delay. Electroencephalogram recordings at 19 months of age revealed poor sleep architecture and the presence of multifocal epileptiform discharges. The individual's fraternal twin was neurotypical, and there was no family history of neurodevelopmental delay or seizures. Whole genome sequencing at 33 months of age for the proband revealed a de novo variant in KCNB1 [c.1154C > T/p.Pro385Leu], encoding a proline-to-leucine substitution at residue 385, in the extracellular region immediately preceding Kv2.1 transmembrane segment 6 (S6). Cellular electrophysiological analysis of the effects of the gene variant in heterologously expressed Kv2.1 demonstrated that homozygous Kv2.1-P385L channels were completely non-functional. Channels generated by a 50/50 expression of wild-type Kv2.1 and Kv2.1-P385L, designed to mimic the proband's heterozygous status, revealed a partially dominant-negative effect, resulting in an 81% reduction in current magnitude. The dramatic loss of function in Kv2.1 is the most likely cause of the severe developmental delay and seizure activity in the proband, further enriching our phenotypic understanding of KCNB1 developmental encephalopathies.

Comparison of intravenous dexmedetomidine versus ketamine-dexmedetomidine combination on spinal block characteristics in patients undergoing lower limb orthopaedic surgery - A randomised clinical trial.

One major limitation of the spinal block remains the inability to extend the duration of the block intraoperatively unless planned before with spinal or epidural catheters and/or intrathecal additives. This study was designed to compare the effects of intravenous dexmedetomidine versus low-dose ketamine-dexmedetomidine combination infusion on spinal anaesthesia in lower limb orthopaedic surgeries. This randomised study was conducted in 60 patients scheduled for unilateral lower limb surgeries under spinal anaesthesia. Patients were randomised into Group D (n = 30) (0.5 µg/kg of intravenous (IV) dexmedetomidine bolus followed by maintenance infusion at 0.5 µg/kg/h) and Group LKD (n = 30) (IV bolus of 0.5 µg/kg of dexmedetomidine and 0.2 mg/kg of ketamine, followed by maintenance infusions of dexmedetomidine and ketamine at 0.5 µg/kg/h and 0.2 mg/kg/h, respectively). Ramsay Sedation Scale score of 3-4 was maintained. The t-test or the Wilcoxon-Mann-Whitney U test was used to compare the parameters between groups. The mean sacral segment 1 (S1) regression time was 390.3 [standard deviation (SD):84.38] [95% confidence interval (CI): 360.13, 420.53] versus 393.23 (SD: 93.01) (95% CI: 363.04, 423.43) min in Group D versus Group LKD respectively ((P = 0.701). The number of episodes of hypotension was significantly higher in Group D (19 patients) compared to Group LKD (nine patients) (P = 0.001). Pre- and postoperative stress markers (24 h) and the incidence of postoperative nausea and shivering were comparable between the two groups (P > 0.05). Tramadol requirement in the postoperative period was significantly less in Group LKD compared to Group D (P = 0.003). The duration of S1 regression was similar between group dexmedetomidine (Group D) and group low-dose ketamine and dexmedetomidine (Group LKD).

Comparison of laparoscopic liver resection for the ventral versus the dorsal areas of segment 8.

The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear. We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023. Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences. The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss. B230165 (approved at December 26, 2023).

ICG-Enhanced Compression Anatomical Segment 7 Segmentectomy in Laparoscopic and Robotic Approach.

Minimally invasive anatomical resection (AR) for posterosuperior lesions is technically challenging.1,2 The Glissonean approach or puncture technique is generally selected.3,4 The tumor-feeding portal pedicle compression AR (C-AR) is an established procedure in open surgery.5 This technique has benefited from the association with indocyanine green (ICG) fluorescence, used to enhance the anatomical area to be resected.6 Recently, C-AR via the minimal access approach has been reported.7 Herein, we report the first cases of laparoscopic and robotic segment 7 (S7) segmentectomy using the ICG-enhanced compression technique. Two cases of CHILD-class A hepatocellular carcinoma (HCC) in segment 7 with a liver stiffness less than 7 kPa treated by laparoscopic and robotic anatomical S7 segmentectomies were reported. Using the intraoperative ultrasound (IOUS), the tumor-bearing portal pedicle and the level targeted for compression were identified. The right hemiliver was adequately mobilized to allow handling of the organ during dissection. Using the grasper and the probe itself, the S7 Glissonean pedicle was transparenchymally compressed under real-time IOUS control. To further enhance the visibility of the discolored S7, ICG was administered intravenously, obtaining the compressed area to be resected as a non-stained one. Dissection was performed under intermittent Pringle maneuver up to exposing the right hepatic vein, dividing the Glissonean pedicle to segment 7 and then completing the resection. Pathologic findings demonstrated a 4.9 cm and 7.3 cm HCC with a R0-resection margin (> 1 cm in both). Postoperative complications were nil. The patients were discharged 6 days after surgery. This preliminary experience shows that the C-AR is a feasible and reliable technique in laparoscopic and robotic approach for posterosuperior lesions. Further studies are needed to investigate its applicability and standardization.

Analysis of respiratory-induced motion trajectories of individual liver segments in patients with hepatocellular carcinoma.

To analyze the respiratory-induced motion trajectories of each liver segment for hepatocellular carcinoma (HCC) to derive a more accurate internal margin and optimize treatment protocol selection. Ten-phase-gated four-dimensional computed tomography (4DCT) scans of 14 patients with HCC were analyzed. For each patient, eight representative regions of interest (ROI) were delineated on each liver segment in all 10 phases. The coordinates of the center of gravity of each ROI were obtained for each phase, and then the respiratory motion in the left-right (LR), anteroposterior (AP), and craniocaudal (CC) directions was analyzed. Two sets of motion in each direction were also compared in terms of only two extreme phases and all 10 phases. Motion of less than 5mm was detected in 12 (86%) and 10 patients (71%) in the LR and AP directions, respectively, while none in the CC direction. Motion was largest in the CC direction with a maximal value of 19.5mm, with significant differences between liver segment 7 (S7) and other segments: S1 (p<0.036), S2 (p<0.041), S3 (p<0.016), S4 (p<0.041), and S5 (p<0.027). Of the 112 segments, hysteresis>1mm was observed in 4 (4%), 2 (2%), and 15 (13%) in the LR, AP, and CC directions, respectively, with a maximal value of 5.0mm in the CC direction. A significant amount of respiratory motion was detected in the CC direction, especially in S7, and S8. Despite the small effect of hysteresis, it can be observed specifically in the right lobe. Therefore, caution is required when using 4DCT to determine IM using only end-inspiration and end-expiration. Understanding the respiratory motion in individual liver segments can be helpful when selecting an appropriate treatment protocol.

Novel KCNQ1 Q234K variant, identified in patients with long QT syndrome and epileptiform activity, induces both gain- and loss-of-function of slowly activating delayed rectifier potassium currents.

KCNQ1 and KCNE1 form slowly activating delayed rectifier potassium currents (IKs). Loss-of-function of IKs by KCNQ1 variants causes type-1 long QT syndrome (LQTS). Also, some KCNQ1 variants are reported to cause epilepsy. Segment 4 (S4) of voltage-gated potassium channels has several positively-charged amino acids that are periodically aligned, and acts as a voltage-sensor. Intriguingly, KCNQ1 has a neutral-charge glutamine at the third position (Q3) in the S4 (Q234 position in KCNQ1), which suggests that the Q3 (Q234) may play an important role in the gating properties of IKs. We identified a novel KCNQ1 Q234K (substituted for a positively-charged lysine) variant in patients (a girl and her mother) with LQTS and epileptiform activity on electroencephalogram. The mother had been diagnosed with epilepsy. Therefore, we sought to elucidate the effects of the KCNQ1 Q234K on gating properties of IKs. Wild-type (WT)-KCNQ1 and/or Q234K-KCNQ1 were transiently expressed in tsA201-cells with KCNE1 (E1) (WT + E1-channels, Q234K + E1-channels, and WT + Q234K + E1-channels), and membrane currents were recorded using whole-cell patch-clamp techniques. At 8-s depolarization, current density (CD) of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly larger than the WT + E1-channels (WT + E1: 701 ± 59pA/pF; Q234K + E1: 912 ± 50pA/pF, p < 0.01; WT + Q234K + E1: 867 ± 48pA/pF, p < 0.05). Voltage dependence of activation (VDA) of the Q234K + E1-channels or WT + Q234K + E1-channels was slightly but significantly shifted to depolarizing potentials in comparison to the WT + E1-channels ([V1/2] WT + E1: 25.6 ± 2.6mV; Q234K + E1: 31.8 ± 1.7mV, p < 0.05; WT + Q234K + E1: 32.3 ± 1.9mV, p < 0.05). Activation rate of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly delayed in comparison to the WT + E1-channels ([half activation time] WT + E1: 664 ± 37ms; Q234K + E1: 1,417 ± 60ms, p < 0.01; WT + Q234K + E1: 1,177 ± 71ms, p < 0.01). At 400-ms depolarization, CD of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly decreased in comparison to the WT + E1-channels (WT + E1: 392 ± 42pA/pF; Q234K + E1: 143 ± 12pA/pF, p < 0.01; WT + Q234K + E1: 209 ± 24pA/pF, p < 0.01) due to delayed activation rate and depolarizing shift of VDA. The KCNQ1 Q234K induced IKs gain-of-function during long (8-s)-depolarization, while loss of-function during short (400-ms)-depolarization, which indicates that the variant causes LQTS, and raises a possibility that the variant may also cause epilepsy. Our data provide novel insights into the functional consequences of charge addition on the Q3 in the S4 of KCNQ1.

A safe and simple exposure and Pringle maneuver in laparoscopic anatomical liver resection of segment 7

BackgroundLaparoscopic access to liver segment 7 (S7) is difficult for deep surgical situations and bleeding control. Herein, our proposed laparoscopic technique for S7 lesions using a self-designed tube method is introduced.MethodsClinical data of patients who underwent laparoscopic anatomical liver resection of S7 (LALR-S7) with the help of our self-designed tube to improve the exposure of S7 and bleeding control in the Second Affiliated Hospital, Third Military Medical University (Army Medical University) from April 2019 to December 2021 were retrospectively analyzed to evaluate feasibility and safety.ResultsNineteen patients were retrospectively reviewed. The mean age was 51.3 ± 10.3 years; mean operation time, 194.5 ± 22.7 min; median blood loss, 160.0 ml (150.0–205.0 ml); and median length of hospital stay, 8.0 days (7.0–9.0 days). There was no case conversion to open surgery. Postoperative pathology revealed all cases of hepatocellular carcinoma (HCC). Free surgical margins were achieved in all patients. No major postoperative complications were observed. Patients with postoperative complications recovered after conservative treatment. During outpatient follow-up examination, no other abnormality was presented. All patients survived without tumor recurrence.ConclusionsThe preliminary clinical effect of our method was safe, reproducible and effective for LALR-S7. Further research is needed due to some limitations of this study.

Augmented Reality Navigation Plus Indocyanine Green Fluorescence Imaging Can Accurately Guide Laparoscopic Anatomical Segment 8 Resection.

Laparoscopic anatomical Segment 8 (S8) resection is a highly challenging hepatectomy. Augmented reality navigation (ARN), which could be combined with indocyanine green (ICG) fluorescence imaging, has been applied in various complex liver resections and may also be applied in laparoscopic anatomical S8 resection. However, no study has explored how to apply ARN plus ICG fluorescence imaging (ARN-FI) in laparoscopic anatomical S8 resection, or explored its accuracy. This study is a post hoc analysis that included 31 patients undergoing laparoscopic anatomical S8 resection from the clinical NaLLRFI trial, and the resected liver volume was measured in each patient. The perioperative parameters of safety and feasibility, as well as the accuracy analysis outcomes were compared. There were 16 patients in the ARN-FI group and 15 patients underwent conventional laparoscopic hepatectomy without ARN or fluorescence imaging (non-ARN-FI group). There was no significant difference in baseline characteristics between the two groups. Compared with the non-ARN-FI group, the ARN-FI group had lower intraoperative bleeding (median 125 vs. 300 mL, P = 0.003). No significant difference was observed in other postoperative short-term outcomes. Accuracy analysis indicated that the actual resected liver volume (ARLV) in the ARN-FI group was more accurate. ARN-FI was associated with less intraoperative bleeding and more accurate resection volume. These techniques may address existing challenges and provide rational guidance for laparoscopic anatomical S8 resection.

Intrahepatic Glissonean Approach for Robotic Anatomical Liver Resection of Segment 7 Using the Saline-Linked Monopolar Cautery Scissors (SLiC-Scissors) Method: A Technical Case Report With Videos.

Anatomical hepatectomy of segment 7 (S7) is technically difficult due to its difficult accessibility. Here, we present our experience of robotic anatomical S7 subsectionectomy of the liver employing the saline-linked cauteryscissors (SLiC-Scissors) technique. After the right lobe was fully mobilized, dissection of the Glissonean pedicle and hepatic venous branch of S7, as well as the liver parenchymal transection, were safely performed using the SLiC-Scissors method. Despite its technological complexity, the intrahepatic Glissonean approach for robotic anatomical S7 subsectionectomy of the liver employing the SLiC scissors method is safe and efficient.

Combining Phage Display Technology with In Silico-Designed Epitope Vaccine to Elicit Robust Antibody Responses against Emerging Pathogen Tilapia Lake Virus.

Antigen epitope identification is a critical step in the vaccine development process and is a momentous cornerstone for the development of safe and efficient epitope vaccines. In particular, vaccine design is difficult when the function of the protein encoded by the pathogen is unknown. The genome of Tilapia lake virus (TiLV), an emerging virus from fish, encodes protein functions that have not been elucidated, resulting in a lag and uncertainty in vaccine development. Here, we propose a feasible strategy for emerging viral disease epitope vaccine development using TiLV. We determined the targets of specific antibodies in serum from a TiLV survivor by panning a Ph.D.-12 phage library, and we identified a mimotope, TYTTRMHITLPI, referred to as Pep3, which provided protection against TiLV after prime-boost vaccination; its immune protection rate was 57.6%. Based on amino acid sequence alignment and structure analysis of the target protein from TiLV, we further identified a protective antigenic site (399TYTTRNEDFLPT410) which is located on TiLV segment 1 (S1). The epitope vaccine with keyhole limpet hemocyanin (KLH-S1399-410) corresponding to the mimotope induced the tilapia to produce a durable and effective antibody response after immunization, and the antibody depletion test confirmed that the specific antibody against S1399-410 was necessary to neutralize TiLV. Surprisingly, the challenge studies in tilapia demonstrated that the epitope vaccine elicited a robust protective response against TiLV challenge, and the survival rate reached 81.8%. In conclusion, this study revealed a concept for screening antigen epitopes of emerging viral diseases, providing promising approaches for development and evaluation of protective epitope vaccines against viral diseases. IMPORTANCE Antigen epitope determination is an important cornerstone for developing efficient vaccines. In this study, we attempted to explore a novel approach for epitope discovery of TiLV, which is a new virus in fish. We investigated the immunogenicity and protective efficacy of all antigenic sites (mimotopes) identified in serum of primary TiLV survivors by using a Ph.D.-12 phage library. We also recognized and identified the natural epitope of TiLV by bioinformatics, evaluated the immunogenicity and protective effect of this antigenic site by immunization, and revealed 2 amino acid residues that play important roles in this epitope. Both Pep3 and S1399-410 (a natural epitope identified by Pep3) elicited antibody titers in tilapia, but S1399-410 was more prominent. Antibody depletion studies showed that anti-S1399-410-specific antibodies were essential for neutralizing TiLV. Our study demonstrated a model for combining experimental and computational screens to identify antigen epitopes, which is attractive for epitope-based vaccine development.

Application of Laparoscopic Hepatectomy Combined with Intraoperative Microwave Ablation in Colorectal Cancer Liver Metastasis

Laparoscopic hepatectomy is a common treatment for colorectal cancer liver metastasis. Previously, a sufficient number of functional liver masses had to be maintained during laparoscopic hepatectomy, with a residual liver volume of >40% in cirrhotic patients and >30% in non-cirrhotic patients. The high incidence of complications such as bleeding, bile leakage, or liver failure due to the exposure and difficulty of the resection of specific liver segments such as S2 and S7 reduces the success rate of liver resection. At present, microwave ablation is mainly applied in the treatment of liver metastasis using a percutaneous approach, which makes it difficult to identify hidden parts or small lesions. For some liver segments, the percutaneous puncture of liver segment 7 (S7) is likely to pass through the thoracic cavity, and the percutaneous puncture of liver segment 2 (S2) adjacent to the diaphragm is likely to injure the diaphragm and heart; these issues restrict the application of percutaneous ablation in colorectal cancer liver metastasis. Considering multiple lesions, laparoscopic microwave ablation combined with hepatectomy was performed in this study. The location of the lesions was determined by contrast-enhanced ultrasound under laparoscopy, and small lesions that were difficult to detect before the operation were identified. For the scattered lesions, which had diameters less than 3 cm and were difficult to resect, ablation was adopted to substitute hepatectomy. This technique helped to more explicitly locate the tumors, simplified the operation procedures, reduced the risk of complications such as bleeding and bile leakage, shortened the operation time, accelerated the postoperative recovery, significantly improved the success rate of operation, and enhanced the clinical prognosis of colorectal cancer liver metastasis by surgical resection.

Anatomic Laparoscopic Partial Hepatectomy of a Segment 4a B-Catenin Mutated Adenoma.

Although a β-catenin mutated hepatocellular adenoma (HCA) is a benign liver tumor, it can cause bleeding, obstruction, pain, and hepatocellular carcinoma.1-3 Because surgery needs to balance these risks with its morbidity, a minimally invasive approach may be well suited.4-6 In this report, a strategic approach to minimally invasive resection of HCA encompassing segment 4a (S4a) is reviewed. A 22-year-old woman with abdominal pain was found to have two liver lesions involving segment 4a (5 cm) and segment 8 (S8) (4.5 cm). Liver biopsy confirmed a β-catenin mutated HCA in the S4a lesion. After embolization, an anatomic S4a segmentectomy and a partial S8 resection were planned. Three-dimensional modeling was used to perform a preoperative virtual hepatectomy; to visualize the spatial relationship between the HCA, the portal bifurcation, and the hepatic veins; and to preplan the port sites.7 With the patient in the French position, after port placement, intraoperative ultrasound was performed to identify the transection plane.8 The main left portal pedicle and Rex's recessus were exposed, and the branches of S4a were dissected out, clipped, and divided. Using ultrasound, the middle hepatic vein was exposed to define the lateral border of the dissection plane. Although a β-catenin mutated HCA in S4a does not necessitate a formal segmentectomy, understanding the anatomic structures outlining its borders can facilitate the resection, especially for a large HCA. Virtual hepatectomy helps to achieve a detailed comprehension of the complex borders of segment 4a. Preoperative embolization can firm up the tumor and minimize the risk of intraoperative rupture from manipulation.

A comprehensive survey of permethrin resistance in human head louse populations from northwest Iran: ex vivo and molecular monitoring of knockdown resistance alleles

BackgroundHead louse infestation is an important public health problem, and expanding resistance to permethrin is a major challenge to its control. The mapping and detection of pyrethroid resistance are essential to the development of appropriate treatments and ensure the effectiveness of current measures. The aim of this study was to present the phenotypic and genotypic basis of permethrin resistance and identify knockdown resistance (kdr) mutations in head louse populations in northwestern Iran.MethodsAdult head lice were collected from 1059 infested girls in Ardebil, East Azerbaijan, West Azerbaijan and Zanjan Provinces, northwestern Iran. The toxicity of permethrin and the possible synergistic effect of piperonyl butoxide (PBO) on this toxicity were assessed using bioassays. Fragments of voltage-sensitive sodium channels (vssc) and cytochrome b (cytb) genes were amplified and analyzed for the detection of knockdown resistance (kdr) mutations and mitochondrial groups. Moreover, genotypes of the two hot spot regions of the vssc gene were determined by melting curve analysis of amplicons.ResultsA total of 1450 adult head lice were collected during 2016–2021. Live lice were exposed to a dose of 1% permethrin for 12 h, and the median lethal time (LT50) and time to achieve 90% mortality (LT90) were determined to be 6 and 14.8 h, respectively. Topical application of 2 and 16 ng permethrin per louse resulted in 25% and 42.11% mortality, respectively. Pre-exposure of samples to 3% piperonyl butoxide had no synergistic effect on the effects of permethrin. Analysis of the 774-bp vssc gene fragment showed the presence of the M815I, T917I and L920F mutations, wild-type and T917I mutation, in 91.6%, 4.2% and 4.2% of samples, respectively. Investigation of the mitochondrial cytb gene demonstrated the predominance of clade B. The frequency of domain II segment 4 (S4)-S5 kdr genotypes in mitochondrial groups was identical, and heterozygotes were present in 93.5% of samples. A significant difference was detected in the frequency of domain IIS1-S3 kdr genotypes, and the frequency of resistant alleles and heterozygotes was higher in clade B than in clade A.ConclusionsThe presence of kdr mutations in the vssc gene and the non-synergist effect of PBO indicate that pyrethroid target site insensitivity is the main resistance mechanism. This phenomenon and the high frequency of resistant alleles necessitate that new pediculosis management programs be developed. Further studies need to be conducted to identify all factors contributing this resistance and to develop alternative pediculicides.Graphical

The Importance of Segment 4 Anatomy on Outcomes Following Living Donor Left Lateral Segmentectomy

BackgroundDuring left lateral section (LLS) resection for live liver donation, the vascular inflow and the bile drainage of segment 4 (S4) are compromised. We investigated the long-term changes of S4 after donation and their potential prognostic impact on living liver donors. Materials and methodsThis was a retrospective analysis of 42 consecutive left lateral (LLS, S2/3) liver resections for living donation. ResultsThere were 25 female and 17 male donors. Median age was 33 y and median body mass index was 26. Median LLS, S2/3, volume was 262 cc, and median sS4 volume was 160 cc. Complications were encountered in three donors (7%). An independent extrahepatic S4 artery (S4A) (with a proximal left heptic artery or a right hepatic artery origin) was identified in 41% of the donors. Ligation of the independent S4A was not associated with the rate of post resection liver dysfunction, complications, or the degree of S4 atrophy. Having a dominant S4 portal triad pedicle feeding the right anterior sectors, segment 5/8, of the liver was associated with increased parenchymal damage as evidenced by a higher peak of alanine aminotransferase but was not associated with postoperative complications. The median degree of atrophy of S4 at 1 y post donation as noted on imaging was 66%. The presence of a dominant S4 portal triad pedicle and the peak alanine aminotransferase early postoperatively were both predictors of the degree of S4 atrophy post donation. ConclusionsThe presence of an independent S4A or dominant S4 portal triad pedicle feeding the liver right anterior sectors, segment 5/8, should not be a contraindication for left lateral segment living donation.

Minimally invasive transthoracic resection of a segment eight liver tumor

Despite advances in technology and technique of minimally invasive liver surgery, resection of lesions in the posterosuperior segments such as segment 8 (S8) remains challenging. Compared to open surgery, there are specific differences that make minimally invasive access to S8 challenging. These include the caudal view along the axis of the hepatoduodenal ligament, increased distance between trocars and the operative field, and the liver fulcrum created by the anterolateral segments limiting the view. However, several advancements have helped to overcome these challenges, such as the use of intercostal trocars (combined lateral-abdominal approach) and a flexible tip camera. Consequently, a total thoracoscopic (transthoracic) approach was developed to resect subdiaphragmatic tumors, which may particularly benefit patients with a hostile abdomen. This article summarizes the anatomic, technical, and technological considerations for safe resection of lesions in S8.

Pure laparoscopic left lateral graft procurement with removing segment 3 employing Glissonean approach, indocyanine green fluorescence imaging and in situ splitting for a small infant.

We report on a pure laparoscopic left lateral graft procurement with removing segment 3 that employs the Glissonean approach, indocyanine green (ICG) fluorescence imaging and in situ splitting. We first mobilised the liver and confirmed the root of the left hepatic vein (LHV). We then encircled the left Glissonean pedicle, and the segment 3 Glissonean pedicle (G3) was also individually encircled. We performed parenchymal transection of the left lateral segmentectomy using Pringle's manoeuvre. We clipped G3 and confirmed the demarcation line using ICG fluorescence imaging. The inflow in the S2 area was confirmed via intraoperative sonography, and we split segment 3 (S3) from the left lateral sector graft in situ. The left hepatic artery, left portal vein and left hepatic duct were also encircled and divided. The LHV was transected using a linear stapler, and the S2 monosegment liver graft and removed S3 were procured. Our technique reasonably prevents graft-related complications.