Introduction
The Iwate Score (IS) have not been well-validated for specific procedures, especially for right posterior sectionectomy (RPS). In this study, the utility of the IS was determined for ...laparoscopic (L)RPS and the effect of tumor location on surgical outcomes was investigated.
Methods
Post-hoc analysis of 647 L-RPS performed in 40 international centers of which 596L-RPS cases met the inclusion criteria. Baseline characteristics and perioperative outcomes of patients stratified based on the Iwate score were compared to determine whether a correlation with surgical difficulty existed. A 1:1 Mahalanobis distance matching was utilized to investigate the effect of tumor location on L-RPS outcomes.
Results
The patients were stratified into 3 levels of difficulty (31 intermediate, 143 advanced, and 422 expert) based on the IS. When using a stepwise increase of the IS excluding the tumor location score, only Pringle’s maneuver was more frequently used in the higher surgical difficulty level (35.5%, 54.6%, and 65.2%, intermediate, advanced, and expert levels, respectively,
Z
= 3.34,
p
= 0.001). Other perioperative results were not associated with a statistical gradation toward higher difficulty level. 80 of 85 patients with a segment VI lesion and 511 patients with a segment VII lesion were matched 1:1. There were no significant differences in the perioperative outcomes of the two groups including open conversion, operating time, blood loss, intraoperative blood transfusion, postoperative stay, major morbidity, and mortality.
Conclusion
Among patients undergoing L-RPS, the IS did not significantly correlate with most outcome measures associated with intraoperative difficulty and postoperative outcomes. Similarly, tumor location had no effect on L-RPS outcomes.
The diagnostic value of tests for antimyeloperoxidase antibodies (anti-MPO) for systemic vasculitis is less established than that for cytoplasmic antineutrophil cytoplasmic antibody ...(cANCA)/antiproteinase 3 antibodies (anti-PR3). Controversy exists regarding the optimal utilization of indirect immunofluorescence (IIF) ANCA testing versus antigen-specific ANCA testing. To summarize the pertinent data, we conducted a metaanalysis examining the diagnostic value of ANCA testing systems that include assays for anti-MPO.
We performed a structured Medline search and reference list review. Target articles in the search strategy were those reporting the diagnostic value of immunoassays for anti-MPO for the spectrum of systemic necrotizing vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis, the Churg-Strauss syndrome, and isolated pauci-immune necrotizing or crescentic glomerulonephritis, regardless of other types of ANCA tests. Inclusion criteria required specification of a consecutive or random patient selection method and the use of acceptable criteria for the diagnosis of vasculitis exclusive of ANCA test results. Weighted pooled summary estimates of sensitivity and specificity were calculated for anti-MPO alone, anti-MPO + perinuclear ANCA (pANCA), and anti-MPO/pANCA + anti-PR3/cANCA.
Of 457 articles reviewed, only 7 met the selection criteria. Summary estimates of sensitivity and specificity (against disease controls only) of assays for anti-MPO for the diagnosis of systemic necrotizing vasculitides were 37.1% (confidence interval 26.6% to 47.6%) and 96.3% (CI 94.1% to 98.5%), respectively. When the pANCA pattern by IIF was combined with anti-MPO testing, the specificity improved to 99.4%, with a lower sensitivity, 31.5%. The combined ANCA testing system (anti-PR3/cANCA + anti-MPO/pANCA) increased the sensitivity to 85.5% with a specificity of 98.6%.
These results suggest that while anti-MPO is relatively specific for the diagnosis of systemic vasculitis, the combination system of immunoassays for anti-MPO and IIF for pANCA is highly specific and both tests should be used together given the high diagnostic precision required for these conditions. Because patients with ANCA associated vasculitis have either anti-MPO with pANCA or anti-PR3 with cANCA, and rarely both, a combined ANCA testing system including anti-PR3/cANCA and anti-MPO/pANCA is recommended to optimize the diagnostic performance of ANCA testing.
Leptin acts as a potential growth stimulator in several normal and neoplastic cells. Recent studies have shown the presence of increased levels of leptin in the peritoneal fluid of patients with ...endometriosis, implicating leptin in the pathogenesis of endometriosis. However, the specific function of leptin in the induction of mitogenesis in endometriosis is not known. This study investigated the expression of the leptin receptor (ObR) in endometrioma tissues and immortalized endometriotic cells, and the effect of leptin on cell growth. ObR expression was higher in endometriomas than in the normal endometrium, and it was detected in 74% of epithelial and 30% of stromal endometrioma tissues. In addition, human endometriotic epithelial cells (11Z and 12Z) showed a high level of ObR when compared with endometrial cells and endometriotic stromal cells (22B). Furthermore, leptin treatment stimulated the growth of 11Z and 12Z cells, but not that of 22B cells. Knockdown of the ObR in 11Z and 12Z cells impaired the ability of leptin to induce cell growth. Leptin induced the activation of Janus Kinases 2 (JAK2), signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) in endometriotic epithelial cells. Moreover, pretreatment with the JAK2/STAT3 inhibitor AG490 and the ERK inhibitor PD98059 significantly inhibited leptin-induced cell growth. The present results show that the ObR is induced in endometriosis, and that leptin stimulates the growth of endometriotic epithelial cells through the JAK2/STAT3 and ERK pathways.
The aim of this multicentric study was to investigate the impact of tumor location and size on the difficulty of Laparoscopic-Left Hepatectomy (L-LH).
Patients who underwent L-LH performed across 46 ...centers from 2004 to 2020 were analyzed. Of 1236 L-LH, 770 patients met the study criteria. Baseline clinical and surgical characteristics with a potential impact on LLR were included in a multi-label conditional interference tree. Tumor size cut-off was algorithmically determined.
Patients were stratified into 3 groups based on tumor location and dimension: 457 in antero-lateral location (Group 1), 144 in postero-superior segment (4a) with tumor size ≤40 mm (Group 2), and 169 in postero-superior segment (4a) with tumor size >40 mm (Group 3). Patients in the Group 3 had higher conversion rate (7.0% vs. 7.6% vs. 13.0%, p-value .048), longer operating time (median, 240 min vs. 285 min vs. 286 min, p-value <.001), greater blood loss (median, 150 mL vs. 200 mL vs. 250 mL, p-value <.001) and higher intraoperative blood transfusion rate (5.7% vs. 5.6% vs. 11.3%, p-value .039). Pringle's maneuver was also utilized more frequently in Group 3 (66.7%), compared to Group 1 (53.2%) and Group 2 (51.8%) (p = .006). There were no significant differences in postoperative stay, major morbidity, and mortality between the three groups.
L-LH for tumors that are >40 mm in diameter and located in PS Segment 4a are associated with the highest degree of technical difficulty. However, post-operative outcomes were not different from L-LH of smaller tumors located in PS segments, or tumors located in the antero-lateral segments.
Objective: We aimed to establish global benchmark outcomes indicators for L-RPS/H67. Background: Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, ...challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted. Methods: This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75 th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff Results: There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively. Conclusions: The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking.
The vanilloid receptor subtype 1 (TRPV1 or VR1) is expressed in nociceptive primary afferents of the C-fiber ‘pain’ pathway and has attracted considerable attention as a therapeutic target. Here, ...using rat TRPV1 heterologously expressed in Chinese hamster ovary cells, we show that different agonists show different patterns of modulation of the intracellular Ca
2+ concentration, monitored in individual cells by fura-2 Ca
2+ imaging. We identified 5 parameters (potency, maximal response, latency of response, variability of latency of response among individual cells, and desensitization) which behaved differently for different compounds. The potencies of the compounds examined ranged from EC
50 values of 80 pM to 9 μM. Peak levels of induced Ca
2+
i were observed either higher (RTX) or lower (anandamide) than for capsaicin. Significant latencies of response were observed for some (e.g. RTX) but not other derivatives, with great variation among individual cells in this latency. Marked desensitization after stimulation was detected in some cases (e.g. anandamide, capsaicin); for others, no desensitization was observed. We conclude that structurally diverse vanilloid agonists induce marked diversity in the patterns of Ca
2+ response. This diversity of response may provide opportunities for pharmacological exploitation.
Objective: To compare the outcomes of robotic minor liver resections (RMLR) versus laparoscopic (L) MLR of the anterolateral segments. Background: Robotic liver surgery has been gaining prominence ...over the years with increasing usage for a myriad of hepatic resections. Robotic liver resections(RLR) has demonstrated non-inferiority to laparoscopic(L)LR while illustrating advantages over conventional laparoscopy especially for technically difficult and major LR. However, the advantage of RMLR for the anterolateral(AL) (segments II, III, IVb, V and VI) segments, has not been clearly demonstrated. Methods: Between 2008 to 2022, 15,356 of 29,861 patients from 68 international centres underwent robotic(R) or laparoscopic minor liver resections (LMLR) for the AL segments Propensity score matching (PSM) analysis was performed for matched analysis. Results: 10,517 patients met the study criteria of which 1,481 underwent RMLR and 9,036 underwent LMLR. A PSM cohort of 1,401 patients in each group were identified for analysis. Compared to the LMLR cohort, the RMLR cohort demonstrated significantly lower median blood loss (75ml vs. 100ml, P <0.001), decreased blood transfusion (3.1% vs. 5.4%, P =0.003), lower incidence of major morbidity (2.5% vs. 4.6%, P =0.004), lower proportion of open conversion (1.2% vs. 4.5%, P <0.001), shorter post operative stay (4 days vs. 5 days, P <0.001), but higher rate of 30-day readmission (3.5% vs. 2.1%, P =0.042). These results were then validated by a 1:2 PSM analysis. In the subset analysis for 3,614 patients with cirrhosis, RMLR showed lower median blood loss, decreased blood transfusion, lower open conversion and shorter post operative stay than LMLR. Conclusion: RMLR demonstrated statistically significant advantages over LMLR even for resections in the AL segments although most of the observed clinical differences were minimal.
This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, ...the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
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