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Background: Robotic pancreaticoduodenectomy (RPD) is an emerging alternative to open pancreaticoduodenectomy (OPD). Although RPD offers various theoretical advantages, it is used in less than 10% of all pancreaticoduodenectomies. The aim of this study was to report our 10-year experience and compare RPD outcomes with international benchmarks for OPD., Methods: A retrospective review of a prospectively maintained institutional database was performed of consecutive patients who underwent RPD between January 2011 and December 2021. Patients were categorized into low-risk and high-risk groups according to the selection criteria set by the benchmark study. Their outcomes were compared to the international benchmark cut off values. Outcomes were then evaluated over time to identify improvements in practice and establish a learning curve., Results: Of 201 RPDs, 36 were low-risk and 165 high-risk patients. Compared to the OPD benchmarks, outcomes of low-risk patients were within the cutoff values. High-risk patients were outside the cutoff for blood transfusions (26% vs. ≤ 23%), overall complications (78% vs. ≤ 73%), grade I-II complications (68% vs. ≤ 62%), and readmissions (22% vs ≤ 21%). Oncologic outcomes for high-risk patients were within benchmark cutoffs. Cases at the end of the learning curve included more pancreatic cancer (42% from 17%) and fewer low-risk patients (10% from 24%) than those at the beginning. After 41 RPD there was a decline in conversion rates and operative time. Between 95 and 143 cases operative time, transfusion rates, and LOS declined significantly. Complications did not differ over time., Conclusion: RPD yields results comparable to the established benchmarks in OPD in both low- and high-risk patients. Along the learning curve, RPD evolved with the inclusion of more high-risk cases while outcomes remained within benchmarks. Addition of a robotic HPB surgery fellowship did not compromise outcomes. These results suggest that RPD may be an option for high-risk patients at specialized centers., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Robotic surgery has been increasingly utilized, yet its application for hepato-pancreato-biliary (HPB) procedures remains low due to technical complexity, perceived financial burden, and unproven clinical benefits. We hypothesized that the robotic approach would be associated with improved clinical outcomes following major hepatectomy compared with the laparoscopic approach among elderly patients who would benefit from the advantages of minimally invasive surgery., Methods: A retrospective review of consecutive patients who underwent major hepatectomy between January 2010 and December 2021 at Carolinas Medical Center was performed. Inclusion criteria were age ≥ 65 years and major hepatectomy of three segments or more. Patients who underwent multiple liver resections, vascular/biliary reconstruction, or concomitant extrahepatic procedures (except cholecystectomy) were excluded. Categorical variables were compared using Chi-square or Fisher's exact test when more than 20% of cells had expected frequencies less than five, and Wilcoxon two-sample or Kruskal-Wallis tests were used for continuous or ordinal variables. Results are described as median and interquartile range (IQR). Multivariate analyses were used on postoperative admission days., Results: There were 399 major hepatectomies performed during this time period, of which 125 met the criteria and were included. There were no differences in perioperative demographics among patients who underwent robotic hepatectomy (RH, n = 39) and laparoscopic hepatectomy (LH, n = 32). There was no difference in operative time, blood loss, or major complication rates. However, RH had lower rates of conversion to an open procedure (2.6% versus 31.3%, p = 0.002), shorter length of hospital stay [LOS, 4 (3-7) versus 6 (4-8.5) days, p ≤ 0.0001], cumulative LOS [4 (3-7) versus 6 (4.5-9) days, p ≤ 0.0001], and lower rates of intensive care unit (ICU) admission (7.7% versus 75%, p ≤ 0.001), with a trend toward fewer rehabilitation requirements., Conclusions: Robot major hepatectomy shows clinical advantages in elderly patients, including shorter hospital and ICU stays. These advantages, as well as reduced rehabilitation requirements associated with minimally invasive surgery, could overcome the current perceived financial disadvantages of robotic hepatectomy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Minimally invasive resection of the retroperitoneal duodenum is complicated because of its anatomical location, and the proximity of the ampulla of Vater and vascular structures. Benign or indolent pathology can add complexity to operative decision-making for these already challenging surgeries, and operations associated with lower morbidity may be considered. This study describes a novel robotic transmesenteric approach to duodenal sleeve resection for non-malignant lesions., Methods: A retrospective review was performed on a prospectively maintained institutional database between 2011 and 2021. The Da Vinci XI or SI platform (Intuitive Surgical, Sunnyvale, CA) was used in all cases., Results: Critical steps in robotic sleeve duodenectomy include the following: (1) techniques for avoiding damage to the ampulla; (2) Kocherization and reverse Kocherization; and (3) A transmesenteric approach for further mobilization of the duodenum. Nineteen patients were referred by experienced gastrointestinal endoscopists after endoscopic management was deemed unsuitable or their resections were incomplete. The histological diagnoses were either symptomatic benign or indolent duodenal pathology. All 19 patients underwent robotic duodenal sleeve resection during the study period. Lesions were located in the third to fourth parts of the duodenum. The median operative time was 216 min (IQR: 199-225), and the estimated intraoperative blood loss was 50 ml (IQR: 50.0-93.7). The 90 day readmission rate was 15.7% (3/19), and no 90-day mortality was observed., Conclusion: This small case series of a transmesenteric approach for robotic sleeve duodenectomy demonstrates its feasibility and safety in this potentially challenging operation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In endometriosis, M2 macrophages (MΦ) are dominant and promote the development of endometriosis lesions. However, the factor(s) which induces M2 MΦ are unknown. In the present study, we focused on interleukin (IL)-33, known as an alarmin and investigated its expression and its role in endometriosis, especially from the point of the relevance with MΦ. The expression of IL-33 in endometriosis lesions was examined by immunohistochemistry. The cystic fluid of ovarian cysts/tumors was obtained and used to measure IL-33 concentration. Endometriotic stromal cells (ESC) and MΦ derived from patients were used for in vitro experiments. IL-33 was detected in the epithelium and stromal cells of endometriotic lesions. The mean IL-33 concentration in the cystic fluid of endometriomas was significantly higher than that in non-endometriomas (2.2 ng/ml vs. 0.02 ng/ml, P < 0.01). IL-1β induced IL-33 mRNA expression in ESC via p38 MAPK activation. With IL-33 stimulation, peritoneal MΦ polarized to M2 MΦ and produced IL-1β mRNA with a 2.2-fold increase, which was negated with soluble ST2, a decoy receptor of IL-33. IL-33, derived from endometriotic lesions, stimulated MΦ to produce IL-1β, which results in increasing IL-33 production in ESC. This cycle may continue to exacerbate the endometriotic lesions.

Objects: There is growing evidence that sphingosine 1-phosphate (S1P) is involved in inflammatory diseases. As endometriosis is known as an inflammatory disease, we investigated the role of S1P system in the development of endometriosis., Methods: The expression of sphingosine kinase (SphK) 1 in endometriosis lesions was examined by immunohistochemistry. The cystic fluid of ovarian cysts/tumors were obtained to measure S1P concentrations. Endometriotic stromal cells (ESC) derived from endometrioma were used for in vitro experiments., Results: Sphingosine kinase 1 was detected in epithelium and stromal cells of endometriotic lesions. The mean S1P concentration in the cystic fluid of endometriomas was higher than that in nonendometriomas significantly (98.2 nM vs less than 1.5 nM, P < .01). Interleukin-1β (IL-1β) or transforming growth factor-β exhibited 2.7-fold and 11.5-fold increase in SphK1 messenger RNA (mRNA) expression in ESC, respectively ( P < .01). Higher dose of S1P (125nM) increased the cell number of ESC by 20%, and low dose of S1P (1.25 nM and 12.5 nM) induced IL-6 mRNA production and IL-6 secretion by ESC dose-dependently. JTE013, an antagonist for S1PR2, partially suppressed IL-6 induction by S1P ( P < .05). JTE013 and VPC23019, an antagonist for S1PR1 and S1PR3, suppressed the ESC proliferation induced by S1P., Conclusion: The present study for the first time proved that the SphK-S1P-S1PR axis play a role of accelerating inflammation and growth of endometriotic cells.

Objective: The aim of this study was to clarify the expression of Ninj1 in endometriosis and adenomyosis lesions, and its inductive factor in human endometriotic stromal cells (ESCs)., Background: Nerve injury-induced protein 1 (Ninj1) is a molecule originally identified in dorsal root ganglion neurons and Schwann cells after nerve injury and promotes neurite outgrowth. The aim of this study was to clarify the expression of Ninj1 in endometriosis and adenomyosis lesions, and its inductive factor in human endometriotic stromal cells (ESCs)., Materials and Methods: Tissues were obtained with consent from patients diagnosed with ovarian endometrioma (n = 15 in total), peritoneal endometriosis (n = 5), adenomyosis (n = 5), and other gynecological disorders (n = 5, control) during surgery. Immunohistochemistry was conducted in order to detect Ninj1 protein expression in the lesion of endometriosis, adenomyosis, and eutopic endometrium. Nerve fibers in the ovarian endometrioma were detected by positive staining of PGP-9.5. To evaluate the effects of IL-1β on Ninj1 gene expression in endometriosis, ESCs isolated from ovarian endometrioma (n = 5) were treated with IL-1β (5 ng/mL) for 3 or 6 hours. Messenger RNA (mRNA) expression for Ninj1 was examined using quantitative RT-PCR., Results: The Ninj1 protein was expressed by ovarian endometrioma, peritoneal endometriotic, and adenomyotic tissue. Nerve fibers were found in the areas of positive staining for Ninj1 in ovarian endometrioma. IL-1β, an indicator of inflammation in endometriosis, significantly increased Ninj1 mRNA expression by ESC., Conclusion: Our study demonstrates that Ninj1 is expressed in endometriosis and adenomyosis and is induced by the inflammatory stimuli. Given the neurogenetic property of Ninj1, our results imply that Ninj1, induced by inflammation in endometriosis lesion, may contribute to the pathogenesis of pain symptoms characteristic of endometriosis.

The fetus is a semi-allograft for the maternal host in natural pregnancy, but the fetus is a complete allograft after oocyte donation (OD), and there is greater antigenic dissimilarity with the mother. Thus, OD pregnancy is a good model for understanding how the fetus is protected by the maternal immune system. Recent clinical data have revealed a higher risk of miscarriage, gestational hypertension, preterm birth, and low birth weight with OD pregnancy. There is also a higher incidence of chorionic deciduitis, dense fibrinoid deposits in the chorionic basal plate, inflammatory lesions in the chorionic plate, and C4d deposition on syncytiotrophoblasts in OD pregnancy. Impaired accumulation of T cells, regulatory T (Treg) cells, natural killer (NK) cells, and monocytes in the decidua basalis and poor remodeling of spiral arteries are observed in OD pregnancy irrespective of whether preeclampsia occurs. These findings may partly explain why OD pregnancy is associated with a high risk of gestational hypertension and preeclampsia. We need to clarify the immunological and pathological differences between uncomplicated and complicated OD pregnancy. In uncomplicated OD pregnancy, the level of HLA match between mother and baby is significantly higher than would be expected by chance, suggesting that miscarriage may be frequent with marked HLA mismatch. This review discusses the relationship between various aspects of the immune system and complications of OD pregnancy.

Bone morphogenetic protein (BMP) cytokine is known to regulate ovulation, as BMP-6 null mice exhibit a decrease in the number of ovulatory follicles without effect on either the morphology or the dynamics of follicular development. In the present study, the role of BMP-6 in ovulatory process was investigated using human granulosa-lutein cells (GCs). Granulosa-lutein cells, obtained from in vitro fertilization patients, were cultured with BMP-6 followed by RNA extraction. The neutrophil-chemotactic activity of the supernatant of cultured GC was investigated. Bone morphogenetic protein 6 significantly increased growth-regulated oncogene α (GRO-α) messenger RNA (mRNA) and protein expression in GC. In the neutrophil-chemotaxis assay, the GC supernatant cultured with BMP-6 attracted more neutrophils than control samples, which was negated with anti-GRO-α neutralizing antibody. Bone morphogenetic protein 6 also suppressed the relative expression of the protease inhibitors, secretory leukocyte peptidase inhibitor, and whey acid protein 14 mRNA in GC. Bone morphogenetic protein 6 might play a role in ovulation by increasing the accumulation of neutrophils in the ovulatory follicle and suppressing the effect of protease inhibitors.

The formation of an individual capillary network in the theca cell layer is required for ovarian folliculogenesis. Although vascular endothelial growth factor (VEGF) is critical for this process, the regulation of VEGF has been unclear. In the present study, the relationship between VEGF and intraovarian cytokine, bone morphogenetic protein 7 (BMP-7) was investigated. Granulosa cells (GC), obtained from in vitro fertilization patients, were cultured with BMP-7 followed by RNA extraction. Human umbilical vein endothelial cells (HUVECs) were also cultured with BMP-7 followed by RNA extraction, tube formation assay, or cell count analysis. The BMP-7 stimulated VEGF messenger RNA (mRNA) and protein expression in GC significantly. In HUVEC, BMP-7 increased an approximately 1.8-fold in the cell number and induced the tube formation significantly compared to control. The BMP-7 also induced a 2-fold increase in VEGF receptor mRNA transcript relative abundance in HUVEC. The BMP-7, a theca cell-derived factor, may stimulate endothelial cell to form vasculature in the follicle via 2 distinct mechanisms, induction of VEGF expression in GC and increased sensitivity of endothelial cells to VEGF.

Purpose: Although studies of serum anti-Müllerian hormone (AMH) in predicting ovarian reserve are numerous, many studies utilized patients under age 40. However, the assessment of ovarian reserve is especially critical in older infertile women. This study evaluates the significance of AMH level in patients over age 40 at the time of their first in vitro fertilization (IVF) treatment., Methods: Forty-nine women over age 40 were studied. Although serum samples were taken prior to their IVF treatments, the data of serum AMH of patients were not taken into consideration to determine the therapy strategy, including follicle induction in which clomiphene citrate and human menopausal gonadotropin were used., Result(s): Twelve out of 49 patients achieved a clinical pregnancy (24.4 %). There was a positive correlation between serum AMH levels and the number of oocytes retrieved (P < 0.0001). The ROC curve analysis for prediction of poor ovarian response, ≤3 retrieved oocytes, showed that the optimum cut-off level was < 1.0 ng/mL for AMH. The lower AMH group (AMH < 1.0 ng/ml) showed less chance of undergoing embryo transfer than the higher AMH group (AMH ≥1.0 ng/ml). There was no difference in pregnancy rate between the two groups. Five out of 12 pregnant women exhibited AMH levels of less than 0.4 ng/ml., Conclusion(s): Assessment of serum AMH concentration in older patients is useful for the prediction of oocytes numbers which may be obtained in IVF. A cut-off level of 1.0 ng/ml AMH can be used to predict poor ovarian response. This cut-off level of AMH of 1.0 ng/ml might be useful to predict whether patients could have an embryo transfer, but had no power to predict achieving pregnancy. On the other hand, our data also showed that patients over age 40 with extreme low levels of AMH still had a chance of pregnancy.

The aim of this study is to examine the regulation of follistatin, an activin-binding protein, in endometriosis. Endometrioma stromal cells (EoSCs) were obtained from 9 patients undergoing laparoscopy of the ovarian endometrioma. In cultured EoSCs, interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), which could induce activin-A, also induced follistatin messenger RNA (mRNA) and protein. The cystic fluid of endometrioma from 8 patients was obtained to measure the concentration of activin-A and follistatin by enzyme-linked immunosorbent assay (ELISA). Also, activin activity in the fluid was examined by erythroid differentiation assay using mouse erythroleukemia F5-5.fl cells. In the cystic fluid of endometrioma, the mean values of activin-A and follistatin concentration were 36.8 ng/mL and 4.0 ng/mL, respectively. In a bioassay, all 8 samples exhibited activin activity, which was equivalent to recombinant activin-A activity of 12.8 ± 1.4 ng/mL. Although follistatin was present in the cystic fluid of endometrioma, the activity of activin, which is an exacerbation factor of endometriosis, was predominant in vivo.

Background: Although the advantages of epidural anesthesia in open surgery have been established, its usefulness in the setting of laparoscopic surgery remains to be studied., Methods: Patients undergoing laparoscopic surgery for infertility were randomly administered epidural anesthesia (group A, n = 11) or general anesthesia (group B, n = 9). The operation was performed under 4 mmHg pneumoperitoneum and in the 20 degrees Trendelenburg position. Respiratory function tests using a spirometer and blood gas analysis were performed during the intra- or perioperative period. Pain status was evaluated with visual analog scale scoring. The number of postoperative recovery days needed to resume daily activities was obtained by a questionnaire., Results: Respiratory rate, minute volume, P(a)CO2, % vital capacity (VC), and forced expiratory volume in 1 s (FEV1) % were virtually constant throughout the study period in group A, whereas %VC was decreased immediately after operation in group B (p < 0.05). Minute volume immediately after operation was significantly increased in group B compared with group A (p < 0.01), suggesting shallow respiration in women undergoing general anesthesia. Observed pain scores on abdominal pain, shoulder pain, and dyspnea were very low during operation in group A. Pain scores immediately and 3 h after operation were also minimal in group A, whereas abdominal pain scores at these points were significantly higher in group B than those in group A (both p < 0.01). The number of days required for a half reduction in wound pain, trotting, and full recuperation for group A were less than those for group B (p < 0.05)., Conclusions: Epidural anesthesia, when used in laparoscopic surgery for infertility treatment, has advantages over general anesthesia in terms of analgesic effects, postoperative respiratory function, and a return to preoperative daily activities.