Effects of laparoscopic sleeve gastrectomy on nonalcoholic fatty liver disease and TGF-ß signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) develops as a result of unhealthy lifestyle but improves with laparoscopic sleeve gastrectomy (LSG). The transforming growth factor (TGF)-ß signaling pathway reportedly contributes to liver fibrosis, mainly in animal experiments. The aim of the present study was to evaluate changes in serum proteins before and after LSG by proteomic analysis and to investigate their association with NAFLD. This study enrolled 36 severely obese patients who underwent LSG at our hospital from January 2020 to April 2022. As a pilot study, proteomic analysis was conducted on six patients using serum collected before and at 6 months after LSG, and significantly fluctuating proteins were extracted. Subsequently, verification by enzyme-linked immunosorbent assay (ELISA) using collected serum was performed on the remaining 30 patients. The mean weight of enrolled patients was 118.5 kg. Proteomic analysis identified 1,912 proteins, many of which were related to the TGF-ß signaling pathway. Among these proteins, we focused on five TGF-ß-related proteins: asporin, EMILIN-1, platelet factor-4, serglycin, and thrombospondin-1. Verification by ELISA revealed that asporin (p = 0.006) and thrombospondin-1 (p = 0.043) levels significantly fluctuated before and after LSG. Univariate analysis with a linear regression model showed that aspartate aminotransferase (p = 0.045), asporin (p = 0.011), and thrombospondin-1 (p = 0.022) levels were significantly associated with postoperative liver fibrosis. On multivariate analysis, asporin was an independent prognostic factor for postoperative liver fibrosis (95% confidence interval: 0.114-1.291, p = 0.002). TGF-ß-related proteins dramatically fluctuated before and after LSG and were correlated with NAFLD pathogenesis. Asporin may be a useful prognostic marker of liver fibrosis in NAFLD after LSG.

Risk-Adjusted Assessment of the Learning Curve for Pure Laparoscopic Donor Hepatectomy for Adult Recipients.

BACKGROUND: Studies on pure laparoscopic donor hepatectomy (PLDH) have been reported. However, only few studies have reported on the learning curve of PLDH. In this report, we aimed to determine the learning curve of PLDH in adult patients using cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) analyses. METHODS: The data of donors who underwent PLDH at a single center between December 2012 and May 2022 were retrospectively reviewed. The learning curve was evaluated using the CUSUM and RA-CUSUM methods based on surgery duration. RESULTS: Forty-eight patients were finally included in the present study. The mean operation time was 393.6 ± 80.3 min. PLDH was converted to laparotomy in three cases (6.3%). According to the Clavien-Dindo classification, nine cases (18.8%) had higher-than-grade III postoperative complications and the most frequent complications were biliary complications. The CUSUM graph shows two peaks, at the 13th and 27th case. The multivariate analysis revealed that a body mass index ≥ 23 kg/m2 and intraoperative cholangiography were the only factors that were independently associated with longer operation time. Based on these results, an RA-CUSUM analysis was performed to assess the learning curve, which showed a decrease in the learning curve after 33 to 34 PLDH procedures. CONCLUSIONS: A learning curve effect was demonstrated in this study after 33 to 34 PLDH procedures. There are relatively many biliary complications, and it is necessary to further examine the method of bile duct transection.

Relationship between the changes in hepatokine levels and metabolic effects after laparoscopic sleeve gastrectomy in severely obese patients.

PURPOSE: To clarify the relationships between the changes in hepatokines and weight loss, and between these changes and the metabolic effects, and the roles played by these changes, after laparoscopic sleeve gastrectomy (LSG). METHODS: We recruited 25 Japanese patients with severe obesity, who underwent LSG. We measured two hepatokines: selenoprotein P (SeP) and leukocyte cell-derived chemotaxin 2 (LECT2), at the baseline, and then 6 months and 1 year after LSG. Finally, we compared the changes in the hepatokines with the parameters of type 2 diabetes (T2D) and non-alcoholic steatohepatitis (NASH). RESULTS: Changes in LECT2 were correlated with the percentage of total weight loss (ρ = - 0.499, P = 0.024) and the decrease in total fat area (ρ = 0.559, P = 0.003). The changes in SeP were correlated with those in hemoglobin A1c (ρ = 0.526, P = 0.043) and the insulinogenic index (ρ = 0.638, P = 0.010) in T2D patients. In patients with NASH, the LECT2 levels were correlated with liver steatosis (ρ = 0.601). CONCLUSIONS: SeP levels decrease in association with HbA1c reduction, whereas LECT2 levels are associated with reductions in fat mass and NASH scores after LSG. Hepatokines may be involved in the pathology of obesity and its complications.

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.

Improvements of lung volumes and respiratory symptoms after weight loss through laparoscopic sleeve gastrectomy.

PURPOSE: This study evaluated the improvement of respiratory function and airway volumes using spirometry and computed tomography (CT) in severely obese Japanese patients undergoing laparoscopic sleeve gastrectomy (LSG). We also evaluated the quality of life (QOL) of enrolled patients using questionnaires. METHODS: A total of 71 patients who underwent LSG at Iwate Medical University Hospital between October 2013 and September 2020 were enrolled. The changes and relationships between respiratory parameters including CT volumetry and weight-loss effects were evaluated. Improvements to QOL and bronchial asthma (BA) were also assessed before LSG and 1 year after LSG. RESULTS: The mean excess weight loss percentage (%EWL) and total weight loss percentage (%TWL) were measured at 55.1% and 26.1%, respectively. The attack frequency of BA significantly decreased (6.1/month vs. 1.5/month; P < 0.001), and the disease severity decreased according to severity classification (P = 0.032). Almost spirometric parameters, lung volume (LV) (4905.0 mL vs. 5490.3 mL; P < 0.001), and airway volume (AV) (108.6 mL vs. 119.3 mL; P = 0.022) significantly improved. The change of functional residual capacity (FRC) was correlated with both %EWL (ρ = 0.69, P < 0.001) and %TWL (ρ = 0.62, P < 0.001). The increase of LV (ρ = 0.79, P < 0.001) and AV (ρ = 0.69, P < 0.001) were correlated with the increase of FRC. Scores of QOL questionnaires dramatically became better owing to improvements in dyspnea. CONCLUSION: Weight loss effects and the reduction of body fat mass correlated significantly with increase in LV and AV. Improvements of respiratory functions after LSG contributes to QOL and BA symptoms.

Standardized single-incision plus one-port laparoscopic left lateral sectionectomy: a safe alternative to the conventional procedure.

PURPOSE: Laparoscopic left lateral sectionectomy (LLLS) is a feasible and safe procedure with a relatively smooth learning curve. However, single-incision LLLS requires extensive surgical experience and advanced techniques. The aim of this study is to report the standardized single-incision plus one-port LLLS (reduced port LLLS, RPLLLS) technique and evaluate its safety, feasibility, and effectiveness for junior surgeons. METHODS: Between January 2008 and November 2020, the clinical records of 49 patients who underwent LLLS, divided into the conventional LLLS (n = 37) and the RPLLLS group (n = 12), were retrospectively reviewed. The patient characteristics, pathologic results, and operative outcomes were evaluated. RESULTS: A history of previous abdominal surgery in the RPLLLS group was significantly high (56.8% vs. 91.7%, p = 0.552). Notably, junior surgeons performed 62.2% of the conventional LLLSs and 58.4% of the standardized RPLLLSs. There were no significant differences between the two groups in terms of median operative time (121.0 vs. 113.5, p = 0.387), median blood loss (13.0 vs. 8.5, p = 0.518), median length of hospital stays (7.0 vs. 7.0, p = 0.408), and morbidity rate (2.7% vs. 0%, p = 0.565), respectively. CONCLUSION: This standardized RPLLLS is a feasible and safe alternative to conventional LLLS and may become the ideal training procedure for both junior surgeons and surgeons aiming to learn more complex procedures.

Predictive scoring system for advanced liver fibrosis in Japanese patients with severe obesity.

PURPOSE: The aim of this study was to examine the predictive scoring system of advanced liver fibrosis in severely obese Japanese patients. METHODS: Seventy-two patients underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies. We classified these patients into two groups: Brunt stage ≥ 2 (advanced fibrosis) and 0/1 (none/mild fibrosis). A logistic regression analysis was performed to identify the predictors of advanced fibrosis. RESULTS: Sixteen patients had advanced fibrosis, while 56 had no/mild fibrosis. The prevalence of type 2 diabetes mellitus (T2DM) in advanced fibrosis group was significantly higher than in none/mild fibrosis. An univariate analysis of the factors predicting advanced fibrosis showed significant differences in AST/ALT ratio, serum insulin levels, HOMA-IR, and type IV collagen 7S in the T2DM group. According to a multivariate analysis, type IV collagen 7S was an independent predictor and the cutoff value was 5.6 ng/mL. We created a flow chart; high risk (T2DM and type IV collagen 7S ≥ 5.6 ng/mL), moderate risk (T2DM and type IV collagen 7S < 5.6 ng/mL), and low risk (non-DM). For those at high risk, the sensitivity, specificity, positive predictive value, and negative predictive value were 56.2%, 94.4%, 75.0%, and 87.9%, respectively. CONCLUSION: This classification system has the potential to accurately categorize the risk of liver fibrosis.

Indocyanine green fluorescence imaging via endoscopic nasal biliary drainage during laparoscopic deroofing of liver cysts.

Laparoscopic deroofing of liver cysts is widely accepted as the treatment of symptomatic huge liver cysts. As bile leakage is a common complication of this procedure, indocyanine green (ICG) imaging has played an active role in detecting intrahepatic biliary tract. However, infusion ICG imaging needs time rag after injection due to moving from bloodstream to bile, and also, additional injection is needed when the fluorescent imaging is not clear. To cover this weakness of ICG imaging, we first applied ICG imaging via 5-Fr endoscopic nasal biliary drainage (ENBD) during laparoscopic deroofing of liver cysts. This technique promptly gives us ICG imaging after ICG injection from ENBD; in addition, direct ICG imaging sometimes reveals minor leakage from sealing line and staple lines; therefore, we believe that direct ICG imaging via ENBD helps us to prevent post-operative bile leakage.

Anterior approach for pure laparoscopic donor right hepatectomy.

BACKGROUND: Pure laparoscopic donor hepatectomy (PLDH) is being increasingly performed at centers with experienced surgeons [1-6]. This procedure is still developing and is associated with several challenges owing to its technical difficulty [7-9]. Conversely, the anterior approach is sometimes applied to both laparoscopic and open right hepatectomy for management of tumors in the liver [10, 11]. However, there are no reports regarding the use of the anterior approach for PLDH. We found this method to be useful; therefore, we aimed to introduce the novel procedure using a video clip. METHODS: The donor was placed in the supine position. First, the right side of the inferior vena cava was dissected instead of performing the liver hanging maneuver. The right Glissonean pedicle was encircled and controlled, and the liver parenchyma was completely transected. Thereafter, the ligaments around the liver were dissected, and the graft was mobilized. The hilar vessels were respectively separated. Finally, the right hepatic duct, right hepatic artery, right portal vein, and right hepatic vein were divided, and the graft liver was retrieved. This study was approved by institutional ethics board (MH2019-119), and informed consent was taken from the patient. RESULTS: The overall surgical time was 400 min, the volume of blood loss was 31 mL, the warm ischemic time was 7 min, and no complications were seen. CONCLUSION: The advantages of the anterior approach for right-sided PLDH might be attribute to reduction of compression injury and incidence of subcapsular hematoma, as liver mobilization is easily performed because of increased liver mobility. However, PLDH is a highly-skilled procedure, and indications for PLDH should be extended in a step-wise manner. Further, the procedure should be performed only by highly proficient surgeons having extensive experience in both laparoscopic liver resection and living donor liver transplantation.

Prognostic factors and a new preliminary scoring system for remission of type 2 diabetes mellitus after laparoscopic sleeve gastrectomy.

PURPOSE: To evaluate the early remission rate of type 2 diabetes mellitus (T2DM) after laparoscopic sleeve gastrectomy (LSG) and establish a preliminary scoring system that predicts T2DM remission. METHODS: We assessed the outcomes of 49 morbidly obese patients with T2DM who underwent LSG between 2008 and 2018. The prognostic factors for T2DM remission 1 year post-LSG were identified and an original scoring system was established. We validated our scoring system by comparing it with the individualized metabolic surgery score and the ABCD score. RESULTS: The patients' mean body weight loss and percentage of excess weight loss were 34.4 kg and 59.4%, respectively, while the T2DM remission rate was 77.5%. The serum insulin level and the T2DM duration were independent predictive factors, the receiver-operating characteristic (ROC) curves for which revealed cutoff values of 12.7 ng/mL and 72 months, respectively. We set our system's score range at 0-2, whereby patients with higher scores have a good T2DM remission prognosis, as higher insulin levels, and/or shorter T2DM duration. Our scoring system had accuracy levels similar to those of the ABCD score with a simple stratification. CONCLUSION: Our preliminary scoring system attains a good level of accuracy for predicting T2DM remission.

Comparison of Single-Incision Laparoscopic Cholecystectomy versus Needlescopic Cholecystectomy: A Single Institutional Randomized Clinical Trial.

BACKGROUND: Both single-incision laparoscopic cholecystectomy (SILC) and needlescopic cholecystectomy (NSC) are superior to conventional laparoscopic cholecystectomy in terms of cosmetic outcome and incisional pain. We conducted a prospective, randomized clinical trial to evaluate the surgical outcome, postoperative pain, and cosmetic outcome for SILC and NSC procedures. METHODS: In this trial, 105 patients were enrolled (52 in the SILC group; 53 in the NSC group). A visual analogue scale (VAS) was used to evaluate the cosmetic outcome and incisional pain for patients. Logistic regression analyses were used to evaluate the operative difficulty that was present for both procedures. RESULTS: There were no significant differences in patient characteristics or surgical outcomes, including operative time and blood loss. The mean VAS scores for cosmetic satisfaction were similar in both groups. There were significant differences in the mean VAS scores for incisional pain on postoperative day 1 (p = 0.009), and analgesics were required within 12 h of surgery (p = 0.007). Obesity (body mass index ≥25 kg/m2) was the only significant influential factor for operating time over 100 min (p = 0.031). CONCLUSION: NSC is superior to SILC in terms of short-term incisional pain. Experienced laparoscopic surgeons can perform both SILC and NSC without an increase in operative time.

Retrospective case-matched study between reduced port laparoscopic rectopexy and conventional laparoscopic rectopexy for rectal prolapse.

INTRODUCTION: Reduced port laparoscopic Well's procedure (RPLWP) is a novel technique used to overcome the limitations of single-incision laparoscopic surgery. The aim of this study was to compare outcomes between RPLWP and conventional laparoscopic Well's procedure (CLWP) and to investigate the learning curve of RPLWP. PATIENTS AND METHODS: From January 2006 to March 2017, a retrospective review of a prospectively maintained laparoscopic surgery database was performed to identify patients had undergone CLWP and RPLWP. From these patients, each of 10 cases were manually matched for age, sex, body mass index. From January 2006 to March 2015, CLWP was used for all procedures whereas, from April 2015, RPLWP was routinely performed as a standard procedure for rectal prolapse. RESULTS: No significant differences were observed between the two groups in terms of operating time, blood loss, intraoperative complications, and conversion to CLWP or open rectopexy. Based on the postoperative outcomes, the hospital stay was significantly shorter in the RPLWP group. The estimated learning curve for RPLWP was fitted and defined as y = 278.47e-0.064x with R2 = 0.838; therefore, a significant decrease in operative time was observed by using the more advanced surgical procedure. CONCLUSIONS: RPLWP is an effective, safe, minimally invasive procedural alternative to CLWP with no disadvantage for patients when a skilled surgeon performs it.

Outcomes of esophagectomy after chemotherapy with biweekly docetaxel plus cisplatin and fluorouracil for advanced esophageal cancer: a retrospective cohort analysis.

BACKGROUND: Docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy can cause severe adverse events, including neutropenia and febrile neutropenia. The feasibility of DCF therapy is a concern, particularly for elderly patients, patients with moderate organ disorders, and patients suffering from malnutrition caused by dysphagia or insufficient oral intake. We introduced a biweekly DCF therapy (bDCF) for the purpose of reducing severe adverse events for these fragile patients. This study investigated the feasibility and outcome of an esophagectomy after bDCF therapy for patients with advanced esophageal squamous cell carcinoma. METHODS: Fifty-nine patients with esophageal carcinoma underwent an esophagectomy after DCF or bDCF therapy as primary chemotherapy. DCF was administered to 37 patients in the DCF group, whereas bDCF was administered to 22 patients in the bDCF group. RESULTS: Patients in the bDCF group were significantly older than those in the DCF group (p = 0.016). Heart and pulmonary comorbidities were significantly more common in the bDCF than in the DCF group (p < 0.001 and p = 0.039, respectively). Grade 3 or 4 neutropenia was less frequent in the bDCF than in the DCF group (40.9 vs. 81.1%, p = 0.002). Anorexia was more frequent in the DCF group than in the bDCF group (18.9 vs. 0%, p = 0.030). The clinical response rate of the bDCF group was significantly higher than that of the DCF group (86.4 vs. 62.2%, p = 0.047). There was no significant between-group difference in the postoperative morbidity rate (bDCF 45.5% vs. DCF 32.4%) or in the histological therapeutic effect. CONCLUSION: The results demonstrate that primary bDCF therapy for high-risk patients with advanced esophageal cancer is feasible and safe in both chemotherapeutic and perioperative periods without a reduction in the efficacy of DCF therapy.

A novel model for prediction of pure laparoscopic liver resection surgical difficulty.

BACKGROUND: Extending the clinical indications for laparoscopic liver resection (LLR) should be carefully considered based on a surgeon's experience and skill. However, objective indexes to help surgeons assess the estimated difficulty of LLR are scarce. The aim of our study was to develop the first objective numerical rating scale to predict the surgical difficulty of various LLR procedures. METHODS: We performed a retrospective review of the operative outcomes of 187 patients who underwent a pure LLR. First, the value of preoperative factors for predicting surgical time was evaluated by multivariate linear regression analyses, and a scoring system was constructed. Next, the integrity of our predictive linear model was evaluated against the documented operative outcomes for patients forming our study group. RESULTS: Four predictive factors were identified and scored based on the weighted contribution of each factor predicting surgical time: extent of resection (scored 0, 2, or 3); location of tumor (scored 0, 1, or 2); obesity (scored 0 or 1); and platelet count (scored 0 or 1). The scores were summed to classify surgical difficulty into three levels: low (total score ≤1); medium (total score 2-3); and high (total score ≥4). Operative outcomes, including surgical time, volume of blood loss, length of hospital stay, and rate of morbidity, were significantly different between the three surgical difficulty levels. CONCLUSION: Our novel model will be useful for surgeons to predict the difficulty of an LLR procedure relative to their own experience and skill.

Pancreas volume reduction and metabolic effects in Japanese patients with severe obesity following laparoscopic sleeve gastrectomy.

This study aimed to assess the relationship between the metabolic effect after laparoscopic sleeve gastrectomy (LSG) in morbidly obese Japanese patients, with or without type 2 diabetes mellitus (T2DM), and improved pancreatic steatosis (PS). The study enrolled 27 morbidly obese Japanese patients who were undergoing LSG. Their clinical and metabolic effects were evaluated at baseline and six months after LSG. Pancreas volume (PV), pancreatic attenuation (PA), and splenic attenuation (SA) were measured using a 64-row computed tomography (CT). Changes in PV, PA-SA, and PA/SA were evaluated. The mean body-weight loss, body mass index loss, and percentage of excess weight loss (%EWL) were -34.4 kg (p < 0.001), -11.0 kg/m2 (p < 0.001), and 43.7%, respectively. The mean PV was 96.7 mL at baseline, and it decreased six months after LSG (-16.3mL, p < 0.001). The mean PA significantly increased six months after LSG (9.5 HU, p < 0.001). PA-SA (-23.2 HU vs. -13.3 HU, p = 0.003), and PA/SA (0.54 vs. 0.73, p < 0.001) also significantly increased six months after LSG. In T2DM patients, decreased PV correlated with decreased fasting blood sugar, decreased insulin, and reduced liver volume. In conclusion, PV significantly decreased after LSG in morbidly obese Japanese patients, and that decrease correlated with improvements in PS. In addition, PS plays an important role of development and progression of insulin resistance and T2DM.

[Fluorescence-Imaging of Nerves - A Novel Trial of Intraoperative Nerve-Preservation].

Nerve-preservation technique during surgery is important. Intraoperative nerve injury often causes permanent palsy or numbness and/or neurogenic functional disorders. To evade such intraoperative nerve injuries, we proposed a novel manner to specifically visualize peripheral nerve fibers. Low-toxic agents clinically available, amphotericin B(AmB)or fluorescein isothiocyanate(FITC)were used as neuro-indicators. In in vitro, we used Schwann cells as nerve models to basically confirm these agents effectively functioned as neural markers. In in vivo, we examined whether this novel method was clinically applicable. The Schwann cells reacted with AmB or FITC emitted blue or yellow-green fluorescence in a dark environment. The rat nerve models also fluorescently glimmered in blue-tone when each agent was given. These data suggested that we could clinically discriminate nerve fibers from the surrounding tissues. Our fluorescent-imaging methods warrant further studies for clinical applications.

Effects of changes in adipocyte hormones and visceral adipose tissue and the reduction of obesity-related comorbidities after laparoscopic sleeve gastrectomy in Japanese patients with severe obesity.

The aim of this study was to evaluate the relative contribution of serum adipokines and adipokines from the patient's omentum-derived adipocytes (PODAs) and visceral adipose tissue (VAT) of Japanese patients with severe obesity. Secondarily, we analyzed patients' metabolic changes after laparoscopic sleeve gastrectomy (LSG). Twenty-three LSG patients and 23 non-obese patients undergoing elective abdominal surgery were enrolled. The levels of adipokines in the serum and the PODAs were measured. The clinical and metabolic data were evaluated at 6 months after LSG. The mean serum leptin levels and the mean serum plasminogen activator inhibitor type-1 (PAI-1) levels were significantly greater (p < 0.001) and the mean adiponectin levels were significantly lower in the LSG group (p = 0.006). In the measurements of the PODAs, the mean leptin levels (p < 0.001) were significantly greater and the mean adiponectin levels (p < 0.001) were significantly lower in the LSG group. The mean BMI (-12 kg/m², p < 0.001) and mean VAT (-135.5 cm², p = 0.001) were significantly decreased after LSG. In nine patients with type 2 diabetes mellitus, the reduction in VAT correlated with the change in high-sensitivity C-reactive protein (p = 0.006) and the homeostasis model of assessment of insulin resistance (p = 0.001). After 6 months, LSG markedly improved most obesity-related comorbidities. Our results suggest that LSG may contribute to VAT reduction, improved adipocyte hormone levels, and changes in gut physiology and endocrinology.