Effect of hardware removal and second-look arthroscopy after open-wedge high tibial osteotomy.

INTRODUCTION: Open-wedge high tibial osteotomy (OWHTO) is the standard and safe procedure for medial compartment osteoarthritis. Although hardware removal (HWR) is performed after post-OWHTO bone union, the effects of HWR on OWHTO have been rarely reported. We hypothesised that HWR would improve range of motion (ROM) and implant-related complications. Thus, this study aimed to investigate the effects of HWR on postoperative ROM, the Japan Orthopaedic Association (JOA) score/visual analogue scale (VAS) score and hardware-related complications after OWHTO. METHODS: Patients who underwent OWHTO between January 2016 and June 2018 and HWR were retrospectively reviewed. To perform OWHTO, locking plates and prosthetic bone were used to achieve optimal stabilisation of biplanar osteotomy. HWR was performed after a second-look arthroscopy through the previous skin incision. For clinical evaluation, the JOA score, VAS score, and ROM were assessed before and 1 year after HWR using the Wilcoxon rank test. Logistic regression analysis was performed to identify the predictors of post-HWR improvement. RESULTS: Of 98 knees examined (91 patients), 80 (73 patients; 39 men and 34 women) were included. At the time of OWHTO, mean age was 64.0 ± 9.7 years and body mass index, 25.5 ± 3.1 kg/m2; Kellgren-Lawrence (KL) grade 1 was seen in 20 cases, KL-2 in 46, and KL-3 in 14. Mean periods between OWHTO and HWR were 13.4 ± 2.0 months, and 11.9 ± 1.2 months between HWR and evaluation. The JOA score and flexion angle significantly improved after HWR (The JOA score: p = 0.026 flexion angle: p < 0.001); however, the VAS score and extension angle did not (VAS score: p = 0.162, extension angle: p = 0.934). Hardware irritation was observed in four cases (5%), which improved after HWR. Logistic regression analysis revealed that lower preoperative KL grade and flexion angle were predictors of improvement after HWR [KL grade: p = 0.008; odds ratio 3.244, 95% confidence interval (CI) 1.350-7.794; flexion angle: p < 0.001; odds ratio 1.150, 95% CI 1.062-1.245]. CONCLUSION: HWR improves flexion angle, clinical outcomes and hardware-related complications after OWHTO. Preoperative KL grade and flexion angle are predictors of improvement after HWR in patients who have undergone OWHTO.

Is routine lymph node dissection recommended for liver resection of intrahepatic cholangiocarcinoma? A systematic review and meta-analysis.

BACKGROUND/PURPOSE: This meta-analysis aimed to elucidate the therapeutic effects of routine lymph node dissection (LND) with liver resection on intrahepatic cholangiocarcinoma (ICC). METHODS: Databases, including MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials, were searched to identify studies comparing LND and non-LND for ICC liver resection. The primary outcome was overall survival (OS), and secondary outcomes were disease-free survival (DFS), in-hospital morbidity, blood loss, and R0 rate. RESULTS: Seventeen studies involving 4407 patients were included. The OS did not differ between the LND (n = 2158) and non-LND (n = 2249) groups (HR, 1.05; 95% CI, 0.83-1.32). The secondary outcomes did not differ significantly between the groups. Subgroup analyses stratified by the risk of bias showed a significant difference in OS between the high- and low-risk groups (P = 0.0008). In the low-risk group, LND (vs. non-LND) was associated with superior OS (HR, 0.76; 95% CI, 0.59-0.98). Most studies in low-risk groups involved patients who were clinically node-negative. CONCLUSIONS: The therapeutic effects of routine LND for ICC have not been demonstrated. However, LND had a positive impact on OS in studies with a low risk of bias, thus suggesting that there may be a subset of ICC patients who would benefit from LND.

Preoperative Endoscopic Minor Papilla Sphincterotomy for Pancreas Divisum in a Patient with Pancreatic Cancer Who Underwent Laparoscopic Distal Pancreatectomy.

BACKGROUND: Pancreas divisum (PD) is a congenital anomaly that occurs due to failure of fusion of the dorsal and ventral pancreatic ductal systems.1-3 In PD, pancreatic juice drains mainly through the minor papilla via the dorsal duct, leading to high intraductal pressure, which can cause pancreatitis.1-3 We report a case of PD that underwent preoperative decompression using endoscopic minor papilla sphincterotomy (EMPS) before laparoscopic distal pancreatectomy (LDP) for pancreatic cancer.3 METHODS: The patient was a 74-year-old woman with pancreatic tail cancer, measuring 35 mm in size, in PD with an entirely dilated dorsal duct, implying high, intraductal pressure caused by minor papillary dysfunction. We performed EMPS to prevent postoperative pancreatitis and pancreatic fistula before LDP using a left-posterior approach, as previously described.4 As the pancreatic transection margin was positive for high-grade pancreatic intraepithelial neoplasia on intraoperative pathology, an additional resection of the pancreatic head to the right side of the portal vein was performed after the liberation of the gastroduodenal artery with both the dorsal and ventral pancreatic ducts ligated and divided. RESULTS: The operative time was 421 min, and blood loss was 70 mL. The postoperative course was uneventful, with no evidence of pancreatitis or pancreatic fistula. The patient was discharged on postoperative Day 10. Postoperative computed tomography revealed reduced dilatation of the dorsal duct. CONCLUSIONS: Preoperative EMPS may be effective in preventing pancreatic fistula after LDP in patients with PD.

A Conceptual Classification of Resectability for Hepatocellular Carcinoma.

BACKGROUNDS: In the era of multidisciplinary treatment strategy, resectability for hepatocellular carcinoma (HCC) should be defined. This study aimed to propose and validate a resectability classification of HCC. METHODS: We proposed following the three groups; resectable-(R), borderline resectable-(BR), and unresectable (UR)-HCCs. Resectable two groups were sub-divided according to the value of indocyanine green clearance of remnant liver (ICG-Krem) and presence of macrovascular invasion (MVI); BR-HCC was defined as resectable HCCs with MVI and/or ICG-Krem≥0.03-<0.05, and R-HCC was the remaining. Consecutive patients with HCC who underwent liver resection (LR) and non-surgical treatment(s) (i.e., UR-HCC) between 2011 and 2017 were retrospectively analyzed to validate the proposed classification. RESULTS: A total of 361 patients were enrolled in the study. Of these, R-, BR- and UR-HCC were found in 251, 46, and 64 patients, respectively. In patients with resected HCC, ICG-Krem≥0.05 was associated with decreased risk of clinically relevant posthepatectomy liver failure (p=0.013) and the presence of MVI was associated with worse overall survival (OS) (p<0.001). The 3-5-years OS rates according to the proposed classification were 80.3, and 68.3% versus 51.4, and 35.6%, in the R and BR groups, respectively (both p<0.001). Multivariate analysis showed BR-HCC was independently associated with poorer OS (p<0.001) after adjusting for known tumor prognostic factors. Meanwhile, BR-HCC was associated with benefit in terms of OS compared with UR-HCC (p<0.001). CONCLUSION: Our proposal of resectability for HCC allows for stratifying survival outcomes of HCC and may help to determine treatment strategy.

Impact of liver volumetric regeneration on survival outcomes in patients with hepatocellular carcinoma after major hepatectomy.

PURPOSE: Prognostic value of liver volumetric regeneration (LVR) in patients with hepatocellular carcinoma (HCC) who undergo major hepatectomy remains unknown. The aim of this study was to investigate the impact of LVR on long-term outcomes in these patients. METHODS: Data of 399 consecutive patients with HCC who underwent major hepatectomy between 2000 to 2018 were retrieved from a prospectively maintained institutional database. The LVR-index was defined as the relative increase in liver volume from 7 days to 3 months (RLV3m/RLV7d, where RLV3m and RLV7d is the remnant liver volume around 3 months and postoperative 7 days after surgery). The optimal cut-off value was determined using the median value of LVR-index. RESULTS: A total of 131 patients were eligible in this study. The optimal cut off value of LVR-index was 1.194. The 1-, 3-, 5- and 10-year overall survival (OS) rate of patients in the high LVR-index group were significantly better compared to those in the low LVR-index group (95.5%, 84.8%, 75.4% and 49.1% vs. 95.4%, 70.2%, 56.4%, and 19.9%, p = 0.002). Meanwhile, there was no significant difference with regards to time to recurrence between the two groups (p = 0.607). Significance of LVR-index for OS was retained after adjusting for known prognostic factors (p = 0.002). CONCLUSION: In patients with HCC undergoing major hepatectomy, LVR-index may serve as a prognostic indicator for OS.

Good clinical outcomes and return to sports after hybrid closed-wedge high tibial osteotomy.

PURPOSE: This study aimed to investigate preoperative sports participation and postoperative clinical outcomes including a return to sports (RTS) after hybrid closed-wedge high tibial osteotomy (CWHTO) for medial compartment osteoarthritis of the knee. Characteristic of Hybrid CWHTO was defined as extra-articular lateral closed and medial open wedge osteotomy. METHODS: The patients who underwent hybrid CWHTO from January 2016 to December 2018 were retrospectively reviewed and divided them into sports and non-sports groups. The preoperative demographic and radiographic characteristics were compared in both groups. And the clinical outcomes including the Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS), Lysholm score, University of California at Los Angeles (UCLA) activity score, and RTS in the sports group were also investigated. Statistical analysis was performed for comparisons among the preoperative factors between the two groups. Influence of sports impact and bone union of fibular osteotomy was also statistically investigated for RTS. RESULTS: Of the 161 knees (129 patients; 46 males, 83 females), 20 knees (16 patients; 13 males, 3 females; 12.3%) belonged to sports group. Although there were no significant differences regarding the age and radiographic parameters, there were significant differences in the body mass index and proportion of males between both groups. The JOA, VAS, Lysholm, and UCLA activity scores significantly improved after surgery. RTS was 80% at a mean duration of 7.2 ± 3.1 months. RTS in the high-impact sports group was significantly lower than that in the low-impact sports group (high-impact 60% vs. low-impact 100%, p = 0.043). There was no significant difference in RTS regarding bone union after fibular osteotomy. CONCLUSION: The clinical outcomes including RTS were satisfactory in patients with hybrid CWHTO. LEVEL OF EVIDENCE: IV.

Mid-term results of medial open-wedge high tibial osteotomy based on radiological grading of osteoarthritis.

PURPOSE: To evaluate the mid-term results of medial open-wedge high tibial osteotomy (OWHTO) based on Kellgren-Lawrence (KL) grades. MATERIALS AND METHODS: We retrospectively evaluated clinical and radiographic outcomes of 93 patients (mean age 61.4 years, mean follow-up 64.2 months, 109 consecutive knees) who underwent OWHTO for medial compartment osteoarthritis (OA). KL grade was used to evaluate knee OA (KL-1 22 cases; KL-2, 51 cases; KL-3, 36 cases). The clinical outcomes were assessed using Japanese Orthopaedic Association (JOA) and Lysholm scores. Radiographic outcomes were assessed using pre- and post-operative mechanical axis percentage, femorotibial angle, medial proximal tibial angle, and joint line convergence angle. Hinge fracture frequency and OA progression were also evaluated based on KL grades. RESULTS: The JOA score improved significantly from 70.3 ± 14.9 to 96.2 ± 4.4, 64.1 ± 12.5 to 95.1 ± 5.1, and 68.6 ± 11.4 to 92.1 ± 6.1 in the KL-1, KL-2, and KL-3 groups, respectively. The JOA score in the KL-3 group was significantly lower than in the other groups. The Lysholm score improved significantly from 62.6 ± 8.8 to 97.7 ± 4.7, 62.1 ± 8.1 to 96.7 ± 4.2, and 59.2 ± 9.2 to 95.8 ± 4.6 in the KL-1, KL-2, and KL-3 groups, respectively. The post-operative Lysholm scores were not significantly different among the groups. There were significant differences in radiographic parameters pre-operatively, but not post-operatively, among the groups. Although there were no significant differences in hinge fracture frequency and OA progression, the KL-3 grade predicted OA progression on multivariate analysis. CONCLUSIONS: Mid-term results of OWHTO significantly improved. However, clinical score in the KL-3 group was lower than that in the KL-1 and KL-2 groups; radiological OA progression was a risk factor in KL-3.

Impact of patient-specific three-dimensional printed liver models on hepatic surgery safety: a pilot study.

BACKGROUND: Simulation and navigation technologies in hepatobiliary surgery have been developed recently. In this prospective clinical trial, we evaluated the accuracy and utility of our patient-specific three dimensional (3D)-printed liver models as an intraoperative navigation system to ensure surgical safety. METHOD: Patients requiring advanced hepatobiliary surgeries during the study period were enrolled. Three cases were selected for comparison of the computed tomography (CT) scan data of the models with the patients' original data. Questionnaires were completed after surgeries to evaluate the utility of the models. Psychological stress was used as subjective data and operation time and blood loss as objective data. RESULTS: Thirteen patients underwent surgery using the patient-specific 3D liver models. The difference between patient-specific 3D liver models and the original data was less than 0.6 mm in the 90% area. The 3D model assisted with intra-liver hepatic vein recognition and the definition of the cutting line. According to the post-operative subjective evaluation, surgeons found the models improved safety and reduced psychological stress during operations. However, the models did not reduce operative time or blood loss. CONCLUSION: The patient-specific 3D-printed liver models accurately reflected patients' original data and were an effective intraoperative navigation tool for meticulously difficult liver surgeries. CLINICAL TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trial Registry (UMIN000025732).

[Simultaneous living donor liver transplantation and pancreatoduodenectomy for an extensive cholangiocarcinoma with primary sclerosing cholangitis: a case report].

The treatment of choice for a resectable hilar cholangiocarcinoma is hepatectomy. Alternative treatment for unresectable cases includes liver transplantation;however, curative surgery is hindered by a distal cholangiocarcinoma extension into the intrapancreatic duct. Herein, we present a case of simultaneous living donor liver transplantation and pancreaticoduodenectomy for an extensive cholangiocarcinoma that is associated with primary sclerosing cholangitis, involving the perihilar and intrapancreatic duct. The treatment strategy involved neoadjuvant chemotherapy and radiation therapy, an exploratory laparoscopy and laparotomy for accurate staging, en-bloc whole bile duct and hepatoduodenal ligament resection, portal vein reconstruction with an interposition graft, and arterial reconstruction with the middle colic artery. The patient was discharged 122 days postoperatively although she suffered from postoperative ascites and delayed gastric emptying. Simultaneous living donor liver transplantation and pancreatoduodenectomy should be considered as treatment options for advanced cholangiocarcinoma.

Up-regulation of FOXO1 and reduced inflammation by ß-hydroxybutyric acid are essential diet restriction benefits against liver injury.

Liver ischemia and reperfusion injury (IRI) is a major challenge in liver surgery. Diet restriction reduces liver damage by increasing stress resistance; however, the underlying molecular mechanisms remain unclear. We investigated the preventive effect of 12-h fasting on mouse liver IRI. Partial warm hepatic IRI model in wild-type male C57BL/6 mice was used. The control ischemia and reperfusion (IR) group of mice was given food and water ad libitum, while the fasting IR group was given water but not food for 12 h before ischemic insult. In 12-h fasting mice, serum liver-derived enzyme level and tissue damages due to IR were strongly suppressed. Serum ß-hydroxybutyric acid (BHB) was significantly raised before ischemia and during reperfusion. Up-regulated BHB induced an increment in the expression of FOXO1 transcription factor by raising the level of acetylated histone. Antioxidative enzyme heme oxigenase 1 (HO-1), a target gene of FOXO1, then increased. Autophagy activity was also enhanced. Serum high-mobility group box 1 was remarkably lowered by the 12-h fasting, and activation of NF-κB and NLRP3 inflammasome was suppressed. Consequently, inflammatory cytokine production and liver injury were reduced. Exogenous BHB administration or histone deacetylase inhibitor administration into the control fed mice ameliorated liver IRI, while FOXO1 inhibitor administration to the 12-h fasting group exacerbated liver IRI. The 12-h fasting exerted beneficial effects on the prevention of liver IRI by increasing BHB, thus up-regulating FOXO1 and HO-1, and by reducing the inflammatory responses and apoptotic cell death via the down-regulation of NF-κB and NLRP3 inflammasome.

The lectin-like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice.

Ischemia and reperfusion injury (IRI) can occur in any tissue or organ. With respect to liver transplantation, the liver grafts from donors by definition experience transient ischemia and subsequent blood reflow. IRI is a problem not only in organ transplantation but also in cases of thrombosis or circulatory disorders such as mesenteric ischemia, myocardial, or cerebral infarction. We have reported that recombinant human soluble thrombomodulin (rTM), which is currently used in Japan to treat disseminated intravascular coagulation (DIC), has a protective effect and suppresses liver IRI in mice. However, rTM may not be fully safe to use in humans because of its inherent anticoagulant activity. In the present study, we used a mouse liver IRI model to explore the possibility that the isolated lectin-like domain of rTM (rTMD1), which has no anticoagulant activity, could be effective as a therapeutic modality for IRI. Our results indicated that rTMD1 could suppress ischemia and reperfusion-induced liver damage in a dose-dependent manner without concern of associated hemorrhage. Surprisingly, rTMD1 suppressed the liver damage even after IR insult had occurred. Taken together, we conclude that rTMD1 may be a candidate drug for prevention of and therapy for human liver IRI without the possible risk of hemorrhage.

A Prospective, Randomized Phase II Study of Adjuvant Gemcitabine Versus S-1 After Major Hepatectomy for Biliary Tract Cancer (KHBO 1208): Kansai Hepato-Biliary Oncology Group.

OBJECTIVE: To evaluate each arm independently and compare adjuvant gemcitabine (GEM) and S-1 chemotherapy after major hepatectomy (hemihepatectomy or trisectionectomy) for biliary tract cancer (BTC). BACKGROUND: Standardized adjuvant therapy is not performed after major hepatectomy for BTC, and we determined the recommended dose in the former study (KHBO1003). METHODS: We performed a multicenter, randomized phase II study. The primary measure was 1-year recurrence-free survival (RFS); the secondary measures were other RFS, overall survival (OS), and others. The following 6-month adjuvant chemotherapy was administered within 12 weeks of R0/1: GEM (1000 mg/m) every 2 weeks; or S-1 (80 mg/m/d) for 28 days every 6 weeks. Thirty-five patients were assigned to each arm (alpha error, 10%; beta error, 20%). RESULTS: No patients were excluded for the per-protocol analysis. There were no statistically significant differences in the patient characteristics of the 2 arms. The 1-year RFS and 1-year OS rates of the GEM arm were 51.4% and 80.0%, respectively, whereas those of the S-1 group were 62.9% and 97.1%. The comparison of the 2 arms revealed that 2-year RFS rate, 1 and 2-year OS rates, and OS curve of the S-1 arm were superior to GEM. With regard to OS, the hazard ratio of the S-1 group was 0.477 (90% confidence interval 0.245-0.927). CONCLUSION: The comparison of the survival of the 2 groups revealed that adjuvant S-1 therapy may be superior to adjuvant GEM therapy after major hepatectomy for BTC.

Time to Bone Union after Hybrid Closed-Wedge High Tibial Osteotomy.

Medial open- and lateral closed-wedge high tibial osteotomy (hybrid CWHTO) can overcome the limitations of conventional CWHTO and open-wedge HTO (OWHTO) for medial compartmental osteoarthritis (OA) of the knee. Hybrid CWHTO increases stability by using a rigid locking plate and allows early full weight-bearing. However, the literature contains no information about time to bone union after this new procedure. The aim of this study is to evaluate the time to bone union after hybrid CWHTO. We reviewed 44 knees treated with hybrid CWHTO. Patients were able to stand on both legs on the day after surgery and walked with full weight-bearing within 4 weeks of the procedure. The time to achievement of bone union at the osteotomy site was defined as the number of months until bone union was confirmed on radiographic imaging. The mean time to radiographic confirmation of bone union was 4.5±1.5 months after surgery. Eleven knees (25.0%) required 6 months or more. Radiographic analysis and JOA score improved significantly between before and 1 year after surgery (p<0.01). Hybrid CWHTO is a very useful method for treating medial OA, but radiographic bone union requires 4.5 months on average. We must be aware of bone union after hybrid CWHTO.

Two Cases of High Tibial Osteotomy in Patients with Rheumatoid Arthritis Treated with Biologic Disease-modifying Anti-rheumatic Drugs.

High tibial osteotomy (HTO) procedure is generally contraindicated in rheumatoid arthritis (RA) patients because synovial inflammation may exacerbate joint damage post-surgery. The natural course of joint destruction in RA changed dramatically with new treatment strategies and the introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDs). We report the cases of two RA patients who underwent HTO and whose disease activities were well controlled by bDMARDs. Despite their short follow-up periods, they showed acceptable objective and subjective clinical results. We believe that the combination of bDMARDs and HTO can be indicated for selected RA patients before total knee arthroplasty.

A case of neuroendocrine carcinoma in the hepatic hilar lymph nodes concomitant with an adenocarcinoma of the gallbladder.

BACKGROUND: Neuroendocrine tumors (NETs) are rare especially in the gallbladder. They have not been elucidated in the pathogenesis, clinicopathological characteristics, and treatment options. CASE PRESENTATION: We present a 76-year-old woman with a gallbladder tumor and hepatic hilar lymph node swelling. The lymph node biopsy demonstrated neuroendocrine carcinoma (NEC). We performed cholecystectomy, hepatic hilar lymphadenectomy, extrahepatic biliary duct resection, and hepaticojejunostomy prior to chemotherapy. Pathological examination revealed the gallbladder mass was an adenocarcinoma invading to the muscular layer without any NEC components, whereas the hepatic hilar lymph nodes were filled with high-grade NEC cells with negligible area of adenocarcinoma. The patient received general chemotherapy consisting of carboplatin and etoposide, but a recurrence in the para-aortic lymph nodes occurred 4 months after surgery. CONCLUSIONS: We report a rare case of NEC of the hepatic hilar lymph nodes that were concomitant with an adenocarcinoma of the gallbladder. High-grade NEC generally has an aggressive behavior and an optimal treatment strategy should be chosen for each patient.

The protective function of galectin-9 in liver ischemia and reperfusion injury in mice.

Galectin-9 (Gal-9) has gained attention as a multifaceted player in adaptive and innate immunity. To elucidate the role of Gal-9, we used a mouse model of partial liver ischemia/reperfusion injury (IRI) with wild type (WT) and Gal-9 knockout (KO) mice as well as a recombinant galectin-9 (reGal-9) protein. We found that the expression of Gal-9 was enhanced endogenously in the liver especially by hepatocytes and Kupffer cells during warm IRI for a mouse liver, which causes massive destruction of liver tissue. Gal-9 was released into the extracellular space in the liver and the highest levels in the plasma at 1 hour after reperfusion. The present study elucidates a novel role of Gal-9 signaling in mouse liver IRI, by using Gal-9-deficient mice and a stable form of reGal-9 protein. In the circumstance of Gal-9 absence, liver damage due to ischemia/reperfusion (IR) exacerbated the severity as compared with WT. On the other hand, exogenously administered reGal-9 significantly ameliorated hepatocellular damage. It decreased the local infiltration of the inflammatory cells such as T cells, neutrophils, and macrophages, and it reduced the expression of proinflammatory cytokines/chemokines; then, it strongly suppressed the apoptosis of the liver cells. Interestingly, severe liver damage due to IR in Gal-9 KO mice was improved by the administration of reGal-9. In conclusion, Gal-9 engagement ameliorated local inflammation and liver damage induced by IR, and the present study suggests a significant role of Gal-9 in the maintenance of hepatic homeostasis. In conclusion, targeting Gal-9 represents a novel approach to protect from inflammation such as liver IRI. Exogenous Gal-9 treatment will be a new therapeutic strategy against innate immunity-dominated liver tissue damage.