Hepatic arterial infusion of autologous CD34+ cells for hepatitis C virus-related decompensated cirrhosis: A multicenter, open-label, exploratory randomized controlled trial.

Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G-CSF)-mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

Donor Complications Following Living Donor Hepatectomy: 17-Year Experience of a Single Team in One Institution of Japan.

OBJECTIVES: Donor safety is paramount in living donor liver transplantation. However, there remains a risk of postoperative complications for some donors. Here, we provide a comprehensive assessment of donor morbidity by a single team with 17 years of experience at a single center. MATERIALS AND METHODS: We retrospectively reviewed 453 donor hepatectomies of living donor liver transplants at Kumamoto University from August 2000 to March 2017. Posterior segment graft cases were excluded in this study. RESULTS: The donors were classified by graft type as follows: right lobe (n = 173), left lobe (n = 149), and left lateral segment (n = 131). The overall complication rate was 29.8%, and the severe complication (Clavien-Dindo grade IIIa or higher) rate was 9.1%. The most frequent complication was bile leakage, with an overall incidence of 13.9% and severe incidence of 4.6%. Among the 3 types of graft, there were no significant differences in bile leakage with any Clavien-Dindo grade. However, upper gastrointestinal complications, such as a duodenal ulcer and gastric stasis, were related to left lobe donation. CONCLUSIONS: There were no significant differences in the incidence of postoperative donor complications, except upper gastrointestinal complications, among the 3 types of graft.

Stent Graft Placement for Injured Visceral Artery.

Injury of the visceral artery is a potentially fatal complication of iatrogenic procedures, trauma, and tumors. A stent graft can achieve rapid exclusion of the injured arterial portion and minimize the risk of ischemic complications by preserving arterial flow to organs. Although various types of stent grafts are available worldwide, Viabahn has only been approved for visceral arterial injury in Japan. The reported technical and clinical success rates, including cases with injured pelvic or thoracic arterial branches, are 80%-100% and 66.7%-100%, respectively. Severe ischemic complications are rare; however, fatal ischemia occurs when the stent graft is immediately occluded. The necessity of antiplatelet therapy is controversial, and a target artery diameter ≤ 4 mm is a significantly higher risk factor of stent-graft occlusion.

The Prognostic Impact of ABO Blood Group in Hepatocellular Carcinoma Following Hepatectomy.

BACKGROUND/PURPOSE: The effect of the ABO blood group on the survival of patients with hepatocellular carcinoma (HCC) is unclear. The aim of the present study is to determine the prognostic impact of ABO blood types on the survival of a Japanese population of patients with HCC who underwent surgical resection. METHODS: Patients with HCC (n = 480) who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed. Survival outcomes were investigated according to ABO blood type (A, B, O, or AB). Outcomes for type A (n = 173) and non-type A (n = 173) groups after surgery were compared using 1-to-1 propensity score matching to control for variables. RESULTS: In the study cohort, 173 (36.0%), 133 (27.7%), 131 (27.3%), and 43 (9.0%) of participants had Type A, O, B, and AB, respectively. Type A and non-type A patients were successfully matched based on liver function and tumor characteristics. Recurrence-free survival (RFS; hazard ratio [HR] 0.75, 95% confidence interval [Cl] 0.58-0.98, p = 0.038) and overall survival (OS; HR: 0.67, 95% Cl: 0.48-0.95, p = 0.023) for patients with blood type A were both significantly decreased relative to non-type A patients. Cox proportional hazard analysis demonstrated that patients with HCC who have blood type A had a worse prognosis than those with non-type A blood. CONCLUSION: ABO blood type may have a prognostic impact on patients with HCC after hepatectomy. Blood type A is an independent unfavorable prognostic factor for recurrence-free and overall survival (RFS and OS) after hepatectomy.

Application of a Titanium Screw for the Hemorrhage from the Bone Channel during the Lateral Window Technique: A Technical Note.

Pulsatile and profuse hemorrhage occurred in the lateral window technique for implant placement. The surgery was performed in the dental clinic under local anesthesia. The posterior superior alveolar artery was suspected to be the main feeder. Ordinary methods for hemostasis, such as vasoconstrictor-soaked gauze compression, electrocautery hemostasis, absorbable hemostat packing, and bone wax application, were tried. However, strong pulsatile bleeding could not be controlled at all. Complete hemostasis was hardly expected. The idea came up when the titanium screws came into sight. The sterilized screw was always stocked for bone grafting. After visualizing the bleeding point clearly by suction, and the screw was inserted into the bone channel. The bleeding was completely stopped immediately. It may not be a novel method, but is certainly a reliable application of the screw, which is fundamentally the same as arterial catheter embolization.

Efficacy and Safety of Liver Resection in Super Elderly Patients with Hepatocellular Carcinoma.

OBJECTIVE: Liver resection in the super elderly patients remains challenging because of comorbidities and operative tolerability. METHODS: In this study, we compared postoperative complications and survival in patients aged ≥85 yr included five patients aged ≥90 yr with those aged 70-79 and 80-84 yr at a single institution. RESULTS: Three hundred sixty-seven patients aged ≥70 yr underwent liver resection and were divided into three groups based on age at operation between 2010 and 2022; (a) 70-79 yr (median of 74 yr, n=245), (b) 80-84 yr (median of 82 yr, n=81), and (c) ≥85 yr (median of 87 yr, n=41). In the ≥85 yr group (90-yr-old group), twenty-five patients (four) had hypertension, fourteen (one) had diabetes mellitus, seven (one) had cardiovascular disease, and five patients (one) had dementia. The rate of comorbidities did not differ significantly among three groups. The rate of postoperative complications (Clavien-Dindo grade 3a≤) was 25% in the 70- to 79-yr-old group, 27% in the 80- to 84-yr-old group, and 17% in the ≥85-yr-old group (20% in the ≥90-yr-old group) (N.S.). The 1- and 5-yr patient survival rates in the ≥85-yr-old group were 90.1% and 48.5% respectively, compared with 86.7% and 60.9% in the 70- to 79-yr-old group and 83.8% and 66.3% in the 80- to 84-yr-old group, respectively (N.S.). CONCLUSION: Despite the management of comorbidities, liver resection for well-selected super elderly patients, such as those aged ≥85 yr included ≥90yr, has acceptable outcomes. The age of patient is not an absolute contraindication to liver resection.

A case of mesenteric venous thrombosis complicating appendiceal diverticulitis.

BACKGROUND: Mesenteric venous thrombosis (MVT) and appendiceal diverticulitis are rare diseases. There has been no previous report on MVT complicating appendiceal diverticulitis. Herein, we report the first case of MVT complicating appendiceal diverticulitis. CASE PRESENTATION: A 70-year-old male patient with right lower abdominal pain presented to our hospital. Abdominal contrast-enhanced computed tomography (CT) suggested MVT complicating appendiceal diverticulitis. Initially, we started conservative treatment with antibacterial drugs, but on the 2nd hospital day his general condition deteriorated due to sepsis that seemed to be caused by appendiceal diverticulitis. Therefore, we performed laparoscopic appendectomy. Histopathological findings of the specimen showed appendiceal diverticulitis. After the operation, he gradually improved. He was discharged on the 30th hospital day. CONCLUSIONS: We report a successfully treated case of MVT complicating appendiceal diverticulitis by surgical intervention. This is the first case of MVT complicating appendiceal diverticulitis.

Modified Albumin-Bilirubin Grade and Alpha-Fetoprotein Score (mALF Score) for Predicting the Prognosis of Hepatocellular Carcinoma after Hepatectomy.

We developed and evaluated a modified albumin-bilirubin grade and α-fetoprotein (mALF) score, a nutritional and oncological assessment tool for patients with hepatocellular carcinoma (HCC) after surgical resection. Patients (n = 480) who underwent R0 resection between 2010 and 2020 were analyzed retrospectively. The mALF score assigned one point for a modified albumin-bilirubin (mALBI) grade 2b or 3 and one point for an α-fetoprotein (AFP) level ≥ 100 ng/mL. Patients were classified by mALF scores of 0 (mALBI grade 1/2a, AFP < 100 ng/mL), 1 (mALBI grade 2b/3 or AFP ≥ 100 ng/mL), or 2 (mALBI grade 2b/3, AFP ≥ 100 ng/mL) points. Liver reserve deteriorated and cancer progressed with increasing score. Postoperative complications (Clavien−Dindo classification ≥ 3) differed significantly among groups. The 5-year recurrence-free survival (RFS) rates were 34.8%, 11.2%, and 0.0% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The 5-year overall survival (OS) rates were 66.0%, 29.7%, and 17.8% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The mALF score was an independent prognostic predictor of RFS and OS. In HCC, the mALF score was effective for predicting postoperative complications and long-term survival.

A Novel Variation of the Lateral Window Approach for Sinus Floor Elevation in a Case of Bony Nodular Prominence.

Introduction: In sinus floor augmentation, bony nodular prominence at the floor of the maxillary sinus is an obstruction to lateral window approach. It is challenging to detach and elevate the sinus membrane without making any perforations around the nodular prominence, because the membrane is very thin. To overcome these difficulties, we developed a novel method. Method: The membrane was not detached from the surface of the nodular prominence except for at the basal point, but the nodular prominence was cut at the base. Nodular prominence and sinus membrane were elevated upward together. A resorbable collagen membrane was placed beneath it to provide mechanical support and cover any partial tear in the sinus membrane. Autogenous bone and/or bone substitute were packed in the vacant compartment depending on the condition. Conclusion: This method is very easy to be carried out without any difficulties and worries. It gives us great benefit on the sinus floor augmentation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-021-01572-7.

Redo pancreaticojejunal anastomosis for late-onset complete pancreaticocutaneous fistula after pancreaticojejunostomy.

BACKGROUND: Pancreaticojejunal (PJ) anastomosis occasionally fails several months after pancreaticoduodenectomy (PD) with Child reconstruction and can ultimately result in a late-onset complete pancreaticocutaneous fistula (Lc-PF). Since the remnant pancreas is an isolated segment, surgical intervention is necessary to create internal drainage for the pancreatic juice; however, surgery at the previous PJ anastomosis site is technically challenging even for experienced surgeons. Here we describe a simple surgical procedure for Lc-PF, termed redo PJ anastomosis, which was developed at our facility.  METHODS: Between January 2008 and December 2020, six consecutive patients with Lc-PF after PD underwent a redo PJ anastomosis, and the short- and long-term clinical outcomes have been evaluated. The abdominal cavity is carefully dissected through a 10-cm midline skin incision, and the PJ anastomosis site is identified using a percutaneous drain through the fistula tract as a guide, along with the main pancreatic duct (MPD) stump on the pancreatic stump. Next, the pancreatic stump is deliberately immobilized from the dorsal plane to prevent injury to the underlying major vessels. After fixing a stent tube to both the MPD and the Roux-limb using two-sided purse-string sutures, the redo PJ anastomosis is completed using single-layer interrupted sutures. Full-thickness pancreatic sutures are deliberately avoided by passing the needle through only two-thirds of the anterior side of the pancreatic stump. RESULTS: The redo PJ anastomosis was performed without any intraoperative complications in all cases. The median intraoperative bleeding and operative time were 71 (range 10-137) mL and 123 (range 56-175) min, respectively. Even though a new mild pancreatic fistula developed postoperatively in all cases, it could be conservatively treated within 3 weeks, and no other postoperative complications were recorded. During the median follow-up period of 92 (range 12-112) months, no complications at the redo PJ anastomosis site were observed. CONCLUSIONS: This research shows that the redo PJ anastomosis for Lc-PF we developed is a safe, feasible, and technically no demanding procedure with acceptable short- and long-term clinical outcomes. This procedure has the potential to become the preferred treatment strategy for Lc-PF after PD.

Performance of Idylla™ RAS-BRAF mutation test for formalin-fixed paraffin-embedded tissues of colorectal cancer.

BACKGROUND: The Biocartis Idylla™ platform is a fully automated, real-time PCR-based diagnostic system. The Idylla™ KRAS and NRAS-BRAF Mutation Tests have been developed for the qualitative detection of mutations in KRAS, NRAS and BRAF genes, facilitating the genomic profiling of patients with colorectal cancer. The aim of the present study was to evaluate clinical performances of these tests in Japan. METHODS: The RAS and BRAF mutation statuses of 253 formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissues were analyzed using the Investigational Use Only Idylla™ KRAS Mutation Test and the Idylla™ NRAS-BRAF Mutation Test and an in vitro diagnostics (IVD) kit (MEBGEN RASKET™-B kit). RESULTS: The success rate for obtaining a valid mutational data without retest of the Idylla tests was 97.6% (247/253): 111 KRAS mutations (43.8%), 9 NRAS mutations (3.6%), and 36 BRAF V600E mutations (14.2%) were detected using the Idylla tests. Compared with the MEBGEN RASKET-B results, the positive concordance rate was 97.4%, the negative concordance rate was 95.7%, and the overall concordance rate was 95.3% (κ = 0.919, 95% CI 0.871-0.967). The average turnaround time to Idylla™ KRAS and NRAS-BRAF Mutation Test was 5.6 working days (range: 3-11 days). CONCLUSION: This result demonstrates a high concordance between the Idylla™ KRAS and NRAS-BRAF Mutation Tests and an existing IVD kit. In this manner, the Idylla™ mutation tests were validated for the detection of clinically significant KRAS, NRAS, and BRAF mutations in FFPE samples from colorectal cancer patients.

Iron Deficiency Anemia Improved by Dental Implantation: A Case Report.

Treatments for improving iron deficiency anemia are generally aimed at increasing oral iron intake and/or administration. Such treatments, however, have been unsuccessful in managing nutritional disorders, including anemia, in patients with masticatory dysfunction caused by impaired occlusion. Nevertheless, few studies have assessed the potential benefits of providing optimal occlusion in such cases. Here, we report a case involving a 53-year-old woman with iron deficiency anemia, wherein we attempted to facilitate efficient mastication by establishing functional occlusion with dental implant placement. The patient was diagnosed with iron deficiency anemia and hospitalized for blood transfusion 2 years before she visited our dental clinic. At the first visit, her hemoglobin (Hb) and mean corpuscular volume values were low; sodium ferrous citrate administration and dietary guidance led to slight improvement. However, blood transfusions and iron supplementation had been ineffective over longer duration. After dental implant placement, her Hb and mean corpuscular volume values were restored and maintained for >4 years without medication. Through this report, we highlight an alternative, non-pharmacological treatment strategy for iron deficiency anemia.

Predicting Complications following Surgical Resection of Hepatocellular Carcinoma Using Newly Developed Neo-Glasgow Prognostic Score with ALBI Grade: Comparison of Open and Laparoscopic Surgery Cases.

Background/Aim: Nutritional assessment is known to be important for predicting prognosis in patients with malignant diseases. This study examined the usefulness of a prognostic predictive nutritional assessment tool for hepatocellular carcinoma (HCC) patients treated with surgical resection. Materials/Methods: HCC patients (n = 429) classified as Child−Pugh A who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed (median age 73 years, males 326 (76.0%), Child−Pugh score 5:6 = 326:103, single tumor 340 (79.2%), median tumor size 3.5 cm, open:laparoscopic = 304:125). Glasgow prognostic score (GPS) and the newly developed neo-GPS method, which uses albumin−bilirubin grade 1 instead of albumin, were evaluated to compare their usefulness for prognosis prediction. Results: Median survival time for patients with a GPS score of 0, 1, and 2 was 120, 51, and 20 months, respectively. As for neo-GPS, that for those with a score of 0, 1, and 2 was not applicable (NA), 53 months, and 35 months, respectively (each p < 0.001; c-index: 0.556 and 0.611, respectively). Furthermore, median progression-free survival was 33, 22, and 9 months, and 41, 24, and 15 months, respectively (each p < 0.001; c-index: 0.539 and 0.578, respectively). As compared to patients with a high GPS (≥1), those with a high neo-GPS (≥1) showed a greater rate of high Clavien−Dindo classification (≥3) (39.2% vs. 65.1%). A comparison of patients with a high GPS (≥1) with those with a high neo-GPS (≥1) showed no significant difference regarding frequency of open or laparoscopic hepatectomy (17.4% vs. 15.2%, p = 0.670; 44.7% vs. 43.2%, p = 0.831, respectively), while the frequency of high Clavien−Dindo classification (≥3) was lower in patients who underwent a laparoscopic hepatectomy (11.2% vs. 22.7%, p = 0.007). Conclusion: The present findings suggest that the newly developed neo-GPS based on ALBI grade is an effective prognostic nutritional assessment tool and can be used for prediction of postoperative complications.

Surgical Outcomes of Domino Liver Transplantation Using Grafts From Living Donors With Familial Amyloid Polyneuropathy.

Domino liver transplantation (DLT) using grafts from donors with familial amyloid polyneuropathy is an acceptable procedure for expanding the donor pool. The vascular and biliary reconstructions in living donor DLT (LDDLT) are technically demanding, and data on the short-term and long-term surgical outcomes of domino donors and recipients in LDDLT are limited. In this study, we identified 25 domino recipients from our liver transplantation program (1999-2018), analyzed the vascular and biliary reconstructions performed, and evaluated the surgical outcomes, including graft survival. Piggyback technique was adopted in all 25 domino donors. The only surgical complication in domino donors was hepatic vein (HV) stenosis with an incidence rate of 4%. In 22 domino recipients, right HV and middle/left HV were reconstructed separately. A total of 10 recipients had 2 arteries anastomosed, and 18 underwent duct-to-duct biliary anastomosis. HV stenosis and biliary stricture had incidence rates of 8% and 24%, respectively, in the recipients, but none of them developed hepatic artery thrombosis. The 1-year and 5-year graft survival rates were 100% each in the domino donors, and 84.0% and 67.3% in the domino recipients, respectively. In conclusion, LDDLT has acceptable outcomes without increasing the operative risk in donors despite the demanding surgical technique involved.

Prospective Study to Evaluate the Safety and Efficacy of a New Surgical Tube Fixation Method: A Pilot Study.

BACKGROUND: Various tubes may be fixed to the skin by ligation using silk sutures after gastrointestinal surgery. We investigated the effects of a skin substitute, "Nonaht®," on pain and skin inflammation at the fixation sites of various tubes. METHODS: The effects of tubes (abdominal drains, small intestinal feeding tubes, and bile duct drainage tubes) fixed in place using either silk sutures or Nonaht were compared for 1-3 months. RESULTS: The median pain scores at the fixation site when abdominal drains were removed were 1.0 with silk sutures and 0 with Nonaht (p < 0.001). Scarring at the fixation site at postoperative month (POM) 1 occurred in 13 of 28 cases in the silk suture group and in no cases in the Nonaht group (p < 0.001). The median pain scores at the fixation site with long-term tubes on postoperative day (POD) 14 and POM 1 were 2.0 and 1.0, respectively, with silk sutures, and none at all time points with Nonaht (p < 0.001). Scarring at the fixation site at POM 3 occurred in all 10 cases in the silk suture group and in no cases in the Nonaht group (p < 0.001). CONCLUSIONS: Patients with conventional skin fixation of tubes using silk sutures were continuously aware of pain at the fixation site and developed skin damage and subsequent scar formation, especially for tubes inserted for ≥ 1 month. The use of Nonaht may reduce the incidence of dermatitis and wound infections at tube fixation sites, thereby promoting early postoperative recovery.

The feasibility of combined resection and subsequent reconstruction of the right hepatic artery in left hepatectomy for cholangiocarcinoma.

BACKGROUND: Combined resection of the right hepatic artery (RHA) is sometimes required to achieve complete resection of hilar cholangiocarcinoma. The present study aimed to evaluate the feasibility of combined resection and subsequent reconstruction by continuous suture of the RHA during left hepatectomy for cholangiocarcinoma. MATERIALS AND METHODS: We retrospectively compared the outcomes after left hepatectomy with biliary reconstruction for cholangiocarcinoma between patients with and without RHA resection and reconstruction. RESULTS: Of the 25 patients who underwent left hepatectomy combined with biliary reconstruction, eight patients (32%) underwent combined resection and reconstruction of the RHA (AR group). The demographic characteristics were not different between the AR and non-AR groups. The amount of intraoperative bleeding was significantly greater in patients with AR (2350 mL vs. 900 mL, p = 0.017). The prevalence of early complications above grade III in Clavien-Dindo classification and late complications were not significantly different between the AR and non-AR groups. In the AR group, complications directly associated with AR, such as thrombosis or reanastomosis, were not observed. On Kaplan-Meier analysis, recurrence-free survival (p = 0.618) and overall survival (p = 0.803) were comparable between the two groups despite the advanced T stages in the AR group. CONCLUSIONS: Combined resection and subsequent reconstruction of the RHA during left-sided hepatectomy is a feasible treatment alternative for cholangiocarcinoma.

Intellectual development of patients with biliary atresia who underwent living donor liver transplantation in infancy.

BACKGROUND: The impact of pediatric liver transplantation on intellectual development has yet to be determined. We investigated the intellectual outcomes of school-aged patients after living donor liver transplantation for biliary atresia in infancy. METHODS: The Wechsler Intelligence Scale for Children-fourth edition test was administered to 20 patients who survived [Formula: see text] 5 years after living donor liver transplantation. Borderline full scale intelligence quotient was defined as ≤ 85. Pre-, peri-, and postoperative data were compared between patients with > 85 and ≤ 85 to identify predictive factors of borderline performance. RESULTS: The one-sample t test demonstrated that the mean full scale intelligence quotient of patients after transplantation for biliary atresia was significantly lower than that of the general population (91.8 vs. 100.0, p = 0.026) and 7 (35%) were classified as intellectual borderline functioning. Multivariable logistic regression models were unable to identify any factors predictive of full scale intelligence quotients of ≤ 85. CONCLUSION: This is the first study to indicate that the mean full scale intelligence quotient among school-aged patients who underwent living donor liver transplantation for biliary atresia in infancy is significantly lower than that of the general population.