Published papers

Introduction: Reports of liver transplantation (LT) after Kasai portoenterostomy (KPE) in adult patients with biliary atresia are scarce. The aim of this study was to evaluate the outcomes and investigate the risk factors of LT after KPE in both pediatric and adult patients. Methods: We retrospectively reviewed a prospective database of patients with biliary atresia who underwent LT after KPE. Eighty-nine consecutive patients were included, and risk factors for in-hospital mortality after LT were assessed. Results: The median age of the patients was 2 y (range, 0-45 y). Forty-six patients (51.7%) had a history of upper abdominal surgery after KPE. The in-hospital mortality rate was 5.6% (5 patients). Of these, 80% of patients with mortality were aged ≥17 y, and all patients with mortality had a history of two or more upper abdominal surgeries. In the univariate and receiver operating characteristic curve analyses, age ≥17 y and the number of previous upper abdominal surgeries ≥2 were identified as possible risk factors. Conclusions: Our study suggests that older age and multiple previous upper abdominal surgeries are important risk factors for mortality after LT following KPE. We believe that these findings will serve as indications for safe LT in future patients.

Aim: Using nationwide data collected over the past 20 years, we aimed to investigate deceased donor liver transplantation (DDLT) outcomes to develop a unique risk model that can be used to establish a standard for organ acceptance in Japan. Methods: Data were collected for 449 recipients aged ≥18 years who underwent DDLT between 1999 and 2019. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to develop an original risk score model for 1-year graft loss (termed the Japan Risk Index [JRI]). We developed risk indices according to recipient, donor, and surgery components (termed JRI-R, D, and S, respectively). The JRI was validated via a 5-fold cross-validation. We also compared DDLT outcomes and risk indices among Era1 (−2011), Era2 (−2015), and Era3 (−2019). Results: The 1-year graft survival rate was 89.5% and improved significantly, reaching 84.7%, 87.6%, and 93.9% in Era1, Era2, and Era3, respectively. The JRI was calculated as JRI-R (re-transplantation, Model for End-Stage Liver Disease score, medical condition in intensive care unit) × JRI-D (age, catecholamine index, maximum sodium, maximum total bilirubin) × JRI-S (total ischemic time) × 0.84. The risk model achieved a mean C-statistic value of 0.81 in the validation analysis. The risk index was significantly lower in Era3 than in Era2. Conclusion: Changes in the risk index over time indicated that avoiding risks contributed to the improved outcomes in Era3. The JRI is unique to adult DDLT in Japan and may be useful as a reference for organ acceptance in the future.

Background: Several studies have demonstrated that prehabilitation helps reduce the incidence of postoperative complications. In this study, we investigated the safety and efficacy of enhanced prehabilitation (EP) in the hospital for patients with esophageal cancer. Methods: We retrospectively reviewed the data of 48 consecutive patients who underwent radical esophagectomy with gastric tube reconstruction between September 2015 and June 2019. EP program had been introduced in August 2017. In the EP group, patients received the EP program during hospitalization 7 days before surgery in addition to conventional perioperative rehabilitation. The EP program consisted of aerobic exercise and muscle strength training in the morning and afternoon. Operative outcomes were compared between patients who received EP (EP group; 23 patients) and patients who did not receive EP (control group; 25 patients). Results: The preoperative (EP group vs. control group, 492.9 ± 79.7 vs. 418.9 ± 71.8 m, p < 0.001) and postoperative (EP group vs. control group, 431.5 ± 80 vs. 378 ± 68.7 m, p < 0.001) 6-min walk distance was significantly higher in the EP group than in the control group. The respiratory complications rate was significantly lower in the EP group (4.3%) than in the control group (36%) (p = 0.007). The incidence of atelectasis was particularly significantly lower in the EP group (0%) than in the control group (24%) (p = 0.012). Conclusions: EP was performed safely for patients before esophagectomy. EP improved the exercise tolerance of the patients before esophagectomy and might be useful in preventing respiratory complications.

Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.

Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole-exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first-degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer.

Background and Aims: Immune cells and tumor vessels constitute important elements in tumor tissue; however, their detailed relationship in human tumors, including HCC, is still largely unknown. Consequently, we expanded our previous study on the immune microenvironment of HCC and analyzed the relationship among the immune microenvironment, inflammatory/angiostatic factor expression, angiogenic factor expression, and tumor vessel findings, including vessels encapsulating tumor clusters (VETC) and macrotrabecular-massive (MTM) patterns. Approach and Results: We classified HCC into four distinct immunovascular subtypes (immune-high/angiostatic [IH/AS], immune-mid/angio-mid [IM/AM], immune-low/angiogenic [IL/AG], and immune-low/angio-low [IL/AL]). IH/AS, IM/AM, and IL/AG subtypes were associated with decreasing lymphocytic infiltration and increasing angiogenic factor expression and VETC/MTM positivity, reflecting their reciprocal interaction in the tumor microenvironment of HCC. IL/AG subtype was further characterized by CTNNB1 mutation and activation of Wnt/β-catenin pathway. IL/AL subtype was not associated with increased lymphocyte infiltration or angiogenic factor expression. Prognostically, IH/AS subtype and VETC/MTM positivity were independently significant in two independent cohorts. Increased angiogenic factor expression was not necessarily associated with VETC/MTM positivity and poor prognosis, especially when inflammatory/angiostatic milieu coexisted around tumor vessels. These results may provide insights on the therapeutic effects of immunotherapy, antiangiogenic therapies, and their combinations. The potential of evaluating the immunovascular microenvironment in predicting the clinical effect of these therapies in nonresectable HCC needs to be analyzed in the future study. Conclusions: HCC can be classified into four distinct immunovascular subtypes (IH/AS, IM/AM, IL/AG, and IL/AL) that reflect the reciprocal interaction between the antitumor immune microenvironment and tumor angiogenesis. In addition to its clinicopathological significance, immunovascular classification may also provide pathological insights on the therapeutic effect of immunotherapy, antiangiogenic therapy, and their combination.

Aim: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection from blood products for hemophilia has been a social problem in Japan, and liver transplantation (LT) for these patients has been a challenging procedure. However, with the advent of the direct-acting antiviral agent for HCV and change in the policy for prioritization of deceased donor LT, the results of LT for patients co-infected with HCV/HIV may have improved. Methods: This study was conducted to provide updated results of our nationwide survey of LT for patients co-infected with HCV/HIV, from January 1997 to December 2019. We collected data on 17 patients with HIV/HCV co-infection who underwent either deceased donor LT (n = 5) or living donor LT (n = 12). Results: All the patients were men with hemophilia, and the median age was 41 (range, 23–61) years. The median CD4 count before LT was 258 (range, 63–751). Most patients had poor liver function before surgery with Child–Pugh grade C and a Model for End-stage Liver Disease score of 20 (range, 11–48). The right lobe was used for most grafts for living donor liver transplantation (n = 10). Overall survival was significantly better with a sustained viral response (SVR) than without an SVR, and a univariate analysis indicated that SVR after direct-acting antiviral or interferon/ribavirin showed the highest hazard ratio for patient survival after LT. A multivariate analysis was not possible because of the limited number of cases. Conclusion: SVR for HCV showed the highest impact on the outcome of LT for patients with hemophilia co-infected with HIV/HCV. SVR for HCV should be achieved before or after LT for patients with hemophilia co-infected with HIV/HCV for a better outcome.

Background/Objectives: According to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs. Methods: We enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN. Results: Fifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45). Conclusions: Large nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.

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.

Background/Aim: Pancreatic cancer, which exhibits resistance to cytotoxic and molecular targeted drugs, has an extremely poor prognosis. Nuclear factor-ĸB (NF-ĸB) is constitutively activated in many pancreatic cancer cases. Although the NF-ĸB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) has exhibited anti-cancer effects in pancreatic cancer models, its poor solubility limits its use to intraperitoneal administration. Materials and Methods: Poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) forms stable polymer aggregates with DHMEQ. The stability of DHMEQ aggregated with PMB in the human blood was measured by high-performance liquid chromatography–mass spectrometry (HPLC-MS) ex vivo. Anti-pancreatic cancer effects in AsPC-1 and MIA PaCa-2 pancreatic cancer cells were evaluated by cell growth inhibition assay in vitro and tumor growth inhibition assay in vivo. Results: DHMEQ aggregated with PMB (PMBDHMEQ) remained detectable after 60 min of incubation in the human blood, whereas DHMEQ aggregated with carboxymethyl cellulose (CMC-DHMEQ) was barely detectable. PMB-DHMEQ significantly inhibited AsPC-1 and MIA PaCa-2 cell growth in vitro compared to CMC-DHMEQ. Intravenous administration of PMB-DHMEQ reduced the tumor volume and liver metastasis compared to untreated or CMC-DHMEQ-treated mice. Conclusion: Aggregation with PMB improved the solubility of DHMEQ, and effectively inhibited pancreatic cancer cell growth both in vitro and in vivo.

Purpose: Invasive pulmonary aspergillosis (IPA) after liver transplantation (LT) is most often fatal. We analyzed the outcomes of IPA in a single center. Methods: We reviewed, retrospectively, the medical records of recipients of living donor LT (LDLT) or deceased donor LT (DDLT) performed between 1995 and 2019 at our institute. We analyzed the incidence of IPA and assessed the treatment courses of patients treated successfully and those not treatment successfully. Results: Among 326 recipients, IPA was diagnosed in 6 (1.8%). The incidence of IPA was significantly higher in patients with acute liver failure (ALF, 9.8%) than in those without ALF (0.4%), after DDLT (8.8%) than after LDLT (1.0%), and in recipients who received preoperative steroid pulse therapy (16.0%) than in those who did not (0.7%). Complete cure of IPA was achieved in the most recent three patients, by administering voriconazole immediately after the diagnosis of IPA and performing lung resection, while the IPA lesion was single and localized. Conclusions: Patients with risk factors for IPA must be monitored closely. Our three successfully treated cases demonstrate that initiating immediate voriconazole treatment and making a calculated decision about lung resection can contribute to a favorable outcome.

Patient: Female, 70-year-old Final Diagnosis: Hepatocellular carcinoma with extrahepatic portal vein obstruction Symptoms: — Medication: — Clinical Procedure: Preoperative simulation and intraoperative navigation technique Specialty: Surgery Objective: Background: Case Report: Conclusions: Unusual setting of medical care Extrahepatic portal vein obstruction (EHPVO) is one of the most important diseases that causes pre-hepatic portal hypertension, and EHPVO sometimes develops cavernous transformation to maintain hepatopetal flow. In this report, we describe the first case of hepatocellular carcinoma (HCC) with EHPVO having underwent pure laparoscopic left hepatectomy with middle hepatic vein (MHV) resection. A 70-year-old woman with a diagnosis of mixed-type HCC or cholangiocarcinoma located in segment 4b was referred to our hospital, and computed tomography revealed EHPVO with cavernous transformation. We suc-cessfully performed pure laparoscopic left hepatectomy with MHV resection by using the individual hilar ap-proach, frequent intraoperative sonography, and indocyanine green imaging. In this case, the routine Glissonian approach was impossible due to cavernous transformation growth and the absence of a portal vein. Therefore, frequent confirmation of intrahepatic flow was crucial to avoid intraoperative complications. The patient was discharged with no complications on postoperative day 7. A histopathological examination revealed that the moderately differentiated HCC formed a pseudoglandular pattern and cord-like structures, thereby defined as type II according to Edmondson’s classification. Currently, difficulty scoring systems for laparoscopic liver resection (LLR) usually contain the procedure and location of the hepatic tumor, but they do not contain the variety of anatomical abnormality due to its rarity. However, the false recognition of hilar vessels and biliary ducts in patients with an anatomical abnormality, in-cluding EHPVO, leads to severe injury; therefore, anatomical variety and abnormality are also important fac-tors increasing the difficulty of LLR.

BACKGROUND Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a biopsy technique widely used to diagnose pancreatic tumors because of its high sensitivity and specificity. Although needle-tract seeding caused by EUS-FNA has been recently reported, dissemination of pancreatic cancer cells is generally considered to be a rare complication that does not affect patient prognosis. However, the frequency of dissemination and needle-tract seeding appears to have been underestimated. We present a case of peritoneal dissemination of pancreatic cancer due to preoperative EUS-FNA. CASE SUMMARY An 81-year-old man was referred to the Department of Surgery of our hospital in Japan owing to the detection of a pancreatic mass on computed tomography during medical screening. Trans-gastric EUS-FNA revealed that the mass was an adenocarcinoma; hence laparoscopic distal pancreatectomy with lymphadenectomy was performed. No intraoperative peritoneal dissemination and liver metastasis were visually detected, and pelvic lavage cytology was negative for carcinoma cells. The postoperative surgical specimen was negative for carcinoma cells at the dissected margin and the cut end margin; however, pathological findings revealed adenocarcinoma cells on the peritoneal surface proximal to the needle puncture site, and the cells were suspected to be disseminated via EUS-FNA. Hence, the patient received adjuvant therapy with S-1 (tegafur, gimeracil, and oteracil potassium); however, computed tomography performed 5 mo after surgery revealed liver metastasis and cancerous peritonitis. The patient received palliative therapy and died 8 mo after the operation. CONCLUSION The indications of EUS-FNA should be carefully considered to avoid iatrogenic dissemination, especially for cancers in the pancreatic body or tail.

Background: Loss of skeletal muscle mass is a prognostic factor after surgery for gastrointestinal cancers. The treatment for perihilar cholangiocarcinoma (PHC) is a highly invasive surgery. Biliary drainage and portal vein embolization, which can prolong the preoperative waiting time (PWT), are often required before surgery. Assuming that the skeletal muscle mass can change during PWT, we investigated the clinical effect of skeletal muscle change on surgical outcomes of PHC. Methods: We retrospectively reviewed the medical records of 89 patients who underwent curative surgery for PHC from January 2013 to December 2019. We defined the psoas muscle area (PMA) at the third lumbar vertebra as the skeletal muscle mass. The PMA just before surgery was divided by that at the time of diagnosis, and we defined it as the rate of change of PMA (CPMA). Patients were divided into two groups according to CPMA: wasting (n = 44, below the median CPMA) and no-change (n = 45, above the median CPMA). Results: The median PWT was 63 d, and CPMA was 96.1%. The median recurrence-free survival and overall survival were significantly shorter in the wasting group than in the no-change group (8.0 vs 33.2 mo, P = 0.001 and 14.2 vs 48.7 mo, P < 0.001, respectively). Multivariate analysis revealed that histological differentiation, R1 resection, lymph node metastasis, and preoperative skeletal muscle wasting were independent prognostic factors of PHC. Conclusion: This study suggests that preoperative skeletal muscle wasting in patients with PHC has a negative effect on survival outcomes.

Background: The use of laparoscopic liver resection (LLR) is widespread owing to its several advantages, especially smaller incision (Kaneko et al., Ann Gastroenterol Surg 1:33–43, 1; Ciria et al., Surg Endosc 34:349–360, 2). However, both posterior sectionectomy and donor hepatectomy are extremely difficult procedures to perform in LLR (Hasegawa et al., Ann Gastroenterol Surg 2:376–382, 3; Soubrane and Kwon, J Hepatobiliary Pancreat Sci 24:E1–E5, 4; Takahara et al., Transplantation 101:1628–1636, 5; Lee et al., Clin Transplant 33:e13683, 6; Hong et al., Surg Endosc 33:3741–3748, 7; Rhu et al., J Hepatobiliary Pancreat Sci 27:16–25, 8). Moreover, the right posterior section graft procurement is also difficult even in open laparotomy procedure (Sugawara et al., Transplantation 73:111–114, 9; Hwang et al., Liver Transpl 10:1150–1155, 10; Hori, Kirino, and Uemoto, Hepatol Res 45:1076–1082, 11; Kusakabe et al., Liver Transpl 26:299–303, 12). The pure laparoscopic donor posterior sectionectomy has not been reported yet. Therefore, we aimed to introduce a novel procedure through a video clip. Methods: The donor was placed in the semi-left lateral decubitus position with the reverse Trendelenburg position using a bean bag device. The right liver was mobilized, and the right hepatic vein was exposed. To adopt the liver hanging maneuver, a tape was inserted between the middle and right hepatic veins along the inferior vena cava. The posterior Glissonean pedicle was encircled and controlled, and the liver parenchyma was completely transected using the liver hanging maneuver. The vessels to the posterior section were respectively isolated. The posterior branches of the hepatic duct, hepatic artery, and portal vein were cut. The right hepatic vein was divided, and the graft liver was retrieved via a suprapubic incision. This study was approved by institutional ethics board (No. MH2019-119), and informed consent was taken from the patient. Results: The overall surgical time was 503 min, and the blood loss was 400 mL. No complications were observed, and the donor was discharged from the hospital on postoperative day 11. Conclusion: This is the first report of pure laparoscopic donor hepatectomy of the posterior section graft. This procedure is more difficult than other laparoscopic donor hepatectomies because it involves parenchymal transection in the right intersectional plane and dissection of the posterior branches of hilar vessels.

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.

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life-saving procedure and to correct the underlying enzymatic defect, respectively. Case presentation: We report a 20-year-old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP-induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late-onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high-risk situation for bile leakage from the non-communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. Conclusion: Physicians should recognize the potentially rapid and life-threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft.

Background: The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. Methods: In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. Results: Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0–100.0, p = 0.001 and OR 8.7, 95% CI 1.5–52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5–23) tumor size for a median of 34 (range 2.4–114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0–3.33) per year. Conclusion: Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.

Biliary complications after hepatectomy in living donors have yet to be eradicated. We hypothesized that a standardized upfront Glissonean approach and liver hanging maneuver (GH) would prevent mechanical and thermal injuries to the hilar plate of the remnant liver by determining the point of bile duct division and the final destination of hepatectomy preceding liver parenchymal transection (safety) and facilitate liver transection deep within the parenchyma and allow maximum length of hilar structures (rationality). GH was implemented in 2016 and its incidence of bile leakage was retrospectively compared against the conventional technique. GH comprises six steps: (1) development of the retrohepatic avascular plane between the right hepatic vein (RHV) and the middle hepatic vein (MHV) and isolation of the hepatic vein(s); (2) isolation of the right or left Glissonean pedicle with the corresponding Glissonean pedicles of the caudate lobe; (3) for right liver grafts and left liver grafts with the caudate lobe, passage of the tape for the liver hanging maneuver along the retrohepatic avascular plane and above the hilar plate, and for left liver grafts without the caudate lobe and for left lateral section grafts, passage of the tape from between the RHV and the MHV, along the Arantius ligament, and to the right of the umbilical portion; (4) liver transection; (5) isolation of hilar structures; and (6) graft procurement. Until 2020, 62 consecutive living donors underwent GH (success rate, 100%). The incidence of bile leakage from the hepatic hilum (0%) was significantly lower than that among 59 donors who underwent the conventional technique in 2011-2015 (9%; p = 0.01). In conclusion, GH is highly effective in reducing bile leakage from the hepatic hilum in living donors.

Objectives: The Tokyo Guidelines 2018 have been widely adopted since their publication. However, the few reports on clinical outcomes following laparoscopic cho-lecystectomy have not taken into account the severity of the acute cholecystitis and the patient's general condition, as estimated by the Charlson comorbidity index. This study aimed to assess the relationships between severity, Charlson comorbidity index, and clinical outcomes subsequent to laparoscopic cholecystectomy. Methods: We extracted the retrospective data for 370 Japanese patients who underwent emergency or scheduled early laparoscopic cholecystectomy within 72 hours from onset between February 2015 and August 2018. We compared postoperative factors in relationship to severity (grade I versus grade II/III). Then, we made a similar comparison between those with low (< 4) and high Charlson comorbidity index (> 4). Results: According to the Tokyo guideline 2018 levels of severity, there were 282 (76.2%), 61 (16.5%), and 27 (7.3%) patients in grades I, II, and III, respectively. With regards to surgical outcomes, the mean operating time was 62.3 minutes and the mean blood loss was 24.4 mL. The mean hospital stay was 3.6 days, with no mortalities. Blood loss was the only factor affected by severity (20.9 mL versus 60.1 mL, P = 0.0164), and operating time was the only factor affected by high Charlson comorbidity index (53.4 versus 67.8 minutes, P = 0.0153). Conclusion: Our aggressive strategy is acceptable, and severity and Charlson comorbidity index are not critical factors suggesting the disqualification of early laparoscopic cholecystectomy in patients with any grade acute cholecystitis.