Middle-segment preserving pancreatectomy: a literature review and case report.

PURPOSE: Middle segment-preserving pancreatectomy (MSPP) is a relatively new parenchymal-sparing surgery that has been introduced as an alternative to total pancreatectomy (TP) for multicentric benign and borderline pancreatic diseases. To date, only 36 cases have been reported in English. METHODS: We reviewed 22 published articles on MSPP and reported an additional case. RESULTS: Our patient was a 49-year-old Japanese man diagnosed with Zollinger-Elison syndrome (ZES) caused by duodenal and pancreatic gastrinoma associated with multiple endocrine neoplasia syndrome type 1. We avoided TP and chose MSPP as the operative technique due to his relatively young age. The patient developed a grade B postoperative pancreatic fistula (POPF), which improved with conservative treatment. He was discharged without further treatment. To date, no tumor has recurred, and pancreatic function seems to be maintained. According to a literature review, the morbidity rate of MSPP is as high as 54%, mainly due to the high incidence of POPF (32%). In contrast, there was no perioperative mortality, and postoperative pancreatic function was comparable to that after conventional pancreatectomy. CONCLUSIONS: Despite the high incidence of POPF, MSPP appears to be safe, with low perioperative mortality and good postoperative pancreatic sufficiency.

Three-Dimensional Bio-Printed Tubular Tissue Using Dermal Fibroblast Cells as a New Tissue-Engineered Vascular Graft for Venous Replacement.

The current study was a preliminary evaluation of the feasibility and biologic features of three-dimensionally bio-printed tissue-engineered (3D bio-printed) vascular grafts comprising dermal fibroblast spheroids for venous replacement in rats and swine. The scaffold-free tubular tissue was made by the 3D bio-printer with normal human dermal fibroblasts. The tubular tissues were implanted into the infrarenal inferior vena cava of 4 male F344-rnu/rnu athymic nude rats and the short-term patency and histologic features were analyzed. A larger 3D bio-printed swine dermal fibroblast-derived prototype of tubular tissue was implanted into the right jugular vein of a swine and patency was evaluated at 4 weeks. The short-term patency rate was 100%. Immunohistochemistry analysis showed von Willebrand factor positivity on day 2, with more limited positivity observed on the luminal surface on day 5. Although the cross-sectional area of the wall differed significantly between preimplantation and days 2 and 5, suggesting swelling of the tubular tissue wall (both p < 0.01), the luminal diameter of the tubular tissues was not significantly altered during this period. The 3D bio-printed scaffold-free tubular tissues using human dermal or swine fibroblast spheroids may produce better tissue-engineered vascular grafts for venous replacement in rats or swine.

A unique case of a typical pancreatic ductal adenocarcinoma that initially presented with a cystic component but underwent morphological changes.

A 66-year-old man was initially suspected of having a microcystic serous cystic neoplasm based on magnetic resonance imaging findings of a multifocal mass measuring 46 mm in the pancreatic head, with a cystic component showing a high signal on T2-weighted images. The tumor marker levels were within normal limits. However, contrast-enhanced computed tomography revealed thick cyst walls with delayed staining, which was atypical for serous cystic neoplasms; therefore, the patient was followed up closely. Twenty-two months later, the delayed contrast area was enlarged, carbohydrate antigen 19-9 levels were elevated, and 18 F-fluorodeoxyglucose-positron emission tomography revealed increased accumulation, indicating a potentially malignant lesion. Pancreatoduodenectomy was performed and histopathological examination confirmed the diagnosis of normal-type pancreatic carcinoma with predominantly poorly differentiated cells. Based on the pathological findings and a literature review, it is highly likely that this case represents pancreatic ductal adenocarcinoma with a cystic structure from the beginning. While distinguishing pancreatic ductal adenocarcinoma from other pancreatic cystic tumors, such as serous cystic neoplasms, is critical owing to differing treatments and prognoses, caution is warranted as they may exhibit similar imaging features, as observed in our patient.

Laparoscopic minor liver resection for hepatocellular carcinoma.

BACKGROUND: Previous studies have suggested that laparoscopic liver resection for hepatocellular carcinoma is associated with lower postoperative complications compared with open liver resection. METHODS: We conducted a retrospective analysis of 109 hepatocellular carcinoma patients who underwent minor liver resection at a Japanese tertiary care hospital from November 2010 to December 2022. RESULTS: The laparoscopic liver resection group experienced significantly lower median intraoperative blood loss compared with the open liver resection group (P = 0.0001). Furthermore, the laparoscopic liver resection group had a significantly shorter median hospital stay compared with the open liver resection group (P = 0.0002). However, there was no significant difference in median postoperative survival between the laparoscopic liver resection group and the open liver resection group (P = 0.717). CONCLUSIONS: Laparoscopic minor liver resection for hepatocellular carcinoma resulted in reduced blood loss and hospital stay without compromising long-term survival outcomes.

Liver Resection for Hepatocellular Carcinoma With Tumor Thrombus in the Inferior Vena Cava or Right Atrium: A Large-scale Multicenter Survey Conducted in Japan.

OBJECTIVE: To clarify the short and long-term postoperative outcomes and surgical indications for patients accompanied by hepatocellular carcinoma with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA). BACKGROUND: These patients are known to have an extremely poor prognosis; however, the postoperative outcomes have not been fully verified because of the rarity of this disease. METHODS: We contacted 211 specialized centers in Japan and collected data on liver resection for hepatocellular carcinoma with TT in the IVC or RA from centers with experience performing surgery for such patients. The patient characteristics, operative procedures, and surgical outcomes were then analyzed. RESULTS: A total of 119 patients from 23 institutions were enrolled; 49 patients had TT in the IVC below the diaphragm (type I), 42 had TT in the IVC above the diaphragm (type II), and 28 had TT entering the RA (type III). The severity and frequency of postoperative complications did not differ among the 3 groups. There was one surgery-related death in the type III group. The median survival times were 2.47 years in the type I group, 1.77 years in the type II group, and 1.02 years in the type III group. Multivariate analysis identified an indocyanine green retention rate at 15 minutes >15% and ≥3 tumors as prognostic factors affecting survival, whereas the use of cardiopulmonary bypass and ≥3 tumors were risk factors for recurrence. CONCLUSIONS: As the postoperative prognosis of patients with type I or type II disease and of patients with no risk factors is relatively good, surgery should be considered for these patient populations.

Optimal tumor numbers in surgical candidates for multiple hepatocellular carcinomas.

BACKGROUND: According to the American Association for the Study of Liver Diseases guidelines, liver resection is not recommended for multiple hepatocellular carcinomas, although it is performed in Asian countries, including Japan. However, the maximum number, location, and recurrence types of tumors have not been reported in detail. METHODS: This retrospective study analyzed data for 1,170 patients who underwent surgical resection for hepatocellular carcinoma between October 2002 and December 2020 in a Japanese tertiary care hospital. Statistical analysis was performed to compare the surgical short-term and long-term outcomes among patients with >3 tumors and those with ≤3 tumors. RESULTS: This study of patients who underwent liver resection identified 775 who had a single tumor and compared overall survival rates with 477 who had multiple hepatocellular carcinomas: 242 had 2 hepatocellular carcinomas, 79 had 3 hepatocellular carcinomas, and 74 had >3 hepatocellular carcinomas. The median survival times based on the number of tumors were 9.74 years for a single tumor, 6.36 years for 2 tumors, 7.21 years for 3 tumors, 3.31 years for 4 tumors, and 3.48 years for 5 tumors. The median survival time was significantly worse in patients with >3 tumors than in those with 3 tumors (P < .0001). Concerning the type of treatments for recurrence, the patients who underwent surgical treatment had significantly better survival after recurrence than patients who underwent other treatments (8.32 vs 3.19 years; P < .001). CONCLUSION: The overall survival after liver resection was significantly worse for patients with >3 tumors than for those with <3 tumors. However, liver resection can be recommended for patients with 2 or 3 hepatocellular carcinomas because an acceptable median survival (>5 years) can be expected.

Probe electrospray ionization mass spectrometry-based rapid diagnosis of liver tumors.

BACKGROUND AND AIM: Prompt differential diagnosis of liver tumors is clinically important and sometimes difficult. A new diagnostic device that combines probe electrospray ionization-mass spectrometry (PESI-MS) and machine learning may help provide the differential diagnosis of liver tumors. METHODS: We evaluated the diagnostic accuracy of this new PESI-MS device using tissues obtained and stored from previous surgically resected specimens. The following cancer tissues (with collection dates): hepatocellular carcinoma (HCC, 2016-2019), intrahepatic cholangiocellular carcinoma (ICC, 2014-2019), and colorectal liver metastasis (CRLM, 2014-2019) from patients who underwent hepatic resection were considered for use in this study. Non-cancerous liver tissues (NL) taken from CRLM cases were also incorporated into the analysis. Each mass spectrum provided by PESI-MS was tested using support vector machine, a type of machine learning, to evaluate the discriminatory ability of the device. RESULTS: In this study, we used samples from 91 of 139 patients with HCC, all 24 ICC samples, and 103 of 202 CRLM samples; 80 NL from CRLM cases were also used. Each mass spectrum was obtained by PESI-MS in a few minutes and was evaluated by machine learning. The sensitivity, specificity, and diagnostic accuracy of the PESI-MS device for discriminating HCC, ICC, and CRLM from among a mix of all three tumors and from NL were 98.9%, 98.1%, and 98.3%; 87.5%, 93.1%, and 92.6%; and 99.0%, 97.9%, and 98.3%, respectively. CONCLUSION: This study demonstrated that PESI-MS and machine learning could discriminate liver tumors accurately and rapidly.

The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection.

BACKGROUND: We assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection. METHODS: Among 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay. RESULTS: HBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001. CONCLUSION: HBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.

Role of Liver Resection for Hepatocellular Carcinoma with Vascular Invasion: Emerging Evidence from Western Countries.

Patients with advanced hepatocellular carcinoma (HCC) with macrovascular invasion, that is, tumor thrombosis in the portal vein or hepatic vein, are generally considered not eligible for liver resection in Western countries, and only systemic therapy is recommended. However, there is a subgroup of patients who can survive long after surgical treatment despite having a very advanced stage of the disease. Some Asian surgical centers and a few Western surgical centers have been using surgery to treat BCLC stage C HCC as long as it is operable, and those centers have reported acceptable outcomes. In this issue of Liver Cancer, Govalan et al. report on the superiority of surgical resection over other treatments for patients with vascular invasion based on data from the National Cancer Database. This is a first report analyzing a large set of contemporary US cohort data, and its findings may catch the attention of many hepatologists in Western countries who are hesitant about sending eligible patients to surgeons. In this era of advanced systemic therapy using molecular targeted agents and immuno-check point inhibitors, a combination of promising systemic therapy and surgery may be a future path to improve survival for patients with this very advanced disease.

Impact of hepatitis C virus on survival in patients undergoing resection of intrahepatic cholangiocarcinoma: Report of a Japanese nationwide survey.

AIM: We reviewed the data of a nationwide follow-up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass-forming (MF) type, and combined mass-forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC). METHODS: In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV-related ICC (n = 138, 14.4%), hepatitis B virus (HBV)-related ICC (n = 43, 4.5%) and non-virus-related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score-matching to compare outcomes after surgery between HCV-related (n = 102) and non-virus-related ICC cases (n = 102). RESULTS: We successfully matched HCV-related and non-virus-related ICC cases with similar liver function and tumor characteristics. Patients with HCV-related ICC had significantly shorter recurrence-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37-0.88, p = 0.011) than patients with non-virus-related ICC. Cox proportional hazard analysis showed that HCV-related ICC offered a worse prognosis than non-virus-related ICC. CONCLUSIONS: HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC.

Impact of board certification system and adherence to the clinical practice guidelines for liver cancer on post-hepatectomy risk-adjusted mortality rate in Japan: A questionnaire survey of departments registered with the National Clinical Database.

BACKGROUND: It is unclear to what extent a board certification system and implementation of clinical guidelines improves the quality of hepatectomy. METHODS: A web-based questionnaire survey was administered to departments registered with the National Clinical Database (NCD) in Japan between 1 October 2014 and 31 January 2015. Quality indicators (QIs), including affiliations with academic societies, numbers of board-certified doctors affiliated with each institute, and adherence to clinical practice guidelines for hepatocellular carcinoma, were evaluated by calculating risk-adjusted odds ratios (AORs) for 90-day postoperative mortality of patients who had undergone hepatectomy in 2013 and 2014. RESULTS: Of 1255 departments that had registered at least one hepatectomy in NCD, 592 departments, performing 8601 hepatectomies in total, responded to the questionnaire. AORs were significantly lower in departments that were certified as training hospitals by the Japanese Society of Gastroenterological Society, Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), and Japan Society of Hepatology than in non-certified departments. Affiliation of three or more JSHBPS-certified experts or instructors with an institution also contributed to low AORs. None of the QIs regarding implementation of guidelines significantly impacted on the AOR. CONCLUSIONS: Quality indicator measurements may improve quality of post-hepatectomy outcomes in Japan.

Adjuvant chemotherapy can prolong recurrence-free survival but did not influence the type of recurrence or subsequent treatment in patients with colorectal liver metastases.

BACKGROUND: Although liver resection is the only potentially curative treatment for colorectal liver metastases, recurrence is frequent. We previously published the early results of a randomized controlled phase 3 trial showing that adjuvant therapy with uracil-tegafur and leucovorin significantly prolongs recurrence-free survival. This study sought to elucidate the impact of adjuvant chemotherapy on patient survival after an additional follow-up period, building upon the results of our previous study. METHODS: After resection for colorectal liver metastases, patients were randomly assigned in a 1:1 ratio to receive adjuvant uracil-tegafur and leucovorin or surgery alone. Patients assigned to the uracil-tegafur and leucovorin group received 5 cycles of uracil-tegafur and leucovorin within 8 weeks after surgery. RESULTS: Patients were assigned to an adjuvant uracil-tegafur and leucovorin (n = 90) or a surgery alone (n = 90) group; 3 patients were excluded because of protocol violations. After a median follow-up period of 7.36 years (95% confidence interval, 6.93-7.87), 60 (68.2%) patients in the uracil-tegafur and leucovorin group and 61 (68.5%) patients in the surgery alone group developed recurrences. The median recurrence-free survival was 1.45 years (95% confidence interval, 0.96-2.16) in the uracil-tegafur and leucovorin group and 0.70 years (95% confidence interval, 0.44-1.07) in the surgery alone group. The locations and treatments of the first recurrences did not differ between the groups, nor did the overall survival (hazard ratio, 0.86; 95% confidence interval, 0.54-1.38; P = .54). The overall survival was significantly longer in patients who underwent curative repeated resection than in patients who received non-surgical treatment (hazard ratio, 0.25; 95% confidence interval, 0.15-0.40; P < .0001). CONCLUSION: Adjuvant uracil-tegafur and leucovorin significantly prolonged the recurrence-free survival but not the overall survival. The repeated resection was the most important factor influencing overall survival.

Effect of Diameter and Number of Hepatocellular Carcinomas on Survival After Resection, Transarterial Chemoembolization, and Ablation.

INTRODUCTION: Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables. METHODS: The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort. RESULTS: Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%-20% higher compared with patients undergoing TACE for 1-6 HCC lesions <10 cm and were also 10%-20% higher compared with patients undergoing ablation when the HCC diameter was 2-3 cm. For patients undergoing resection and TACE, the model performed well in the external cohort. DISCUSSION: Our novel prognostic model performed well in predicting OS after resection and TACE for HCC and demonstrated that resection may have a survival benefit over TACE and ablation based on the diameter and number of HCCs.

Correlation Between Portal Pressure and Indocyanine Green Retention Rate is Unaffected by the Cause of Cirrhosis: A Prospective Study.

BACKGROUND: Accurate estimation of the hepatic functional reserve before liver resection is important to avoid post-hepatectomy liver failure (PHLF). The aim of the present study was to evaluate the association of indocyanine green retention test with portal pressure by the cause of cirrhosis (non-viral vs. viral) and assessed postoperative outcomes including incidence of PHLF in patients with viral and non-viral cirrhosis. METHODS: The cohort includes 50 consecutive patients with liver cirrhosis scheduled for liver resection for primary liver tumors at the Lausanne University Hospital between 2009 and 2018. RESULTS: There were 31 patients with non-viral liver cirrhosis (Non-virus group) and 19 with viral liver cirrhosis (virus group). The indocyanine green retention rate at 15 min (ICG-R15) (p = 0.276), Hepatic Venous Portal Gradient (HVPG; p = 0.301), and postoperative outcomes did not differ between the non-virus group and viral group. ICG-R15 and HVPG showed a significant linear correlation in all patients (Spearman's rank correlation coefficient, ρ = 0.599, p < 0.001), the non-virus group (ρ = 0.555, p = 0.026), and the virus group (ρ = 0.534, p = 0.007). A receiver operating characteristic curve analysis showed that ICG-R15 was a predictor for presence of portal hypertension (PH; HVPG ≥ 12 mmHg) (area under the curve [AUC] = 0.780). The cut-off value of ICG-R15 for predicting the presence of PH was 16.0% with 72.3% of sensitivity and 79.0% of specificity. CONCLUSIONS: The ICG-R15 level was associated with portal pressure in both patients with non-virus cirrhosis and patients with virus cirrhosis and predicts the incidence of PH with relatively good discriminatory ability. CLINICAL TRIAL NUMBER: https://clinicalTrials.gov(ID:NCT00827723) LOCAL ETHICS COMMITTEE NUMBER: CER-VD 251.08.

A new rapid diagnostic system with ambient mass spectrometry and machine learning for colorectal liver metastasis.

BACKGROUND: Probe electrospray ionization-mass spectrometry (PESI-MS) can rapidly visualize mass spectra of small, surgically obtained tissue samples, and is a promising novel diagnostic tool when combined with machine learning which discriminates malignant spectrum patterns from others. The present study was performed to evaluate the utility of this device for rapid diagnosis of colorectal liver metastasis (CRLM). METHODS: A prospectively planned study using retrospectively obtained tissues was performed. In total, 103 CRLM samples and 80 non-cancer liver tissues cut from surgically extracted specimens were analyzed using PESI-MS. Mass spectra obtained by PESI-MS were classified into cancer or non-cancer groups by using logistic regression, a kind of machine learning. Next, to identify the exact molecules responsible for the difference between CRLM and non-cancerous tissues, we performed liquid chromatography-electrospray ionization-MS (LC-ESI-MS), which visualizes sample molecular composition in more detail. RESULTS: This diagnostic system distinguished CRLM from non-cancer liver parenchyma with an accuracy rate of 99.5%. The area under the receiver operating characteristic curve reached 0.9999. LC-ESI-MS analysis showed higher ion intensities of phosphatidylcholine and phosphatidylethanolamine in CRLM than in non-cancer liver parenchyma (P < 0.01, respectively). The proportion of phospholipids categorized as monounsaturated fatty acids was higher in CRLM (37.2%) than in non-cancer liver parenchyma (10.7%; P < 0.01). CONCLUSION: The combination of PESI-MS and machine learning distinguished CRLM from non-cancer tissue with high accuracy. Phospholipids categorized as monounsaturated fatty acids contributed to the difference between CRLM and normal parenchyma and might also be a useful diagnostic biomarker and therapeutic target for CRLM.

Impact of Abdominal Incision Type on Postoperative Pain and Quality of Life Following Hepatectomy.

BACKGROUND: The aim of this prospective study was to analyze the impact of abdominal incision type on postoperative pain and quality of life (QOL) in hepatectomy. METHODS: In patients undergoing hepatectomy by open, hybrid, or pure laparoscopic approaches, we classified abdominal incisions as: pure laparoscopic (LAP), midline (MID), J-shaped (J), and J-shaped incision plus thoracotomy (TRC). Postoperative pain was measured on postoperative day (POD) 3, 7, 30, and 90 using a visual analog scale (VAS). QOL was evaluated using the short-form-36 questionnaire preoperatively and on POD 30 and 90. RESULTS: We categorized 165 patients into LAP (n = 9, 5%), MID (n = 21, 13%), J (n = 95, 58%), and TRC (n = 40, 24%) groups. Median VAS scores on PODs 3/7/30/90 were: LAP, 27.5/7.5/10/10; MID, 30/10/15/5; J, 50/27.5/20/10, and TRC, 50/30/30/19. The J and TRC groups had significantly higher VAS scores vs. MID on PODs 3 and 7; the LAP and MID groups did not differ significantly. No significant positive correlations were observed between incision length and postoperative VAS, when we stratified patients into two groups according to the presence or absence of a transverse incision. Physical QOL summary scores did not return to preoperative levels even on POD 90, in patients with an additional transverse incision. Mental QOL summary scores worsened with postoperative complications rather than with abdominal incision type. CONCLUSIONS: Transverse incisions, rather than incision length, led to worse midline incision pain and poorer QOL recovery post-hepatectomy. A hybrid approach may be a considerable option when pure laparoscopic hepatectomy is technically difficult. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (registration number: UMIN000017467; http://www.umin.ac.jp/ctr/index.htm ).