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The effect of bevacizumab plus mFOLFOX6 on downsizing of liver metastases for curative resection has not been well assessed for patients with advanced colorectal liver metastases (CRLMs). This multicenter phase II trial aimed to examine the efficacy and safety of bevacizumab plus mFOLFOX6 for advanced CRLMs harboring mutant-type KRAS.Patients with advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included. Surgical indication was evaluated every 4 cycles of bevacizumab plus mFOLFOX6. Liver resection was planned if the CRLMs were resectable. The primary endpoint was R0 resection rate. The secondary endpoints included overall survival (OS), recurrence-free survival, progression-free survival, and safety.Between 2013 and 2017, 29 patients from six centers were registered. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). No mortality occurred. During the median follow-up of 30.7 months, the 3-year OS rate for all the patients was 64.4% with the median survival of 49.1 months.For advanced CRLMs harboring mutant-type KRAS, bevacizumab plus mFOLFOX6 achieved a high R0 resection rate, leading to favorable survival.

The aim of this study was to assess the relevance of highlighting T1a invasive intraductal papillary mucinous carcinoma as a separate subcategory and to compare the tumor biology between invasive intraductal papillary mucinous carcinoma and pancreatic ductal adenocarcinoma.A total of 144 and 328 consecutive patients with intraductal papillary mucinous neoplasms and pancreatic ductal adenocarcinoma, respectively, were analyzed.Patients with T1a invasive intraductal papillary mucinous carcinoma comprised 25% (11/44) of the overall subject population with invasive intraductal papillary mucinous carcinoma with 5-year disease-specific survival rate being 100%. None of the patients with pancreatic ductal adenocarcinoma were classified as having T1a disease. When patients with invasive intraductal papillary mucinous carcinoma and pancreatic ductal adenocarcinoma were compared after excluding patients with T1a invasive intraductal papillary mucinous carcinoma, the 5-year disease-specific survival rates were 63% vs 40% in node-negative status (P = .018); and they were 20% vs 13% in node-positive status (P = .385). Subsequent analyses revealed that this survival superiority was limited to patients without evidence of lymphatic invasion.T1a invasive intraductal papillary mucinous carcinoma is a clinical entity specifically observed in patients with intraductal papillary mucinous carcinoma, but not in patients with pancreatic ductal adenocarcinoma, and is associated with excellent postoperative survival outcomes. In the survival comparison after exclusion of patients with T1a tumors, when the analysis was limited to patients without lymphatic invasion or lymph node metastasis, the disease-specific survival rate remained higher in patients with invasive intraductal papillary mucinous carcinoma compared with those with pancreatic ductal adenocarcinoma, and this difference was considered as being attributable to the intrinsic indolent biological behavior of invasive intraductal papillary mucinous carcinoma. However, this survival advantage was lost once lymphatic invasion occurred.

Although modified Blumgart anastomosis (MBA) in robotic pancreaticoduodenectomy has been accepted as a simple and safe procedure that provides non-inferior surgical outcomes compared to open MBA, the details of the standardization of robotic MBAs have never been established. In this report, we detail the technical tips to reproduce MBA in the robotic environment.From January to December in 2021, 16 patients underwent our novel robotic MBA technique, which included clipless Blumgart suture and duct-to-mucosa anastomosis. To simplify the manipulation of sutures in robotic environment, short double-armed sutures in 15 cm length were created and used for Blumgart suture. Duct-to-mucosa anastomosis were done by 5-0 monofilament of 6 cm length. These tips enabled clipless anastomosis and minimized the burden of the patient-side assistant. Surgical and short-term outcomes were compared between patients with robotic MBA (Robo group) and those who underwent open MBA during 2021 (32 patients, Open group).The median operation time was significantly longer in the Robo group than in the Open group (551 vs. 485.5 min, P = 0.0027). Estimated blood loss was significantly lower in the Robo group than in the open group (95 vs. 355 mL, P 0.0002). The median duration of clipless MBA in the Robo group was 56 (46-68) min. The incidence of POPF (grade B or C) was not significantly different among the groups (19% vs. 22%, P = 0.71). The mean length of hospital stay was significantly shorter in the Robo group than in the Open group (18 vs. 24 days, P = 0.019).Clipless MBA in a robotic environment was safely performed with acceptable short-term outcomes and can be proposed as a standard technique for robotic pancreatojejunostomy.

Immunotherapy has become the standard-of-care treatment for hepatocellular carcinoma (HCC), but its efficacy remains limited. To identify immunotherapy-susceptible HCC, we profiled the molecular abnormalities and tumor immune microenvironment (TIME) of rapidly increasing nonviral HCC.We performed RNA-seq of tumor tissues in 113 patients with nonviral HCC and cancer genome sequencing of 69 genes with recurrent genetic alterations reported in HCC. Unsupervised hierarchical clustering classified nonviral HCCs into three molecular classes (Class I, II, III), which stratified patient prognosis. Class I, with the poorest prognosis, was associated with TP53 mutations, whereas class III, with the best prognosis, was associated with cadherin-associated protein beta 1 (CTNNB1) mutations. Thirty-eight percent of nonviral HCC was defined as an immune class characterized by a high frequency of intratumoral steatosis and a low frequency of CTNNB1 mutations. Steatotic HCC, which accounts for 23% of nonviral HCC cases, presented an immune-enriched but immune-exhausted TIME characterized by T cell exhaustion, M2 macrophage and cancer-associated fibroblast (CAF) infiltration, high PD-L1 expression, and TGF-β signaling activation. Spatial transcriptome analysis suggested that M2 macrophages and CAFs may be in close proximity to exhausted CD8+ T cells in steatotic HCC. An in vitro study showed that palmitic acid-induced lipid accumulation in HCC cells upregulated PD-L1 expression and promoted immunosuppressive phenotypes of cocultured macrophages and fibroblasts. Patients with steatotic HCC, confirmed by chemical-shift MR imaging, had significantly longer PFS with combined immunotherapy using anti-PD-L1 and anti-VEGF antibodies.Multiomics stratified nonviral HCCs according to prognosis or TIME. We identified the link between intratumoral steatosis and immune-exhausted immunotherapy-susceptible TIME.

To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM.Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS).There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69-2.01], P = 0.539: OS, 1.03 [0.46-2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS.There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).

For pancreatic ductal adenocarcinoma (PDAC) surgery, extended dissection of the nerve plexus (pl) around the superior mesenteric artery (SMA) or celiac artery (CA) is sometimes necessary. This consequently results in postoperative refractory diarrhea. This study aimed to evaluate the clinical impact of extended nerve plexus dissection around major arteries on postoperative diarrhea.Patients who underwent pancreatoduodenectomy (PD) for PDAC between January 2013 and December 2016 were included. The frequency of diarrhea (defined as a condition requiring opioid antidiarrheal drug for at least 6 months after surgery) and its short- and long-term outcomes were reviewed.Of 200 consecutive patients who underwent PD, 78 (39.0%) developed postoperative refractory diarrhea (diarrhea group), and 73 of them (93.6%) underwent hemi-circumferential or more nerve dissection for SMA or CA; both plSMA and plCA dissection were associated with diarrhea. Borderline resectable artery (BR-A) PDAC was included more in the diarrhea group (32.0% vs. 13.1%, P = 0.001); however, the local recurrence rate in the diarrhea group was significantly lower than that in the non-diarrhea group (14.1% vs. 26.2%, P = 0.036). The completion of adjuvant chemotherapy and overall survival were comparable between the two groups. The pre-albumin level improved in 2 years, and 61.3% of patients with diarrhea could stop opioid antidiarrheal drugs within 3 years of surgery.Although the frequency of diarrhea increased following nerve plexus dissection around arteries, diarrhea was controllable and resulted in a reduced local recurrence rate. Aggressive dissection of the nerve plexus may be justified for local disease control in BR-A PDAC.

Hepatic resection combined with perioperative chemotherapy is the standard of care for patients with multiple colorectal liver metastases (CLMs). However, the optimal surgical strategy for treating advanced CLMs remains unclear. The role of the two-stage hepatectomy (TSH) strategy in the management of multiple CLMs remains challenging. This study aimed to compare the outcomes of one-step hepatectomy (OSH)-treated and TSH-treated patients with multiple CLMs.This single-institution study included 742 consecutive patients who underwent initial liver resection for histologically confirmed CLMs. The study enrolled patients with 10 or more tumors (n = 106). Clinicopathologic characteristics and long-term outcomes were compared between patients who underwent OSH and those who underwent TSH for 10 or more CLMs.The study planned OSH for 67 patients (63%) and TSH for 39 patients (37%). One of the OSH-planned patients and two of the TSH-planned patients underwent a trial laparotomy because of non-curative factors. Five patients (13%) did not progress to the second stage of TSH. In the entire cohort, the cumulative 3-year overall survival rate was 58.4% for the patients who had 10 or more CLMs treated with OSH compared with 61.1% for the patients treated with TSH (P = 0.746). In the curative resection cohort, the cumulative 1-year recurrence-free survival rate was 18.2% for the patients treated with OSH and 17.9% for the patients treated with TSH (P = 0.640).Hepatectomy with perioperative chemotherapy for advanced CLMs with 10 or more tumors is feasible and effective. To prolong survival, TSH is a promising option when curative resection with OSH is impossible.

Background RAS mutation status is considered a powerful prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (CLM). However, whether its prognostic power is robust regardless of administration of preoperative chemotherapy or tumor burden remains unclear. Methods Consecutive patients who underwent initial hepatectomy for CLM from April 2010 through March 2017 in two hospitals were included. The prognostic value of KRAS was compared based on whether patients received preoperative chemotherapy and their tumor burden score (TBS). Results We included 409 patients (median follow-up 38 months). In the preoperative chemotherapy group, patients with mutant KRAS (mt-KRAS) CLM had poorer overall survival (OS) than those with wild KRAS (wt-KRAS; 5-year OS: 37.7% vs 53.8%, p = 0.024), although their OS was not different from patients undergoing upfront surgery. Similarly, patients with mt-KRAS had poorer OS than those with wt-KRAS in TBS of 3-9 (5-year OS: 33.1% vs 63.2%, p = 0.001), although their OS was not different from patients with TBS 3 or ≥ 9. Conclusions In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.

The most appropriate venous reconstruction method remains debatable when a long section of portal vein (PV) and/or superior mesenteric vein (SMV) must be resected in patients undergoing a pancreaticoduodenectomy (PD). The aim of the present study was to describe the technical details of the parachute technique, a modified end-to-end anastomotic maneuver that can be used in the above-mentioned circumstances, and to investigate its safety and feasibility. Patients who underwent venous reconstruction using the parachute technique after receiving a PD with PV resection for pancreatic cancer between January 2014 and March 2019 were retrospectively reviewed. For the parachute technique, the posterior wall was sutured in a continuous fashion while the stitches were left untightened. The stitches were then tightened from both sides after the running suture of the posterior wall had been completed, thereby dispersing the tension applied to the stitched venous wall when the venous ends were brought together and solving any problems that would otherwise have been caused by over-tension. The postoperative outcomes and PV patency were then investigated. Fifteen patients were identified. The median length of the resected PV/SMV measured in vivo was 5 cm (range, 3–6 cm). The splenic vein was resected in all the patients and was reconstructed in 13 patients (87%). The overall postoperative complication rate (≥ Clavien-Dindo grade I) was 60%, while a major complication (≥ Clavien-Dindo grade IIIa) occurred in 1 patient (7%). No postoperative deaths occurred in this series. The PV patency at 1 year was 87%. The parachute technique is both safe and feasible and is a simple venous reconstruction procedure suitable for use in cases undergoing PD when the distance between the resected PV and SMV is relatively long.

The oncologic advantage of anatomic resection (AR) for primary hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the clinical advantages of AR for primary HCC by using propensity score-matching and by assessing treatment strategies for recurrence after surgery. The study reviewed data of patients who underwent AR or non-anatomic resection (NAR) for solitary HCC (≤ 5 cm) in two institutions between 2004 and 2017. Surgical outcomes were compared between the two groups in a propensity score-adjusted cohort. The time-to-interventional failure (TIF), defined as the elapsed time from resection to unresectable/unablatable recurrence, also was evaluated. The inclusion criteria were met by 250 patients: 77 patients (31%) with AR and 173 patients (69%) with NAR. In the propensity score-matched populations (AR, 67; NAR, 67), the 5-year recurrence-free survival (RFS) for AR was better than for NAR (62% vs 35%; P = 0.005). No differences, however, were found in the 5-year overall survival between the two groups (72% vs 78%; P = 0.666). The 5-year TIF rates for the NAR group (60%) also were similar to those for the AR group (66%) (P = 0.413). In the cohort of 67 patients, curative repeat resection or ablation therapy was performed more frequently for the NAR patients (42%) than for the AR patients (10%) (P

Curative resection is the only potential treatment for cure in patients with perihilar biliary tract cancer (PBTC). However, post hepatectomy liver failure (PHLF) due to insufficient future liver remnant volume (FRLV) remains a lingering risk even after portal vein embolization (PVE). This study aimed to investigate the feasibility and efficacy of a sequential treatment strategy consisting of PVE followed by preoperative chemotherapy before surgery.Between April 2019 and December 2021, 15 patients with locally advanced PBTC (LA-PBTC) underwent sequential treatment consisting of PVE followed by preoperative chemotherapy. The feasibility and efficacy, including resection rate, changes of FRLV, and chemotherapeutic effect, were investigated retrospectively.Thirteen of 15 patients (86.6%) underwent curative resection. The median duration time between PVE and surgery was 144 days. FRLV/TLV ratio was 31.3% at prePVE, 38.4%, at two weeks after PVE, and 45.7% before surgery, respectively. There was significant increase in FRLV/TLV ratio two weeks after PVE. Additional increase in FRLV/TLV ratio was significantly achieved before surgery. PHLF occurred in 5 patients (38.4%). Pathological complete response was found in 2 of 13 patients (15.3%).Sequential PVE and systemic chemotherapy contribute to the sufficient hypertrophy of FRLV without compromising resectability in patients with LA-PBTC.

The prediction of conversion surgery in patients with technically unresectable colorectal liver metastases has not been generalized or well-established. We developed a predictive model for conversion surgery and assessed the long-term outcomes of patients with technically unresectable colorectal liver metastases.In this single-center, retrospective study, we analyzed the perioperative parameters and outcomes of 892 consecutive patients (2014-2021). Conversion surgery was indicated when the chemotherapy response allowed the complete resection of colorectal liver metastases with negative margins and adequate remnant liver volume.Of the 892 patients, 122 had technically unresectable colorectal liver metastases; 61 underwent conversion surgery (conversion surgery group) and 61 did not (nonconversion surgery group). The median overall survival was significantly higher in the conversion surgery group than in the nonconversion surgery group (5.6 vs 1.8 years, P.001). After univariate and multivariate analyses, the predictive model for conversion surgery was constructed using 4 predictive factors: Rat sarcoma viral oncogene homolog status (mutant, +2 points), tumor number (≥15, +1), hepatic vein contact (≥2 hepatic veins, +1), and the presence of preservable sections (absence of preservable sections, +2). The area under the curve for conversion surgery was 0.889. Patients were graded according to the scores (A [0-2], B [3-4], and C [5-6]), and the conversion rates were 91.5% (A), 32.6% (B), and 10.3% (C) (P.001). Grade A patients (median survival time, 5.7 years) had significantly better overall survival than grade B and C patients (median survival time, 2.2 and 1.6 years, respectively; P.001).Patients who underwent conversion surgery for technically unresectable colorectal liver metastases had better prognoses, and our novel predictive model was useful in predicting conversion surgery and prognosis.

A modified Fong clinical score (m-Fong CS) that includes the RAS mutation status has recently been proposed and offered an improved survival stratification of patients who undergo surgery and systemic chemotherapy for colorectal liver metastases (CLM). The aim of this study is to assess whether a CS that includes RAS status is influenced by whether patients receive perioperative chemotherapy. We created a new CS using multivariate analysis of data of patients who underwent hepatectomy for CLM for the first time between 2010 and 2016 at a single hospital (n = 341, 79% received perioperative chemotherapy). The resulting CS and m-Fong CS were then validated in the patient cohort at three other hospitals (n = 309). Furthermore, the applicability of the two CS in the total cohort (n = 650) was tested according to whether the patients received perioperative chemotherapy. The new CS comprised mutant RAS status, ≥4 CLMs, and a CA19-9 level ≥100 U/mL (1 point per factor). Both the new CS and m-Fong CS failed to stratify the survival of the 309 patients in the validation cohort, including those who did not receive perioperative chemotherapy (29%). Both of the CS accurately stratified the survival of patients who underwent perioperative chemotherapy but not of those who underwent surgery alone. A CS that includes the RAS mutation status can stratify the survival of patients who undergo hepatectomy combined with perioperative chemotherapy, but it has limited value for patients who undergo surgery alone.

Although endoscopic naso-biliary drainage (ENBD) is a popular preoperative biliary drainage (PBD) method for patients with perihilar biliary malignancy (PHBM), patient discomfort caused by the nasal tube remains a problem. This study aimed to analyze the safety and efficacy of PBD with the placement of a plastic stent above the papilla [inside-stent (IS)] as a bridging therapy. The outcomes of 78 patients with potentially resectable PHBM, of whom 29 underwent IS placement and 49 underwent ENBD were evaluated. The stent-associated complication rates were not different between the two groups (7% in the IS group and 10% in the ENBD group, P = 0.621). Catheter dislocation occurred less frequently (0% vs. 22%, P = 0.016), and the median time to recurrent biliary obstruction was longer (not reached vs. 32 days, P = 0.039) in the IS group than in the ENBD group. Among the patients who underwent resection, their postoperative severe complication rates were not substantially different (26% vs. 25%, P = 0.923). IS placement is a possible alternative to ENBD as a bridge to a definitive operation for patients with resectable PHBM and a prospective trial to prove its feasibility and safety is therefore warranted.

Background Although the Couinaud classification of liver segments has been challenged by several studies, whether the cranio-caudal boundaries can be delineated in the right liver has not yet been assessed. This study scrutinized the third-order branching pattern of the portal vein in the right liver with attention to the validity of cranio-caudal segmentation. Methods Three-dimensional reconstruction of the portal vein and hepatic vein, using non-contrast-enhanced magnetic resonance imaging was performed in 50 healthy participants. Results In the right paramedian sector, the portal vein ramified into 2 thick P8s (P8vent and P8dor) in all the participants. Additional thick P8s that ran laterally and/or medially (P8lat and/or P8med) were observed in 18 (32%) participants. In contrast, multiple thin P5s, ranging in number from 2 to 6 (median, 4), branched from the right paramedian trunk, the right portal trunk, and/or even from P8s. In the right lateral sector, an arch-like type in which multiple P6s ramified from a single thick P7 was observed in 26 (52%) participants. A bifurcation type composed of a single P7 and a single P6 was observed in 23 (46%) participants, and a trifurcation type was observed in 1 participant. Conclusion No clear cranio-caudal intersegmental plane could be delineated in the right liver in most of the participants. The resection of a whole Couinaud segment in the right liver should not be regarded as a systematic, anatomic resection from an oncologic viewpoint. In contrast, detailed information on the third-order portal vein ramification pattern is likely to be helpful when performing smaller anatomic resections.

Summary Background Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images. Methods We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score. Findings Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71–0·76), whereas that of the fundus model was 0·68 (0·65–0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91–0·94; slit-lamp) and 0·84 (0·81–0·86; fundus) for liver cancer, 0·90 (0·88–0·91; slit-lamp) and 0·83 (0·81–0·86; fundus) for liver cirrhosis, and ranged 0·58–0·69 (0·55–0·71; slit-lamp) and 0·62–0·70 (0·58–0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification. Interpretation Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool. Funding Science and Technology Planning Projects of Guangdong Province; National Key RD Guangzhou Key Laboratory Project; National Natural Science Foundation of China.

Background Previous studies on borderline resectable (BR) pancreatic cancer (PC) included patients with heterogenous preoperative states; however, the definition of resectability for PC has evolved. We aimed to investigate the prognostic factors for PC other than anatomical resectability in those who underwent upfront resection and discuss the optimal treatment strategy for PC. Methods We retrospectively examined 431 patients who underwent upfront surgery with curative intent between 2007 and 2014. The association between clinical characteristics and survival outcomes was assessed by stratifying patients according to risk factors. The patients were categorized into four groups based on anatomical (resectable [R]/BR) and biological features (CA19-9 ≤500/>500 U/mL): anatomical R with CA19-9 ≤500 U/mL (favorable-R); anatomical BR with CA19-9 ≤500 U/mL (favorable-BR); anatomical R with CA19-9 >500 U/mL (risky-R); and anatomical BR with CA19-9 >500 U/mL (risky-BR). Results Overall, 320 and 111 patients had anatomical R- and BR-PC, respectively. A modified Glasgow prognostic score = 2 (hazard ratio [HR]: 1.73), NLR>5 (hazard ratio [HR]: 1.54), CA19-9 >500 U/mL (HR: 1.86), and anatomical BR (HR: 1.38) were independent prognostic factors for overall survival. The risky-R group had likely worse prognosis (16 months vs. 19 months, P = 0.0605) and a significantly higher early recurrence rate (36% vs 18%, P = 0.0231) than the favorable-BR group. Conclusions It is essential to stratify and distinguish PC patients at a high risk of worse prognosis. Risky-R was an unfavorable prognostic factor and should thus be considered in the decision-making for treatment with neoadjuvant chemotherapy, in addition to anatomical BR-PC.

BACKGROUND Among grade B/C postoperative pancreatic fistula (POPF), the clinical burden of patients treated with persistent drainage alone was reported to be less. As the clinical difference might depend on drain management, we evaluated their clinical burden under conservative drain management. METHODS We included 292 patients who underwent pancreaticoduodenectomy or distal pancreatectomy between 2013 and 2015. Patients with grade B POPF were categorized into those receiving persistent drainage alone (B-drain) and those receiving other treatments (B-other). The clinical burden of these groups and patients with biochemical leakage (BL) was compared. RESULTS BL, grade B POPF, and grade C POPF occurred in 42 (14%), 93 (32%), and 4 (1.4%) patients, respectively. The B-drain group comprised 61% of grade B POPF. The overall major morbidity (Clavien-Dindo grade ≥ 3) in the B-drain group was significantly lower than in the B-other group (18% vs 50%, P = .001) but was comparable to that of the BL group (19%, P = .848). The POPF-related major morbidity in the B-drain and B-other group were 0% and 25%, respectively (P

Background/purpose We evaluated efficacy of neoadjuvant therapy with gemcitabine and nab-paclitaxel (GNP-NAT) in borderline resectable pancreatic cancer (BR-PC) patients compared to conventional upfront surgery (UPS). Methods This single-center retrospective study assessed 151 consecutive patients: 96 diagnosed in 2008-2014 underwent UPS (UPS group) and 55 diagnosed in 2015-2017 underwent GNP-NAT (GN group). Patient background, surgical, pathological, and survival outcomes were compared between groups. Results Age, sex, and pretreatment carbohydrate antigen 19-9 were similar between groups. After four courses of NAT-GNP, 46 GN patients (84%) underwent surgery while all UPS patients underwent surgery. Only three GN patients (5%) underwent non-therapeutic procedures, compared to 23 (24%) in the UPS group (P = .004). In the whole cohort, R0-resection was achieved in 40 GN patients (73%) vs 46 UPS patients (48%; P = .004) and the 3-year overall survival was significantly higher in the GN group (median survival time, 31.9 vs 18.1 months, P = .014). In the resection cohort, the R0-resection rate was 93% (GN) vs 63% (UPS; P = .0007). There was no 90-day mortalities in either group. Conclusions Intention-to-treat-based analysis indicated considerable benefits of GNP-NAT in BR-PCs for long-term survival, contributing to improved tumor suppression and patient selection.

Radical antegrade modular pancreatosplenectomy (RAMPS) was developed to enhance curability in patients with left-sided pancreatic cancer. However, no evidence is available regarding the prognostic superiority of RAMPS compared with conventional distal pancreatectomy (cDP). Here, we aimed to assess the oncological benefit of RAMPS by comparing surgical outcomes between patients who underwent cDP and RAMPS with propensity score (PS) adjustment.Clinical data of 174 patients undergoing cDP and RAMPS between 2009 and 2016 at two high-volume centers were analyzed with PS matching. Recurrence-free survival (RFS), overall survival (OS), and local recurrence rates were compared between patients who underwent cDP and RAMPS.The cDP and RAMPS groups were successfully matched with baseline characteristics. No differences were found in the 3-year RFS and OS rates between the two groups (3-year RFS: cDP 46% vs RAMPS 40%, p = 0.451, 3-year OS: cDP 57% vs RAMPS 53%, p = 0.692). However, the 3-year local recurrence rate was lower in the RAMPS (10%) than that in the cDP group (34%) (hazard ratio 0.275, 95% confidence interval 0.090-0.842, p = 0.02).RAMPS is oncologically superior to conventional procedure in achieving local control of the disease in patients with left-sided pancreatic cancer.

Background Pancreaticoduodenectomy after esophageal resection is technically difficult, because blood flow of the gastric conduit should be preserved. Celiac axis stenosis (CAS) is also a problem for pancreaticoduodenectomy, because arterial blood supply for the liver comes mainly through the collateral route from the superior mesenteric artery (SMA) via the gastroduodenal artery (GDA). Herein, we report the case of a patient with pancreatic head cancer who underwent a pancreaticoduodenectomy after esophagectomy with concomitant CAS. Case presentation A 76-year-old man with pancreatic head cancer was referred to our department. He had a history of esophagectomy with retrosternal gastric conduit reconstruction for esophageal cancer. Computed tomography showed severe CAS and a dilated collateral route between the SMA and the splenic artery (SPA). We prepared several surgical options depending on the intraoperative findings, and performed radical pancreaticoduodenectomy with concomitant resection of the distal gastric conduit. The right gastroepiploic artery (RGEA) of the remnant gastric conduit was fed from the left middle colic artery (MCA) with microvascular anastomosis. Despite CAS, when the GDA was dissected and clamped, good blood flow was confirmed, and the proper hepatic artery did not require reconstruction. The patient was discharged on postoperative day 90. Conclusions We successfully performed radical pancreaticoduodenectomy after esophagectomy with concomitant CAS, having prepared multiple surgical options depending upon the intraoperative findings.

Introduction The efficacy of laparoscopic simultaneous resection of primary colorectal cancer and synchronous colorectal liver metastases (SCRLM) remains unclear. Methods We retrospectively evaluated data from 258 patients who had undergone simultaneous curative resection of the primary tumor and SCRLM from 2006 to 2017. We compared surgical outcomes between open, hybrid (laparoscopic colorectal resection and open hepatectomy), and pure laparoscopic approaches. Surgical outcomes were also evaluated between the open hepatectomy (OH) group (ie, open/hybrid surgery) and the laparoscopic hepatectomy (LH) group (ie, pure laparoscopic surgery) in 141 patients later in the study period (2013-2017), when the clinical indications for laparoscopic hepatectomy were restricted to simple wedge resection and/or left lateral sectionectomy in our center. Results The pure laparoscopic approach was associated with significantly less intraoperative blood loss and a significantly shorter postoperative hospital stay than the open and hybrid approaches. Late in the study period, operative outcomes in the LH group (n = 37) were more favorable than for the OH group (n = 104) in terms of intraoperative blood loss and postoperative hospital stay. In patients with rectal cancer, however, earlier postoperative recovery in the LH group did not differ significantly from the OH group. Conclusion Laparoscopic simultaneous resection of SCRLM with the primary tumor by simple hepatectomy is safe and may enhance patients' postoperative recovery, especially in patients with colon cancer.

Aim Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Because liver fibrosis is associated with the long-term prognosis of patients with NAFLD, there is an urgent need for non-invasive markers of liver fibrosis. Sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is an immunomodulatory molecule expressed on various immune cells, including macrophages, which plays a key role in liver inflammation and fibrosis in NAFLD. We aimed to determine whether serum levels of soluble Siglec-7 (sSiglec-7) could have utility at a marker of fibrosis in this patient population. Methods We examined serum samples from 93 NAFLD patients and 19 healthy donors for macrophage-associated protein, including sSiglec-7, soluble CD163, and YKL-40, and examined their correlation with liver fibrosis scores, tissue elastography, and histological findings. Independent factors associated with advanced fibrosis were analyzed using a logistic regression model and a decision tree. To clarify the source of sSiglec-7, we examined its expression in liver tissue-derived macrophages and cultured monocyte-derived macrophages. Results Serum sSiglec-7 levels were significantly higher in NAFLD patients compared with healthy donors, and correlated positively with sCD163 and YKL-40 levels. Serum sSiglec-7 was an independent diagnostic marker with high specificity (96.3%) for advanced fibrosis (F3 and F4) in NAFLD patients. Siglec-7 was mainly expressed on CCR2+ macrophages in the liver, and sSiglec-7 production by monocyte-derived macrophages in vitro was increased after stimulation by pro-inflammatory factors. Conclusions Elevated serum sSiglec-7 could serve as an independent marker with high specificity for advanced liver fibrosis in patients with NAFLD.

Background Pancreatoduodenectomy (PD) with portal vein resection (PVR) is a standard operation for pancreatic ductal adenocarcinoma (PDAC) with portal vein (PV) invasion, but positive margin rates remain high. It was hypothesized that regional pancreatoduodenectomy (RPD), in which soft tissue around the PV is resected en bloc, could enhance oncological clearance and survival. Methods This retrospective study included consecutive patients who underwent PD with PVR between January 2005 and December 2016 in a single high‐volume centre. In standard PD (SPD) with PVR, the PV was skeletonized and the surrounding soft tissue dissected. In RPD, the retropancreatic segment of the PV was resected en bloc with its surrounding soft tissue. The extent of lymphadenectomy was similar between the procedures. Results A total of 268 patients were included (177 SPD, 91 RPD). Tumours were more often resectable in patients undergoing SPD (60·5 per cent versus 38 per cent in those having RPD; P = 0·014), and consequently they received neoadjuvant therapy less often (7·9 versus 25 per cent respectively; P, A regional pancreatoduodenectomy (RPD) procedure was employed to enhance oncological clearance around the mesenteric vein in patients with locally advanced pancreatic cancer. This provided better local control with longer overall survival than a standard pancreatoduodenectomy procedure. Regional pancreatectomy associated with increased R0‐rate and survival

Pancreatoduodenectomy is the standard procedure for duodenal carcinoma of the third or fourth portion. As an alternative option, we developed a novel segmental resection (SR) with partial mesopancreatic and mesojejunal excision (pMME) that enhances radicality. In this report, the surgical technique with video and outcomes are described.We performed SR with pMME on seven consecutive patients with third or fourth duodenal carcinoma between 2009 and 2021. We divided the procedure into four sections, including (1) wide Kocher's maneuver, (2) supracolic anterior artery-first approach, (3) dissection of the mesopancreas and mesojejunum, and (4) devascularization of the uncinate process and dissection of duodenum.Median operative time was 348 min (range, 222-391 min), and median blood loss was 100 mL (range, 30-580 mL). Major complications of Clavien-Dindo classification grade 3a or more occurred in one patient. All patients achieved R0 resections with 10 mm or more proximal margin. Six cases (85%) were alive without recurrence.We developed a radical and safe procedure of SR with pMME as an alternative and less invasive approach for duodenal carcinoma of the third or fourth portion.

The short-term outcomes after hepatic vein reconstruction (HVR) were evaluated in 41 patients. HVR can be performed safely using autologous vein graft. HVR can increase the functional remnant liver volume, facilitating parenchyma-sparing one-step hepatectomy as well as expanding resectability even in patients with all major hepatic veins involved.

As complete prevention of postoperative pancreatic fistula (POPF) after pancreatic surgery remains difficult, many risk factors for clinically relevant POPF (CR-POPF) have been reported. However, their clinical impact could be limited because all previous reports included patients without biochemical leakage (BL) that rarely developed to CR-POPF. Therefore, a new strategy for identifying high-risk patients who develop delayed complications from patients with confirmed BL and for implementing interventions for such patients in the early postoperative period is required. This study aimed to examine the role of fistulography in predicting CR-POPF from confirmed BL. Consecutive patients diagnosed with BL on postoperative day 3 after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) from January 2013 to June 2015 in our institution were included. Fistulography was performed 1 week after the operation, and the associations between findings on fistulography and delayed complications associated with POPF were evaluated. Eighty-four (37%) of 227 patients who underwent PD and 45 (48%) of 94 patients who underwent DP were included and divided to two groups according to fistulographic findings (simple type, n = 107, 83%; cavity type, n = 22, 17%). The latter finding was associated with a greater morbidity rate (Clavien–Dindo grade ≥ 2: 36% vs 59%, p = 0.018) and a worse final POPF grade (B/C 64% vs 95%, p = 0.003). In the multivariate analysis, cavity type on fistulography was a significant predictive factor for grade B/C POPF. Fistulography is a useful examination for identifying patients with a high risk of developing delayed complications associated with POPF.

This study aimed to clarify the key factors for minimizing unsuitable surgical interventions for patients with radiologically occult metastatic pancreatic cancer (ROMPC), defined as a distant metastasis detected during surgery or within 6 months after resection. This study involved 502 patients planned to undergo curative resection for pancreatic cancer between 2008 and 2015. Patients were divided into ROMPC and non-ROMPC groups and evaluated preoperative factors associated with ROMPC. Overall survival (OS) was significantly lower in the ROMPC group (n = 145) than the non-ROMPC group (n = 357, median survival time [MST] 10.8 vs. 35.3 months, P

BackgroundFibrolamellar hepatocellular carcinoma (FL-HCC) is a liver tumor that occurs almost exclusively in young adults without underlying liver disease. In spite of its distinct clinical characteristics and specific imaging findings, preoperative diagnosis is often difficult due to the extremely low incidence of the tumor. Although FL-HCC shows particular morphological features on H&E-stained tissue sections, differential diagnosis from ordinary HCC, especially the scirrhous variant of HCC, and intrahepatic cholangiocarcinoma needs additional immunohistochemical (IHC) analyses and/or molecular genetic testing.Case presentationA 21-year-old male patient was referred to our hospital for further evaluation of a large liver mass. Abdominal ultrasound examination, contrast-enhanced computed tomography, and magnetic resonance imaging revealed a well-defined hypervascular lobulated liver mass, 11 × 11 cm in diameter, with a central scar and calcification, in segments 5/8. Under the diagnosis of FL-HCC, we carried out extended anterior sectorectomy, including a part of segment 4. On microscopic examination, the tumor was composed of proliferating polygonal cells with abundant eosinophilic granular cytoplasm containing nuclei with vesicular chromatin and enlarged nucleoli, in an abundant stroma. Collagen fibers arranged in a parallel lamellar pattern were seen in the tumor stroma. These findings, together with the results of subsequent IHC analyses using HAS, CK7, and CD 67, we made the diagnosis of FL-HCC, which was further confirmed by detection of theDNAJB1-PRKACAfusion gene in the tumor cells by RT-PCR.ConclusionFL-HCC shows distinct imaging appearances. Although it also has characteristic morphological features, combined use of IHC and/or molecular genetic studies are necessary for the final diagnosis.