Multiomics identifies the link between intratumor steatosis and the exhausted tumor immune microenvironment in hepatocellular carcinoma.

BACKGROUND AND AIMS: 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. APPROACHES AND RESULTS: 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-ß 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. CONCLUSIONS: Multiomics stratified nonviral HCCs according to prognosis or TIME. We identified the link between intratumoral steatosis and immune-exhausted immunotherapy-susceptible TIME.

Robot-Assisted Pancreaticoduodenectomy with Hemicircumferential Dissection of Nerve Plexus Around the Superior Mesenteric Artery.

BACKGROUND: Pancreatic head cancer with perineural invasion of the superior mesenteric artery (SMA) requires dissection of the nerve plexus around the SMA (PLsma, superior mesenteric nerve plexus) to obtain cancer-free margins.1,2 Technically challenging robot-assisted pancreaticoduodenectomy with PLsma resection is rarely performed owing to the technical limitations of the robot. In this multimedia article, we present our approach to robot-assisted pancreaticoduodenectomy with PLsma dissection.3-5 METHODS: We performed a robot-assisted pancreaticoduodenectomy with resection of the hemicircle of the PLsma in a 78-year-old woman with resectable pancreatic cancer extending to the root of the inferior pancreaticoduodenal artery. In this video, we show how to obtain an optimal view using the multiple scope transition method,4 and technical tips to perform a PLsma dissection with a robot to perform this difficult surgery safely. RESULTS: The operative time was 568 min and 300 mL of blood was lost. The pathological diagnosis was invasive pancreatic ductal carcinoma with lymph node metastasis, and R0 resection was performed. The distance margin from the SMA was 2 mm. The patient was discharged on the 18th postoperative day without postoperative complications. CONCLUSIONS: Robot-assisted pancreaticoduodenectomy with dissection of the hemicircle of the PLsma, which is difficult to perform, can be performed safely with an optimal view using the multiple-scope transition method, and delicate dissection using a robot.

Laparoscopic Portal Vein Ligation and Embolization During First-Stage Hepatectomy for Initially Unresectable Colorectal Liver Metastases.

BACKGROUND: Two-stage hepatectomy (TSH) is the only treatment for the patients with multiple bilobar colorectal liver metastases (CRMs) who are not candidates for one-step hepatectomy because of insufficient future remnant liver volume and/or impaired liver function.1-5 Although laparoscopic approaches have been introduced for TSH,6-8 the postoperative morbidity and mortality remains high because of the technical difficulties during second-stage hepatectomy.9,10 The authors present a video of laparoscopic TSH with portal vein (PV) ligation and embolization, which minimizes adhesions and PV thrombosis risk in the remnant liver, thereby facilitating second-stage hepatectomy. METHODS: Three patients with initially unresectable bilateral CRMs received a median of chemotherapy 12 cycles, followed by conversion TSH. After right PV ligation, laproscopic PV embolization was performed by injection of 100% ethanol into the hepatic side of the right PV using a 23-gauge winged needle. After PV embolization, a spray adhesion barrier (AdSpray, Terumo, Tokyo, Japan)11 was applied. RESULTS: During the first stage of hepatectomy, two patients underwent simultaneous laparoscopic colorectal resection (left hemicolectomy and high anterior resection). In the initial hepatectomy, two patients underwent two limited hepatectomies each, and one patient underwent six hepatectomies in the left lobe. After hepatectomy, all the patients underwent right PV embolization. During the second stage, two patients underwent open extended right hepatectomy (right adrenalectomy was performed because of adrenal invasion in one patient), and one patient underwent laparoscopic extended right hepatectomy. No postoperative complications occurred in the six surgeries. CONCLUSIONS: Laparoscopic TSH with PV embolization is recommended for safe completion of the second hepatectomy.

Unique Biology of Pancreatic Ductal Adenocarcinoma Accompanied by Rapidly Impaired Diabetes: A Favorable Long-Term Survival Following Curative Resection.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are sometimes diagnosed accompanied by rapidly impaired diabetes (PDAC-RID). Although this type of PDAC may have unusual biological features, these features have not been explained. METHODS: Patients with PDAC who underwent upfront pancreatectomy between 2010 and 2018 were retrospectively reviewed. PDAC-RID was defined as a glycated hemoglobin (HbA1c) value of ≥ 8.0% of newly diagnosed diabetes, and acute exacerbation of previously diagnosed diabetes. Other patients were classified as PDAC with stable glycometabolism (PDAC-SG). Clinicopathological factors, long-term survival rates, and recurrence patterns were evaluated. RESULTS: Of the 520 enrolled patients, 104 were classified as PDAC-RID and 416 as PDAC-SG. There was no significant difference regarding TNM staging, resectability, or adjuvant chemotherapy rate between the groups. However, 5-years cancer-specific survival (CSS) was significantly higher in the PDAC-RID group than in the PDAC-SG group (45.3% vs. 31.1%; p = 0.02). This survival difference was highlighted in relatively early-stage PDAC (≤ pT2N1) (CSS: 60.8% vs. 43.6%; p = 0.01), but the difference was not significant for advanced-stage PDAC. A multivariate analysis of early-stage PDAC showed that PDAC-SG was an independent risk factor of shorter CSS (hazard ratio 1.76; p = 0.02). The hematogenous metastatic rate in early-stage PDAC was lower in the PDAC-RID group than in the PDAC-SG group (18.3% vs. 35.8%; p = 0.01). CONCLUSIONS: PDAC-RID showed a favorable long-term survival rate after curative resection with low hematogenous metastases, which may be due to its unique biology.

Technical Strategy for Pancreatic Body Cancers: A Raison d'etre of Distal Pancreatectomy with Portal Resection.

BACKGROUND: Advancements in multiagent chemotherapy have expanded the surgical indications for pancreatic cancer. Although pancreaticoduodenectomy (PD) with portal vein resection (PVR) has become widely adopted, distal pancreatectomy (DP) with PVR remains rarely performed because of its technical complexity. This study was designed to assess the feasibility of DP-PVR compared with PD-PVR for pancreatic body cancers, with a focus on PV complications and providing optimal reconstruction techniques when DP-PVR is necessary. METHODS: A retrospective review was conducted on consecutive pancreatic body cancer patients who underwent pancreatectomy with PVR between 2005 and 2020. An algorithm based on the anatomical relationship between the arteries and PV was used for optimal surgical selection. RESULTS: Among 119 patients, 32 underwent DP-PVR and 87 underwent PD-PVR. Various reconstruction techniques were employed in DP-PVR cases, including patch reconstruction, graft interposition, and wedge resection. The majority of PD-PVR cases involved end-to-end anastomosis. The length of PVR was shorter in DP-PVR (25 vs. 40 mm; p < 0.001). Although Clavien-Dindo ≥3a was higher in DP-PVR (p = 0.002), inpatient mortality and R0 status were similar. Complete PV occlusion occurred more frequently in DP-PVR than in PD-PVR (21.9% vs. 1.1%; p < 0.001). A cutoff value of 30 mm for PVR length was determined to be predictive of nonrecurrence-related PV occlusion after DP-PVR. The two groups did not differ significantly in recurrence or overall survival. CONCLUSIONS: DP-PVR had higher occlusion and postoperative complication rates than PD-PVR. These findings support the proposed algorithm and emphasize the importance of meticulous surgical manipulation when DP-PVR is deemed necessary.

Caveolin-1 expression is a predictor of survival and recurrence patterns in resected pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVE: Caveolin-1 (Cav1) expressed in cancer cells (cCav1) or cancer-associated fibroblasts (fCav1) exerts either pro- or anti-tumorigenic effects depending on the cancer type or stage of cancer. We aimed to clarify the impact of cCav1 or fCav1 on survival, recurrence patterns, and efficacy of neoadjuvant chemotherapy (NAC) in resected pancreatic ductal adenocarcinoma (PDAC). METHODS: Tissue microarrays were constructed including 615 patients who underwent curative resection for PDAC. Cav1 expression was evaluated by immunohistochemistry. Patients were divided into two groups based on Cav1 expression in cancer cells (cCav1high vs. cCav1low) or cancer-associated fibroblasts (fCav1high vs. fCav1low). RESULTS: Among all 615 patients, 40.7% were cCav1high and 72.7% were fCav1high. cCav1high was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1low, and was an independent prognostic factor in multivariate analysis of OS and RFS (OS: p = 0.001, hazard ratio [HR] 1.361; RFS: p = 0.001, HR 1.348). Among 596 patients with resectable/borderline resectable PDAC, cCav1high patients with NAC showed better OS than those without, while there was no significant difference between cCav1low patients with NAC and those without. cCav1high was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1high as an independent predictor of liver metastasis. CONCLUSIONS: cCav1high correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1high patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC.

Development of the multiple scope transition method in robotic pancreaticoduodenectomy.

BACKGROUND: Since robotic pancreaticoduodenectomy (R-PD) has emerged as a promising technique for treating periampullary tumors, optimal surgical views across various stages of the surgery are vital. This study aimed to describe the evolution and optimization of the multiple scope transition (MST) method using comprehensive videos and illustrations, particularly from the perspective of the patient-side assistants, to enhance the efficiency and safety of R-PD through its different phases. METHODS: We retrospectively analyzed 61 patients who underwent R-PD from April 2021 to May 2023. RESULTS: The median total operation duration was 599 min (415-840 min). The median scope transition times for redocking from the left to central lower position, transition from the central lower to upper position, and port-hopping from the central to right position were 169 s (53-725 s), 55 s (26-165 s), and 120 s (41-260 s), respectively. Owing to the advancements in the scope transition procedures, these scope transition times became shorter with an increase in the number of experiences. No intraoperative complications relevant to scope transition was reported, and the incidence of significant postoperative complications greater than Grade IIIa of the Clavien-Dindo classification was 8.2%. CONCLUSION: We reported the established role and evolution of the MST method from the standpoint of the patient-side assistants. The comfortable surgical field expansion provided by the MST method can ensure the safe and widespread application of R-PD.

Scope transition and early arterial inflow control provide safe and comfortable dissection in robotic distal pancreatectomy.

PURPOSE: We describe details and outcomes of a novel technique for optimizing the surgical field during robotic distal pancreatectomy (RDP) for distal pancreatic lesions, which has become common with potential advantages over laparoscopic surgery. METHODS: For suprapancreatic lymph node dissection and splenic artery ligation, we used the basic center position with a scope through the midline port. During manipulation of the perisplenic area, the left position was used by moving the scope to the left medial side. The left lateral position is optionally used by moving the scope to the left lateral port when scope access to the perisplenic area is difficult. In addition, early splenic artery clipping and short gastric artery dissection for inflow block were performed to minimize bleeding around the spleen. We evaluated retrospectively the surgical outcomes of our method using a scoring system that allocated one point for blood inflow control and one point for optimizing the surgical view in the left position. RESULTS: We analyzed 34 patients who underwent RDP or R-radical antegrade modular pancreatosplenectomy (RAMPS). The left position was applied in 14 patients, and the left lateral position was applied in 6. Based on the scoring system, only the 0-point group (n = 8) had four bleeding cases (50%) with splenic injury or blood pooling; the other 1-point or 2-point groups (n = 13, respectively) had no bleeding cases (p = 0.0046). CONCLUSION: Optimization of the surgical field using scope transition and inflow control ensured safe dissection during RDP.

Management of potential portal vein thrombus during laparoscopic right hemihepatectomy following portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) is often performed prior to right hemihepatectomy (RH) to increase the future liver remnants. However, intraoperative removal of portal vein thrombus (PVT) is occasionally required. An algorithm for treating the right branch of the PV using laparoscopic RH (LRH) after PVE is lacking and requires further investigation. METHODS: In our department, after the confirmation of a lack of extension of PVT to the main portal trunk or left branch on preoperative examination (ultrasound and contrast-enhanced computed tomography), a final evaluation was performed using intraoperative ultrasonography (IOUS). Here we present the cases of eight patients who underwent LRH after PVE and examine the safety of our treatment strategies. RESULTS: IOUS revealed PVT extension into the main portal trunk in two cases. For the other six patients without PVT extension, we continued the laparoscopic procedure. In contrast, in the two cases with PVT extension, we converted to laparotomy after hepatic transection and removed the PVT. The median operation time for hepatectomy was 562 min (421-659 min), the median blood loss was 293 mL (85-1010 mL), no liver-related postoperative complications were observed, and the median length of stay was 10 days (6-34 days). CONCLUSIONS: PVT evaluation and removal are important in cases of LRH after PVE. Our strategy is safe and IOUS is particularly useful for laparoscopically evaluating PVT extension.

Hepatitis C virus modulates signal peptide peptidase to alter host protein processing.

Immunoevasins are viral proteins that prevent antigen presentation on major histocompatibility complex (MHC) class I, thus evading host immune recognition. Hepatitis C virus (HCV) evades immune surveillance to induce chronic infection; however, how HCV-infected hepatocytes affect immune cells and evade immune recognition remains unclear. Herein, we demonstrate that HCV core protein functions as an immunoevasin. Its expression interfered with the maturation of MHC class I molecules catalyzed by the signal peptide peptidase (SPP) and induced their degradation via HMG-CoA reductase degradation 1 homolog, thereby impairing antigen presentation to CD8+ T cells. The expression of MHC class I in the livers of HCV core transgenic mice and chronic hepatitis C patients was impaired but was restored in patients achieving sustained virological response. Finally, we show that the human cytomegalovirus US2 protein, possessing a transmembrane region structurally similar to the HCV core protein, targets SPP to impair MHC class I molecule expression. Thus, SPP represents a potential target for the impairment of MHC class I molecules by DNA and RNA viruses.

Neoadjuvant chemotherapy for borderline resectable colorectal cancer liver metastases: a single-institution retrospective study.

INTRODUCTION: This study aimed to extract prognostic factors in patients undergoing neoadjuvant chemotherapy (NAC) for borderline resectable colorectal liver metastasis (BR-CRLM) (tumor size ≥5 cm, number of tumors ≥4, or resectable extrahepatic diseases) and assess validity of this strategy. MATERIALS AND METHODS: Since 2010, patients with BR-CRLM were treated with hepatectomy after six cycles of NAC. Prognostic factors of these patients were evaluated using clinicopathological data. RESULTS: Of 650 patients who underwent initial hepatectomy for CRLM from 2010 to 2018, 246 BR-CRLM cases underwent hepatectomy after NAC (BR-NAC). The 5-year recurrence-free survival rate was 16.7% and the 5-year overall survival rate (5y-OS) was 52.9%. Number of tumors ≥6, carcinoembryonic antigen (CEA) level ≥25 ng/mL, tumor diameter ≥5 cm, and progressive disease (PD) after NAC were identified as independent poor prognostic factors for OS. Patients were divided into four groups according to the number of risk factors, and prognoses of the four groups were well stratified. CONCLUSION: In patients with BR-NAC, number of tumors ≥6, CEA ≥25 ng/mL, tumor diameter ≥5 cm, and PD after NAC were independent poor prognostic factors. Patients with three or four risk factors showed poor prognosis and may need to switch chemotherapy.

Serum DUPAN-2 could be an Alternative Biological Marker for CA19-9 Nonsecretors with Pancreatic Cancer.

OBJECTIVE: This study investigates the use of serum DUPAN-2 in predicting the PC progression in CA19-9 nonsecretors. BACKGROUND: Although we previously reported that serum CA19-9 >500U/ mL is a poor prognostic factor and an indication for enhanced neoadjuvant treatment, there is not a biomarker surrogate that equivalently predicts prognosis for CA19-9 nonsecretors. METHODS: We evaluated consecutive PC patients who underwent pancreatectomy from 2005 to 2019. All patients were categorized as either nonsecretor or secretor (CA19-9 ≤ or >2.0U/mL). RESULTS: Of the 984 resected PC patients, 94 (9.6%) were nonsecretors and 890 (90.4%) were secretors. The baseline characteristics were not statistically different between the 2 groups except for the level of DUPAN-2 (720 vs. 100U/mL, P < 0.001). Survival curves after resection were similar between the 2 groups (29.4 months vs. 31.3 months, P = 0.900). Survival curves of patients with DUPAN-2 >2000U/mL in the nonsecretors and patients with CA19-9 >500U/mL in the secretors were nearly equivalent as well (hazard ratio 2.08 vs. 1.89). In the multivariate analysis, DUPAN-2 >2000U/mL (hazard ratio 2.53, P = 0.010) was identified as independent prognostic factor after resection. CONCLUSION: DUPAN-2 >2000U/mL in CA19-9 nonsecretors can be an unfavorable factor that corresponds to CA19-9 >500U/mL in CA19-9 secretors which is an indicator for enhanced neoadjuvant treatment. The current results shed light on the subset of nonsecretors with poor prognosis that were traditionally categorized in a group with a more favorable prognosis group.

Role of Intraoperative Assessment of Proximal Bile Duct Margin Status and Additional Resection of Perihilar Cholangiocarcinoma: Can Local Clearance Trump Tumor Biology? A Retrospective Cohort Study.

BACKGROUND: The aim of this study was to evaluate the clinical implications of the proximal bile duct margin status in resection of perihilar cholangiocarcinoma (PHCC). Intraoperative frozen section (IFS) analysis to assess the bile duct margin status is commonly used during PHCC resection. However, the impact of additional resection after obtaining a positive margin on the long-term outcome remains unclear. PATIENTS AND METHODS: Among the 257 patients who underwent PHCC resection, 190 patients with a negative distal margin were included and analyzed. IFS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of either invasive cancer, or carcinoma, in situ. RESULTS: IFS analysis revealed an initial positive margin in 69 (36%) patients. Among 20 patients who underwent re-resection, only 11 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes: recurrence-free survival (RFS) and overall survival (OS) were 16 and 25 months for patients with an initial positive margin, but 47 and 63 months for patients with an initial negative margin, respectively (p < 0.0001). In contrast, there was no difference in RFS or OS between patients with a secondary R0 margin, and those with a final R1 margin (14 vs. 16 months for RFS, p = 0.98, and 23 versus 25 months for OS, p = 0.63, respectively). CONCLUSION: An IFS-positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable PHCC. Additional resection has minimal impact on survival, even when negative margin is achieved.

Jejunum Patch Technique During Robot-Assisted Central Pancreatectomy: A Lesson from Open Procedure Experience.

BACKGROUND: Central pancreatectomy (CP) has been established as the most common type of parenchyma-sparing pancreatectomy;1 however, CP is associated with higher morbidity and a higher pancreatic fistula (PF) rate than distal pancreatectomy or pancreaticoduodenectomy.2,3 The jejunum patch technique (JPT) for distal pancreatectomy has recently been applied, which efficiently decreases the incidence of PF.4 We have adapted this technique to CP as well as distal pancreatectomy with celiac axis resection.5 Here, we retrospectively evaluated the usefulness of JPT for open CP cases, and report the experience of robot-assisted CP using the JPT. METHODS: Among 37 consecutive cases who underwent CP at our institution between 2011 and 2022, clinical characteristics and postoperative short-term outcomes were compared between patients who underwent CP with and without the JPT. In robot-assisted CP using the JPT, after resection of the middle of the pancreas the transected jejunum was elevated through the retrocolic route in a Roux-en-Y fashion. The pancreatic stump was covered by the JPT using a modified Blumgart technique, following pancreaticojejunostomy for the distal side.6 RESULTS: Among the entire cohort, 19 patients underwent CP using the JPT. The clinically relevant PF rate of the JPT group was significantly lower (47.4%) than the no-JPT group (83.3%, p = 0.022), and the length of drainage and hospital stay were shorter in the JPT group (p= 0.010 and p = 0.017, respectively). The blood loss of robot-assisted CP using the JPT was 20 mL, and the JPT took only 15 min. CONCLUSION: Robot-assisted CP using the JPT is an easy-to-use and promising procedure, based on experience and outcomes from open surgery.

Robotic Splenic Vessels Preserving Distal Pancreatectomy in a Post-Distal Gastrectomy Patient.

BACKGROUND: The optimal procedure during distal pancreatectomy (DP) for patients who have undergone distal gastrectomy (DG) remains unclear. Several papers on remnant gastric ischemia have reported that the preserved splenic vessels are essential for the proximal remnant stomach.1-4 We evaluated the outcomes of DP for post-DG patients in our hospital and introduced robotic splenic vessels preserving DP (R-SPDP). METHODS: Postoperative short-term outcomes of DP for post-DG patients during 2014 and 2021 were evaluated. Next, R-SPDP was performed for a post-DG patient with the intention of preserving the remnant stomach safely. The double bipolar method was used to dissect the adhesions around the splenic vessels.5,6 The splenic artery was clamped at the root side to prevent bleeding.7 All short gastric arteries and veins, which were the main feeders of the remnant stomach, were preserved and resection was completed. After resection, the indocyanine green (ICG) fluorescence angiography confirmed blood flow in the short gastric arteries and veins and good return blood flow to the splenic vein.8 RESULTS: Of four patients (50.0%, of 8 DP patients) in whom the remnant stomach was preserved, one conventional DP case had poor ICG perfusion and presented with remnant stomach ischemia postoperatively. The R-SPDP case with good ICG perfusion had a total operation time of 371 minutes and intraoperative blood loss of 10 mL. The oral diet was started on postoperative Day 3, and the postoperative course was uneventful. CONCLUSIONS: R-SPDP can be a good option for post-DG patients to preserve the remnant stomach safely.

Prognostic Impact of Tumor Markers (CEA and CA19-9) on Patients with Resectable Colorectal Liver Metastases Stratified by Tumor Number and Size: Potentially Valuable Biologic Markers for Preoperative Treatment.

BACKGROUND: Although patients with resectable colorectal liver metastasis (CLM), a population with good prognosis, have been treated with upfront surgery, some patients have had a poor prognosis. This study aimed to investigate biologic prognostic factors in patients with resectable CLMs. METHODS: This single-center retrospective study enrolled consecutive patients who underwent liver resection for initial CLMs at the Cancer Institute Hospital between 2010 and 2020. The study defined CLMs as resectable (tumor size < 5 cm; < 4 tumors; no extrahepatic metastasis) or borderline resectable (BR). Preoperative chemotherapy was administered to patients with BR CLMs. RESULTS: During the study period, 309 CLMs were classified as resectable without preoperative chemotherapy and 345 as BR with preoperative chemotherapy. For the 309 patients with resectable CLMs, the independent poor prognostic factors associated with overall survival in the multivariable analysis were high tumor marker levels (CEA ≥ 25 ng/mL and/or CA19-9 ≥ 50 U/mL; (hazard ratio [HR], 2.45; p = 0.0007), no adjuvant chemotherapy (HR, 1.69; p = 0.043), and age of 75 years or older (HR, 2.09; p = 0.012). The 5-year survival rates for the patients with high tumor marker (TM) levels (CEA ≥25 ng/mL and/or CA19-9 ≥50 U/mL) were significantly worse than for those with low TM levels (CEA < 25 ng/mL and CA19-9 < 50 U/mL) (55.3% vs. 81.1%; p <0.0001) and similar to the rate for those with BR CLMs (52.1%; p = 0.864). Postoperative adjuvant chemotherapy had an impact on prognosis only in the high-TM group (HR, 2.65; p = 0.007). CONCLUSIONS: High TM levels have a prognostic impact on patients with resectable CLMs stratified by tumor number and size. Perioperative chemotherapy improves long-term outcomes for patients with CLM and high TM levels.

Clinical Efficacy of Neoadjuvant Chemotherapy with Gemcitabine plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma Compared with Upfront Surgery.

BACKGROUND: The efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) in the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) has been reported. NAC-GS is now assumed to be a standard regimen for resectable PDAC in Japan. However, the reason for this improvement in prognosis remains unclear. METHODS: In 2019, we introduced NAC-GS for resectable PDAC. From 2015 to 2021, 340 patients were diagnosed with resectable PDAC (anatomical and biological [carbohydrate antigen (CA) 19-9 < 500 U/mL]) and were divided according to the treatment period (upfront surgery [UPS] group, 2015-2019, n = 241; NAC-GS group, 2019-2021, n = 80). We used "intention-to-treat" analysis to compare the clinical outcomes of NAC-GS to those of UPS. RESULTS: Of the 80 patients with NAC-GS, 75 (93.8%) completed two cycles of NAC-GS, and the resection rate of the NAC-GS group was comparable to that of the UPS group (92.5 vs. 91.3%, P = 0.73). The R0 resection rate was significantly higher in the NAC-GS group than in the UPS group (91.3 vs. 82.6%, P = 0.04), even though the surgical burden was smaller. Progression-free survival tended to be better (hazard ratio [HR] = 0.70, P = 0.06), and overall survival was significantly better in the NAC-GS group than in the UPS group (HR 0.55, P = 0.02). CONCLUSIONS: NAC-GS provided improvements in microscopic invasion leading to a high R0 rate and smooth administration and completion of adjuvant therapy, which might lead to an improved prognosis in patients with resectable PDAC.

Diagnosis and management of postpancreatectomy hemorrhage: A single-center experience of consecutive 1,096 pancreatoduodenectomies.

BACKGROUND/OBJECTIVES: This study aimed to assess the outcomes and characteristics of post-pancreatectomy hemorrhage (PPH) in over 1000 patients who underwent pancreatoduodenectomy (PD) at a high-volume hepatopancreaticobiliary center. METHODS: This retrospective study analyzed consecutive patients who underwent PD from 2010 through 2021. PPH was diagnosed and managed using our algorithm based on timing of onset and location of hemorrhage. RESULTS: Of 1096 patients who underwent PD, 33 patients (3.0%) had PPH; incidence of in-hospital and 90-day mortality relevant to PPH were one patient (3.0%) and zero patients, respectively. Early (≤24 h after surgery) and late (>24 h) PPH affected 9 patients and 24 patients, respectively; 16 patients experienced late-extraluminal PPH. The incidence of postoperative pancreatic fistula (p < 0.001), abdominal infection (p < 0.001), highest values of drain fluid amylase (DFA) within 3 days, and highest value of C-reactive protein (CRP) within 3 days after surgery (DFA: p < 0.001) (CRP: p = 0.010) were significantly higher in the late-extraluminal-PPH group. The highest values of DFA≥10000U/l (p = 0.022), CRP≥15 mg/dl (p < 0.001), and incidence of abdominal infection (p = 0.004) were identified as independent risk factors for PPH in the multivariate analysis. Although the hospital stay was significantly longer in the late-extraluminal-PPH group (p < 0.001), discharge to patient's home (p = 0.751) and readmission rate within 30-day (p = 0.765) and 90-day (p = 0.062) did not differ between groups. CONCLUSIONS: Standardized management of PPH according to the onset and source of hemorrhage minimizes the incidence of serious deterioration and mortality. High-risk patients with PPH can be predicted based on the DFA values, CRP levels, and incidence of abdominal infections.

Laparoscopic dissection around the superior mesenteric artery by left posterior approach during pancreaticoduodenectomy.

BACKGROUND: In pancreaticoduodenectomy (PD), the approach to superior mesenteric artery (SMA) is a critical process that supports adequate surgical margins and radicality for pancreatic tumors. In most of the reports on laparoscopic PD, the right-sided approach in which the jejunum is pulled out to the right side for peri-SMA dissection is used, since the left side of the SMA is difficult to dissect, and the only way to do this is to dissect the vein first. METHODS: We devised a method to simplify and safely perform peri-SMA dissection by reversing the process, starting from the left side of the SMA. The first step involves the mobilization of the pancreatic head, which allows for rotation around the SMA. The second step involves the dissection of the left side of the SMA and transection of the jejunum. The key point is to change the incision line between the anterior and posterior mesojejunum. The third process includes the inferior pancreatoduodenal artery (IPDA) and first jejunal artery (J1A) dissection, which can be easily performed from the left side because the SMA rotates by simply continuing the dissection along the previously exposed SMA, and the IPDA/J1A are safely dissected at the root because they are drawn to the left side. The remaining processes are performed on the right side. RESULTS: This method was performed in 16 cases, and in most cases IPDA/J1A were divided from the left side. CONCLUSION: The technique for SMA dissection from the left posterior side was described with illustrations and video. Our method allows safe oncologic dissection around SMA avoiding anatomical misorientation during laparoscopic PD.

Treatment Strategy of Pancreas-Sparing Distal Duodenectomy for Distal Duodenal Malignancies with Adjustable Dissection Levels According to Disease Progression (with Video).

BACKGROUND: Pancreas-sparing distal duodenectomy (PSDD) is a favorable option for distal duodenal neoplasms, and its procedure, including the extent of lymphadenectomy, should be modified according to the malignancy of the tumor. However, there are no coherent reports on the details of this procedure or long-term outcomes after each resection. METHODS: This study included 24 patients who underwent PSDD at our institution between January 2009 and October 2020. Patients were divided into two groups according to the tumor progression: nine with (Lv-II) and fifteen without (Lv-I) mesopancreas dissection. Postoperative outcomes were compared between the two groups. RESULTS: Two groups had similar operation times, blood loss, hospital stay, and the rate of delayed gastric emptying (DGE): 40% versus 44%. There were no Clavien-Dindo classification ≥ III complications in the Lv-II group. The Lv-II group had a larger number of examined lymph nodes (median: 29), and three (33%) patients had lymph node metastasis. No local recurrence was observed, although two patients in the Lv-II group had liver metastasis. The 5-year overall survival rates of the Lv-I and Lv-II groups were 100% and 78%, respectively. None of the patients had an impaired nutrition status after one year of surgery, and no rehospitalization was observed in either group. CONCLUSION: Although PSDD with or without mesopancreas dissection entailed a high risk of DGE, this procedure showed favorable long-term outcomes and may be an alternative to pancreatoduodenectomy in patients with distal duodenal neoplasms.