We evaluated how perioperative changes in the prognostic nutritional index (PNI) influence recurrence and survival after hepatectomy for colorectal cancer liver metastases (CRLM). We conducted a retrospective analysis of 108 patients who underwent hepatectomy for CRLM. Preoperative and postoperative PNI levels were compared, and patients were categorized into high (postoperative PNI equal to or higher than preoperative PNI) and low (postoperative PNI lower than preoperative PNI) groups. Statistical analyses included the Kaplan-Meier analysis, log-rank tests, Cox proportional hazards regression models, and Akaike information criterion. The median observation period was 3.3 years. The Kaplan-Meier analysis showed worse overall survival and recurrence-free survival in the low group. Subgroup analysis demonstrated reproducibility regardless of patient background, era of surgery, surgical outcomes, neoadjuvant or adjuvant chemotherapy, and liver metastasis status. Multivariate analysis identified low group assignment and synchronous liver metastasis as independent predictors of recurrence (hazard ratio [HR], 3.788; 95% confidence interval [CI], 2.030-7.621; HR, 3.338; 95% CI, 1.715-6.964, respectively) and survival (HR, 4.484; 95% CI, 1.945-10.334; HR, 2.529; 95% CI, 1.183-5.407, respectively). The Akaike information criterion analysis showed that perioperative shifts in PNI were superior to preoperative or postoperative PNI alone in predicting outcomes. Perioperative shifts in PNI predicted recurrence and prognosis post-hepatectomy for CRLM more accurately compared to using preoperative or postoperative PNI alone.

INTRODUCTION:Intrahepatic cholangiocarcinoma (ICC) is a highly malignant cancer for which surgery is the only curative treatment. The prognosis of ICC is extremely poor, especially in cases of lymph node metastasis (LNM), owing to the high postoperative recurrence rate. Herein, we present a case of advanced ICC with a breast cancer susceptibility gene-2 (BRCA2) mutation, treated with preoperative chemotherapy, including cisplatin, followed by surgery, in which we achieved a pathologic complete response. CASE PRESENTATION:A 52-year-old woman was referred to our hospital and was subsequently diagnosed with bilateral breast cancer. Computed tomography (CT) and magnetic resonance imaging incidentally detected a liver tumor in the hilar region and lymph node enlargement in the hepatoduodenal ligament. A 19 mm tumor was observed in the area surrounded by the right and left branches of the portal vein and an abnormal portal branch of segment 7. Positron emission tomography-CT showed fluorodeoxyglucose uptake in the liver tumor, hepatoduodenal ligament lymph nodes, and bilateral breasts. A tumor biopsy showed a papillary tumor, and ICC was suspected. As ICC with LNM has a poor prognosis, neoadjuvant chemotherapy was planned. Genetic testing using a blood sample revealed a BRCA2 mutation, indicating the patient would benefit from chemotherapy, particularly cisplatin. The patient received a chemotherapy regimen comprised of gemcitabine, cisplatin, and S-1 (GCS), and after 7 courses, her carbohydrate antigen 19-9 level decreased from 2433 to 15 U/mL. CT showed that the tumor had shrunk and the LNMs were indistinct. The patient was referred to our department for curative surgery, which included a left hepatectomy, caudate lobectomy, hepatoduodenal ligament lymph node dissection, bile duct resection, and choledocojejunostomy. The postoperative course was generally uneventful, and the patient was discharged on postoperative day 18. Pathological examination of the resected specimen revealed an absence of malignant cells. At 24 months postoperative, there was no evidence of recurrence. CONCLUSIONS:We encountered a patient with advanced ICC with a BRCA2 mutation, which was successfully treated with preoperative GCS therapy followed by surgical resection, and a pathologic complete response was achieved. GCS therapy, therefore, appears promising as neoadjuvant chemotherapy for the treatment of ICC.

Objectives Although systemic chemotherapy for pancreatic ductal adenocarcinoma (PDAC) has made progress, ensuring long-term survival remains difficult. There are several reports on the usefulness of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of PDAC, but few reports in systemic chemotherapy. We hereby investigated the usefulness of NLR in systemic chemotherapy for PDAC.Materials and methods A retrospective study was conducted on patients with advanced PDAC treated with first-line systemic chemotherapy. Cox regression hazards models were performed to analyze the association between baseline patient characteristics and the initial treatment response, and overall survival (OS).Results A total of 60 patients with PDAC were enrolled. At baseline, there were significant differences in NLR and carbohydrate antigen 19-9 (CA19-9), as well as the selection rate of combination chemotherapy, between patients with partial response or stable disease and those with progressive disease. Univariate and multivariate analysis showed that NLR < 3.10, combination chemotherapy, and CA19-9 < 1011 U/mL were significant and independent predictive factors of the initial treatment response. Meanwhile, NLR < 3.10 and combination chemotherapy were independently associated with longer OS. Moreover, OS was significantly prolonged in patients with NLR < 3.10, regardless of whether combination chemotherapy or monotherapy. Patients with NLR < 3.10 at baseline had a significantly higher conversion rate to third-line chemotherapy and a longer duration of total chemotherapy.Conclusions This study suggests that NLR may be a useful marker for predicting the initial treatment response to first-line chemotherapy and the prognosis for patients with advanced PDAC.

膵癌根治術後の単発肺転移再発に対し転移巣切除を行い,長期生存を得た症例を報告する.症例は71歳の男性で,IPMNフォロー中に膵腫瘍を指摘され,亜全胃温存膵頭十二指腸切除術を施行した.診断は中~高分化型腺癌でpT3N1aM0,pStage IIB(膵癌取扱い規約第7版)であった.術後補助化学療法としてgemcitabineを1年間投与した.術後21か月時点のCTで右肺上葉に結節影を認め,肺転移または原発性肺癌を疑って右肺上葉切除を行った.病理組織学的検査にて肺腫瘍は膵癌肺転移と診断した.膵癌術後10年,肺転移切除後8年の現在も無再発生存中である.膵癌術後肺転移は症例の適切な選択によって切除による予後延長が得られることが報告されている.本症例のように転移巣切除後も長期生存している症例の報告が増加しており,転移巣切除で治癒が得られる可能性についても期待される.

Background Median arcuate ligament compression syndrome (MALS) causes upper abdominal pain and at times hemodynamic abnormalities in the pancreaticoduodenal region. Herein, we present a case of a 70 year-old man, initially diagnosed with splenic infarction and was successfully treated laparoscopically. Case presentation A 70-year-old man with abdominal pain admitted to our hospital. Abdominal-enhanced computed tomography revealed a poorly contrasted area in the spleen and stenosis at the root of the celiac artery. Arterial dilatation was observed around the pancreaticoduodenal arcade, however, no obvious aneurysm formation or arterial dissection was observed. Abdominal-enhanced magnetic resonance imaging indicated the disappearance of the flow void at the root of the celiac artery. The patient had no history of atrial fibrillation and was diagnosed with splenic infarction due to median arcuate ligament compression syndrome. We performed a laparoscopic median arcuate ligament section with five ports. Intraoperative ultrasonography showed a retrograde blood flow in the common hepatic artery and the celiac artery. After releasing the compression, the antegrade blood flow from the celiac artery to the splenic artery, and the common hepatic artery were visualized using intraoperative ultrasonography. The postoperative course of the patient was uneventful, and he was discharged on postoperative day 9. Postoperative computed tomography a month after surgery revealed no residual stenosis of the celiac artery or dilation of the pancreaticoduodenal arcade. Furthermore, the poorly contrasted area of the spleen improved. Conclusions Reports indicate that hemodynamic changes in the abdominal visceral arteries due to median arcuate ligament compression are related to the formation of pancreaticoduodenal aneurysms. In this case, median arcuate ligament compression syndrome caused splenic infarction by reducing blood flow to the splenic artery.

Tenascin C (TNC) is an extracellular matrix glycoprotein that is highly expressed in cancer stroma and is associated with tumor progression in pancreatic adenocarcinoma (PAAD). In this study, we aimed to investigate the potential involvement of TNC in the response to immune checkpoint inhibitors (ICI) among PAAD patients. Transcriptomic profiles were obtained from public databases and analyzed to compare TNC mRNA levels between tumor and normal tissues. Bioinformatic programs were used to predict paracrine communications between cancer cells and cancer-associated fibroblasts (CAFs), and the Tumor Immune Dysfunction and Exclusion (TIDE) score was calculated to predict response to ICI treatment in PAAD patients. An independent immunotherapeutic cohort was used to validate the clinical impact of the signatures. Results showed that TNC mRNA levels were significantly upregulated in tumors compared to normal tissues in PAAD, and patients with high TNC expression had significantly shorter overall survival than those with low TNC expression (P = 0.0125). TNC was predominantly expressed in CAFs of PAAD patients and was found to potentially enhance the epithelial-mesenchymal transition (EMT) of cancer cells via integrin receptors, contributing to resistance to ICI treatment. Patients with high TNC expression and high ITGαV or ITGB3 expression were associated with poor response to ICI therapy. In conclusion, these findings suggest that TNC-high CAFs play a crucial role in tumor progression and resistance to ICI therapy in PAAD patients, and targeting TNC and its interactions with cancer cells may provide a potential strategy for improving the efficacy of ICI therapy in PAAD.

Laparoscopic liver resection has become safer over time, making it a viable option for patients previously considered high-risk. We discuss a case in which a 73-year-old man underwent laparoscopic liver resection after coronary artery bypass grafting using the right gastroepiploic artery (RGEA). The patient was noted to have liver metastases of rectal cancer in the medial segment. Laparoscopic hepatic S4 partial resection was done after preoperative assessment of the RGEA graft pathway by computed tomography. During the operation, the RGEA graft was adherent to the dorsal surface of the liver, but the laparoscopic approach allowed fine dissection. The tumor was then safely removed, and the patient was discharged without complications. Preoperative assessment of the graft pathway is necessary because of the lack of tactile sensation during laparoscopic surgery. However, a magnified view of the laparoscope enabled us to perform fine dissection to avoid injury to the graft vessels.

Background Pseudoaneurysm (PA) rupture after pancreaticoduodenectomy (PD) is a life-threatening complication. Most PA cases originate from postoperative pancreatic fistulas (POPFs). Although several risk factors for POPF have been identified, specific risk factors for PA formation remain unclear. Therefore, we retrospectively analyzed PD cases with soft pancreas and proposed a novel strategy for early detection of PA formation. Methods Overall, 120 patients underwent PD between 2010 and 2020 at our institution; of these, 65 patients with soft pancreas were enrolled. We evaluated the clinicopathological factors influencing PA formation and developed a risk score to predict PA formation. Results In total, 11 of the 65 patients developed PAs (PA formation group: PAG), and 8 of these 11 PAs ruptured. The median time to PA formation was 15 days, with a minimum of 5 days. The PAG was significantly older than the non-PA formation group, were predominantly men, and had comorbid diabetes mellitus. Pre- and intra-operative findings were similar between the two groups. Importantly, no significant differences were found in postoperative drain amylase levels and total drain amylase content. Cholinesterase and C-reactive protein (CRP) levels on postoperative day (POD) 3 were significantly different between the two groups. Multivariate analysis showed that cholinesterase ≤ 112 U/L and CRP ≥ 16.0 mg/dl on POD 3 were independent predictors of PA formation. Conclusions Decreased cholinesterase and elevated CRP on POD 3 (Cho-C score) are useful predictors of PA formation in cases with soft pancreas. In such cases, periodic computed tomography evaluations and strict drain management are necessary to prevent life-threatening hemorrhage.

Abstract Background The usefulness of static monitoring using central venous pressure has been reported for anesthetic management in hepatectomy. It is unclear whether intra-hepatectomy dynamic monitoring can predict the postoperative course. We aimed to investigate the association between intraoperative dynamic monitoring and post-hepatectomy complications. Furthermore, we propose a novel anesthetic management strategy to reduce postoperative complication. Methods From 2018 to 2021, 93 patients underwent hepatectomy at our hospital. Fifty-three patients who underwent dynamic monitoring during hepatectomy were enrolled. Flo Trac system was used for dynamic monitoring. The baseline central venous oxygen saturation (ScvO2) was defined as the average ScvO2 for 30 min after anesthesia induction. ScvO2 fluctuation (ΔScvO2) was defined as the difference between the baseline and minimum ScvO2. Postoperative complications were evaluated using the comprehensive complication index (CCI). Results Patients with ΔScvO2 ≥ 10% had significantly higher CCI scores (0 vs. 20.9: p = 0.043). In univariate analysis, patients with higher CCI scores demonstrated significantly higher preoperative C-reactive protein-to-lymphocyte ratio (7.51 vs. 24.49: p = 0.039), intraoperative bleeding (105 vs. 581 ml: p = 0.008), number of patients with major hepatectomy (4/45 vs. 3/8: p = 0.028), and number of patients with ΔScvO2 ≥ 10% (11/45 vs. 6/8; p = 0.010). Multivariate logistic regression analysis revealed that ΔScvO2 ≥ 10% (odds ratio: 9.53, p = 0.016) was the only independent predictor of elevated CCI. Conclusions Central venous oxygen saturation fluctuation during hepatectomy is a predictor of postoperative complications. Anesthetic management based on intraoperative dynamic monitoring and minimizing the change in ScvO2 is a potential strategy for decreasing the risk of post-hepatectomy complications.

切除困難な巨大肝細胞癌に対する術前治療として分子標的薬を用いた報告はいまだ少数である.今回,巨大肝細胞癌に対し術前にlenvatinibの投与により腫瘍が縮小し,切除後の残肝容積を温存できた症例を経験した.症例は78歳の男性で,肝S5・S6から肝外に突出する19 cm大の肝細胞癌ならびに肝S8の肝内転移を認めた.腫瘍はG7にも近接し,根治切除には拡大後区域切除+肝S8部分切除(31.9%切除)が想定されたが,ICG停滞率が28.3%と高値かつ,術後の早期再発も危惧されたため,lenvatinibを投与した後に切除する方針とした.投与開始後6週間で主腫瘍は縮小し,肝内転移も消失した.肝下区域切除(10.7%切除)を施行し,残肝容積を保つことが可能となった.Lenvatinibは巨大肝細胞癌の術前治療の選択肢になりうると思われた.

BACKGROUND:Owing to the lack of definite diagnostic modalities, it is challenging to distinguish malignant cases of cholangiocarcinoma (CCA), which often causes biliary tract obstruction, from benign ones. Here, we investigated a novel lipid biomarker of CCA in bile-derived small extracellular vesicles (sEVs) and developed a simple detection method for clinical application. METHODS:Bile samples from seven patients with malignant diseases (hilar CCA = 4, distal CCA = 3) and eight patients with benign diseases (gallstones = 6, primary sclerosing cholangitis = 1, autoimmune pancreatitis = 1) were collected through a nasal biliary drainage tube. sEVs were isolated via serial ultracentrifugation and characterized using nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting (with CD9, CD63, CD81, and TSG101). Comprehensive lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry. Using a measurement kit, we further confirmed whether lipid concentrations could be used as a potential CCA marker. RESULTS:Lipidomic analysis of bile sEVs in the two groups identified 209 significantly increased lipid species in the malignant group. When focusing on lipid class, phosphatidylcholine (PC) level was 4.98-fold higher in the malignant group than in the benign group (P = 0.037). The receiver operating characteristic (ROC) curve showed a sensitivity of 71.4%, a specificity of 100%, and an area under the curve (AUC) of 0.857 (95% confidence interval [CI]:0.643-1.000). Using a PC assay kit, the ROC curve showed a cutoff value of 16.1 μg/mL, a sensitivity of 71.4%, a specificity of 100%, and an AUC of 0.839 (95% CI: 0.620-1.000). CONCLUSION:PC level in sEVs from human bile is a potential diagnostic marker for CCA and can be assessed by a commercially available assay kit.

Background/Objective: Pancreaticoduodenectomy (PD) is highly invasive with unsatisfactory postoperative complication rates. Nutritional and fluid management after major surgery attracts much attention with regard to the reduction in severe postoperative complications. We retrospectively analyzed PD cases and proposed a novel strategy for perioperative fluid and nutritional therapy according to the risk stratification by pancreatic fistula (PF) and delayed gastric emptying (DGE). Methods: Between 2003 and 2018, 140 patients underwent PD at our institute of which 134 patients were enrolled. We evaluated the clinicopathological factors affecting severe (>10%) body weight loss (BWL), factors affecting the incidence of PF and intraabdominal complications (IAC), and factors related to DGE. Results: Multivariate analysis indicated that male sex, severe PF, and DGE are significant risk factors for BWL >10%. PF and IAC were predominantly observed in male patients and those with non-pancreatic cancer. A fluid balance >6000 ml on postoperative day 2 was the sole risk factor for primary DGE. Secondary DGE significantly correlated with stomach preserving PD. Importantly, the average BWL was around 15% in grade B or C secondary DGE. Conclusion: Severe postoperative complications resulted in significant BWL. Enteral feeding is unnecessary in cases with a hard pancreas and dilated pancreatic duct if appropriate perioperative fluid management is performed. Secondary DGE followed by PF or IAC is unavoidable to some extent, especially in the case of soft pancreas with a fine pancreatic duct. In such cases, enteral feeding with tube ileostomy should be considered, and stomach preserving PD is likely to be harmful. (c) 2021 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Bleeding is a fatal complication after pancreatectomy. Although coil embolization is a widely accepted treatment option, ischemia of the remaining organs should be prevented. This study reports the successful treatment of intra-abdominal hemorrhage following distal pancreatectomy with en bloc celiac axis resection (DP-CAR) using balloon-assisted coil embolization (BACE). A 59-year-old man was diagnosed with locally advanced pancreatic cancer. The tumor involves the common hepatic artery, splenic artery, and celiac artery. After four cycles of treatment with gemcitabine/nab-paclitaxel, the soft-density masses, surrounding the artery, shrunk. DP-CAR and R0 resections were performed. A minor postoperative pancreatic fistula occurred. Six months postoperatively, the computed tomography showed delayed asymptomatic bleeding from an anterior superior pancreaticoduodenal artery (ASPDA) pseudoaneurysm located near the gastroduodenal artery confluence. BACE was performed by placing a microballoon catheter in the region of confluence of the ASPDA and posterior superior pancreaticoduodenal artery (PSPDA) to prevent coil migration. After inserting the microballoon catheter, coil embolization was performed in the ASPDA. Hepatic blood flow was maintained from the PSPDA. BACE is a useful technique to preserve blood flow to the remnant organs when performing coil embolization for bleeding following a distal pancreatectomy, especially following a DP-CAR.

Background Staphylococcus hominis ( S. hominis ) is an opportunistic pathogen that is often highly resistant to antibiotics and is difficult to treat. In patients diagnosed with an adrenocorticotropic hormone (ACTH)-producing tumor that compromises the immune system due to hypercortisolemia, cancer treatment and infection control should be considered simultaneously. This report presents a case of refractory postoperative S. hominis bacteremia requiring the prolonged administration of several antibiotics in a patient with an ACTH-producing pancreatic neuroendocrine neoplasm (pNEN). Case presentation A 35-year-old man visited a neighboring hospital for a thorough examination after experiencing weight gain and lower limb weakness for several months. Enhanced computed tomography revealed a pancreatic tail tumor and bilateral adrenal enlargement. Elevated plasma ACTH and serum cortisol were noted. Biopsy under endoscopic ultrasonography revealed the tumor as an ACTH-producing pNEN. The patient was transferred to our hospital for further treatment. Pneumocystis pneumonia was noted and treated with sulfamethoxazole and adjunctive glucocorticoids. Hypercortisolism was controlled with metyrapone and trilostane. Somatostatin receptor scintigraphy and ethoxybenzyl magnetic resonance imaging detected other lesions in the pancreatic head. A total pancreatectomy was performed given that the lesions were found in both the pancreatic head and tail. Plasma ACTH and serum cortisol levels decreased immediately after the resection. Pathological examination revealed that the pancreatic tail tumor was NEN G2 and T3N1aM0 Stage IIB and the pancreatic head lesions were SSTR-positive hyperplasia of the islet of Langerhans cells. On postoperative day 11, catheter-associated bacteremia occurred. Initially, meropenem hydrate and vancomycin hydrochloride were administered empirically. S. hominis was identified and appeared sensitive to these antibiotics according to susceptibility testing. However, S. hominis was repeatedly positive in blood cultures for more than one month, despite treatment with several antibiotics. Eventually, with the combined use of three antibiotics (meropenem hydrate, vancomycin hydrochloride, and clindamycin phosphate) for more than 3 weeks, the S. hominis -associated bacteremia improved. He was discharged 79 days after surgery. Conclusions Our patient with an ACTH-producing pNEN was immunocompromised and needed meticulous attention for infectious complications even after successful tumor removal. Specifically, S. hominis bacteremia in such patients demands intensive treatments, such as with combinational antibiotics.

Background Various hemostatic devices have been utilized to reduce blood loss during hepatectomy. Nonetheless, a comparison between monopolar and bipolar coagulation, particularly their usefulness or inferiority, has been poorly documented. The aim of this study is to reveal the characteristics of these hemostatic devices. Methods A total of 264 patients who underwent open hepatectomy at our institution from January 2009 to December 2018 were included. Monopolar and bipolar hemostatic devices were used in 160 (monopolar group) and 104 (bipolar group) cases, respectively. Operative outcomes and thermal damage to the resected specimens were compared between these groups using propensity score matching according to background factors. Multivariate logistic regression analysis was performed to identify predictive factors for postoperative complications. Results After propensity score matching, 73 patients per group were enrolled. The monopolar group had significantly lower total operative time (239 vs. 275 min; P = 0.013) and intraoperative blood loss (487 vs. 790 mL; P < 0.001). However, the incidence rates of ascites (27.4% vs. 8.2%; P = 0.002) and grade ≥ 3 intra-abdominal infection (12.3% vs. 2.7%; P = 0.028) were significantly higher in the monopolar group. Thermal damage to the resected specimens was significantly longer in the monopolar group (4.6 vs. 1.2 mm; P < 0.001). Use of monopolar hemostatic device was an independent risk factor for ascites (odds ratio, 5.626, 95% confidence interval 1.881–16.827; P = 0.002) and severe intra-abdominal infection (odds ratio, 5.905, 95% confidence interval 1.096–31.825; P = 0.039). Conclusions Although monopolar devices have an excellent hemostatic ability, they might damage the remnant liver. The use of monopolar devices can be one of the factors that increase the frequency of complications.

Background/Aim: We sought to identify the mechanisms of perineural invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: We utilized in vitro cancer cell-nerve co-culture models comprising human PDAC cell lines (MIA Paca2 and PANC-1) and a dorsal root ganglion (DRG) isolated from neonatal mice. We compared gene expression profiles between cell lines with/without DRG conditioned medium (DRG-CM) using RNA-sequencing (RNA-seq). Results: Migration, invasion, and neurotropism were significantly enhanced in MIA Paca2 but not in PANC-1 cells co-cultured with DRGs. Among 285 genes which showed significant differences in expression levels between cell lines in RNA-seq, we focused on Ephrin receptor A4 (EPHA4), which was upregulated in MIA Paca2 cells treated with DRG-CM. The abilities of migration, invasion, and neurotropism enhanced by DRG co-culture were abolished when EPHA4 was knocked down by siRNA in MIA Paca2 cells. Conclusion: EPHA4 can be a potential target gene to regulate perineural invasion in PDAC cells.