脇屋 太一

Liver transplant (LT) recipients, particularly pediatric survivors, face an elevated lifetime risk of de novo malignancies due to prolonged immunosuppressive therapy. Alpha-fetoprotein (AFP) is widely used as a biomarker for hepatocellular carcinoma (HCC) in post-LT surveillance, but elevations may also reflect extrahepatic tumors. Here, we report a rare case of a testicular tumor incidentally detected through AFP monitoring in a pediatric LT survivor. A 20-year-old male with situs inversus totalis underwent living donor LT for biliary atresia at 1 year of age. Nineteen years post-transplant, AFP was elevated to 493 ng/mL during routine surveillance, raising suspicion for de novo HCC. Imaging studies revealed no liver lesions, but physical examination identified testicular swelling. Scrotal ultrasonography demonstrated a heterogeneous mass, and orchiectomy confirmed a mixed germ cell tumor composed of seminoma, yolk sac tumor, and embryonal carcinoma. AFP normalized postoperatively, and the patient is being carefully monitored during postoperative surveillance. This case highlights both the benefits and limitations of AFP-driven surveillance: while it facilitated early detection of a curable extrahepatic tumor, reliance on AFP alone may miss AFP-negative testicular cancers. Comprehensive surveillance strategies incorporating tumor markers, structured physical examinations, and patient education are warranted, with future emphasis on standardized guidelines for pediatric LT survivors.

Liver transplantation (LT) from donors with von Willebrand factor (VWF) abnormalities is rarely reported, largely due to concerns over donor safety and potential hemostatic complications in the recipient. Low VWF activity is more prevalent than von Willebrand disease and may present without bleeding symptoms, yet its implications in the context of living donor LT (LDLT) remain poorly characterized. We report a case of successful LDLT from a donor with borderline low VWF activity, highlighting detailed perioperative and long-term coagulation profiles in both donor and recipient. The donor, a healthy young woman with no personal or family history of bleeding, was found to have mildly decreased ristocetin cofactor activity. A test infusion of VWF/FVIII concentrate elicited a favorable biological response. Based on these findings and in accordance with clinical guidelines, open right hepatectomy was performed under perioperative VWF replacement. The donor experienced no bleeding or thrombotic complications and remained clinically stable during 18 months of follow-up. VWF-related parameters remained elevated postoperatively and ultimately returned to baseline or higher, indicating preserved long-term hemostasis. The recipient, who received the graft from the low-VWF donor, showed stable VWF-related coagulation parameters post-transplantation. Despite a transient decline following reperfusion, levels normalized within the expected timeframe and remained within normal range throughout follow-up. This case supports the safety of LDLT from donors with low VWF levels when appropriate perioperative management is applied. It also highlights that low donor VWF activity may not compromise recipient hemostasis, offering important implications for donor eligibility assessment in clinical practice.

BACKGROUND: The usefulness of subcutaneous immunoglobulin (SCIG) for the treatment of hypogammaglobulinemia has been reported, but there are no reports in the field of pediatric liver transplantation (LT). We herein report the therapeutic efficacy of SCIG in the postoperative management after pediatric living donor LT (LDLT). METHODS: Subjects were 112 pediatric recipients who underwent LDLT between March 2012 and December 2021. SCIG administration was started in February 2017 and performed in 43 patients with hypogammaglobulinemia (< 870 mg/dL). Intravenous immunoglobulin (IVIG) administration was performed in 69 patients before January 2017. SCIG was administered subcutaneously at 130 (82-238) mg/kg/dose every week from postoperative day (POD) 2 until discharge. RESULTS: The preoperative serum IgG level in the SCIG group was 906 (249-1987) mg/dL, and the IgG level at the end of LDLT was 491 (246-823) mg/dL, showing a significant difference (p < 0.001). The median IgG levels in the SCIG group after LT were 697, 607, 579, 691, 665, and 795 mg/dL at 1, 2, 3, 4, and 5 weeks after surgery and after discharge, respectively. The incidence of bacteremia was significantly lower in the SCIG group than in the IVIG group (p = 0.025). The recipient's survival rate was not significantly different between the SCIG and IVIG groups (p = 0.080), but the recipient's survival rate in the SCIG group was 100%. The multivariate analysis revealed that the IVIG group and CMV viremia were a significant risk factors for bacteremia (p = 0.023 and 0.001, respectively). CONCLUSIONS: Postoperative SCIG administration effectively maintained serum IgG levels and was useful for preventing bacteremia.

While endogenous cortisol secretion rises in the early morning, the number of lymphocytes in the blood is higher at night, thus exhibiting an antiphase pattern to cortisol secretion. Therefore, compared with the daytime, the infiltration of lymphocytes into immune-reactive tissues is enhanced at night. This study aimed to determine whether the administration of methylprednisolone (mPSL) in the evening is more effective against T cell-mediated rejection (TCMR) after liver transplantation compared with morning administration. This study used a randomized, open-label, parallel-group comparison design. Pediatric patients scheduled to undergo living-donor liver transplantation were randomly divided into morning (8:00 a.m.) and evening (8:00 p.m.) mPSL administration groups. The primary endpoint was the occurrence of TCMR within 14 days of surgery. Sixty-two patients were enrolled between 2014 and 2023, and six patients were excluded from the analysis as their dose of mPSL deviated from the protocol within 14 days after surgery. Of the 56 subjects analyzed, TCMR was detected in 10 of the morning group (n = 29) and three of the evening group (n = 27) within 14 days after surgery. Stratified analysis of patients who did not receive preoperative rituximab treatment showed that none of the evening group and 36.4% of the morning group developed TCMR within 14 days after surgery (P < 0.01, 95% confidence interval; 2.00-infinity). Safety evaluation results were comparable between the two groups. This study shows that the evening administration of mPSL is an effective approach for suppressing TCMR. This study is hypothesis generating, and replication in further studies is needed.

BACKGROUND: Cytomegalovirus (CMV) is a major infectious complication in solid-organ transplant recipients, particularly in the context of pediatric liver transplantation. CMV serostatus is a well-established risk factor for postoperative CMV infection, with CMV seronegative recipients who receive organs from seropositive donors (D+/R-) being at the highest risk. Our previous research indicated a higher incidence of CMV infection in recipients with inherited metabolic diseases (IMDs) compared with those with biliary atresia (BA). This study aimed to determine whether IMDs constitute an independent risk factor for postoperative CMV infection. METHODS: We retrospectively analyzed data from 45 IMD and 230 BA recipients. We collected information on the occurrence and timing of episodes of CMV infections, methylprednisolone (mPSL) pulse therapy, patient characteristics, and peri- and postoperative data. RESULTS: Multivariable analysis identified mPSL pulse therapy (Odds Ratio (OR): 4.43), CMV serostatus (D+/R-) (OR: 6.03), and underlying IMDs (OR: 3.28) as independent risk factors for CMV infection. Further stratified analysis, which considered the timing of CMV infection diagnosis relative to mPSL pulse therapy, confirmed that CMV serostatus with (D+/R-) (OR: 5.61) and underlying IMDs (OR: 2.83) remained independent predictors of CMV infection, even when excluding the influence of mPSL pulse therapy. CONCLUSIONS: This study demonstrates that IMDs are a potent independent risk factor for CMV infection following pediatric liver transplantation. CLINICAL TRIAL NUMBER: Not applicable.

INTRODUCTION: When a thrombus extends to the suprahepatic inferior vena cava (IVC) in patients with Budd-Chiari syndrome (BCS) requiring liver transplantation (LT), there is a risk of thrombus migration during hepatectomy that can potentially lead to pulmonary embolism. Intraoperative pulmonary embolism can be life-threatening and may necessitate urgent thrombectomy. However, preventive strategies for pulmonary embolism during LT in BCS cases with IVC thrombosis have seldom been discussed in the literature. We report a case involving a 51-year-old woman with BCS complicated by thrombi extending into the suprahepatic IVC who underwent deceased donor LT (DDLT) for acute liver failure (ALF). CASE PRESENTATION: A previously healthy 51-year-old woman with ALF secondary to BCS was admitted to our hospital. 19 days back, BCS was diagnosed at another hospital, where computed tomography revealed thrombi in the hepatic veins and IVC. She subsequently developed grade II hepatic encephalopathy and severe liver dysfunction. Conservative treatment was ineffective, and 4 days before the current admission, she experienced grade III hepatic encephalopathy and showed hepatofugal portal flow on ultrasonography. DDLT was performed on day 13 after admission. Median sternotomy was performed to clamp the suprahepatic IVC near the right atrium, mitigating the risk of thrombus migration during hepatectomy and allowing for urgent thrombectomy in case of pulmonary embolism. Additionally, because a large-for-size graft was being used, the median sternotomy enhanced visibility and provided adequate space, facilitating suprahepatic IVC anastomosis. Postoperatively, the patient experienced no complications related to the sternotomy and was discharged 58 days after surgery. CONCLUSIONS: This case report highlights the potential utility of median sternotomy during LT for BCS, particularly for cases with concerns regarding thrombus migration from the suprahepatic IVC, the need for rapid thrombectomy in the event of pulmonary embolism, and anticipated challenges in suprahepatic IVC anastomosis due to large-for-size grafts.

Portal cavernoma cholangiopathy (PCC) is a complex condition associated with portal hypertension, particularly in patients with extrahepatic portal vein obstruction (EHPVO). Herein, we present a case of liver failure with PCC in a 55-year-old male successfully treated with living-donor liver transplantation (LDLT). The patient had a history of gastrointestinal bleeding and recurrence of cholangitis. Imaging studies confirmed cavernous transformation and pericholedochal varices. Preoperative angiography verified hepatopetal flow in the pericholedochal varix, which facilitated successful anastomosis with the donor's portal vein during LDLT. Histological examination of the explanted liver confirmed vanishing bile duct syndrome (VBDS) and secondary bile stasis was considered to have caused liver failure. No postoperative complications were observed within 13 months of LDLT. We report the first case of VBDS in the PCC resulting from EHPVO that was successfully managed with LDLT. Careful management of similar cases should involve angiography and long-term postoperative monitoring of portal vein complications.

Nicotinamide adenine dinucleotide (NAD +) plays a pivotal role in numerous cellular functions. Reduced NAD + levels are postulated to be associated with cancer. As interest in understanding NAD + dynamics in cancer patients with therapeutic applications in mind grows, there remains a shortage of comprehensive data. This study delves into NAD + dynamics in patients undergoing surgery for different digestive system cancers. This prospective study enrolled 99 patients with eight different cancers. Fasting blood samples were obtained during the perioperative period. The concentrations of NAD + , nicotinamide mononucleotide (NMN), and nicotinamide riboside were analyzed using tandem mass spectrometry. After erythrocyte volume adjustment, NAD + remained relatively stable after surgery. Meanwhile, NMN decreased the day after surgery and displayed a recovery trend. Interestingly, liver and pancreatic cancer patients exhibited poor postoperative NMN recovery, suggesting a potential cancer type-specific influence on NAD + metabolism. This study illuminated the behavior of NAD + in surgically treated cancer patients. We identified which cancer types have particularly low levels and at what point depletion occurs during the perioperative period. These insights suggest the need for personalized NAD + supplementation strategies, calibrated to individual patient needs and treatment timelines. Clinical trial registration jRCT1020210066.

BACKGROUND: Peripancreatic bacterial contamination (PBC) is a critical factor contributing to the development of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). Controlling pathogenic bacteria is essential in preventing CR-POPF; however, the precise relationship between specific bacteria and CR-POPF remains unclear. This study aimed to investigate the relationship between PBC and CR-POPF after PD, with a focus on identifying potentially causative bacteria. METHODS: This prospective observational study enrolled 370 patients who underwent PD. Microbial cultures were routinely collected from peripancreatic drain fluid on postoperative days (PODs) 1, 3, and 6. Predictive factors for CR-POPF and the bacteria involved in PBC were investigated. RESULTS: CR-POPF occurred in 86 (23.2%) patients. In multivariate analysis, PBC on POD1 (Odds ratio [OR] = 3.59; P = 0.005) was one of the main independent predictive factors for CR-POPF, while prophylactic use of antibiotics other than piperacillin/tazobactam independently influenced PBC on POD1 (OR = 2.95; P = 0.010). Notably, Enterococcus spp., particularly Enterococcus faecalis, were significantly isolated from PBC in patients with CR-POPF compared to those without CR-POPF on PODs 1 and 3 (P < 0.001), and they displayed high resistance to all cephalosporins. CONCLUSIONS: Early PBC plays a pivotal role in the development of CR-POPF following PD. Prophylactic antibiotic administration, specifically targeting Enterococcus faecalis, may effectively mitigate early PBC and subsequently reduce the risk of CR-POPF. This research sheds light on the importance of bacterial control strategies in preventing CR-POPF after PD.

Alanine aminotransferase (ALT) is an enzyme that catalyzes the transfer of amino groups from alanine to ketoglutaric acid. ALT is an established marker of liver diseases. Occasionally, ALT levels may be abnormally low due to various factors, making accurate assessment difficult. To date, no studies have documented ALT alterations following Living donor liver transplantation (LDLT) in patients with low ALT levels. Here, we present a case of abnormally low ALT levels that were ameliorated by LDLT. A 27-year-old woman underwent LDLT for refractory cholangitis with biliary atresia. The patient's preoperative ALT level was 1 IU/L. Following graft reperfusion, ALT levels increased (peak value, 456 IU/L), primarily attributed to the donor liver. After LDLT, ALT levels consistently surpassed the lower limit. The differential diagnosis of abnormally low ALT levels suggested a genetic mutation as the most probable underlying cause. Even after LDLT, ALT levels in organs other than the transplanted liver would remain abnormally low. Therefore, to prevent underestimating liver damage, the standard ALT range for such cases should be set lower than the typical range.

Acute normovolemic hemodilution (ANH) is a useful intraoperative blood conservation technique. However, the impact on long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study investigated the impact of ANH on long-term outcomes in patients with PDAC undergoing radical surgery. Data from 155 resectable PDAC cases were collected. Patients were categorized according to whether or not they had received intraoperative allogeneic blood transfusion (ABT) or ANH. Postoperative complications, recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ANH. A total of 44 patients (28.4%) were included in the ANH group and 30 patients (19.4%) were included in the ABT group; 81 (52.3%) patients, comprising the standard management (STD) group, received neither ANH nor ABT. The ABT group had the worst prognosis among them. Before PSM, ANH was significantly associated with decreased RFS (P=0.043) and DSS (P=0.029) compared with the STD group before applying Bonferroni correction; however, no significant difference was observed after applying Bonferroni correction. Cox regression analysis identified ANH as an independent prognostic factor for RFS [relative risk (RR), 1.696; P=0.019] and DSS (RR, 1.876; P=0.009). After PSM, the ANH group exhibited less favorable RFS [median survival time (MST), 12.1 vs. 18.1 months; P=0.097] and DSS (MST, 32.1 vs. 50.5 months; P=0.097) compared with the STD group; however, these differences were not statistically significant. In conclusion, while ANH was not as harmful as ABT, it exhibited potentially more negative effects on long-term postoperative outcomes in PDAC than STD.

A 72-year-old man was referred to our hospital for the examination of a pancreatic head mass. Abdominal computed tomography revealed a contrasted 8-cm-diameter tumor extending from the dorsal pancreatic head to the porta hepatis. The preoperative diagnosis was challenging due to the absence of specific imaging findings and the inability to perform a biopsy. Positron emission tomography/computed tomography and diffusion-weighted imaging suggested a malignant tumor originating from the organs surrounding the pancreatic head. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed, as dissection from the pancreatic head proved unfeasible. Pathological examination identified the tumor as an enlarged lymph node consisting of pleomorphic large cells forming clusters, positive for follicular dendritic cell markers cluster of differentiation (CD) 21 and CD23. No evidence of tumor capsule infiltration, other organ infiltration, or metastasis to other lymph nodes was observed. The final diagnosis was nodal follicular dendritic cell sarcoma (FDCS) originating from the pancreatic head lymph nodes. No recurrence occurred at 3 years postoperatively with no postoperative treatment. Intraperitoneal nodal FDCS is extremely rare, and occasionally, it can lead to postoperative recurrence and progression. It is crucial to differentiate neoplastic lymph node enlargement around the pancreatic head from nodal FDCS.

The liver and pancreas work together to recover homeostasis after hepatectomy. This study aimed to investigate the effect of liver resection volume on the pancreas. We collected clinical data from 336 living liver donors. They were categorized into left lateral sectionectomy (LLS), left lobectomy, and right lobectomy (RL) groups. Serum pancreatic enzymes were compared among the groups. Serum amylase values peaked on postoperative day (POD) 1. Though they quickly returned to preoperative levels on POD 3, 46% of cases showed abnormal values on POD 7 in the RL group. Serum lipase levels were highest at POD 7. Lipase values increased 5.7-fold on POD 7 in the RL group and 82% of cases showed abnormal values. The RL group's lipase was twice that of the LLS group. A negative correlation existed between the remnant liver volume and amylase (r = - 0.326)/lipase (r = - 0.367) on POD 7. Furthermore, a significant correlation was observed between POD 7 serum bilirubin and amylase (r = 0.379)/lipase (r = 0.381) levels, indicating cooccurrence with liver and pancreatic strain. Pancreatic strain due to hepatectomy occurs in a resection/remnant liver volume-dependent manner. It would be beneficial to closely monitor pancreatic function in patients undergoing a major hepatectomy.

OBJECTIVES: We aimed to predict in vitro chemosensitivity assay results from computed tomography (CT) images by applying deep learning (DL) to optimize chemotherapy for pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Preoperative enhanced abdominal CT images and the histoculture drug response assay (HDRA) results were collected from 33 PDAC patients undergoing surgery. Deep learning was performed using CT images of both the HDRA-positive and HDRA-negative groups. We trimmed small patches from the entire tumor area. We established various prediction labels for HDRA results with 5-fluorouracil (FU), gemcitabine (GEM), and paclitaxel (PTX). We built a predictive model using a residual convolutional neural network and used 3-fold cross-validation. RESULTS: Of the 33 patients, effective response to FU, GEM, and PTX by HDRA was observed in 19 (57.6%), 11 (33.3%), and 23 (88.5%) patients, respectively. The average accuracy and the area under the receiver operating characteristic curve (AUC) of the model for predicting the effective response to FU were 93.4% and 0.979, respectively. In the prediction of GEM, the models demonstrated high accuracy (92.8%) and AUC (0.969). Likewise, the model for predicting response to PTX had a high performance (accuracy, 95.9%; AUC, 0.979). CONCLUSIONS: Our CT patch-based DL model exhibited high predictive performance in projecting HDRA results. Our study suggests that the DL approach could possibly provide a noninvasive means for the optimization of chemotherapy.

BACKGROUND: Extramural vascular invasion (EMVI) and tumor deposits (TD) are poor prognostic factors in rectal cancer (RC), especially when resistant to neoadjuvant chemotherapy (NAC). We aimed to define differential expression in NAC responders and non-responders with concomitant EMVI and TD. METHODS: From 52 RC surgical patients, post-NAC resected specimens were extracted, comprising two groups: cases with residual EMVI and TD (NAC-resistant) and cases without (NAC-effective). Proteomic analysis was conducted to define differential protein expression in the two groups. To validate the findings, immunohistochemistry was performed in another cohort that included 58 RC surgical patients. Based on the findings, chemosensitivity and prognosis were compared. RESULTS: The NAC-resistant group was associated with a lower 3-year disease-free survival rate than the NAC-effective group (p = 0.041). Discriminative proteins in the NAC-resistant group were highly associated with the sulfur metabolism pathway. Among these pathway constituents, selenium-binding protein 1 (SELENBP1) expression in the NAC-resistant group decreased to less than one-third of that of the NAC-effective group. Immunohistochemistry in another RC cohort consistently validated the relationship between decreased SELENBP1 and poorer NAC sensitivity, in both pre-NAC biopsy and post-NAC surgery specimens. Furthermore, decrease in SELENBP1 was associated with a lower 3-year disease-free survival rate (p = 0.047). CONCLUSIONS: We defined one of the differentially expressed proteins in NAC responders and non-responders, concomitant with EMVI and TD. SELENBP1 was suspected to contribute to NAC resistance and poor prognosis in RC.

Lymphatic fluid drains from the liver via the periportal lymphatic, hepatic venous lymphatic, and superficial lymphatic systems. We performed a postmortem study to clarify the three-dimensional structure and flow dynamics of the human hepatic venous lymphatic system, as it still remains unclear. Livers were excised whole from three human cadavers, injected with India ink, and sliced into 1-cm sections from which veins were harvested. The distribution of lymphatic vessels was observed in 5 μm sections immunostained for lymphatic and vascular markers (podoplanin and CD31, respectively) using light microscopy. Continuity and density of lymphatic vessel distribution were assessed in en-face whole-mount preparations of veins using stereomicroscopy. The structure of the external hepatic vein wall was assessed with scanning electron microscopy (SEM). The lymphatic dynamics study suggested that lymphatic fluid flows through an extravascular pathway around the central and sublobular veins. A lymphatic vessel network originates in the wall of sublobular veins, with a diameter greater than 110 μm, and the peripheral portions of hepatic veins and continues to the inferior vena cava. The density distribution of lymphatic vessels is smallest in the peripheral portion of the hepatic vein (0.03%) and increases to the proximal portion (0.22%, p = 0.012) and the main trunk (1.01%, p &lt; 0.001), correlating positively with increasing hepatic vein diameter (Rs = 0.67, p &lt; 0.001). We revealed the three-dimensional structure of the human hepatic venous lymphatic system. The results could improve the understanding of lymphatic physiology and liver pathology.

A 65-year-old woman underwent living-donor liver transplantation (left-lobe graft: GWRW ratio, 0.54) for cirrhosis caused by autoimmune hepatitis. At 68 years, she was diagnosed with obstructive cholangitis due to stricture during a hepaticojejunostomy following impaired liver function. Endoscopic balloon dilation of anastomosis and placement of a plastic stent resulted in improved liver function. However, at 72 years, the patient experienced a flare-up of liver damage. The plastic stent had fallen out, and although endoscopic stenotic dilation was attempted, the anastomotic site was obstructed completely. Therefore, recanalization of the hepaticojejunostomy was attempted using a rendezvous technique. A percutaneous transhepatic biliary drainage tube was inserted through the B3 bile duct, and the complete obstructed anastomosis was confirmed by percutaneous transhepatic and transjejunal approaches. The anastomosis was reopened by excising the scarred tissues from the jejunal side using a 1.5-mm high-frequency knife. A 14-Fr. catheter for the internal fistula tube was percutaneously placed at the opened anastomosis to achieve anastomotic site recanalization. The patient's liver damage improved after the re-internalization, and no symptom recurrence such as obstructive cholangitis developed for 1 year. There are few reports of recanalization of the hepaticojejunostomy with a high-frequency knife. Herein, we report the case with a literature review.

Serous cystic neoplasm (SCN) is a potentially malignant and invasive disease. However, there are no established guidelines regarding the surgical management of SCN. Here, we report a case of SCN with jejunal invasion that ultimately required a distal pancreatectomy with partial resection of the jejunum. The patient was a 65-year-old female who was referred to our department after a diagnosis of SCN in the pancreatic tail. CT and MRI showed a 75-mm multifocal cystic mass with calcifications; the splenic vein and left adrenal vein were entrapped within the tumor. Furthermore, the tumor was in contact with the beginning of the jejunum. Finally, she underwent a posterior radical antegrade modular pancreatosplenectomy with a partial wedge-shaped resection of the jejunum. Histological findings indicated serous cystadenoma. In addition, the tumor cells were found to have infiltrated the jejunal muscularis propria in some areas, suggesting that the tumor had malignant potential. Currently, 14 months have passed since surgery and there is no evidence of metastasis or recurrence. Surveillance and the decision to perform surgical resection should be made based on tumor size and growth rate to avoid malignant transformation as well as to provide SCN patients with organ-sparing, less invasive surgery.

Perineural invasion (PNI) is a characteristic invasion pattern of distal cholangiocarcinoma (DCC). Conventional histopathologic examination is a challenging approach to analyze the spatial relationship between cancer and neural tissue in full-thickness bile duct specimens. Therefore, we used a tissue clearing method to examine PNI in DCC with three-dimensional (3D) structural analysis. The immunolabeling-enabled 3D imaging of solvent-cleared organs method was performed to examine 20 DCC specimens from five patients and 8 non-neoplastic bile duct specimens from two controls. The bile duct epithelium and neural tissue were labeled with CK19 and S100 antibodies, respectively. Two-dimensional hematoxylin/eosin staining revealed only PNI around thick nerve fibers in the deep layer of the bile duct, whereas PNI was not identified in the superficial layer. 3D analysis revealed that the parts of DCC closer to the mucosa exhibited more nerves than the normal bile duct. The nerve fibers were continuously branched and connected with thick nerve fibers in the deep layer of the bile duct. DCC formed a tubular structure invading from the epithelium and extending around thin nerve fibers in the superficial layer. DCC exhibited continuous infiltration around the thick nerve fibers in the deep layer. This is the first study using a tissue clearing method to examine the PNI of DCC, providing new insights into the underlying mechanisms.

BACKGROUND: The differential diagnosis between gallbladder cancer (GBC) and xanthogranulomatous cholecystitis (XGC) remains quite challenging, and can possibly lead to improper surgery. This study aimed to distinguish between XGC and GBC by combining computed tomography (CT) images and deep learning (DL) to maximize the therapeutic success of surgery. METHODS: We collected a dataset, including preoperative CT images, from 28 cases of GBC and 21 XGC patients undergoing surgery at our facility. It was subdivided into training and validation (n = 40), and test (n = 9) datasets. We built a CT patch-based discriminating model using a residual convolutional neural network and employed 5-fold cross-validation. The discriminating performance of the model was analyzed in the test dataset. RESULTS: Of the 40 patients in the training dataset, GBC and XGC were observed in 21 (52.5%), and 19 (47.5%) patients, respectively. A total of 61 126 patches were extracted from the 40 patients. In the validation dataset, the average sensitivity, specificity, and accuracy were 98.8%, 98.0%, and 98.5%, respectively. Furthermore, the area under the receiver operating characteristic curve (AUC) was 0.9985. In the test dataset, which included 11 738 patches, the discriminating accuracy for GBC patients after neoadjuvant chemotherapy (NAC) (n = 3) was insufficient (61.8%). However, the discriminating model demonstrated high accuracy (98.2%) and AUC (0.9893) for cases other than those receiving NAC. CONCLUSION: Our CT-based DL model exhibited high discriminating performance in patients with GBC and XGC. Our study proposes a novel concept for selecting the appropriate procedure and avoiding unnecessary invasive measures.

BACKGROUND: Emphysematous pancreatitis is acute pancreatitis associated with emphysema based on imaging studies and has been considered a subtype of necrotizing pancreatitis. Although some recent studies have reported the successful use of conservative treatment, it is still considered a serious condition. Computed tomography (CT) scan is useful in identifying emphysema associated with acute pancreatitis; however, whether the presence of emphysema correlates with the severity of pancreatitis remains controversial. In this study, we managed two cases of severe acute pancreatitis complicated with retroperitoneal emphysema successfully by treatment with lavage and drainage. CASE PRESENTATION: Case 1: A 76-year-old man was referred to our hospital after being diagnosed with acute pancreatitis. At post-admission, his abdominal symptoms worsened, and a repeat CT scan revealed increased retroperitoneal gas. Due to the high risk for gastrointestinal tract perforation, emergent laparotomy was performed. Fat necrosis was observed on the anterior surface of the pancreas, and a diagnosis of acute necrotizing pancreatitis with retroperitoneal emphysema was made. Thus, retroperitoneal drainage was performed. Case 2: A 50-year-old woman developed anaphylactic shock during the induction of general anesthesia for lumbar spine surgery, and peritoneal irritation symptoms and hypotension occurred on the same day. Contrast-enhanced CT scan showed necrotic changes in the pancreatic body and emphysema surrounding the pancreas. Therefore, she was diagnosed with acute necrotizing pancreatitis with retroperitoneal emphysema, and retroperitoneal cavity lavage and drainage were performed. In the second case, the intraperitoneal abscess occurred postoperatively, requiring time for drainage treatment. Both patients showed no significant postoperative course problems and were discharged on postoperative days 18 and 108, respectively. CONCLUSION: Acute pancreatitis with emphysema from the acute phase highly indicates severe necrotizing pancreatitis. Surgical drainage should be chosen without hesitation in necrotizing pancreatitis with emphysema from early onset.

BACKGROUND: Evolutionary cancer has a supply mechanism to satisfy higher energy demands even in poor-nutrient conditions. Metabolic reprogramming is essential to supply sufficient energy. The relationship between metabolic reprogramming and the clinical course of pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to clarify the differences in metabolic status among PDAC patients. METHODS: We collected clinical data from 128 cases of resectable PDAC patients undergoing surgery. Sixty-three resected tissues, 15 tissues from the low carbohydrate antigen 19-9 (CA19-9), 38-100 U/mL, and high CA19-9, > 500 U/mL groups, and 33 non-tumor control parts, were subjected to tandem mass spectrometry workflow to systematically explore metabolic status. Clinical and proteomic data were compared on the most used PDAC biomarker, preoperative CA19-9 value. RESULTS: Higher CA19-9 levels were clearly associated with higher early recurrence (p < 0.001), decreased RFS (p < 0.001), and decreased DSS (p = 0.025). From proteomic analysis, we discovered that cancer evolution-related as well as various metabolism-related pathways were more notable in the high group. Using resected tissue immunohistochemical staining, we learned that high CA19-9 PDAC demonstrated aerobic glycolysis enhancement, yet no decrease in protein synthesis. We found a heterogeneity of various metabolic processes, including carbohydrates, proteins, amino acids, lipids, and nucleic acids, between the low and the high groups, suggesting differences in metabolic adaptive capacity. CONCLUSIONS: Our study found metabolic adaptation differences among PDAC cases, pertaining to both cancer evolution and the prognosis. CA19-9 can help estimate the metabolic adaptive capacity of energy supply for PDAC evolution.

Preoperatively accurate evaluation of risk for early postoperative recurrence contributes to maximizing the therapeutic success for intrahepatic cholangiocarcinoma (iCCA) patients. This study aimed to investigate the potential of deep learning (DL) algorithms for predicting postoperative early recurrence through the use of preoperative images. We collected the dataset, including preoperative plain computed tomography (CT) images, from 41 patients undergoing curative surgery for iCCA at multiple institutions. We built a CT patch-based predictive model using a residual convolutional neural network and used fivefold cross-validation. The prediction accuracy of the model was analyzed. We defined early recurrence as recurrence within a year after surgical resection. Of the 41 patients, early recurrence was observed in 20 (48.8%). A total of 71,081 patches were extracted from the entire segmented tumor area of each patient. The average accuracy of the ResNet model for predicting early recurrence was 98.2% for the training dataset. In the validation dataset, the average sensitivity, specificity, and accuracy were 97.8%, 94.0%, and 96.5%, respectively. Furthermore, the area under the receiver operating characteristic curve was 0.994. Our CT-based DL model exhibited high predictive performance in projecting postoperative early recurrence, proposing a novel insight into iCCA management.

INTRODUCTION: There have been reports about robotic surgery for rectal cancer with chemoradiotherapy (CRT), but only a few studies have compared the use of robotic surgery with and without neoadjuvant chemotherapy (NAC). The aim of our study was to compare the perioperative outcomes of robotic surgery with and without NAC for lower rectal cancer and to examine the effects of NAC on robotic surgery. METHODS: From January 2016 to July 2021, we compared the short-term outcomes of 45 patients who did not undergo NAC and 55 patients who underwent NAC. RESULTS: The rate of sphincter-preserving surgeries was higher in the NAC group than in the non-NAC group (P = .024). The total operative time was significantly longer in the NAC group than in the non-NAC group (P < .001). The rate of lateral lymph node dissection was significantly higher in the NAC group than in the non-NAC group (P < .001). No significant differences were identified in the rate of incisional surgical site infections (SSI), organ/space SSI postoperative bleeding, small bowel obstruction, anastomotic leakage, urinary dysfunction, or urinary infections between the groups. There were eight incidences of lateral lymph node metastasis (15%) and two cases with positive resection margins (4.0%) in the NAC group. CONCLUSIONS: Robotic surgery after NAC has few complications and a higher sphincter-preserving rate that without NAC.

BACKGROUND: Resectable pancreatic ductal adenocarcinoma (R-PDAC) often recurs early after radical resection, which is associated with poor prognosis. Predicting early recurrence preoperatively is useful for determining the optimal treatment. PATIENTS AND METHODS: One hundred and seventy-eight patients diagnosed with R-PDAC on computed tomography (CT) imaging and undergoing radical resection at Hirosaki University Hospital from 2005 to 2019 were retrospectively analyzed. Patients with recurrence within 6 months after resection formed the early recurrence (ER) group, while other patients constituted the non-early recurrence (non-ER) group. Early recurrence prediction score (ERP score) was developed using preoperative parameters. RESULTS: ER was observed in 45 patients (25.3%). The ER group had significantly higher preoperative CA19-9 (p = 0.03), serum SPan-1 (p = 0.006), and CT tumor diameter (p = 0.01) compared with the non-ER group. The receiver operating characteristic (ROC) curve analysis identified cutoff values for CA19-9 (133 U/mL), SPan-1 (78.2 U/mL), and preoperative tumor diameter (23 mm). When the parameter exceeded the cutoff level, 1 point was given, and the total score of the three factors was defined as the ERP score. The group with an ERP score of 3 had postoperative recurrence-free survival (RFS) of 5.5 months (95% CI 3.02-7.98). Multivariate analysis for ER-related perioperative and surgical factors identified ERP score of 3 [odds ratio (OR) 4.63 (95% CI 1.82-11.78), p = 0.0013] and R1 resection [OR 3.20 (95% CI 1.01-10.17), p = 0.049] as independent predictors of ER. CONCLUSIONS: For R-PDAC, ER could be predicted by the scoring system using preoperative serum CA19-9 and SPan-1 levels and CT tumor diameter, which may have great significance in identifying patients with poor prognoses and avoiding unnecessary surgery.

Perineural invasion (PNI) is a typical poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC). The mechanisms linking PNI to poor prognosis remain unclear. This study aimed to clarify what changes occurred alongside PNI in PDAC. A 128-patient cohort undergoing surgery for early-stage PDAC was evaluated. Subdivided into two groups, according to pathological state, a pancreatic nerve invasion (ne) score of less than three (from none to moderate invasion) was designated as the low-grade ne group. The high-grade (marked invasion) ne group (74 cases, 57.8%) showed a higher incidence of lymphatic metastasis (P = 0.002), a higher incidence of early recurrence (P = 0.004), decreased RFS (P < 0.001), and decreased DSS (P < 0.001). The severity of lymphatic (r = 0.440, P = 0.042) and venous (r = 0.610, P = 0.002) invasions was positively correlated with the ne score. Tumors having abundant stroma often displayed severe ne. Proteomics identified eukaryotic initiation factor 2 (EIF2) signaling as the most significantly enriched pathway in high-grade ne PDAC. Additionally, EIF2 signaling-related ribosome proteins decreased according to severity. Results showed that PNI is linked with lymphatic and vascular invasion in early-stage PDAC. Furthermore, the dysregulation of proteostasis and ribosome biogenesis can yield a difference in PNI severity.

OBJECTIVE: We aimed to investigate the real impact of allogeneic red blood cell transfusion (ABT) on postoperative outcomes in resectable pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: Of 128 patients undergoing resectable PDAC surgery at our facility, 24 (18.8%) received ABT. Recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ABT. RESULTS: In the entire cohort, ABT was significantly associated with decreased RFS (P = 0.002) and DSS (P = 0.014) before PSM. Cox regression analysis identified ABT (risk ratio, 1.884; 95% confidence interval, 1.015-3.497; P = 0.045) as an independent prognostic factor for RFS. Univariate and multivariate analysis identified preoperative hemoglobin value, preoperative total bilirubin value, and intraoperative blood loss as significant independent risk factors for ABT. Using these 3 variables, PSM analysis created 16 pairs of patients. After PSM, the ABT group had significantly poorer RFS rates than the non-ABT group (median, 9.8 vs 15.8 months, P = 0.022). Similar tendencies were found in DSS rates (median, 19.4 vs 40.0 months, P = 0.071). CONCLUSIONS: This study revealed certain negative effects of intraoperative ABT on postoperative survival outcomes in patients with resectable PDAC.

Pancreatic ductal adenocarcinoma (PDAC), with its extremely poor prognosis, presents a substantial health problem worldwide. Outcomes have improved thanks to progress in surgical technique, chemotherapy, pre-/postoperative management, and centralization of patient care to high-volume centers. However, our goals are yet to be met. Recently, exome sequencing using PDAC surgical specimens has demonstrated that the most frequently altered genes were the axon guidance genes, indicating involvement of the nervous system in PDAC carcinogenesis. Moreover, perineural invasion has been widely identified as one poor prognostic factor. The combination of innovative technologies and extensive clinician experience with the nervous system come together here to create a new treatment option. However, evidence has emerged that suggests that the relationship between cancer and nerves in PDAC, the underlying mechanism, is not fully understood. In an attempt to tackle this lethal cancer, this review summarizes the anatomy and physiology of the pancreas and discusses the role of the nervous system in the pathophysiology of PDAC.

PURPOSE: There are no reports showing the significance and effective range of dissection for patients with lateral lymph node metastasis (LLNM). This study aimed to investigate the indications for lateral lymph node dissection (LLND) in patients with LLNM based on prognostic factors and recurrence types. METHODS: We reviewed 379 patients with advanced rectal cancer who were treated with total mesorectal excision plus LLND. We analyzed background factors and survival times of patients who had LLNM to determine prognostic factors and recurrence types. RESULTS: Pathological LLNM occurred in 44 (11.6%). Among patients with LLNM, the predictors of poor prognoses, according to univariate analysis, were > 3 node metastases, the presence of node metastasis on both sides, and spreading beyond the internal iliac lymph nodes. Moreover, LLNM beyond the internal iliac region was found to be an independent prognostic risk factor. Twenty-eight of the 44 patients with lateral lymph node metastasis (64%) relapsed, 22 of whom had distant metastases and 11 of whom experienced local recurrences. Among the latter group, nine (20%) and two (5%) had recurrences in the central and lateral pelvis, respectively. CONCLUSION: The therapeutic benefit of resection was high, especially in patients with ≤ 3 positive lateral lymph nodes, one-sided bilateral lymph node areas, and positive nodes localized near the internal iliac artery.

BACKGROUND: Neoadjuvant chemoradiotherapy and total mesorectal excision comprise the standard of care for rectal cancer in multiple guidelines. However, neoadjuvant chemoradiotherapy has not exhibited clear survival benefits, but rather has led to an increase in adverse events. Conversely, neoadjuvant chemotherapy is expected to prevent adverse events caused by radiation, yet this treatment is still controversial. OBJECTIVE: To evaluate the feasibility and efficacy of S-1 and oxaliplatin neoadjuvant chemotherapy together with total mesorectal excision for resectable locally advanced rectal cancer. DESIGN: The study was a prospective, single-arm phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Fifty-eight patients with resectable locally advanced rectal cancer were enrolled. INTERVENTION: Three cycles of S-1 and oxaliplatin were administered before surgery. S-1 was administered orally at 80 mg/m2/day for 14 consecutive days, followed by a 7-day resting period. Oxaliplatin was given intravenously on the first day at a dose of 130 mg/m2/day. The duration of one cycle was considered to be 21 days. Total mesorectal excision with bilateral lymph node dissection was carried out after neoadjuvant chemotherapy. MAIN OUTCOME MEASURES: The study was designed to detect the feasibility and efficacy of S-1 and oxaliplatin as neoadjuvant chemotherapy. RESULTS: The completion rate of three courses of S-1 and oxaliplatin as neoadjuvant chemotherapy was 94.8% (55/58). The reasons for discontinuation were thrombocytopenia (3.4%) and liver injury (1.7%). The most common severe (grade ≥ 3) adverse effect of neoadjuvant chemotherapy was thrombocytopenia (3.4%). There were no severe adverse clinical symptoms. Consequently, R0 resection was achieved in 51 of 52 patients (98.1%). Pathological complete response occurred in 10 patients (19.2%). LIMITATIONS: This was a single-arm, nonrandomized phase II study. CONCLUSIONS: The combination of S-1 and oxaliplatin neoadjuvant chemotherapy and total mesorectal excision is a feasible and promising treatment option for resectable locally advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B555.

BACKGROUND: Intra-ampullary papillary-tubular neoplasm (IAPN) has been classified as a Vater papillary tumor. The prognosis of IAPN is generally relatively good. Here, we describe a patient with a mucinous adenocarcinoma cluster in the Vater papilla of IAPN origin. CLINICAL PRESENTATION: The patient was a 66-year-old man who was admitted to our hospital after a diagnosis of pancreatic head carcinoma based on a pancreatic duct dilatation found on abdominal ultrasound. CT showed a 40 mm lesion in the pancreatic head and expansion of the main pancreatic duct to a maximum diameter of 9 mm on the caudal side of the lesion. The extrahepatic bile duct had also expanded to a maximum diameter of 8 mm. PET/CT showed fluorodeoxyglucose (FDG) accumulation of SUVmax 6.02 that corresponded to the tumor in the pancreatic head, though it did not suggest distant metastasis. The patient was diagnosed with pancreatic head carcinoma T3 N0 M0 Stage IIA and underwent a pancreaticoduodenectomy. Pathology indicated that the tumor in the pancreatic head was a benign inflammatory lesion. On the other hand, the papillotubular tumor pervading the lumen in the duodenal papillary common channel met the criteria for IAPN, and a mucinous adenocarcinoma cluster found in the surrounding stroma suggested malignant transformation of IAPN. No metastasis to lymph nodes was demonstrated. With regard to the mucus phenotype of each lesion, the IAPN was MUC2 and MUC5AC positive, while the mucinous adenocarcinoma was MUC2-positive and MUC5AC-negative. In addition, CD10 was negative in both lesions, suggesting that mucus transformation from the gastric type to the intestinal type was a key element. A blood test 10 months after surgery showed increased CA19-9 (105 U/mL) and CEA (7.1 ng/mL). Abdominal CT showed multiple cystoid nodes in the liver, which were diagnosed as multiple liver metastases of mucinous adenocarcinoma transformed from the IAPN. CONCLUSIONS: We reported a case with IAPN that developed in the Vater papilla, which took an extremely malignant course. IAPN generally has a good prognosis, but it is important to understand that a malignant course may occur.

Massive intraoperative blood loss (IBL) negatively influence outcomes after surgery for pancreatic ductal adenocarcinoma (PDAC). However, few data or predictive models are available for the identification of patients with a high risk for massive IBL. This study aimed to build a model for massive IBL prediction using a decision tree algorithm, which is one machine learning method. One hundred and seventy-five patients undergoing curative surgery for resectable PDAC at our facility between January 2007 and October 2020 were allocated to training (n = 128) and testing (n = 47) sets. Using the preoperatively available data of the patients (34 variables), we built a decision tree classification algorithm. Of the 175 patients, massive IBL occurred in 88 patients (50.3%). Binary logistic regression analysis indicated that alanine aminotransferase and distal pancreatectomy were significant predictors of massive IBL occurrence with an overall correct prediction rate of 70.3%. Decision tree analysis automatically selected 14 predictive variables. The best predictor was the surgical procedure. Though massive IBL was not common, the outcome of patients with distal pancreatectomy was secondarily split by glutamyl transpeptidase. Among patients who underwent PD (n = 83), diabetes mellitus (DM) was selected as the variable in the second split. Of the 21 patients with DM, massive IBL occurred in 85.7%. Decision tree sensitivity was 98.5% in the training data set and 100% in the testing data set. Our findings suggested that a decision tree can provide a new potential approach to predict massive IBL in surgery for resectable PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is highly malignant. While cancers in other organs have shown clear improvements in 5-year survival, the 5-year survival rate of pancreatic cancer is approximately 10%. Early relapse and metastasis are not uncommon, making it difficult to achieve an acceptable prognosis even after complete surgical resection of the pancreas. Studies have been performed on various treatments to improve the prognosis of PDAC, and multidisciplinary approaches including non-surgical treatments have led to gradual improvement. In the present literature review, we have described the significance of anatomical and biological resectability criteria, the concept of R0 resection in surgical treatment, the feasibility of minimally invasive surgery, the remarkable development of perioperative chemotherapy, the effectiveness of conversion surgery for unresectable PDAC, and ongoing challenges in PDAC treatment. We also provide an essential update on these subjects by focusing on recent trends and topics.