An additional port in difficult laparoscopic cholecystectomy for surgical safety.

BACKGROUND: Tokyo Guidelines 2018, clinical practice guidelines for acute cholangitis and cholecystitis, recommend bailout procedures to prevent bile duct injury (BDI) during laparoscopic cholecystectomy (LC) for difficult gallbladder. We first insert an additional port (AP) for difficult gallbladder that may require bailout procedures. Because the usefulness of an AP during LC is unclear, we therefore examined the efficacy of the AP during LC in this study. METHODS: Data were collected from 115 patients who underwent LC for acute cholecystitis in our department. The indications for AP were excessive bleeding, scarring, and poor visual field around Calot's triangle. AP was inserted into the right middle abdomen so as not to interfere with other trocars and was used by the assistant. Surgical outcomes were evaluated based on AP use during LC. RESULTS: AP was inserted in 19 patients during LC (AP group). The indications for AP were excessive bleeding in nine patients, scarring around Calot's triangle in seven patients, and poor visual field around Calot's triangle in three patients. Open conversion was performed in two patients in the non-AP group. BDI occurred in one patient in the non-AP group. In patients with Difficulty Score 3, operation time was significantly shorter (P = .038) and Critical View of Safety (CVS) score was significantly higher in the AP group (P = .046). CONCLUSION: AP is useful in patients with excessive bleeding to shorten operation time and increase the CVS score. AP may be one useful option for difficult gallbladder.

Risk factors of unplanned intraoperative conversion to hand-assisted laparoscopic surgery or open surgery in laparoscopic liver resection.

BACKGROUND: Laparoscopic liver resection (LLR) is possible in many patients, but pure LLR is sometimes difficult to complete, and unplanned intraoperative hand-assisted laparoscopic surgery (HALS) or open conversion is sometimes necessary. However, appropriate indications and timing for conversion are unclear. This study aimed to clarify the indications for HALS and open conversion from pure LLR. METHODS: We collected data from 208 patients who underwent LLR from January 2010 to February 2021 in our department. We retrospectively examined these data between cases of unplanned intraoperative HALS conversion, open conversion, and pure LLR, and clarified risk factors and indications for HALS or open conversion. RESULTS: There were 191 pure LLRs, nine HALS conversions, and eight open conversions. In the HALS conversion group versus pure LLR group, body mass index (BMI) (27.0 vs. 23.7 kg/m2, p = 0.047), proportions of patients with history of upper abdominal surgery (78% vs. 33%; p = 0.006), repeat hepatectomy (56% vs. 15%; p = 0.002), S7 or S8 tumor location (67% vs. 35%; p = 0.049), and difficulty score (DS) ≥ 7 (56% vs. 19%; p = 0.008) were significantly higher, and surgical time (339 vs. 239 min; p = 0.031) was significantly longer. However, postoperative states were not significantly different between the two groups. The BMI cutoff value for risk of unplanned intraoperative conversion determined by receiver operating characteristic curve analysis was 25 kg/m2, and the proportion of patients with BMI ≥ 25 kg/m2 (89% vs. 31%, p < 0.001) was significantly higher in the HALS conversion versus pure LLR group. In the open conversion group, although there were no significant differences compared to the HALS group in clinicopathological factors except for sex, blood loss was greater (1425 vs. 367 mL; p < 0.001). CONCLUSION: Risk factors for considering HALS during LLR were patients with a history of upper abdominal surgery including repeat hepatectomy, BMI ≥ 25 kg/m2, S7 or S8 tumor location, DS ≥ 7, and prolonged surgical time. Furthermore, uncontrollable intraoperative bleeding was an indication for open conversion.

Minimally invasive anatomic liver resection: Results of a survey of world experts.

BACKGROUND: Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR. METHOD: We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs). RESULTS: All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound. CONCLUSION: Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.

The Tokyo 2020 terminology of liver anatomy and resections: Updates of the Brisbane 2000 system.

BACKGROUND: The Brisbane 2000 Terminology for Liver Anatomy and Resections, based on Couinaud's segments, did not address how to identify segmental borders and anatomic territories of less than one segment. Smaller anatomic resections including segmentectomies and subsegmentectomies, have not been well defined. The advent of minimally invasive liver resection has enhanced the possibilities of more precise resection due to a magnified view and reduced bleeding, and minimally invasive anatomic liver resection (MIALR) is becoming popular gradually. Therefore, there is a need for updating the Brisbane 2000 system, including anatomic segmentectomy or less. An online "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was hosted on February 23, 2021. METHODS: The Steering Committee invited 34 international experts from around the world. The Expert Committee (EC) selected 12 questions and two future research topics in the terminology session. The EC created seven tentative definitions and five recommendations based on the experts' opinions and the literature review performed by the Research Committee. Two Delphi Rounds finalized those definitions and recommendations. RESULTS: This paper presents seven definitions and five recommendations regarding anatomic segmentectomy or less. In addition, two future research topics are discussed. CONCLUSIONS: The PAM-HBP Surgery Consensus has presented the Tokyo 2020 Terminology for Liver Anatomy and Resections. The terminology has added definitions of liver anatomy and resections that were not defined in the Brisbane 2000 system.

Application of a novel surgical difficulty grading system during laparoscopic cholecystectomy.

BACKGROUND: Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS: We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2  = 0.870, 90% CI: 0.768-0.972). CONCLUSION: The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.

Expert Consensus Guidelines: How to safely perform minimally invasive anatomic liver resection.

BACKGROUND: The concept of minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was developed as a special program during the 32nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). METHODS: Thirty-four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network method. Based on the literature review and experts' opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021. RESULTS: Seven clinical questions were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round. CONCLUSIONS: The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts' opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR.

A snapshot of the 2020 conception of anatomic liver resections and their applicability on minimally invasive liver surgery. A preparatory survey for the Expert Consensus Meeting on Precision Anatomy for Minimally Invasive HBP Surgery.

BACKGROUND: The main aim of this survey was to analyze how liver surgeons perform liver resections and to define their conception of anatomic procedures within the incorporation of minimally invasive liver surgery (MILS). METHODS: The survey was distributed among liver surgeons. It mainly focused on personal experience on open and MILS, methods and landmarks, and experience on anatomic resections and Glissonean approach. RESULTS: A total of 445 valid answers from 54 countries was obtained. Surgeons performing MILS mainly have below 10 years of experience (81.8% of responders) and one third has never done complex MILS. New techniques, including indocyanine green demarcation are marginally used (<25%). More than 60% of surgeons do not make a full exposure of hepatic veins during MILS, mainly due to the risk of injury or not considering it to be of utility. Although 88% of responders agreed with the concept of anatomic resection as the "resection along the border/watersheds of each order division identified by the portal vein flow", only 55% of surgeons have ever performed MILS Glissonean approaches. CONCLUSIONS: Liver anatomy is not a static concept. Anatomic resections need training and precision. Standardization of complex anatomic resections by a minimally invasive approach should be encouraged.

Surgical and oncological outcomes of laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic ductal adenocarcinoma.

PURPOSE: To compare the outcomes of laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) with those of open RAMPS (O-RAMPS) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We reviewed, retrospectively, the medical records of 50 patients who underwent RAMPS for PDAC without resection of major vessels and adjacent organs between 2007 and 2019, and analyzed the relationship between the operative method and surgical and oncological outcomes. RESULTS: Nineteen of the 50 patients underwent L-RAMPS and 31 patients underwent O-RAMPS. L-RAMPS was associated with significantly less blood loss (P = 0.034) but a longer operative time (P = 0.001) than O-RAMPS. There were no significant differences in patient characteristics, tumor factors, or postoperative course; or in the rates of recurrence-free survival (P = 0.084) or overall survival (P = 0.402) between the L-RAMPS and O-RAMPS groups. CONCLUSION: L-RAMPS for PDAC resulted in less blood loss but a longer operative time than O-RAMPS. Although L-RAMPS may be feasible, the operative time needs to be reduced by standardizing the procedure.

How Should We Treat Pancreatic Metastases from Renal Cell Carcinoma? A Meta-Analysis.

BACKGROUND: The treatment strategy for pancreatic metastasis (PM) from renal cell carcinoma (RCC) is unclear due to its rarity. The aim of this study was to reveal the role of surgery for PM from RCC. METHODS: A systematic literature search was conducted using PubMed and the Cochrane Library. The effectiveness of surgery for PM was evaluated based on the primary outcome of overall survival (OS), which was investigated in relation to surgical procedures and metastatic sites via subgroup analyses. RESULTS: There was no significant difference in the rate of 2-year OS between the surgery and control group (OR 0.43, 95% CI 0.14-1.26, P = 0.12). However, the rate of 5-year OS was significantly higher in the surgery group than the control group (OR = 0.41, 95% CI 0.18-0.93, P = 0.03). The rates of the complications and OS were not significantly different between radical and conservative pancreatectomies. The rate of 5-year OS of the patients with PM was higher than that with other metastases (OR 0.38, 95% CI 0.20-0.74, P = 0.004). CONCLUSION: Surgical resection for PM from RCC is associated with good prognosis. Limited surgery may be a useful option depending on the location of the lesion.

Simultaneous quantification method for 5-FU, uracil, and tegafur using UPLC-MS/MS and clinical application in monitoring UFT/LV combination therapy after hepatectomy.

Combination therapy of tegafur/uracil (UFT) and leucovorin (LV) is widely used to treat colorectal cancers. Although this therapy has a significant therapeutic effect, severe adverse effects occur frequently. Therapeutic drug monitoring (TDM) may help to prevent adverse effects. A useful assay that can quantitate plasma levels of 5-FU, uracil, and tegafur simultaneously for TDM has been desired, but such a method is not currently available. In this study, we aimed to develop a sensitive method for simultaneous quantification of 5-FU, uracil, and tegafur in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). After preparing plasma samples by protein precipitation and liquid extraction, 5-FU, uracil, and tegafur were analyzed by UPLC-MS/MS in negative electrospray ionization mode. Validation was performed according to US Food and Drugs Administration guidance. The calibration curves were linear over concentration ranges of 2-500 ng/mL for 5-FU, 20-5000 ng/mL for uracil, and 200-50,000 ng/mL for tegafur. The corresponding average recovery rates were 79.9, 80.9, and 87.8%. The method provides accuracy within 11.6% and precision below 13.3% for all three analytes. Matrix effects of 5-FU, uracil, and tegafur were higher than 43.5, 84.9, and 100.2%, respectively. This assay was successfully applied to assess the time courses of plasma 5-FU, uracil, and tegafur concentrations in two patients with colorectal liver metastasis who received UFT/LV therapy after hepatectomy. In conclusion, we succeeded to develop a sensitive and robust UPLC-MS/MS method for simultaneous quantification of 5-FU, uracil, and tegafur in human plasma. This method is potentially useful for TDM in patients receiving UFT/LV combination therapy.

Development of an artificial intelligence system using deep learning to indicate anatomical landmarks during laparoscopic cholecystectomy.

BACKGROUND: The occurrence of bile duct injury (BDI) during laparoscopic cholecystectomy (LC) is an important medical issue. Expert surgeons prevent intraoperative BDI by identifying four landmarks. The present study aimed to develop a system that outlines these landmarks on endoscopic images in real time. METHODS: An intraoperative landmark indication system was constructed using YOLOv3, which is an algorithm for object detection based on deep learning. The training datasets comprised approximately 2000 endoscopic images of the region of Calot's triangle in the gallbladder neck obtained from 76 videos of LC. The YOLOv3 learning model with the training datasets was applied to 23 videos of LC that were not used in training, to evaluate the estimation accuracy of the system to identify four landmarks: the cystic duct, common bile duct, lower edge of the left medial liver segment, and Rouviere's sulcus. Additionally, we constructed a prototype and used it in a verification experiment in an operation for a patient with cholelithiasis. RESULTS: The YOLOv3 learning model was quantitatively and subjectively evaluated in this study. The average precision values for each landmark were as follows: common bile duct: 0.320, cystic duct: 0.074, lower edge of the left medial liver segment: 0.314, and Rouviere's sulcus: 0.101. The two expert surgeons involved in the annotation confirmed consensus regarding valid indications for each landmark in 22 of the 23 LC videos. In the verification experiment, the use of the intraoperative landmark indication system made the surgical team more aware of the landmarks. CONCLUSIONS: Intraoperative landmark indication successfully identified four landmarks during LC, which may help to reduce the incidence of BDI, and thus, increase the safety of LC. The novel system proposed in the present study may prevent BDI during LC in clinical practice.

Relationship between the tumor location and clinicopathological features in left-sided pancreatic ductal adenocarcinoma.

PURPOSE: Although the same distal pancreatectomy (DP) is performed regardless of the location of left-sided pancreatic ductal adenocarcinoma (PDAC), the clinicopathological features may differ depending on the tumor location. The present study investigated the relationship between the tumor location and clinicopathological features in patients with left-sided PDAC. METHODS: The records of 59 patients who underwent DP for PDAC were enrolled. The relationship between the tumor location and clinicopathological features was investigated. The tumor location was classified into three groups according to the 7th AJCC/UICC TNM classification: body (Pb), body and tail (Pbt), and tail (Pt). RESULTS: Tumors were located at the Pb in 26 patients, Pbt in 15, and Pt in 18. There was no metastasis to the lymph nodes around the common hepatic artery in Pt. The rate of peritoneal dissemination in the Pt was higher than that in the Pb (P = 0.034) or Pbt (P = 0.002). There were no significant differences in the overall survival among the three groups. CONCLUSION: There was no metastasis to the lymph nodes around the common hepatic artery, and peritoneal dissemination was the most common site of recurrence in Pt tumors.

Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021.

BACKGROUND: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. METHODS: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. CONCLUSIONS: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.

Efficacy of releasing impacted gallstones after percutaneous transhepatic gallbladder drainage for acute cholecystitis and consideration of the surgical difficulty during laparoscopic cholecystectomy.

INTRODUCTION: Laparoscopic cholecystectomy (LC) is considered difficult in patients with an impacted gallstone (IG). We examined the efficacy of releasing an IG after percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis (AC) and the usefulness of the Difficulty Score (DS) proposed in the Tokyo Guidelines 2018. METHODS: Data were collected from 28 patients who underwent LC after PTGBD for AC caused by an IG in our department. The IG was released by flushing the gallbladder with saline or performing cholecystography. Release of the IG was evaluated based on cholecystography or drainage findings. Surgical outcomes were evaluated by comparing whether the IG could be released. RESULTS: Nine patients had an IG (IG group) and 19 had a released IG at the time of surgery. Operation time was significantly longer (P = .008), Critical View of Safety score was significantly lower (P = .019), and DS was significantly higher (P < .001) in the IG group. In multivariate analysis, DS was the only independent factor for operation time (odds ratio = 8.943, 95% confidence interval 1.179-167.032; P = .033). CONCLUSION: Releasing an IG may reduce surgical difficulty and maintain surgical safety. DS can be useful in predicting surgical outcomes.

Short internal pancreatic stent reduces pancreatic fistula in pancreatoduodenectomy.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a major complication of pancreatoduodenectomy (PD). A pancreatic stent is usually used for drainage of the pancreatic duct, but the best type of the stent remains unclear. The aim of this study was to investigate perioperative factors and their influence on the risk of CR-POPF following PD. METHODS: From 2006 to 2019, the records of 246 patients who underwent PD were retrospectively reviewed, and the relationship between perioperative factors including type of pancreatic stent and CR-POPF was investigated. External or internal pancreatic stents were used for drainage of the pancreatic duct, and the internal stent was inserted 1 cm into the jejunum to decrease stent obstruction. RESULTS: External and internal pancreatic stents were used in 137 and 109 patients, respectively. Multivariate analysis revealed that the diameter of the main pancreatic duct (odds ratio = 0.292, 95% confidence interval = 0.140-0.605, P = 0.001), diagnosis (odds ratio = 3.359, 95% confidence interval = 1.498-7.693, P = 0.003), and type of pancreatic stent (odds ratio = 0.435, 95% confidence interval = 0.203-0.934, P = 0.033) were independent factors related to CR-POPF after PD. Internal stent was associated with a low rate of CR-POPF (P < 0.001) and short postoperative hospital stay (P < 0.001) compared to external stent. CONCLUSION: A short pancreatic internal stent could decrease the incidence of CR-POPF.

Assembling a library of typical surgery video clips to construct a system for assessing the surgical difficulty of laparoscopic cholecystectomy.

BACKGROUND: To explore best practices for acute cholecystitis, it is necessary to construct a system to assess the difficulty of laparoscopic cholecystectomy (LC) based on intraoperative findings. In this study, multiple evaluators assessed videos of LC to assemble a library of typical video clips for 25 intraoperative findings. METHODS: We have previously identified 25 items that contribute to surgical difficulty in LC. For each item, roughly 30-second video clips were submitted from videos of LC performed at member institutions. We then selected one typical video from the collected clips based on simple tabulation of the instances of agreement. Inter-rater agreement was assessed with Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except in the case of two assessment items ("edematous change" and "easy bleeding"), κ or AC significantly exceeded 0.5 and the typical videos were judged to be applicable. For the two remaining items, the evaluation was repeated after clarifying the definitions of positive and negative findings. Eventually, they were recognized as typical. The completed video clip library contains 31 clips and is divided into five categories (http://www.jshbps.jp/modules/project/index.php?content_id=13). CONCLUSIONS: This clip library may be highly useful in clinical settings as a more objective standard for assessing surgical difficulty in LC.

S6 ribosomal protein phosphorylation is associated with malignancy of intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Glucose metabolism of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is unclear. S6 ribosomal protein (S6) phosphorylation is involved not only in controlling cell growth but also in glucose metabolism in cancer. The aim of this study was to investigate the role of S6 phosphorylation and the significance of glucose metabolic changes in IPMN. METHODS: Records of 39 patients who underwent preoperative FDG-PET and curative resection were enrolled in this study. S6 phosphorylation and GLUT1 expression were evaluated immunohistochemically in these patients. The effect of S6 phosphorylation on glucose uptake was examined in cancer cell lines. To examine the change of glucose metabolism in IPMN clinically, the relation between clinical factors including FDG-PET and malignancy of IPMN was investigated. RESULTS: S6 phosphorylation and GLUT1 expression were significantly higher in carcinoma than in normal cells or adenoma. Cell lines with high level of S6 phosphorylation showed high glucose uptake, and inhibition of S6 phosphorylation reduced glucose uptake. In clinical examination, FDG-PET was the independent factor related to the diagnosis of adenoma or carcinoma (odds ratio = 20.0, 95% confidence interval = 1.837-539.9, P = .012). FDG-PET detected carcinoma with a sensitivity of 81.8%, specificity of 96.4%, and accuracy of 92.3%. CONCLUSION: S6 phosphorylation was associated with glucose uptake and malignancy of IPMN. Moreover, glucose uptake increased in malignant cells of IPMN, and FDG-PET is useful for detecting malignancy of IPMN.

Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.

BACKGROUND: Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented. However, few reports have investigated the association between dedifferentiation and glycosylation. Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation. METHODS: We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule. Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein ß-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans. RESULTS: Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans. Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones. Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components. Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis. CONCLUSION: Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans. MGAT1 may play a role in the dedifferentiation of HCC.

A case of ruptured mucinous cystadenoma of the pancreas with recurrence-free survival for 8 years.

BACKGROUND: Pancreatic mucinous cystic neoplasm (MCM) presenting with rupture is extremely rare, and very few studies have followed up patients over the long term after ruptured mucinous cystadenoma (MCA). We report a case of ruptured MCA of the pancreas with recurrence-free survival for 8 years. CASE PRESENTATION: A 28-year-old Japanese woman was admitted to the emergency department of a local hospital after experiencing acute abdominal pain. Abdominal computed tomography revealed massive ascites and the presence of a cystic tumor measuring 60 mm in diameter in the pancreatic tail. Conservative therapy with antibiotics and abdominal drainage were performed to treat peritonitis that occurred secondary to the ruptured pancreatic cystic tumor, after which the patient's symptoms improved. The patient was referred to our department for further examination and treatment. We diagnosed a ruptured MCN and performed laparoscopic spleen-preserving distal pancreatectomy. Histopathological findings revealed ovarian-type stroma, which tested positive for estrogen and progesterone receptors by immunohistochemistry. The histopathological diagnosis was MCA. The postoperative course was uneventful, and the patient remains alive without any evidence of recurrence at 8 years postoperatively. CONCLUSION: A good prognosis is possible even in cases of ruptured MCA. Because of the risk of peritoneal dissemination after ruptured MCA, long-term follow-up is important.

Fucosyltransferase 8 plays a crucial role in the invasion and metastasis of pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It is an aggressive malignancy associated with poor prognosis because of recurrence, metastasis, and treatment resistance. Aberrant glycosylation of cancer cells triggers their migration and invasion and is considered one of the most important prognostic cancer biomarkers. The current study aimed to identify glycan alterations and their relationship with the malignant potential of PDAC. METHODS: Using a lectin microarray, we evaluated glycan expression in 62 PDAC samples. Expression of fucosyltransferase 8 (FUT8), the only enzyme catalyzing core fucosylation, was investigated by immunohistochemistry. The role of FUT8 in PDAC invasion and metastasis was confirmed using an in vitro assay and a xenograft peritoneal metastasis mouse model. RESULTS: The microarray data demonstrated that core fucose-binding lectins were significantly higher in carcinoma than in normal pancreatic duct tissues. Similarly, FUT8 protein expression was significantly higher in carcinoma than in normal pancreatic duct tissues. High FUT8 protein expression was significantly associated with lymph-node metastases and relapse-free survival. FUT8 knockdown significantly reduced the invasion in PDAC cell lines and impaired peritoneal metastasis in the xenograft model. CONCLUSIONS: The findings of this study provide evidence that FUT8 plays a pivotal role in PDAC invasion and metastasis and might be a therapeutic target for this disease.