Mac-2 binding protein glycosylation isomer as a novel predictor of early recurrence after resection for hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) frequently recurs after radical resection, resulting in a poor prognosis. This study assessed the prognostic value of Mac-2 binding protein glycosylation isomer (M2BPGi) for early recurrence (ER) in patients with HCC. METHODS: Patients who underwent radical resection for HCC between 2015 and 2021. HCC recurrence within one year after curative resection was defined as ER. RESULTS: The 150 patients were divided into two groups: non-ER (116, 77.3%) and ER (34, 22.7%). The ER group had a lower overall survival rate (p < 0.0001) and significantly higher levels of M2BPGi (1.06 vs. 2.74 COI, p < 0.0001) than the non-ER group. High M2BPGi levels (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.31-2.41, p < 0.0001) and a large tumor size (OR 1.31, 95% CI, 1.05-1.63; p = 0.0184) were identified as independent predictors of ER. M2BPGi was the best predictor of ER according to a receiver operating characteristic (ROC) analysis (area under the ROC curve 0.82, p < 0.0001). CONCLUSIONS: M2BPGi can predict ER after surgery and is useful for risk stratification in patients with HCC.

A novel combined carbohydrate antigen 19-9 and lymphocyte-to-monocyte ratio score can predict early recurrence of resectable pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, which causes a poor prognosis. This study aimed to establish a scoring model to assess the optimal treatment in patients who underwent surgery for PDAC. METHODS: This single-center retrospective study included 127 patients who underwent radical resection for PDAC between 2005 and 2021. Early recurrence (ER) was defined as recurrence within 12 months after resection. The predictive effect for ER was evaluated using receiver operating characteristic (ROC) curves of preoperative parameters. RESULTS: ER occurred in 43 (33.9%) patients. The ER group had a significantly worse prognosis than the non-ER group (p < 0.0001). The carbohydrate antigen 19-9 (CA19-9) level and lymphocyte-to-monocyte ratio (LMR) were the strongest diagnostic factors (areas under the ROC curves: 0.74 and 0.68, respectively). The ER prediction score was calculated using optimal cutoff values. A higher CA19-9-LMR score was associated with a worse prognosis in terms of the overall and recurrence-free survival (p = 0.0017 and p < 0.0001, respectively). A multivariate analysis identified a high CA19-9-LMR score as an independent predictor of ER. CONCLUSIONS: The CA19-9-LMR scoring model can predict ER after surgery and is applicable for risk stratification in the assessment of patients with resectable PDAC.

Mac-2-Binding Protein Glycosylation Isomer as a Novel Predictor of Hepatocellular Carcinoma Recurrence in Patients with Hepatitis C Virus Eradication.

BACKGROUND: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) can recur even after achievement of a sustained virologic response (SVR). Mac-2-binding protein glycosylation isomer (M2BPGi) is a newly identified biomarker correlated with liver fibrosis. This study aimed to clarify outcomes for patients with an SVR and to assess the prognostic value of M2BPGi. METHODS: This single-center retrospective study analyzed patients who underwent surgical resection for primary HCV-related HCC between 2008 and 2018. The study enrolled 81 patients whose M2BPGi could be evaluated after an SVR. The relationship between liver fibrosis-related factors and scores (including M2BPGi) and HCC recurrence, was evaluated. RESULTS: Of the 81 patients, 57 (70.4%) with HCV-related HCC obtained an SVR, whereas 24 patients (29.6%) did not. The patients with an SVR had a significantly more favorable recurrence-free survival (RFS) than the patients with no SVR (P < 0.0001, log-rank). Among the SVR groups, M2BPGi predicted a shorter RFS after hepatic resection with a higher degree of accuracy than other markers and scores in the SVR group. The high-M2BPGi group had worse liver function, RFS, and overall survival (OS) (P = 0.0014 and 0.0006, log-rank, respectively). In the multivariate analysis, high M2BPGi was significantly associated with worse RFS and OS. CONCLUSIONS: Even after achievement of an SVR, the risk of HCC recurrence cannot be eliminated. Measurement of M2BPGi after an SVR can be applied for risk stratification in the assessment of patients with HCV-related HCC.

Impact of aspartate aminotransferase-to-platelet ratio index based score to assess posthepatectomy liver failure in patients with hepatocellular carcninoma.

BACKGROUND: Posthepatectomy liver failure (PHLF) is a life-threatening complication following hepatic resection. The aspartate aminotransferase-to-platelet ratio index (APRI) is a non-invasive model for assessing the liver functional reserve in patients with hepatocellular carcinoma (HCC). This study aimed to establish a scoring model to stratify patients with HCC at risk for PHLF. METHODS: This single-center retrospective study included 451 patients who underwent hepatic resection for HCC between 2004 and 2017. Preoperative factors, including non-invasive liver fibrosis markers and intraoperative factors, were evaluated. The predictive impact for PHLF was evaluated using receiver operating characteristic (ROC) curves of these factors. RESULTS: Of 451 patients, 30 (6.7%) developed severe PHLF (grade B/C). Multivariate logistic analysis indicated that APRI, model for end-stage liver disease (MELD) score, operating time, and intraoperative blood loss were significantly associated with severe PHLF. A scoring model (over 0-4 points) was calculated using these optimal cutoff values. The area under the ROC curve of the established score for severe PHLF was 0.88, which greatly improved the predictive accuracy compared with these factors alone (p < 0.05 for all). CONCLUSIONS: The scoring model-based APRI, MELD score, operating time, and intraoperative blood loss can predict severe PHLF in patients with HCC.

A novel combined prognostic nutritional index and aspartate aminotransferase-to-platelet ratio index-based score can predict the survival of patients with hepatocellular carcinoma who undergo hepatic resection.

PURPOSE: Inflammation-, nutrition-, and liver fibrosis-related markers are recognized as prognostic for hepatocellular carcinoma (HCC) patients. This study, therefore, assessed the preoperative prognostic utility of the combination of these markers in patients with HCC. METHODS: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2004 and 2017. A total of 454 patients were divided into training (n = 334) and validation (n = 120) cohorts by random sampling. The predictive impact on surgical outcomes was evaluated using receiver operating characteristic (ROC) curves of these prognostic values in the training cohort. RESULTS: The prognostic nutritional index (PNI) and aspartate aminotransferase-to-platelet ratio index (APRI) were the strongest diagnostic values (areas under the ROC curves: 0.627 and 0.646, respectively). A scoring system (over 0-2 points) was developed using optimal cutoff values (for PNI < 46.5 scored as 1 point; for APRI > 0.98 scored as 1 point). An increased PNI-APRI score was an independent prognostic factor for both the overall and disease-free survival in HCC patients. Finally, the clinical feasibility of the PNI-APRI score was confirmed in the validation cohort. CONCLUSIONS: The PNI-APRI score is a useful marker for predicting surgical outcomes of HCC patients.

Evaluation of the 10-year history of a 2-day standardized laparoscopic surgical skills training program at Kyushu University.

PURPOSE: Laparoscopic and open surgical skills differ distinctly from one another. Our institute provides laparoscopic surgical skills training for currently active surgeons throughout Japan. This study was performed to evaluate the effectiveness of our 2-day standardized laparoscopic surgical skills training program over its 10-year history. METHODS: We analyzed the data on trainee characteristics, outcomes of skills assessments at the beginning and end of the program, and self-assessment after 6 months using a questionnaire survey. RESULTS: From January 2004 to December 2013, 914 surgeons completed the 2-day training program. Peaks in postgraduate years of experience occurred at years 2, 8, and 17. Suturing and knot tying times were significantly shorter at the end than beginning of the program (p < 0.001). However, the numbers of misplaced and loose sutures, maximum misplacement distance, and number of injuries to the rubber sheet were significantly higher at the end of the program (p < 0.001). A questionnaire at 6 months post-training revealed significant improvements in the overall skills and forceps manipulation (p < 0.0001) and a significantly shorter mean operation time for laparoscopic cholecystectomy (p < 0.001). CONCLUSION: Our 2-day training program for active Japanese surgeons is thus considered to be effective; however, continued voluntary training is important and further outcomes assessments are needed.

Minimally invasive image analysis of biliary-pancreatic structure for preoperative simulation.

For preoperative assessment of the pancreatic tumors, we developed minimally invasive method to extract the pancreatic duct from multidetector row computed tomography (MD-CT) images and to visualize the biliarypancreatic structures, tumor and adjacent organs simultaneously using an image workstation.

A case of difficult-to-diagnose hepatic reactive lymphoid hyperplasia finally diagnosed by using PCR analysis of IgH-gene rearrangements: a case report.

Reactive lymphoid hyperplasia (RLH) of the liver is extremely rare. Despite advancements in diagnostic imaging technology, it is still difficult to distinguish from hepatocellular carcinoma (HCC). Herein, we present a case of hepatic RLH mimicking HCC that was postoperatively diagnosed using several imaging modalities. A 78-year-old female was referred to our hospital with a positive hepatitis C virus antibody (HCV Ab) test. Ultrasonography revealed a 13 mm isoechoic lesion in segment 8 of the liver. Contrast-enhanced computed tomography (CE-CT) demonstrated arterial hyperintensity and washout during the later phase. On ethoxybenzyl magnetic resonance imaging (EOB-MRI), the lesion was hyperenhanced in the arterial phase and of low intensity in the hepatocyte phase. Although the tumor markers were all within normal limits, the pattern of contrast enhancement of the tumor on CT and MRI was consistent with that of HCC. We performed S8 segmentectomy of the liver. Histological examination of the resected specimen revealed dense lymphoid tissue of variable sizes and shapes with expanded germinal centers. Immunohistochemical examination was positive for CD3, CD10 (germinal center), and CD20, and negative for B-cell lymphoma 2 (bcl-2) (germinal center) and Epstein-Barr virus (EBV). A polymerase chain reaction (PCR) analysis of IgH-gene rearrangements revealed polyclonality. Based on these findings, hepatic RLH was diagnosed. The postoperative course was uneventful, and the patient was discharged on the 10th postoperative day. She had a good quality of life after surgery and no liver nodule recurrence was detected at the 4-month medical follow-up. Hepatic RLH is an extremely rare disease and preoperative diagnosis is difficult. This should be considered in the differential diagnosis of single small hepatic tumors. An echo-guided biopsy and careful observation of imaging may help diagnose hepatic RLH, and a PCR analysis of IgH-gene rearrangements would be necessary for the definitive diagnosis of hepatic RLH.

Skeletal Muscle Mass Index Reduction Rate as a Prognostic Indicator for Patients Undergoing Pancreatectomy for Pancreatic Cancer.

Background/Aim: There have been many studies on skeletal muscle depletion before surgery, and skeletal muscle depletion is a known risk factor for poor prognosis. However, reports on the association between changes in skeletal muscle mass and prognosis after surgery for pancreatic cancer are very few. Patients and Methods: The data of 137 patients who underwent pancreatectomy for pancreatic cancer between 2005 and 2022 were reviewed. Muscle areas were measured at the third lumbar vertebral level, and skeletal muscle mass index (SMI) reduction rates were calculated. Patients were divided into two groups using receiver operating characteristic (ROC) curve analysis based on the SMI reduction rate with a cutoff of 14% reduction rate. The clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS) were compared between the two groups. Survival rates were analyzed both univariately and multivariately to clarify the factors associated with poor prognosis after pancreatectomy. Results: A total of 102 patients met the inclusion criteria. SMI reduction rate ≥14% significantly correlated with advanced age and higher incidence of postoperative complications. In the multivariate Cox regression analysis, preoperative prognostic nutritional index (PNI) <40 and SMI reduction rate ≥14% were significantly associated with poor OS. Tumor size ≥3.0 cm, preoperative neutrophile-lymphocyte ratio ≥3.0, and SMI reduction rate ≥14% were significantly associated with poor RFS. Conclusion: The rate of skeletal muscle mass reduction after pancreatic surgery is an independent prognostic factor for survival in patients with pancreatic cancer.

Image-guided laparoscopic surgery in an open MRI operating theater.

BACKGROUND: The recent development of open magnetic resonance imaging (MRI) has provided an opportunity for the next stage of image-guided surgical and interventional procedures. The purpose of this study was to evaluate the feasibility of laparoscopic surgery under the pneumoperitoneum with the system of an open MRI operating theater. METHODS: Five patients underwent laparoscopic surgery with a real-time augmented reality navigation system that we previously developed in a horizontal-type 0.4-T open MRI operating theater. RESULTS: All procedures were performed in an open MRI operating theater. During the operations, the laparoscopic monitor clearly showed the augmented reality models of the intraperitoneal structures, such as the common bile ducts and the urinary bladder, as well as the proper positions of the prosthesis. The navigation frame rate was 8 frames per min. The mean fiducial registration error was 6.88 ± 6.18 mm in navigated cases. We were able to use magnetic resonance-incompatible surgical instruments out of the 5-Gs restriction area, as well as conventional laparoscopic surgery, and we developed a real-time augmented reality navigation system using open MRI. CONCLUSIONS: Laparoscopic surgery with our real-time augmented reality navigation system in the open MRI operating theater is a feasible option.

Prognostic Impact of a Novel Albumin-Platelet Index as Selection Criterion for Hepatic Resection in Intermediate Stage Hepatocellular Carcinoma.

BACKGROUND/AIM: Hepatic resection for Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate-stage) hepatocellular carcinoma (HCC) is not recommended by BCLC treatment algorithms. We sought to develop a new prognostic model for determining appropriate treatment strategies in patients with intermediate-stage HCC. PATIENTS AND METHODS: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2000 and 2018. A total of 498 patients were classified according to the BCLC staging system (0, n=116; A, n=319; B, n=63). The predictive impact for surgical outcomes was evaluated using receiver operating characteristic (ROC) curves. Based on a survival outcome probability formula, a new predictive model was established. RESULTS: The preoperative albumin level and platelet count were the strongest diagnostic values in patients with intermediate-stage HCC (areas under the ROC curves, AUCs: 0.710 and 0.676, respectively). Logistic regression analysis provided the albumin-platelet index [API; 156.2×albumin (g/dl)+platelet count (×109/l)] was defined as a new prognostic model for the probability of poor survival. The optimal cutoff value (781.2; AUC 0.755) divided patients with BCLC-B into B1 (>781.2, n=27) and B2 (≤781.2, n=36) categories. Patients in substage B2 had a significantly worse prognosis than patients in other stages (p<0.0001), whereas there was no difference in prognosis between patients in substage B1 and those in other stages. CONCLUSION: The API stratifies prognosis in patients with intermediate-stage HCC. For subgroup B1, hepatic resection can be considered a radical treatment, even for intermediate-stage HCC.

Prognostic Impact of Lymphocyte-C-Reactive Protein Ratio in Patients Who Underwent Surgical Resection for Hepatocellular Carcinoma.

BACKGROUND: Systemic inflammation-related factors, either independently or in combination, are recognized as prognostic factors for various cancers. The ratio of lymphocyte count to C-reactive protein concentration (lymphocyte-CRP ratio; LCR) is a recently identified prognostic marker for several cancers. Here, we examined the prognostic value of the LCR in patients with hepatocellular carcinoma (HCC). METHODS: This was a single-center retrospective study of patients who underwent surgical resection for HCC between 2004 and 2017. Patients were divided into high- and low-LCR status groups, and the relationships between LCR status, prognosis, and other clinicopathological characteristics were analyzed. RESULTS: A total of 454 patients with HCC were enrolled and assigned to the high- (n=245) or low- (n=209) LCR groups. Compared with the high-LCR group, patients in the low-LCR group had a significantly lower serum albumin level (median 4.1 vs. 3.9 g/dL, P <0.0001), lower platelet count (median 14.0 vs. 12.0 ×104/µL, P=0.0468), lower prothrombin time (median 93.2 vs. 89.6 %, P=0.0006), and larger tumor size (median 2.3 vs. 2.5 cm, P=0.0056). Patients with low-LCR status had significantly worse outcomes of overall survival and disease-free survival than patients with high-LCR status (P=0.0003 and P=0.0069, respectively). Low-LCR status was significantly associated with worse overall survival in multivariate analysis (hazard ratio 1.57, 95% confidence interval 1.14-2.17, P=0.0058). CONCLUSIONS: Low-LCR status may predict worse outcomes in patients with HCC. Measurement of LCR is routine and can easily be applied for risk stratification in the assessment of patients with HCC.

Objective assessment of laparoscopic suturing skills using a motion-tracking system.

BACKGROUND: Laparoscopic suturing skills are important for advanced laparoscopic surgery. However, objective assessment of these skills has not yet been established. The aim of this study was to assess the laparoscopic suturing skills of novice and experienced surgeons using an electromagnetic motion-tracking system. METHODS: A total of 18 surgeons, who were all right-handed, were divided into the following two groups according to their experience as an operator in laparoscopic surgery: 9 novice surgeons (fewer than 10 laparoscopic procedures) and 9 experienced surgeons (more than 50 laparoscopic procedures). The subjects performed an intracorporeal suturing task in an inanimate box laparoscopic trainer while the movements of their forceps were evaluated using an electromagnetic motion-tracking system. Their laparoscopic skills were assessed on the basis of the time, path length, and average speed of the forceps in each hand. RESULTS: Experienced surgeons completed the suturing task significantly faster than novice surgeons did. The left path length was significantly shorter for experienced surgeons than for novice surgeons, whereas the right path lengths did not differ. The right average speed of knot tying was significantly faster for experienced surgeons than for novice surgeons, whereas the left average speeds did not differ. CONCLUSIONS: Evaluation of psychomotor skills in laparoscopic suturing using an electromagnetic motion-tracking system revealed better results for experienced surgeons than for novice surgeons in terms of the time taken, left path length, and right speed of knot-tying. Furthermore, surgical proficiency due to experience can affect surgical dexterity of each hand differently. The present study also demonstrates the efficacy of this system for objective evaluation of laparoscopic suturing skills.

Successful closure with covered self-expandable metal stent for severe anastomotic leakage in the cervical esophagus.

Anastomotic leakage is one of the major complications of esophageal surgery with a high mortality rate and significant morbidity. We describe a case of severe anastomotic leakage close to the hypopharynx after esophageal cancer resection. Despite the conservative management with external drainage, the severe leak did not improve. A fully covered self-expandable metal stent (SEMS) with short flares, which was designed for the cervical esophagus, was subsequently placed bridging the anastomosis to seal the fistula. The post-procedural course was uneventful, and the stent was endoscopically removed after three weeks without any complications. The patient was discharged home three weeks after the stent removal. Our results suggest that placement of fully covered SEMS with short flares may be a safe and effective treatment in this condition of patients.

Value of laparoscopic splenectomy as salvage treatment for relapsed thrombocytopenia after partial splenic arterial embolization.

BACKGROUND/AIMS: Recently, partial splenic arterial embolization (PSE) has become a supportive intervention for cirrhotic patients with hypersplenism in the administration of interferon therapy. However, relapsed thrombocytopenia is often observed in patients following PSE. This study aimed to report the clinical efficiency of laparoscopic splenectomy as a salvage treatment for relapsed thrombocytopenia following PSE. METHODS: From 2005 to 2009, 6 patients with prior PSE treatment underwent laparoscopic splenectomy. We reviewed the surgical method of laparoscopic splenectomy and the peri- and postoperative outcomes. RESULTS: Laparoscopic splenectomy effectively provided sufficient increases in patient platelet counts. In all patients, laparoscopic splenectomy was performed safely with no significant complications despite PSE-associated dense adhesion to the diaphragm and/or retroperitoneal attachments. CONCLUSION: Laparoscopic splenectomy provides a sufficient increase in patient platelet counts in relapsed thrombocytopenia following PSE. Therefore, laparoscopic splenectomy appears to be a superior supportive therapy for the treatment of thrombocytopenia in cirrhotic patients.

Skills assessment using a virtual reality simulator, LapSim, after training to develop fundamental skills for endoscopic surgery.

Education and training to maintain medical safety are very important within clinical settings. We have established a training center for endoscopic surgery and we regularly hold a unique training course, which focuses on the development of fundamental skills. One hundred and ninety-four surgeons who participated in our training course were divided into four groups according to their experience in performing laparoscopic procedures. Group 1: 0-19 laparoscopic procedures (n=44). Group 2: 20-49 laparoscopic procedures (n=53). Group 3: 50-99 laparoscopic procedures (n=46). Group 4: more than 100 laparoscopic procedures (n=55). All subjects underwent evaluation for "Lifting & Grasping" using a virtual reality (VR) simulator, LapSim, before and after the training course. The mean efficiency score, time to completion and tissue damage after training were significantly improved after the training as compared with before training. Before training, subjects with greater experience had better scores. However, the only significant difference in the score was between the low experience group and greatest experience group. After training, the score increased in all groups compared with that before training, and there was no significant difference between groups. This study demonstrates the feasibility of using a VR simulator to assess fundamental skills for endoscopic surgery after training. We found that the scores for the task were associated with the level of experience of the surgeons.

[Future perspective of gastrointestinal 'intelligent' endoscopy].

Although the flexible endoscopy has been widely used in the medical field for many years, there is still great potential in improving the endoscopist's capability to perform therapeutic tasks. The application of flexible endoscopy tools for natural orifice translumenal endoscopic surgery (NOTES) is constrained due to limitations in dexterity, instrument insertion, navigation, visualization, and retraction. Miniature endolumenal robots can mitigate these constraints by providing a stable platform for visualization and dexterous manipulation. In this paper, we describe the high-functioned 'intelligent' endoscopic surgery system with navigation. This system has equipped with accurate master-slave manipulation micro arms which can be used in tandem with a conventional flexible endoscope. The system also has an integrated ultrasound probe and high intensity focused ultrasound (HIFU) applicator. With the continued development of the techniques and technology of intelligent endoscopy, innovative minimally invasive personalized therapy may realize.

Large surgically resected leiomyosarcoma of the liver: a case report.

BACKGROUND: Primary hepatic leiomyosarcoma (PHL) is an extremely rare type of tumor. We herein report a case of a large surgically resected leiomyosarcoma of the liver. CASE PRESENTATION: A 69-year-old man with a feeling of epigastric compression was referred for examination of an abdominal mass. He had no history of liver disease or alcohol abuse. Liver function tests indicated Child-Pugh class A. Tumor markers were negative. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a relatively well-contrasted 12 × 11 × 8 cm tumor with well-defined boundary replacing the lateral segment of the liver alongside multiple intrahepatic metastases. Several nodules up to 12 mm were found in both lungs, suggestive of metastasis. SUVmax of the liver mass and lung tumor in positron emission tomography were 10.4 and 1.5, respectively. Hepatocellular carcinoma was primarily suspected. Lateral segmentectomy of the liver was performed to confirm diagnosis and prevent tumor rupture. Macroscopically, the lateral segment of the liver had been replaced by a lobular or multinodular tumor with a maximum diameter of 15 cm. In pathological findings, the tumor consisted of bundle-like proliferation of complicated banding spindle-like cells with clear cytoplasm, accompanied by storiform pattern and compressed blood vessels. Nuclear fission images were observed in 8/10 HPF. Partial necrosis was present, with associated venous invasion and intrahepatic metastasis. Immunohistochemical staining for tumor cells revealed desmin, α-smooth muscle actin (αSMA), and h-caldesmon were all positive, informing a final diagnosis of PHL. The postoperative course was uneventful, and he was discharged on the 12th postoperative day. CONCLUSIONS: PHL is a rare malignant disease with relatively poor prognosis. To confirm a diagnosis of PHL, immunohistochemical analysis as well as histopathological findings is important. The preferred treatment is surgical resection, sometimes in combination with adjuvant chemotherapy and radiotherapy. Further studies are needed to elucidate and better understand this uncommon clinical entity.

A case of perforation of Meckel's diverticulum with enterolith.

BACKGROUND: Perforation of Meckel's diverticulum with enteroliths is a rare complication. Here, we report a case of perforation of Meckel's diverticulum with one enterolith, which could not be accurately diagnosed by preoperative computed tomography. CASE PRESENTATION: A 16-year-old male patient with acute onset of severe abdominal pain and a localized muscle guarding in the right hypochondrium had a solitary stone detected in the right abdomen by radiography. Abdominal computed tomography revealed a saclike outpouching of the small intestine, which contained fluid levels and an enterolith, with a mesenteric inflammatory change in the right paraumbilical area. He was diagnosed with peritonitis due to appendicitis or Meckel's diverticulitis with enterolith, and emergency operation was indicated. The perforated Meckel's diverticulum was identified approximately 30 cm proximal to the ileocecal valve. The diverticulum was transected at the base and removed. The patient's postoperative course was uneventful. CONCLUSIONS: It is crucial for clinicians to thoroughly examine patients and appropriately request investigations that consider perforation of Meckel's diverticulum as a possible diagnosis to facilitate prompt treatment.

Mixed adenoneuroendocrine carcinoma of the distal bile duct: a case report.

BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) of the common bile duct (CBD) is very rare, with only 10 reported cases. Here, we report a case of MANEC of the distal bile duct (DBD) that was surgically resected under a diagnosis of cholangiocarcinoma (CCA). CASE PRESENTATION: A 60-year-old male had epigastric pain and was admitted to our hospital for the treatment of a suspected CBD stone. Upon admission, laboratory findings revealed elevated hepatobiliary enzymes including serum aspartate aminotransferase, serum alanine aminotransferase, serum glutamyltransferase, and serum alkaline phosphatase. Both carcinoembryonic antigen and carbohydrate antigen 19-9 were negative. Computed tomography (CT) showed dilation of the CBD. Endoscopic retrograde cholangiopancreatography (ERCP) showed circumferential stenosis and a 5-mm elevated lesion in the DBD. Brush cytology showed atypical ductal cells, indicating adenocarcinoma (AC) of the DBD. Under a diagnosis of CCA of the DBD, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Neither peritoneal dissemination nor lymph node metastasis was found. Microscopically, the lesion was seen to be composed of predominantly well-differentiated tubular AC in the superficial layer of the tumor, admixed with neuroendocrine carcinoma (NEC) in the deeper portion, indicating a diagnosis of MANEC of the DBD. After immunohistochemical staining, NEC components were positive for synaptophysin and CD56 and were for SSTR2, SSTR5, and mammalian target of rapamycin (mTOR). Three months postsurgery, postoperative adjuvant chemotherapy with S-1 was started. More than 3 years postsurgery, he is alive without recurrence. CONCLUSIONS: MANEC is highly malignant, progresses rapidly, and has a poor prognosis. Preoperative diagnosis is difficult; therefore, identifying NEC components by immunohistochemical staining using resected specimens is important.