Atezolizumab, an immune checkpoint inhibitor (ICI), became available for treating hepatocellular carcinoma (HCC) in 2020. It is now widely used in combination with bevacizumab for advanced HCC. However, ICI has been reported to cause severe immune-related adverse events (irAEs), and reports in the treatment of HCC are still very rare. We report a case of autoimmune encephalitis as an irAE in a patient undergoing ICI therapy for HCC. A 66-year-old Japanese man was diagnosed with multiple HCC in the parenchyma of both liver lobes. We initiated combination treatment with atezolizumab and bevacizumab. On day 8, the patient had symptoms of fever, diarrhea, and loss of appetite and was transferred to our hospital due to impaired consciousness on day 10. He was restless and incoherent. Analysis of cerebrospinal fluid revealed an elevated monocyte count. The patient was diagnosed with autoimmune encephalitis due to ICI and started treatment with methylprednisolone 1,000 mg for 3 days. On the second day of treatment, his consciousness improved dramatically, and he was discharged on day 13. The frequency of ICI therapy will increase; therefore, it is necessary to understand the rare irAEs due to ICIs. Moreover, prompt diagnosis and early administration of steroids may contribute to a successful response.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and challenging cancers, causing substantial mortality worldwide. Despite advancements in treatment modalities, the prognosis for patients with PDAC remains dismal, emphasizing the critical need for identifying factors influencing early recurrence and survival post-surgery. This study aimed to clarify the risk factors for early recurrence (within 1 year) in patients who underwent upfront surgery for resectable PDAC.

Background/Aim: Although minimally invasive distal pancreatectomy (MIDP) has become a treatment option for benign and malignant pancreatic tumors, the safety and efficacy of reinforced staplers in MIDP remain controversial. The present study was performed to evaluate the safety of reinforced staplers in MIDP and identify the risk factors for postoperative pancreatic fistula (POPF) after MIDP with reinforced staplers. Patients and Methods: In total, 92 consecutive patients who underwent MIDP at NHO Kyushu Medical Center from July 2016 to August 2023 were enrolled in this retrospective study. In all patients, a reinforced black cartridge triple-row stapler (Covidien Japan, Tokyo, Japan) was used during MIDP. The primary endpoint was the incidence of clinically relevant POPF. The risk factors for POPF were evaluated using multivariate analysis. Results: Among the 92 patients, 74 underwent laparoscopic distal pancreatectomy and 18 underwent robot-assisted distal pancreatectomy. Clinically relevant POPF occurred in seven (7.6%) of 92 patients. The rate of severe complications (Clavien-Dindo grade >= III) was 10.8%, and the mortality rate was 0%. The median postoperative hospital stay was 14 days. Multivariate logistic regression analysis showed that the independent risk factor for clinically relevant POPF after MIDP with a reinforced stapler was a body mass index of >= 22.6 kg/m2 2 (p=0.050, odds ratio=7.60). Conclusion: This study confirmed the safety and efficacy of reinforced staplers for preventing POPF after MIDP. A high body mass index

This study aimed to clarify local recurrence (LR) predictive factors following intraoperative microwave ablation (MWA) for colorectal liver metastases. The data from 195 patients with 1392 CRLM lesions, who were preoperatively diagnosed by gadolinium-enhanced MRI with diffusion-weighted imaging and dynamic CT and treated with intraoperative MWA (2450 MHz) with or without hepatectomy, from January 2005 to December 2019, were retrospectively reviewed and analyzed using logistic regression. In addition, the margins were measured on contrast-enhanced CT 6 weeks post-ablation. Overall, 1066 lesions were ablated. The LRs occurred in 44 lesions (4.1%) among 39 patients (20.0%). The multivariate analysis per patient showed that tumor size > 20 mm and ablation margin < 5 mm were significant predictors for LR. Furthermore, multivariate analysis per lesion revealed that segments 1, 7, and 8 and tumor size > 15 mm, ablation margin < 5 mm, tumor size > 20 mm, and proximity to the Glisson were significant LR predictors. Finally, the outcome of this study may help determine indications for MWA.

Abdominal computed tomography revealed a 19×13mm delayed enhancing mass and dilation of the distal pancreatic duct in the head of the pancreas. Magnetic resonance cholangiopancreatography showed pancreatic duct stenosis in the tail of the pancreas. Endoscopic retrograde pancreatography revealed an abrupt interruption of the main pancreatic duct at the tail of the pancreas. We could not assess the distal side of the pancreatic stenosis due to the large extent of obstruction. The pancreatic head mass was diagnosed as adenocarcinoma using endoscopic ultrasound-fine needle aspiration biopsy. However, we could not determine whether the pancreatic duct stenosis in the tail of the pancreas was malignant. Nevertheless, we performed a total pancreatectomy with splenectomy. Histological examination showed poorly differentiated adenocarcinoma in the pancreatic head mass but the pancreatic duct stenosis in the tail of the pancreas was diagnosed as pancreatic granuloma caused by Cryptococcus. Fungal infections may reportedly promote the development of pancreatic cancer, as further suggested by this case of cryptococcal infection.

Background: The feasibility and safety of laparoscopic distal pancreatectomy (Lap-DP) for elderly patients remains unknown. Methods: A total of 66 patients underwent Lap-DP at our institute from April 2014 to December 2020. Among them, 16 patients were aged 80 or older (elderly-group), and 50 patients were less than 80 years old (young-group). Clinical characteristics and perioperative outcomes were compared between the two groups. Results: The median age was 83 years (80-89) in elderly-group, and 68 years (30-79) in young-group. In elderly-group, seven patients were performed Lap-DP for pancreatic ductal adenocarcinoma (44%), and with 12 patients (24%) in young-group (P=0.139). The median operative time in elderly-group and young-group was 302min (133-446) and 290min (165-477) (P=0.812), and median operative blood loss in elderly-group and young-group was 104ml (5-600) and 82ml (1-1975) (P=0.590). The incidence of clinically relevant POPF occurred in six patients (9.1%), with no patients (0%) in elderly-group and six patients (12%) in young-group (P=0.061). We have never experienced POPF grade C. The major morbidity (Clavien–Dindo classification grade ≥III) occurred in nine patients (13.6%), with no patients (0%) in elderly-group and nine patients (18%) in young-group (P=0.020). The median postoperative hospital stay in elderly-group and young-group was 14days (6-29) and 12days (8-33) (P=0.176). Conclusions: The incidence of clinically relevant POPF and major complication were both less in the elderly-group than the young-group. Lap-DP was feasible and safe for selected elderly patients older than 80 years of age.

Few clinical studies concerning the efficacy of microwave ablation for intermediate stage hepatocellular carcinoma have been published. Our purpose was to examine perioperative and long-term outcomes after operative microwave ablation for intermediate stage hepatocellular carcinoma. This retrospective study included 246 patients who had undergone operative microwave ablation for intermediate stage hepatocellular carcinoma in our institute between January 2001 and December 2017. We analyzed overall and recurrence-free survival and used the Cox proportional hazard model to evaluate potential prognostic factors. The overall median follow-up time was 51 months. The 1-, 3-, 5-, and 10-year overall survival rates were 98%, 74%, 51%, and 28%, respectively, whereas the 1-, 3-, 5-, and 10-year recurrence-free survival rates were 80%, 32%, 18%, and 10%, respectively. The major complication rate (Clavien–Dindo classification IIIa or above) after operative microwave ablation was 7%, with no procedure-related mortality. Multivariate analysis identified beyond up-to-7 criteria (the sum of the largest tumor’s diameter in cm and the total number of tumors), Child–Pugh grade B, and serum alpha-fetoprotein concentration ≥ 100 ng/mL as independent risk factors for overall survival after operative microwave ablation. The overall survival of patients within up-to-7 and Child–Pugh grade A was better than that of the remaining patients, 5-year overall survivals being 67% and 37%, respectively (P < 0.001). Operative microwave ablation is safe and effective in patients with intermediate stage hepatocellular carcinoma. In particular, patients within up-to-7 and Child–Pugh grade A can be expected to have better long-term outcomes after operative microwave ablation.

Background: The prognostic nutritional index (PNI) is used to assess immune and nutritional status, and is a prognostic factor for several malignant tumors. However, little evidence exists regarding the predictive impact of prognostic nutritional index (PNI) after local ablation therapy for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the value of PNI to predict recurrence and survival after operative microwave ablation in patients with early-stage HCC. Methods: This retrospective study included 341 patients who underwent operative microwave ablation for HCC in Barcelona Clinic Liver Cancer (BCLC) stage 0-A at our institute between 2007 and 2015. We analyzed overall survival (OS) and recurrence-free survival (RFS), and evaluated factors related to prognosis in multivariate Cox regression analyses. Results: The OS rates at 1, 3, 5, and 10 years after microwave ablation were 100%, 92.7%, 85.1%, and 57.5% in patients with high-PNI levels, and 96.5%, 78.2%, 59.7%, and 20.7% in patients with low-PNI levels, respectively (P < 0.001). The RFS rates at 1, 3, 5, and 10 years after microwave ablation were 96.3%, 75.2%, 55.4%, and 30.4% in patients with high-PNI levels, and 94.4%, 48.8%, 36.4%, and 13.1% in patients with low-PNI levels, respectively (P < 0.001). In multivariate analyses, preoperative PNI level was an independent prognostic factor for both OS and RFS. Conclusion: Our results revealed the preoperative PNI level was a simple and novel predictive marker of survival and recurrence after microwave ablation in patients with early-stage HCC.

There are few published data regarding long-term outcome survival after microwave ablation (MWA) for hepatocellular carcinoma (HCC) within 3 cm and 3 nodules. The aim of this study was to examine long-term outcomes after operative MWA for HCC within 3 cm and 3 nodules. This cohort of this retrospective study comprised 559 patients who underwent operative MWA for HCC within 3 cm and 3 nodules in our institute between 1996 and 2017. We analyzed overall survival (OS) and recurrence-free survival (RFS), and evaluated factors related to prognosis. Median follow-up time was 69 months for the entire cohort. OS rates were 1-year: 98%, 3-year: 87%, 5-year: 73%, and 10-year:39%; RFS rates were 1-year: 91%, 3-year: 60%, 5-year: 42%, and 10-year: 21%. Multivariate analysis revealed that hepatitis C virus (HCV)–positive status, ALBI grade 2 or 3, maximum tumor diameter ≥ 20 mm, and multiple nodules were independent risk factors for both OS and RFS. A prognostic staging model using one point for each risk factor provided a well-categorized predictive model. The 5-year OS rates were 93%, 81%, and 57% for scores of 0, 1 or 2, and 3 or 4, respectively (P < 0.001). The 5-year RFS rates were 70%, 48%, and 28% for scores of 0, 1 or 2, and 3 or 4, respectively (P < 0.001). Our results revealed good long-term outcomes after operative MWA for HCC within 3 cm and 3 nodules.

Background: The aim of this study was to evaluate whether our standardized procedure with mesh-reinforced stapler (Endo-GIATM with Tri-StapleTM technology; black reload; 60-m long; Covidien) can reduce the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy. Methods: A total of 60 patients underwent mesh-reinforced stapled distal pancreatectomy at our institute from July 2016 to November 2019. Laparoscopic distal pancreatectomy was performed in 43 (71.7%) patients. The incidence of clinically relevant POPF (grade B or C based on the International Study Group on Pancreatic Fistula criteria) was retrospectively analyzed. Surgical procedures: The pancreatic parenchyma was transected by stapler on the transection line with safety margin from the lesion. The closure jaw was carefully clamped over a 1-min period at a fixed speed. The stapler was slowly fired over a 6-min period and then released. Careful, gentle handling of the stapler was required during transection of the pancreatic parenchyma. A closed-suction drain was always placed near the stump of the remnant pancreas. Results: The median operative time was 274min (133-585), and median operative blood loss was 170g (1-2519). The incidence of clinically relevant POPF occurred in 4 patients (6.7%). We have never experienced POPF grade C. The major morbidity rate (Clavien-Dindo classification grade ≥III) occurred in 7 patients (15%). Complications other than POPF grade B occurred in 3 patients (ileus, n=2; delayed gastric emptying, n=1). No surgical mortality or in-hospital death occurred in this study. Conclusions: Our standardized technique with mesh-reinforced stapler can reduce clinically relevant POPF after distal pancreatectomy.

Background: It remains to be clarified whether combined hepatectomy and microwave ablation for multifocal hepatocellular carcinoma (HCC) is feasible. This aim of this study was to examine the perioperative and oncological outcomes after combined hepatectomy and microwave ablation for multifocal HCC. Methods: This retrospective study included 81 patients who underwent combined hepatectomy and microwave ablation for multifocal HCC in our institute between June 1998 and December 2017. We analyzed overall survival (OS) and recurrence-free survival (RFS), and evaluated factors related to prognosis. Results: Median follow-up time was 45.6 months for the entire cohort. OS rates were 1-year: 96%, 3-year: 72%, and 5-year: 54%; RFS rates were 1-year: 77%, 3-year: 37%, and 5-year: 22%. The major complication rate (Clavien-Dindo classification IIIa or above) after surgery was 10%, with one patient of in-hospital mortality. Multivariate analysis revealed that des-gamma-carboxy prothrombin level >200 mAU/mL and >5 tumors were independent risk factors for OS, and des-gamma-carboxy prothrombin level >200 mAU/mL, > 5 tumors, and maximum tumor size >5 cm were independent risk factors for RFS. Conclusions: Our results indicate that combined hepatectomy and microwave ablation is safe and feasible for selected patients with multifocal HCC. (C) 2020 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V.

症例は44歳，女性．生来健康で通院歴は無かった．2カ月前より腹満感・食欲不振を認め，呼吸苦を主訴に当院へ救急搬送となった．血液生化学検査にてHb:1.9g/dlと著明な貧血を認めた．造影CTでは膵尾部に13cm大の多房嚢胞性腫瘤が存在し，胃を圧排していた．上部消化管内視鏡検査にて膵尾部病変の胃壁への浸潤が疑われたが，胃病変の生検では悪性所見は認めなかった．超音波内視鏡検査では嚢胞内に壁在結節なく，膵粘液性嚢胞腫瘍（MCN）の胃壁穿破による上部消化管出血と診断し，貧血改善後に待機的手術を行った．腫瘤は胃壁と広範・強固に癒着しており，脾合併膵体尾部切除+胃全摘術を行った．病理組織診断では標本の一部に高度異型を呈する領域を認め，非浸潤型膵粘液性嚢胞腺癌の診断となった．腫瘍と接する胃壁には腫瘍浸潤は認めなかった．非浸潤型膵粘液性嚢胞腺癌が胃壁に穿破し貧血をきたす症例は非常に稀であり，文献的考察を加え報告する．

Background Gastroenteric neuroendocrine carcinomas (NECs) account for 6.2% of gastroenteric neuroendocrine tumors (NETs), and only 1% or less of gastroenteric NETs occur in the ampulla of Vater (AoV). Clinical features of NEC of the AoV remain obscure. Case presentation A 65-year-old man visited a general practitioner because of jaundice, and an abdominal contrast-enhanced computed tomography scan revealed a tumor of 11 mm in diameter, which was enhanced in the arterial phase at the duodenal papilla, with dilation of the upstream bile duct. Gastrointestinal scope revealed an unexposed tumor of the AoV. Based on a biopsy of the site, a moderately differentiated tubular adenocarcinoma was suspected, and pancreatoduodenectomy was performed. Histopathological examination revealed dysplasia and highly proliferative small tumor cells, with solid and nodular formation at the AoV. Histological analysis showed a high mitotic count, and immunohistochemical staining revealed a Ki-67 index of 40–50% and cells positive for synaptophysin, chromogranin A, and p53. Small cell-type NEC was finally diagnosed. Four months post pancreatoduodenectomy, multiple liver metastases developed, and systemic chemotherapy was administered. Salvage liver resection for liver metastases was performed 14 months after the pancreatoduodenectomy. Unfortunately, multiple liver metastases developed 2 months after liver resection, and the patient died 18 months after the pancreatoduodenectomy. Conclusions Neuroendocrine carcinoma originating from the bile duct is very rare; therefore, in this article, we provide a review of the literature and a case report.

AbstractBackgroundGlomus tumors (GTs) are mesenchymal neoplastic lesions arising from the glomus bodies and generally occur in the fingers and toes. Gastrointestinal GTs are rare, and most of them originate from the stomach; however, GT arising from the duodenum is exceedingly rare.Case presentationA 68-year-old man was admitted due to abdominal pain. Endoscopy showed a round, smooth, elevated mass in the second portion of the duodenum with central ulceration. Abdominal contrast computed tomography showed a hypervascular tumor measuring 26 mm in diameter in the second portion of the duodenum, and pancreatic invasion was suspected. Endoscopic ultrasonography of the lesion confirmed a hypoechoic mass arising from the fourth layer of the duodenal wall. A biopsy was performed for central ulceration, and immunochemical studies showed positive results for smooth muscle actin (SMA) and negative results for S100, C-Kit, and CD34. Leiomyoma or gastrointestinal stromal tumor was suspected and pancreatoduodenectomy was performed. The specimen exhibited a vascular-rich tumor, 24 × 24 × 19 mm in size, with deep ulceration in the duodenum. Histological examination showed uniform small round cells with central nuclei and a pale cytoplasm (glomus cell) with perivascular proliferation. Immunochemical studies showed that the tumor was positive for SMA and collagen type IV, and negative for C-Kit, CD34, desmin, and S100. We diagnosed the tumor as a GT of the duodenum.ConclusionGTs of the duodenum are exceedingly rare, but should be considered in the differential diagnoses of duodenal submucosal lesions.

The feasibility and safety of microwave ablation in elderly hepatocellular carcinoma (HCC) patients remains unknown. The aim of this study was to evaluate the feasibility and safety of surgical microwave ablation for HCC in patients older than 80 years of age. This retrospective study enrolled consecutive 114 patients older than 80 years of age who underwent surgical microwave ablation for HCC between July 1994 and December 2017. We analyzed perioperative outcomes and long-term outcomes to clarify the prognostic factors. The 1-, 3-, 5-year overall survival and recurrence-free survival rates were 97.3%, 76.0%, 49.2% and 84.2%, 44.7%, and 32.5%, respectively. The overall major morbidity rates (Clavien–Dindo grade IIIA or above) were 2.6%. There were no cases of mortality. Multivariate analysis showed that hepatitis C virus antibody (HCV-Ab) positivity and the presence of multiple tumors were independent prognostic factors for long-term outcomes. The overall survival rate of patients with HCV-Ab negative and single tumor was better than that of other patients (p = 0.026). Surgical microwave ablation was feasible and safe for elderly patients with HCC. Elderly patients with HCV-Ab negative and single tumor would be expected to have better long-term outcomes after surgical microwave ablation.

A 73-year-old male was initially treated with sorafenib for advanced stage HCC. However, the disease progressed 2 months after starting sorafenib. Progressive disease (PD) was confirmed by radiological examination, which revealed mediastinal and abdominal lymph node metastasis, pulmonary metastasis, and intrahepatic recurrence. The patient was enrolled in the REACH-2 (NCT02435433) trial and randomized to receive ramucirumab (8 mg/kg div. every 2 weeks). The patient had a Child-Pugh score of 6A and his AFP level was found to be 1,256.8 ng/mL at initiation. Radiological examination revealed PD, 5 months after starting ramucirumab. Ramucirumab treatment was continued after the confirmation of radiological PD, not but clinical progression, as allowed by the study protocol. His AFP level increased after continuous ramucirumab treatment, however, it suddenly decreased from 7,653 ng/mL to within normal limits 10 months after initiation of ramucirumab treatment. Radiological evaluation revealed a significant decrease in the size of the tumors, which constituted a partial response (PR). We reported a rare case of advanced HCC with PR to a continuous ramucirumab treatment after radiological PD.