Backgrounds/Aims: In recent years, many minimally invasive techniques have been introduced to reduce the number of ports in laparoscopic cholecystectomy (LC), offering benefits such as reduced postoperative pain and improved cosmetic outcomes. ArtiSential (R) is a new multi-degree-of-freedom articulating laparoscopic instrument that incorporates the ergonomic features of robotic surgery, potentially overcoming the spatial limitations of laparoscopic surgery. ArtiSential (R) LC can be performed using only two ports. This study aims to compare the surgical outcomes of ArtiSential (R) LC with those of single-fulcrum LC. Methods: This retrospective study compared ArtiSential (R) LC and single-fulcrum LC among LCs performed for gallbladder (GB) stones at the same center, analyzing the basic characteristics of patients; intraoperative outcomes, such as operative time, estimated blood loss, and intraoperative GB rupture; and postoperative outcomes, such as length of hospital stay, incidence of postoperative complications, and postoperative pain. Results: A total of 88 and 63 patients underwent ArtiSential (R) LC and single-fulcrum LC for GB stones, respectively. Analysis showed that ArtiSential (R) LC resulted in significantly fewer cases of surgeries longer than 60 minutes (30 vs. 35 min, p = 0.009) and intraoperative GB ruptures (2 vs. 10, p = 0.007). In terms of postoperative outcomes, ArtiSential (R) LC showed better results in the respective visual analog scale (VAS) scores immediately after surgery (2.59 vs. 3.73, p < 0.001), and before discharge (1.44 vs. 2.02, p = 0.01). Conclusions: ArtiSential (R) LC showed better results in terms of surgical outcomes, especially postoperative pain. Thus, ArtiSential (R) LC is considered the better option for patients, compared to single-fulcrum LC.

Background Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. Methods We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. Results Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables “resection type” and “largest tumor size” for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables “tumor location,” “blood loss,” “complications,” and “operation time.” Conclusion We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.

Middle-segment preserving pancreatectomy (MSPP) serves as an alternative to total pancreatectomy (TP) for preserving the pancreatic body in multifocal pancreatic neoplasms. Despite the potential benefits of TP, the detailed short- and long-term prognoses remain unclear. We evaluated the feasibility of MSPP by comparing the perioperative outcomes and postoperative endocrine and exocrine functions with those of TP. The study included 10 TP and 7 MSPP patients. Patients with pancreatic ductal adenocarcinoma and invasive intraductal papillary mucinous carcinoma were excluded. MSPP was associated with a high incidence (57.1

O6-methylguanine-DNA methyltransferase (MGMT) has been linked with alkylating agent resistance and tumor growth suppression. However, its role remains undetermined in pancreatic neuroendocrine tumors (Pan-NET). The MGMT expression was examined by immunohistochemistry in 142 patients to evaluate MGMT immunoreactivity and clinicopathological factors. We analyzed the relationship between MGMT expression and treatment efficacy in 19 patients who received STZ-based regimens. In 142 Pan-NET, 97 cases (68.3%) were judged as MGMT-positive and 45 cases (31.6%) as negative. MGMT negativity was significantly more common in NET-G2 (62.5%) than in NET-G1 (11.2%, p < 0.001). MGMT-negative cases were associated significantly with larger tumor size (p < 0.01), higher Ki-67 index (p < 0.01), higher mitotic index (p < 0.05), and more frequent liver metastasis (p < 0.05). Of the 19 cases treated with STZ, 6 cases were determined as SD and 4 cases as PD in MGMT-positive patients (N = 10), while 5 cases were determined as PR and 4 cases as SD in MGMT-negative patients (N = 9). Progression-free survival in MGMT-negative cases was significantly better than in MGMT-positive cases (p < 0.05). MGMT expression was lower in NET-G2 than in NET-G1, and STZ-based regimens improved the therapeutic outcomes of MGMT-negative Pan-NET. These findings indicate that NET-G2 may represent a better therapeutic target for STZ treatment.

The invasiveness of pancreatic cancer and its resistance to anticancer drugs define its malignant potential, and are considered to affect the peritumoral microenvironment. Cancer cells with resistance to gemcitabine exposed to external signals induced by anticancer drugs may enhance their malignant transformation. Ribonucleotide reductase large subunit M1 (RRM1), an enzyme in the DNA synthesis pathway, is upregulated during gemcitabine resistance, and its expression is associated with worse prognosis for pancreatic cancer. However, the biological function of RRM1 is unclear. In the present study, it was demonstrated that histone acetylation is involved in the regulatory mechanism related to the acquisition of gemcitabine resistance and subsequent RRM1 upregulation. The current in vitro study indicated that RRM1 expression is critical for the migratory and invasive potential of pancreatic cancer cells. Furthermore, a comprehensive RNA sequencing analysis showed that activated RRM1 induced marked changes in the expression levels of extracellular matrix-related genes, including N-cadherin, tenascin-C and COL11A. RRM1 activation also promoted extracellular matrix remodeling and mesenchymal features, which enhanced the migratory invasiveness and malignant potential of pancreatic cancer cells. The present results demonstrated that RRM1 has a critical role in the biological gene program that regulates the extracellular matrix, which promotes the aggressive malignant phenotype of pancreatic cancer.

Objectives: The dorsal pancreatic artery (DPA) is a pancreatic branch with various anatomical variations. Previous studies mostly focused on the origin of the DPA, and its pathways and branching patterns have rarely been examined. The purpose of this study was to investigate the branching patterns and pathways of the DPA. Methods: This study included 110 patients who underwent computed tomography scans. We examined the pathways and branching patterns of the DPA. Results: The DPA was identified in 101 patients (92%), and originated from the splenic artery in 30 patients (31%), the common hepatic artery in 17 patients (17%), the celiac trunk in 10 patients (10%), the superior mesenteric artery in 27 patients (27%), the replaced right hepatic artery in 7 patients (7%), the inferior pancreaticoduodenal artery in 5 patients (5%), and other arteries in 3 patients (3%). Four distinct types of branches were identified as follows: the superior branch (32%), the inferior branch (86%), the right branch (80%), and the accessory middle colic artery (12%). Additionally, the arcs of Buhler and Riolan were observed in two patients each and their anastomotic vessels followed almost the same pathway as the DPA. Conclusion: A number of variations of the DPA were observed with regard to its origin and branching pattern; however, the DPA and its branches always ran along the same pathway, as summarized in Fig. 4. The anatomical information gained from this study may contribute to performing safe pancreatic resections. (c) 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.

症例は79歳の女性で，遠位胆管癌に対して2020年5月に亜全胃温存膵頭十二指腸切除術，門脈合併切除を施行した．術後膵液瘻を認めたが保存的に軽快し術後26日で退院した．9月に40°Cの発熱および肝胆道系酵素の上昇を認め術後胆管炎として加療し軽快した．その後同様の症状で6回の入退院を繰り返した．腹部造影CTで経時的に肝外門脈狭窄の増悪および挙上空腸の側副血行路発達の所見を認め，門脈狭窄による求肝性静脈瘤からの出血にともなう胆管炎と診断した．翌年1月に経皮経肝門脈ステント留置ならびに挙上空腸側副血行路のコイル塞栓を施行した．処置後胆管炎の発症は見られず術後1年経過した現在，無再発生存中である．膵頭十二指腸切除後の胆管炎は頻度の高い合併症ではあるが，門脈合併切除を施行した場合には門脈狭窄を背景として胆管炎を発症する場合があり注意を要すると考えられた．

IntroductionMalignant tumors, such as hilar cholangiocarcinoma, have shown improved long-term outcomes, and measures to prevent late postoperative complications are important. Postoperative cholangitis after hepatectomy with hepaticojejunostomy (HHJ) may occur and can significantly decrease the quality of life. However, there are few reports on the incidence and pathogenesis of postoperative cholangitis after HHJ.MethodsWe retrospectively reviewed 71 cases post HHJ at Tokyo Medical and Dental University Hospital from January 2010 to December 2021. Cholangitis was diagnosed using the Tokyo Guideline 2018. Cases due to tumor recurrence around the hepaticojejunostomy (HJ) were excluded. Patients with three or more episodes of cholangitis were classified as the "refractory cholangitis group" (RC group). RC group patients were divided into a "stenosis group" and "non-stenosis group" according to intrahepatic bile duct dilatation at the onset of cholangitis. Their clinical characteristics and risk factors were analyzed.ResultsCholangitis occurred in 20 patients (28.1%), with 17 (23.9%) in the RC group. Most patients in the RC group developed their first episode within the first postoperative year. The stenosis group consisted of 6 patients, and their cholangitis was treated with repeated anastomotic dilatation and stent replacement. In the non-stenosis group, cholangitis was relatively mild and treated with antibiotics. Hepatobiliary scintigraphy for these cases showed bile congestion in the jejunum near the site of the hepaticojejunostomy.ConclusionThere are two types of postoperative cholangitis, each with different pathogenesis and treatment. It is essential to assess anastomotic stenosis early and provide the necessary treatment.

Hepatocellular carcinoma (HCC) imposes a huge global burden, arising from various etiological factors such as hepatitis virus infection and metabolic syndrome. While prophylactic vaccination and antiviral treatment have decreased the incidence of viral HCC, the growing prevalence of metabolic syndrome has led to an increase in non-viral HCC. To identify genes downregulated and specifically associated with unfavorable outcome in non-viral HCC cases, screening analysis was conducted using publically available transcriptome data. Among top 500 genes meeting the criteria, which were involved in lipid metabolism and mitochondrial function, a serine transporter located on inner mitochondrial membrane SFXN1 was highlighted. SFXN1 protein expression was significantly reduced in 33 of 105 HCC tissue samples, and correlated to recurrence-free and overall survival only in non-viral HCC. Human HCC cells with SFXN1 knockout (KO) displayed higher cell viability, lower fat intake and diminished reactive oxygen species (ROS) production in response to palmitate administration. In a subcutaneous transplantation mouse model, high-fat diet feeding attenuated tumorigenic potential in the control cells, but not in the SFXN1-KO cells. In summary, loss of SFXN1 expression suppresses lipid accumulation and ROS generation, preventing toxic effects from fat overload in non-viral HCC, and predicts clinical outcome of non-viral HCC patients.

Abstract Background/Purpose: O6-methylguanine-DNA methyltransferase (MGMT) has been linked with alkylating agent resistance and tumor growth suppression. However, its role remains undetermined in pancreatic neuroendocrine neoplasms (Pan-NENs). This study examined the expression of MGMT in Pan-NENs and explored how MGMT affects the efficacy of the alkylating agent streptozocin (STZ). Methods: The expression of MGMT was examined by immunohistochemistry (IHC) staining in 146 Pan-NEN patients at our institute; MGMT immunoreactivity and clinicopathological factors were evaluated. Results: In 146 Pan-NEN, 99 cases (67.8%) were judged as MGMT-positive and 47 cases (32.2%) as negative. MGMT-negative cases were associated significantly with larger tumor size (p<0.001), higher mitotic index (p<0.001), and higher Ki-67 index (p<0.001). Of the 19 cases treated with STZ, 6 cases were determined as SD and 4 cases as PD in MGMT-positive patients (N=10), while 5 cases were determined as PR and 4 cases as SD in MGMT-negative patients (N=9). Progression-free survival in MGMT-negative cases was significantly better than in MGMT-positive cases (p=0.042). Conclusions: MGMT expression was decreased with higher grade Pan-NENs, and STZ improved the therapeutic outcomes of MGMT-negative Pan-NENs. These findings indicate that higher grade Pan-NENs may represent a better therapeutic target for STZ treatment.

Although histone H3K4 methyltransferase SETD1A is overexpressed in various cancer types, the molecular mechanism underlying its overexpression and its target genes in pancreatic ductal adenocarcinoma (PDAC) remain unclarified. We conducted immunohistochemical staining for SETD1A in 105 human PDAC specimens to assess the relationship between SETD1A overexpression and clinicopathological features. The function and target genes of SETD1A were investigated using human pancreatic cancer cell lines. SETD1A expression was upregulated in 51.4% of patients with PDAC and was an independent prognostic factor associated with shorter disease-free survival after resection (p < 0.05). Knockdown and overexpression of SETD1A showed that SETD1A plays a crucial role in increasing the proliferation and motility of PDAC cells. SETD1A overexpression increased tumorigenicity. RNA sequencing of SETD1A-knockdown cells revealed downregulation of RUVBL1, an oncogenic protein ATP-dependent DNA helicase gene. ChIP analysis revealed that SETD1A binds to the RUVBL1 promoter region, resulting in increased H3K4me3 levels. Knockdown of RUVBL1 showed inhibition of cell proliferation, migration, and invasion of PDAC cells, which are similar biological effects to SETD1A knockdown. High expression of both SETD1A and RUVBL1 was an independent prognostic factor not only for disease-free survival but also for overall survival (p < 0.05). In conclusion, we identified RUVBL1 as a novel downstream target gene of the SETD1A-H3K4me3 pathway. Co-expression of SETD1A and RUVBL1 is an important factor for predicting the prognosis of patients with PDAC.

In some patients with metastatic renal cell carcinoma to the pancreas, gastrointestinal hemorrhages occur, but because of the rarity of this condition, treatment strategies have not been established. A 71-year-old man who had undergone a nephrectomy for renal cell carcinoma (RCC) went to a hospital in a state of shock. Computed tomography revealed a hypervascularized tumor in the head of the pancreas, suggesting metastatic RCC. Upper endoscopy revealed bleeding in the duodenum due to tumor invasion. An emergency angiogram showed that the tumor received its blood supply mainly from the gastroduodenal artery. Transarterial embolization (TAE) of the gastroduodenal artery was performed and bleeding was controlled. Two months after TAE, elective pancreaticoduodenectomy was performed. The patient currently continues to undergo outpatient follow-up 2 years later without recurrence. TAE was very effective in controlling the acute phase of severe gastrointestinal hemorrhage from pancreatic metastasis of RCC.

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy. However, the characteristics and prognosis of ICC is not well known. This study aims to reveal the relationship between liver function and prognosis of ICC.

十二指腸乳頭部癌は黄疸を初発症状とするものが多く，十二指腸狭窄で発症した報告は過去に認めない．今回，われわれは十二指腸狭窄で発症した十二指腸乳頭部癌の1例を経験した．症例は57歳の女性で，嘔吐のため当院を紹介受診した．各種検査において悪性所見を認めず，やがて十二指腸の完全閉塞をきたしたため入院となった．腹部造影CTでは，十二指腸粘膜下の肥厚および下行脚の狭窄を認めた．胆管や主膵管の拡張は認めなかった．悪性腫瘍の確定診断に至らず，十二指腸閉塞に対して胃空腸バイパス術を施行され，以後経過観察となっていたが術後2カ月より閉塞性黄疸を認め，再入院となった．複数回の生検や胆汁細胞診でも悪性所見は認めなかったが，悪性腫瘍の可能性を否定できず，亜全胃温存膵頭十二指腸切除術を施行した．術後の病理組織学的検査で乳頭部胆管を主座とする高分化腺癌を認め，免疫染色検査の結果と合わせ乳頭部胆管癌の診断となった．

Objective: To elucidate the role of surgery in patients with high-grade neuroendocrine neoplasms (hg-NENs) and Ki-67 more than 20%. Background: Although surgery is the first treatment choice in patients with low-grade NENs, whether it increases the survival of patients with hg-NENs is debatable. Methods: Between 2005 and 2018, 63 patients pathologically diagnosed with hg-NENs treated at our institution were retrospectively analyzed. The risk factors for overall survival (OS) and recurrence-free survival were analyzed, and OS was compared between each treatment group. Results: The median observation time was 21.2 months, and the median Ki-67 value was 52%. Patients with hg-NENs were classified into low Ki-67 (Ki-67 <52%) and high Ki-67 (Ki-67 ≥52%) groups. Multivariate analysis for OS identified surgery (P = 0.013) and low Ki-67 value (P = 0.007) as independent risk factors, whereas morphological differentiation defined by the WHO 2017 criteria showed no association with OS. Patients with low Ki-67 value subjected to R0/1, R2, and chemotherapy had a median survival time of 83.8, 16.6, and 28.1 months, respectively. The median survival time for R0/1 group was significantly longer than that for chemotherapy group (P = 0.001). However, no difference in survival was reported between patients from R0/1 and chemotherapy groups with high Ki-67. Ki-67 value could determine recurrence-free survival (P = 0.006) in patients who underwent R0/1 surgery for pancreatic hg-NENs. Conclusions: R0/1 surgery predicted prognoses in the low Ki-67 group. The indication of surgery for patients with hg-NENs did not depend on tumor differentiation.

According to the revised staging of the American Joint Committee on Cancer, 8th edition (AJCC8), the N category in pancreatic ductal adenocarcinoma is classified as N0 (0), N1 (1–3), and N2 (≥ 4) based on the number of metastatic lymph nodes (LNs). This study aimed to validate this classification and analyze cutoff values of metastatic LN numbers.