High-mobility group box 1 fragment ameliorates chronic pancreatitis induced by caerulein in mice.

BACKGROUND: Chronic pancreatitis (CP) is a progressive disease characterized by pancreatic fibrosis for which effective treatment options are lacking. Mesenchymal stem cells (MSCs) have shown potential for fibrosis treatment but face limitations in clinical application. The high-mobility group box 1 (HMGB1) fragment mobilizes MSCs from bone marrow into the blood and has emerged as a promising therapeutic agent for tissue regeneration in various pathological conditions. The aim of this study was to investigate the potential therapeutic effects of systemic administration of the HMGB1 fragment in a mouse model of CP. METHODS: A caerulein-induced CP mouse model was used, and the HMGB1 fragment was administered by tail vein injection. Parameters such as body weight, pancreatic tissue damage, fibrosis, inflammatory cytokine expression, and collagen-related gene expression were evaluated using various assays, including immunohistochemistry, real-time PCR, serum analysis, and single-cell transcriptome analysis. And the migration of MSCs to the pancreas was evaluated using the parabiosis model. RESULTS: Administration of the HMGB1 fragment was associated with significant improvements in pancreatic tissue damage and fibrosis. It suppressed the expression of inflammatory cytokines and activated platelet-derived growth factor receptor-α+ MSCs, leading to their accumulation in the pancreas. The HMGB1 fragment also shifted gene expression patterns associated with pancreatic fibrosis toward those of the normal pancreas. Systemic administration of the HMGB1 fragment demonstrated therapeutic efficacy in attenuating pancreatic tissue damage and fibrosis in a CP mouse model. CONCLUSION: These findings highlight the potential of the HMGB1 fragment as a therapeutic target for the treatment of CP.

Caser Report: A Rare Case of Pulmonary Nocardiosis Caused by Nocardia pseudobrasiliensis After Liver Transplantation.

Nocardia is a gram-positive bacillus with the microscopic appearance of branching hyphae and is mainly distributed in the soil. Nocardiosis more frequently occurs in immunosuppressed patients. Since nocardiosis has a high mortality rate, immediate diagnosis and treatment are needed. We report the first case of pulmonary nocardiosis caused by Nocardia pseudobrasiliensis after liver transplantation. A 58-year-old woman underwent living-donor transplantation for primary biliary cholangitis. Seven months after transplantation, she came to our hospital complaining of fever and anorexia. Computed tomography of the lungs showed a 45 mm large nodule affecting the upper lobe of the left lung. We started administering empiric antibiotics and tapering immunosuppression, but the patient's condition gradually worsened, and lung lesions increased. On the fifth day after hospitalization, bacteria developed from sputum cultures were identified as N. pseudobrasiliensis by matrix-assisted laser desorption ionization time of flight mass spectrometry. We started treatment with trimethoprim-sulfamethoxazole. The patient's clinical symptoms and laboratory data improved quickly. After one month of hospitalization, this patient was discharged. Then, the lung lesion almost vanished. Ten years after her transplant, the patient is alive with a well-functioning graft.

Apparent diffusion coefficient in intrahepatic cholangiocarcinoma diffusion-weighted magnetic resonance imaging noninvasively predicts Ki-67 expression.

AIM: Tumor Ki-67 expression reflects prognosis and cancer grade, and biopsy-based preoperative assessment of Ki-67 expression is key to treatment. Apparent diffusion coefficient (ADC) values obtained with this imaging may noninvasively predict Ki-67 by reflecting tumor cell density and limited water molecule movement from irregular alignment. This study aimed to investigate the ability of ADC values to predict Ki-67 expression in intrahepatic cholangiocarcinoma (ICC). METHOD: We retrospectively analyzed 39 cases of ICC confirmed by surgical pathology. All patients had undergone magnetic resonance imaging, and ADC values (mean, minimum, and maximum) were calculated. Ki-67 expression was assessed by immunohistochemistry, and patients were divided into groups of high (n = 18) and low (n = 21) Ki-67 expression. To assess the diagnostic performance of the ADC values for Ki-67 expression, we used the receiver operating characteristic curve and compared the areas under the curve (AUC). RESULTS: The mean and minimum ADC values were significantly lower in the group with high Ki-67 expression. For predicting high Ki-67 expression, the AUC values were 0.701 for mean ADC, 0.818 for minimum ADC, and 0.571 for maximum ADC. The diagnostic sensitivity and specificity of the minimum ADC values were 88.9% and 76.2%, respectively. In addition, with ADC values combined, the AUC increased to 0.831. Apparent diffusion coefficient is a useful predictor of Ki-67 expression level in ICC. CONCLUSION: Apparent diffusion coefficient values, especially minimum ADC values, can noninvasively predict ICC associated with high Ki-67 expression.

Clinical Significance of the Interposition Graft for Reconstruction Between the Common Hepatic Artery and Gastroduodenal Artery for Arterial Patency of the Pancreas Graft in Pancreas Transplantation.

BACKGROUND: Due to the limited number of organ donations from deceased donors in Japan, pancreas grafts for pancreas transplantation (PTx) are frequently harvested from the donor in the same donation surgery as the liver graft. In such a situation, the common hepatic artery (CHA) and gastroduodenal artery (GDA) are dissected, resulting in decreased blood flow to the head of the pancreas graft. Therefore, GDA reconstruction using an interposition graft (I-graft) between the CHA and GDA has been traditionally performed to maintain blood flow. This study investigated the clinical significance of GDA reconstruction with the I-graft regarding the arterial patency of the pancreas graft in patients after PTx. METHODS: Fifty-seven patients underwent PTx for type 1 diabetes mellitus at our hospital between 2000 and 2021. Twenty-four cases in which GDA reconstruction was performed using the I-graft and artery blood flow of the pancreas graft was evaluated by contrast-enhanced computed tomography or angiography were included in this study. RESULTS: The patency of the I-graft was 95.8%, and only one patient had a thrombus in the I-graft. Nineteen patients (79.2%) had no thrombus in the artery of the pancreas graft; the other five cases had thrombus in the superior mesenteric artery (SMA). The patient with the thrombus in the I-graft required graftectomy for the pancreas graft. CONCLUSIONS: The patency of the I-graft was favorable. Furthermore, the clinical significance of the GDA reconstruction with the I-graft is suggested to maintain blood flow in the pancreas head if the SMA is occluded.

[A Case of Pancreaticoduodenectomy for Vater Papillary Cancer with Celiac Axis Stricture].

During the follow‒up of Vater papillary adenoma, a 74‒year‒old man was admitted to our hospital with a chief complaint of upper abdominal pain and diagnosed as cholangitis with obstructive jaundice. Cholestasis had been considered to be caused by papillary adenoma, however, EUS exam showed continuous bile duct wall irregularity from papilla of Vater. So we diagnosed as papillary carcinoma with extension to the distal bile duct. Preoperative CT showed the stenosis at the root of celiac artery, and hepatic blood flow was considered to be supplied via the pancreatic head arcade from superior mesenteric artery, so an anastomosis of gastroduodenal artery and inferior pancreaticoduodenal artery was performed during pancreaticoduodenectomy( PD). Like this case, when performing PD with celiac artery stricture, it is important to evaluate hepatic blood flow before and during surgery and prepare for the arterial reconstruction.

[Analysis of 16 Cases of Primary Duodenal Carcinoma in Our Hospital].

Primary duodenal carcinoma is a rare disease among gastrointestinal malignancies and has little evidence. We evaluated retrospectively the treatment status of 16 cases of primary duodenal carcinoma in our hospital between 2010 and 2019. The median age was 72(58-88)years and 63% of patients were male, and Each stage were Stage 0 in 4 cases, Stage Ⅰ in 1 case, Stage ⅢA in 2 cases, Stage ⅢB in 3 cases, and Stage Ⅳ in 6 cases(UICC 8th edition). Initial treatment was endoscopic therapy in 3 cases, surgery in 10 cases, chemotherapy in 1 case, and best supportive care in 2 case. The 2-year survival rate was 51.3% and the MST was 25.4 months in all cases. The Stage 0, Stage Ⅰ cases had all recurrence-free survival, while the Stage ⅢA or higher cases, 2-year survival rate was 33.8% and the MST was 20.0 months. Also, XELOX was often selected as the first-line treatment for chemotherapy regimens including recurrence treatment.

[Case of Gastric Cancer with Para-Aortic Lymph Node Metastases Successfully Treated with S-1/Docetaxel Chemotherapy].

A 78-year-old man diagnosed with advanced gastric cancer and para-aortic lymph node metastases at clinical stage cT3 (SS)N1M1(LYN), Stage Ⅳwas treated with S-1/docetaxel(S-1/DTX)therapy. Eight months later, lymph node metastases resolved on abdominal CT, and the primary lesion appeared scarred when viewed by upper gastrointestinal endoscopy; this was considered to be a complete response(CR). S-1/DTX therapy was administered for a total of 16 courses, followed by 13 courses ofS -1 therapy. During the treatment, CR was maintained. Though chemotherapy was completed 2 years and 2 months after its initiation, the patient's serum CEA level was found to be elevated. As the serum CEA level gradually increased, S-1/DTX therapy was resumed. Three months after chemotherapy was restarted, PET-CT revealed multiple bone metastases. The chemotherapy protocol was changed to paclitaxel/ramucirumab therapy followed by nivolumab therapy. Disease control was difficult, and the patient died 9 months after reinstituting chemotherapy(3 years and 8 months after the first chemo- therapy). This case report summarizes our treatment ofa patient with advanced gastric cancer using S-1/DTX therapy for an extended period of time.

[A Long-Survived Case of Gastric Cancer with Multiple Liver Metastases Who Underwent Gastrectomy and Received Chemotherapy].

A 70-year-old man visited our hospital because of a body weight loss. Upper gastrointestinal fiberscope revealed a type 3 tumor and an enhanced MRI showed 30 or more liver metastases. He received docetaxel plus cisplatin plus S-1(DCS)therapy. Although main tumor had shrinked only partially, multiple liver metastases could not be detected. Thus, he was performed distal gastrectomy. After gastrectomy, he received S-1 plus oxaliplatin(SOX)therapy followed by S-1 therapy. Two years and 2 months after surgery, chemotherapy was finished because of no signs of tumor progression. He is alive without recurrence for 2 years and 11 months after gastrectomy.

[A Case Report of Hepatocellular Carcinoma with Complete Spontaneous Regression].

This is the case of a 77-year-old man with hepatitis C. AFP was increased by 95.9 ng/mL, and abdominal computed tomography(CT)revealed a 20 mm mass in the S6 segment of the liver. Therefore, the patient was referred to our hospital for further examination. Abdominal echo at our hospital showed a 10 mm, low echoic lesion in S6, which tended to shrink. Similarly, CT showed a low-concentration nodule of 10 mm in S6, but the contrast effect in the arterial phase was not clear. EOB-MRI showed a 10 mm nodule of DWI hyperintensity and hepatocyte phase hypointensity in S6. Based on these, a diagnosis of hepatocellular carcinoma(T1N0M0, StageⅠ)was made, and we decided to perform surgery. Intraoperative findings showed no tumor on the liver surface, and echo did not reveal a reproducible nodule. The tumor site was estimated using a 3-dimensional image analysis system created preoperatively. Laparoscopic partial resection of the liver S6 segment was performed at a position distant from the estimated tumor site. Rapid pathological examination showed no malignant findings, but no significant lesion was found in the residual liver, and the surgery was completed. The postoperative pathological diagnosis revealed no clear tumor. EOB-MRI was performed again postoperatively, but no tumor was found in the residual liver. The tumor site that had been indicated preoperatively was resected, and we hypothesized that the hepatocellular carcinoma had spontaneously regressed. Although several mechanisms have been reported for the spontaneous regression of hepatocellular carcinoma, few cases of spontaneous regression during surgery have been reported. We do not have a definite opinion on the treatment protocol for hepatocellular carcinoma that regresses spontaneously; therefore, we will report on past cases.

[Two Cases of Liver Metastasis from Gastric Cancer Achieving Long-Term Survival Successfully Treated with Stereotactic Body Radiotherapy(SBRT)].

We report 2 cases with long-term survival following stereotactic body radiotherapy(SBRT)for liver metastasis from gastric cancer. Case 1 was a 65-year-old man. We performed distal gastrectomy for gastric cancer with liver metastasis prior to chemotherapy due to pyloric stenosis. Postoperative S-1 chemotherapy was administered. Two liver metastases observed before the operation were temporarily reduced in size but subsequently enlarged; therefore, SBRT was performed 13 months postoperatively. The liver metastases showed a complete response(CR)and the patient is alive 4 years and 11 months after SBRT(6 years postoperatively). Case 2 was a 71-year-old woman. After performing distal gastrectomy, liver metastasis emerged during postoperative S-1 adjuvant chemotherapy; therefore, SBRT was performed 11 months postoperatively. She was then administered weekly paclitaxel. However, she underwent a right hepatic lobectomy 13 months after SBRT for suspected remnant or marginal recurrence by abdominal enhanced CT. Histopathological examination showed that the tumors contained fibrotic connective tissue with no viable cancer cell remnants; therefore, the therapeutic effect was determined to be of Grade 3. The patient is alive without recurrence in the remnant liver 4 years and 7 months after SBRT(5 years and 6 months after the operation of gastric cancer). Thus, SBRT for liver metastasis from gastric cancer may be considered an effective local treatment.

[A Case Report of Long Survival in Pancreatic Cancer with Superior Mesenteric Arterial Invasion Following Multimodal Therapy].

The prognosis of pancreatic cancer with superior mesenteric arterial invasion is very poor and judgment of surgical indication is very difficult. We report a case that received multimodal therapy for pancreatic cancer with superior mesenteric arterial invasion. A 43-year-old woman consulted a local doctor because of upper abdominal pain. Ultrasonography revealed a nodule in the pancreatic body and elevated CA19-9 values. She was referred to our hospital for evaluation and therapy. Computed tomography showed a low-density area in the pancreatic body and around the superior mesenteric artery. The clinical diagnosis was pancreatic cancer with superior mesenteric arterial invasion. She received chemoradiation therapy(RT, 50.4 Gy, gemcitabine[GEM]plus TS-1)followed by distal pancreatectomy. She received adjuvant chemotherapy(TS-1)for 6 months. However, follow-up CTperformed 10 months after surgery revealed local recurrence. The patient received chemotherapy( GEM)for 8 months and GEM plus nab-PTX for 22 months. She died from the cancer 50 months after the primary operation.

[A Case Report of Advanced Gastric Cancer with Synchronous Liver Metastasis Treated with Conversion Surgery after S-1 plus Oxaliplatin Chemotherapy].

Gastroscopy ofa 79-year-old man complaining ofanemia showed a type 3 tumor at the lesser curvature ofthe gastric body. A biopsy revealed poorly differentiated HER2-negative adenocarcinoma. Abdominal CT showed the tumor at the lesser curvature ofthe gastric body, multiple lymph nodes with a maximum diameter of 25mm at the lesser curvature, and a mass measuring 50mm with ring enhancement on S6 ofthe liver. The clinical diagnosis was cT4aN2M1(Hep), cStage Ⅳ. He was treated with chemotherapy comprising 4 courses ofS -1 plus oxaliplatin. Although the tumor had shrunk remarkably, chemotherapy was discontinued because of anorexia. Therefore, we performed total gastrectomy and hepatic partial resection(S6). The final staging was ypT3N0M0, ypStage ⅡA. We achieved R0 resection, and he has shown no recurrence without adjuvant chemotherapy for 3 years.

[A Case of Chemotherapy with Abscess Drainage for Pancreatic Cancer Detected Due to Peritonitis].

A 69-year-old woman was admitted to our hospital because of abdominal pain. Abdominal CT revealed free air, so we performed an emergency operation. Although the perforation site could not be confirmed, pancreatic cancer invading the stomach, spleen, and transverse colon was found. As a splenic abscess and peritoneal dissemination were also found, we created a colostomy and placed drains. Although the postoperative course was good, the splenic abscess continuous with the tumor remained. We thought that early removal of the drain would be difficult, so chemotherapy was introduced while continuing drainage. Fortunately, the pancreatic cancer was controlled, and the abscess tended to shrink, so we removed the tube 137 days after the surgery. After that, we continued chemotherapy, but in the second year after the surgery, the liver metastasis acutely exacerbated and DIC also developed, resulting in cancer death. If surgical intervention is difficult, as in this case, chemotherapy may be considered as an option, keeping in mind the possibility of exacerbation of infection.

[A Case of Gastric Cancer with Ramucirumab-Related Colon Perforation after a Subtotal Colectomy].

A 61-year-old man with advanced gastric cancer underwent distal gastrectomy after chemotherapy. Fifteen months later, peritoneal metastasis and colon stenosis were detected. Therefore, subtotal colectomy and ileosigmoidostomy were performed. Three weeks later, paclitaxel(PTX)treatment was initiated, followed by nab-PTX with ramucirumab(Ram)treatment at 7 weeks postoperatively. The patient experienced sudden abdominal pain diagnosed as gastrointestinal perforation 13 weeks postoperatively. Operative findings showed that the anastomosis of the ileosigmoidostomy was perforated, and this was treated using sutures. Angiogenesis inhibitors should be carefully administered even 4 weeks or more after surgery.

[A Case of Peritoneal Dissemination of Hepatocellular Carcinoma after Laparoscopic Hepatectomy].

A 69-year-old man was found to have a hepatocellular carcinoma of 2.3 cm in diameter, with extrahepatic growth in liver S4 during follow-up for chronic hepatitis C and liver cirrhosis. We performed a laparoscopic partial liver resection, but the tumor capsule was injured by the retractor used to keep the working space at the bleeding site. The pathological diagnosis was moderately differentiated hepatocellular carcinoma(pT2N0M0, pStage Ⅱ). 7 months after the surgery, intrahepatic reoccurrence appeared. Thus, transcatheter arterial chemoembolization(TACE)and radiofrequency ablation were performed. However, a single recurrence ofperitoneal dissemination appeared 8 months after the reoperation. We selected laparoscopic operation this time. Intraperitoneally, we found 4 peritoneal disseminated lesions and resected all the lesions macroscopically. However, even after the resection, peritoneal dissemination recurred and increased. Therefore, we continued treatment with sorafenib and S-1 as systemic therapy, TACE and transcatheter arterial infusion(TAI)for the multiple recurrences in the liver, and radiotherapy for the peritoneal dissemination focuses. However, his general condition worsened, and liver failure occurred. Thus, he was shifted to complete palliative treatment and died 2 years 6 months after the initial operation. The recurrent form ofhepatocellular carcinoma is mainly an intrahepatic recurrence, and recurrence ofperitoneal dissemination is rare. In this case, the intraoperative operation was considered to be the possible cause ofthe recurrence.