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.

Diagnostic impact of postoperative CA19-9 dynamics on pancreatic cancer recurrence: a single-institution retrospective study.

Postoperative CA19-9 elevation after pancreatic cancer resection suggests recurrence but can also occur in benign conditions. This study aimed to investigate the interpretation of postoperative CA19-9 elevation after pancreatic cancer surgery in terms of cancer recurrence. A cohort of patients undergoing pancreatectomy for pancreatic cancer at our hospital was included. Among them, 52 patients exhibited postoperative CA19-9 elevation without radiological evidence of recurrence. These patients were evaluated with follow-up CA19-9 measurements. The CA19-9 increase rates were calculated based on the first elevation and the follow-up measurement. The association between the CA19-9 increase rate and tumor recurrence was assessed. Patients with a CA19-9 increase rate of ≥ 30% had a significantly higher frequency of recurrence within 3 months compared to those without such an increase (p = 0.0002). Multivariate analysis demonstrated that a CA19-9 increase rate of ≥ 30% was an independent risk factor for recurrence (odds ratio 8.17, p = 0.0309). The CA19-9 value at the first elevation (p = 0.1794) and at the follow-up measurement (p = 0.1121) were not associated with recurrence. After the first postoperative CA19-9 elevation, the CA19-9 increase rate based on follow-up measurements can serve as a predictive factor for tumor recurrence.

Preoperative D-dimer Value and Lower Limb Venous Ultrasound for Deep Venous Thrombosis Prevents Postoperative Symptomatic Venous Thromboembolism in Patients Undergoing Colorectal Surgery: A Retrospective Study.

Objectives: Preoperative deep venous thrombosis (DVT) can cause potentially life-threatening postoperative venous thromboembolism (VTE). Lower limb venous ultrasound (LLVU) is a modality that can detect DVT. However, the threshold for performing preoperative LLVU in the population undergoing colorectal resection is controversial. In this context, we evaluated whether a preoperative D-dimer value can identify patients who benefit from LLVU from the perspective of preventing postoperative symptomatic VTE. Methods: Patients undergoing colorectal resection in our institute from 2013 to 2020 were retrospectively enrolled (n=2071). We divided the patients into two groups: the clinical indication group (CG: including patients from 2013 to 2016, n=875) and the D-dimer-orientated group (DG: including patients from 2017 to 2020, n=1196). In the CG, LLVU was performed when DVT was clinically suspected; in the DG, preoperative LLVU was performed in patients with a preoperative D-dimer>1.0 µg/ml. Results: In the surveyed period, 277 LLVUs were performed, among which DVT was detected in 34 cases (12.3%). In the CG, DVT was detected in 0.7% of patients, whereas in the DG, it was detected in 2.3% of patients. Postoperative symptomatic VTE was significantly reduced in the DG at both 3 and 6 months after surgery (p=0.041 and 0.020, respectively). Moreover, Multivariate analysis showed that a past medical history of PE and treatment following the CG protocol were independent risk factors for postoperative symptomatic VTE within 6 months of surgery (p<0.0001 and =0.036, respectively). Conclusions: LLVU in patients with a preoperative D-dimer>1.0 µg/ml is a useful method to prevent postoperative symptomatic VTE.

Efficacy of Autologous Skeletal Myoblast Cell Sheet Transplantation for Liver Regeneration in Liver Failure.

BACKGROUND: No effective therapies have yet been established for liver regeneration in liver failure. Autologous skeletal myoblast cell sheet transplantation has been proven to improve cardiac function in patients with heart failure, and one of the mechanisms has been reported to be a paracrine effect by various growth factors associated with liver regeneration. Therefore, the present study focused on the effect of myoblast cells on liver regeneration in vitro and in vivo. METHODS: We assessed the effect of myoblast cells on the cells comprising the liver in vitro in association with liver regeneration. In addition, we examined in vivo effect of skeletal myoblast cell sheet transplantation in C57/BL/6 mouse models of liver failure, such as liver fibrosis induced by thioacetamide and hepatectomy. RESULTS: In vitro, the myoblast cells exhibited a capacity to promote the proliferation of hepatic epithelial cells and the angiogenesis of liver sinusoidal endothelial cells, and suppress the activation of hepatic stellate cells. In vivo, sheet transplantation significantly suppressed liver fibrosis in the induced liver fibrosis model and accelerated liver regeneration in the hepatectomy model. CONCLUSIONS: Autologous skeletal myoblast cell sheet transplantation significantly improved the liver failure in the in vitro and in vivo models. Sheet transplantation is expected to have the potential to be a clinically therapeutic option for liver regeneration in liver failure.

Hypoattenuated Area at Pancreatojejunostomy Site After Pancreatoduodenectomy Predicts Grade B/C Postoperative Pancreatic Fistula.

BACKGROUND: After pancreatojejunostomy for pancreatic head resection, contrast-enhanced computed tomography sometimes reveals a hypoattenuated area at the pancreatojejunostomy site. The clinical impact of this hypoattenuated area, in terms of postoperative pancreatic fistula, is unknown. METHODS: Among 309 patients undergoing pancreatic head resection with pancreatojejunostomy reconstruction at Osaka University Hospital from 2012 to 2020, 105 exhibited drain amylase levels over 3× the upper limit of normal. According to contrast-enhanced computed tomography on postoperative days 3-14, these patients were divided into two groups-evident hypoattenuated area group (≥ 5 mm; n = 46) and subtle hypoattenuated area group (< 5 mm; n = 59)-and evaluated for clinically relevant pancreatic fistula. RESULTS: Clinically relevant pancreatic fistula was significantly more common with the evident hypoattenuated group (80.4%; 37/46) than the subtle hypoattenuated group (40.7%; 24/59) (P < 0.0001). Multivariate analysis identified four factors related to clinically relevant pancreatic fistula formation: male sex (P = 0.0230), main pancreatic duct diameter < 3 mm (P = 0.0007), operative time > 475 min (P = 0.0161), and evident hypoattenuated area group (P = 0.0050). Hypoattenuated area ≥ 5 mm was associated with clinically relevant pancreatic fistula (60.7% sensitivity; 79.6% specificity). CONCLUSION: Evident hypoattenuated area on postoperative contrast-enhanced computed tomography was an independent risk factor for clinically relevant pancreatic fistula. Patients experiencing increased drain amylase levels may benefit from contrast-enhanced computed tomography assessment to predict clinically relevant pancreatic fistula formation.

The clinical impact of modified transpancreatic mattress sutures with polyglactin 910 woven mesh on postoperative pancreatic fistula in distal pancreatectomy.

BACKGROUND: We previously reported the stump closure method for the remnant pancreas in distal pancreatectomy, in which soft coagulation and polyglycolic acid felt attached with fibrin glue were utilized. Transpancreatic mattress suture with polyglactin 910 woven mesh was recently reported as a novel stump closure technique. We developed the modified transpancreatic mattress suture with polyglactin 910 woven mesh method, which combined our polyglycolic acid felt method with the transpancreatic mattress suture with polyglactin 910 woven mesh method. METHODS: The polyglycolic acid felt group included patients undergoing distal pancreatectomy in whom the pancreatic stump was closed with the polyglycolic acid felt method from 2017 to 2018 (n = 54); whereas the modified transpancreatic mattress suture with polyglactin 910 woven mesh group included those whose stump was closed with the modified transpancreatic mattress suture with polyglactin 910 woven mesh method from 2019 to 2020 (n = 51). Perioperative parameters, including grade B/C postoperative pancreatic fistula (clinically relevant postoperative pancreatic fistula), were assessed according to the stump closure method. RESULTS: The incidence of clinically relevant postoperative pancreatic fistula was significantly lower in the modified transpancreatic mattress suture with polyglactin 910 woven mesh group than in the polyglycolic acid felt group (7.8% vs 22.2%, P = .036). In multivariate analysis, the use of neoadjuvant chemoradiotherapy and the transpancreatic mattress suture with polyglactin 910 woven mesh method were independent factors for preventing clinically relevant postoperative pancreatic fistula (P = .011 and 0.0038, respectively). Moreover, in the modified transpancreatic mattress suture with polyglactin 910 woven mesh group, the incidence of clinically relevant postoperative pancreatic fistula in patients with a thick pancreas (≥13 mm, 6.7%) was comparably as low as that in patients with a thin pancreas (<13 mm, 9.5%). CONCLUSION: The modified transpancreatic mattress suture with polyglactin 910 woven mesh method is an effective stump closure technique to prevent clinically relevant postoperative pancreatic fistula after distal pancreatectomy. Our results warrant further prospective investigation to evaluate the efficacy of the modified transpancreatic mattress suture with polyglactin 910 woven mesh method compared with other standard closure methods (eg, stapler closure or hand-sewn closure).

Combination of extramural venous invasion and lateral lymph node size detected with magnetic resonance imaging is a reliable biomarker for lateral lymph node metastasis in patients with rectal cancer.

PURPOSE: Pathological extramural venous invasion (EMVI) is defined as the active invasion of malignant cells into veins beyond the muscularis propria in colorectal cancer. It is associated with poor prognosis and increases the risk of disease recurrence. Specific findings on MRI (termed MRI-EMVI) are reportedly associated with pathological EMVI. In this study, we aimed to identify risk factors for lateral lymph node (LLN) metastasis related to rectal cancer and to evaluate whether MRI-EMVI could be a new and useful imaging biomarker to help LLN metastasis diagnosis besides LLN size. METHODS: We investigated 67 patients who underwent rectal resection and LLN dissection for rectal cancer. We evaluated MRI-EMVI grading score and examined the relationship between MRI-EMVI and LLN metastasis. RESULTS: Pathological LLN metastasis was detected in 18 cases (26.9%), and MRI-EMVI was observed in 32 cases (47.8%). Patients were divided into two cohorts, according to LLN metastasis. Multivariate analyses demonstrated that higher risk of LLN metastasis was significantly associated with MRI-EMVI (P = 0.0112) and a short lateral lymph node axis (≥ 5 mm) (P = 0.0002). The positive likelihood ratios of MRI-EMVI alone, LLN size alone, and the combination of both factors were 2.12, 4.84, and 16.33, respectively. Patients negative for both showed better 2-year relapse-free survival compared to other patients (84.4% vs. 62.1%, P = 0.0374). CONCLUSIONS: MRI-EMVI was a useful imaging biomarker for identifying LLN metastasis in patients with rectal cancer. The combination of MRI-EMVI and LLN size can improve diagnostic accuracy.

Postoperative aggressive diuresis prevents postoperative tissue edema and complications in patients undergoing distal pancreatectomy.

PURPOSE: Intraoperative fluid restriction is reported to be associated with reduced postoperative tissue edema and decreased incidence of postoperative pancreatic fistula (POPF) in pancreatic surgery. However, there is limited information regarding the postoperative approach to prevent postoperative tissue edema and reduce POPF. METHODS: Patients undergoing distal pancreatectomy from 2013 to 2018 in our institute were retrospectively enrolled (n = 128). The patients were classified into the two groups: an early diuresis group (ED group: patients administered diuretic agents on postoperative day 2 or earlier between 2016 and 2018, n = 69) and a conventional diuresis group (CD group: patients administered diuretic agents on postoperative day 3 or later between 2013 and 2015, n = 59). Postoperative tissue edema assessed by CT imaging and the incidence of clinically relevant POPF (CR-PF; grade B or C) were compared. RESULTS: Postoperative tissue edema was significantly reduced in the ED group (p < 0.0001). The incidence of CR-PF was lower in the ED group (19% vs. 32%, p = 0.082), especially in patients with postoperative diuresis on POD 1 (12%, p = 0.044). CONCLUSION: Early and aggressive postoperative diuresis potentially reduced postoperative visceral tissue edema. This postoperative approach to prevent tissue edema may reduce the incidence of CR-PF in pancreatic surgery.

Coexisting primary tumors from esophageal cancer and myelodysplastic syndromes: A case report.

This is the first report of the double primary cancer of esophageal cancer (EC) and myelodysplastic syndromes (MDS) treated without esophagectomy. Previously reported cases of the double cancer mostly describe secondary MDS arising after treatment for EC. The double primary cancer was manageable with close follow-ups for possible recurrence.

[Two Cases of Advanced Gastric Cancer with Para‒Aortic Lymph Node Metastasis or Recurrence for Which Nivolumab Therapy Were Effective].

A 74‒year‒old man was diagnosed with advanced gastric cancer with para‒aortic lymph node metastasis and ascites. He has been treated with S‒1 plus oxaliplatin as the primary treatment, paclitaxel plus ramucirumab as the secondary treatment and CPT‒11 as the third‒line treatment, but the effect of all treatments were temporary and left adrenal metastasis appeared during the course. Nivolumab was started as the fourth‒line treatment. Two months later, para‒aortic lymph nodes and left adrenal metastasis were markedly shrank and ascites disappeared. A 79 years old woman was performed proximal gastrectomy for advanced gastric cancer of the upper stomach. S‒1 therapy was started as adjuvant chemotherapy, but tumor markers have been increased and para‒aortic lymph node recurrence was observed 4 months after the operation. After ramucirumab as the primary treatment was ineffective, nivolumab was started as the secondary treatment. Two months later, para‒aortic lymph nodes shrank below the significant size and tumor markers were normalized.

[A Case of Gastrointestinal Submucosal Tumor with an Intraluminal Growth Pattern Resected by Laparoscopic Wedge Resection].

We report a case of gastrointestinal submucosal tumor with an intraluminal growth pattern resected by laparoscopic wedge resection. A 62-year-old man was admitted because of melena. Upper gastrointestinal endoscopy revealed gastrointestinal submucosal tumor with an intraluminal growth pattern just below the gastric junction, and the pathological diagnosis was GIST. A laparoscopic wedge resections(percutaneous endoscopic intragastric surgery)was performed by a single access port. After laparotomy 5 cm above the umbilicus, the anterior wall of the middle part of the stomach was incised and fixed to the skin, and the tumor was dissected with a linear stapler. The final pathology result showed a high risk GIST of 70×40 mm with 110 mitotic images/50 HPF, and the patient was treated with imatinib mesylate adjuvant chemotherapy. There were no complications, including postoperative transit disturbances, and there were no local or distant metastatic recurrences.

[A Case of Early Gastric Cancer in the Remnant Stomach after Successful Treatment with ESD].

We report a case of early gastric cancer in the remnant stomach after successful treatment with endoscopic submucosal dissection(ESD). A 64-year-old woman had undergone distal gastrectomy, D2 dissection, and Billroth Ⅰ reconstruction for advanced gastric cancer 11 years previously. During a routine upper gastrointestinal endoscopy, an elevated lesion was detected at the lesser curvature of the upper gastric body of the remnant stomach, and biopsy indicated a Group 4 tumor. Curative en bloc resection of the lesion was achieved via ESD, although there was severe fibrosis along the suture line. The pathological result was 0-I, pT1a, tub1, 3×3 mm, UL(－), ly(－), v(－), HM0(8 mm), VM0(800 µm), indicating curative resection. Surveillance of the upper gastrointestinal tract 5 years after gastric cancer surgery enabled the early detection of the gastric cancer and curative resection with ESD.

[Laparoscopic Repair of Incarcerated Diaphragmatic Hernia as a Complication of Left Hepatectomy for Liver Cancer].

We report a case of laparoscopic repair of a diaphragmatic hernia after left hepatectomy for liver cancer. A woman in her 70s had undergone left hepatectomy for liver cancer 9 months earlier, and she was admitted because of epigastric pain after vomiting immediately following contrast-enhanced CT. On the next day, contrast-enhanced CT revealed an incarcerated diaphragmatic hernia, for which laparoscopic diaphragmatic hernia repair was performed. The incarcerated stomach was pushed back into the abdominal cavity, and the diaphragm was closed with 2-0 proline sutures. Gastric resection was not performed because the blood flow gradually improved. The postoperative course was good; the patient was discharged on the 7th postoperative day and is under outpatient follow-up.

Simultaneous triple cancer of the esophagus, pancreas and rectum treated with multimodal strategies: a case report.

BACKGROUND: Due to the development of diagnostic imaging technology, we have increased chance of detecting multiple primary cancers. However, simultaneous triple cancer is still a very rare finding whose frequency is not yet known. Treatment of simultaneous triple cancer is a clinical challenge because it requires multimodal strategies including surgery, chemotherapy and radiotherapy. CASE PRESENTATION: Here, we present the case of a 74-year-old male with triple cancer involving esophageal and pancreatic cancer, and rectal carcinoma. Each cancer was surgically resectable, but simultaneous resection of all cancers seemed to cause too much surgical stress for the patient. First, we performed a laparoscopic Hartmann's operation for rectal cancer to minimize the risk of postoperative complications. Then treatment for pancreatic cancer was initiated by administering neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel. The pancreatic tumor shrank in size, so pancreatoduodenectomy was performed. We chose S-1 as adjuvant chemotherapy. The esophageal cancer showed regression during the treatment of the other two cancers, likely because the chemotherapeutic agents administered for pancreatic cancer had some effect on the esophageal cancer. Definitive chemoradiotherapy was selected instead of esophagectomy because the patient had already undergone two major surgeries. The patient is still alive nine months after the whole course of treatment with no sign of recurrence. CONCLUSIONS: The treatment of triple cancer requires an elaborate strategy to determine which cancer has to be dealt with first and which can be treated later. An aggressive multimodal treatment strategy may be an important option for a patient with triple cancer.

[Advanced Colon Cancer Resected after a Neoadjuvant Chemotherapy of CAPOXIRI-A Case Report].

We report a case ofadvanced colon cancer, stage cT4bN0M0 in the descending colon with formation ofabscesses in the retroperitoneal space ofa 66-year-old woman. After constructing a transverse colostomy and percutaneous abscess drainage, chemotherapy was initiated with CAPOX. After 4 courses of CAPOX, the tumor had significantly regressed; therefore, the regimen was switched to a triplet combination called CAPOXIRI. After 3 courses of CAPOXIRI, the tumor had become smaller and had separated from the iliopsoas muscle, which led us to perform surgical resection. Left hemicolectomy was performed with R0 resection, and the tumor was pathologically diagnosed as ypT3N0M0. The patient is alive 12 months after the surgery, with no signs of recurrence.

[A Case of Neuroendocrine Carcinoma of Ascending Colon with Early Recurrence after Surgery].

A 65-year-old male received the positive result of fecal occult blood. Colonoscopy was performed to reveal a tumor in the ascending colon. The result of biopsy was neuroendocrine carcinoma. Under the preoperative diagnosis of neuroendocrine carcinoma in the ascending colon, cT3N0M0, cStage Ⅱ, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological result was neuroendocrine carcinoma in the ascending colon, pT4aN2M0, pStage Ⅲc. The R0 resection was achieved. As adjuvant chemotherapy, the regimen of cisplatin plus irinotecan was administered for 4 courses. No recurrence was seen until 9 months after the operation, when multiple peritoneal and hepatic metastasis were detected on CT scan. The chemotherapy regimen of etoposide plus carboplatin was started and is now ongoing. The patient is now alive 13 months after the operation.

[A Case of Rapidly Progressive Gallbladder Cancer Presented with Gallbladder Hemorrhage].

A 96-year-old woman was brought to our hospital for epigastric pain. Abdominal contrast-enhanced CT and MRCP showed wall thickness of the fundus and extravasation in the gallbladder. With a diagnosis of gallbladder hemorrhage from the tumors, we performed laparoscopic cholecystectomy. The histopathological diagnosis was gallbladder cancer. Herein, we report on this case and also provide a literature review.

[A Case of Early Gastric Cancer That Coexisted with Multiple Submucosal Heterotopic Gastric Glands].

We report a case of surgical resection of an early gastric cancer that coexisted with multiple submucosal heterotopic gastric glands.A man in the 80's referred to our department because of an increased level of CEA.He had undergone hepatectomy for heterochronous liver metastasis of colon cancer.Gastrointestinal endoscopy revealed an early gastric cancer that coexisted with multiple submucosal gastric glands.He underwent segmental gastrectomy for gastric cancer.He exhibited no symptoms at the time of discharge.He has had no recurrence of gastric cancer 6 months after the surgery.We should appropriately care for synchronous or heterochronous gastric cancer in the remnant stomach if total gastrectomy is not performed in cases of therapy for gastric cancer with multiple submucosal heterotopic gastric glands.

[A Case of Recurrence in the Lateral Pelvic Lymph Node after Local Excision of Lower Rectal pT1a Cancer].

The patient was a man in his 70s who visited our hospital to undergo an examination for fecal occult blood, which detected a 20 mm, Ⅱa lesion in the lower rectum on colonoscopy. He was diagnosed with SM-invasive cancer and was planned to undergo trans-anal local excision. After the surgery, he had a good postoperative course without complications. The pathological findings were Ⅱa, tub1, 22×16 mm, pT1a(950 mm), int, INF a, ly0, v0, pHM0, pVM0(300 mm). He was followed up after the surgery, but was diagnosed with lateral lymph node recurrence 4 years after a local surgery. The surgery involved right-sided lateral lymphadenectomy with resection of the ureter, spermatic duct, seminal vesicle, and piriformis muscle. He was diagnosed with lymph node metastasis with invasion of the spermatic duct based on pathology. Eight courses of adjuvant chemotherapy containing CapeOX was administered. Unfortunately, primary squamous cell lung cancer was detected, and he died after surgery for recurrence in the second year. It is suggested that it is necessary to note lateral lymph node recurrence on postoperative follow-up for lower rectal cancer at any stage.

[A Case of Pulmonary Metastases of Colon Cancer with Submucosal Invasion].

In general, distant metastasis is uncommon in colorectal submucosal(SM)invasion without lymph node metastasis. We experienced an extremely rare case of synchronous pulmonary metastases for colon cancer in SM invasion. A man in his 70s was seen at the hospital for a positive fecal occult blood test. Colonoscopy revealed 3 lesions in the sigmoid colon and endoscopic mucosalresection revealed 2,000 mm SM invasion in all 3 lesions. Computed tomography showed no signs of distant lymph node or liver metastasis but showed small nodules in both lungs. Radical treatment included laparoscopic anterior resection with lymph node dissection. Histological examination showed no residual tumor in the colon and no lymph node metastasis. Two years after surgery, the number of lung nodules gradually increased and we performed partial resection of the left lung, which was diagnosed as pulmonary metastasis from colon cancer by histological examination. Therefore, we resected the opposite-side pulmonary metastases. The patient has exhibited no other signs of recurrence in the 2 years since the last operation.