[A Case of Recurrent Gastric Cancer with Long-Term Control via Two Resections and Multidisciplinary Treatment Including Nivolumab].

A 78-year-old woman underwent total gastrectomy with distal pancreatectomy and splenectomy for type 3 gastric cancer and a cystic tumor of the pancreas. Her pathological diagnosis was pT4aN3bM0, pStage ⅢC, and HER2-negative. Capecitabine and oxaliplatin was started as an adjuvant therapy, and capecitabine was administered until 1 year postoperatively. Thirteen months after surgery, she had a recurrence in S3 of the liver and underwent liver resection due to solitary metastasis. The postoperative diagnosis was peritoneal dissemination of gastric cancer with invasion of the falciform ligament. S-1 was started postoperatively. Ten months after surgery, she had a recurrence in S3 of the liver and underwent repeated resection. It invaded into the diaphragm and pericardium, and the final diagnosis was recurrent peritoneal dissemination of gastric cancer. After 5 courses of paclitaxel and ramucirumab, nivolumab was started as a fourth-line therapy for the recurrence of the right supraclavicular lymph nodes, bone, and liver. She had some immune-related adverse events(irAE), including hypothyroidism and hypoadrenocorticism, which required management, but she maintained PR more than 2 years after the initiation of the treatment. Multimodality therapies, including repeated resection and nivolumab, were considered to help her long-term survival.

[The Use of Platinum-Based Chemotherapy for Esophageal Cancer Patients with Impaired Renal Function].

INTRODUCTION: The key drugs of first-line chemotherapy for metastatic esophageal cancer are 5-FU and cisplatin(CF). However, the treatment strategy for unfit patients of CF regimen remains controversial. METHODS: Fifty patients who received first-line chemotherapy including platinum-containing drug for metastatic esophageal cancer between 2018-2022 at Osaka National Hospital were analyzed. They were divided into 4 groups according to estimated creatinine clearance(Ccr) at the beginning of the treatment; Group A(over 60 mL/min)31 patients, Group B(50-59 mL/min)12 patients, Group C(30-49 mL/min)5 patients, and Group D(under 30 mL/min)2 patients. The background and treatment outcome data of each group were retrieved retrospectively and compared. RESULTS: Group B, C, D had more elderly patients than Group A. Each Group B, C, D included 1 patient who received FOLFOX regimen. More than half patients in Group B, C, D reduced the dose of CDDP and the initial dose of CDDP was adequately reduced according to Ccr. Group B, C, D had more patients with decreased renal function over Grade 1 than Group A. The clinical response rate was Group A 65%, Group B 42%, Group C 60%, Group D 50%, respectively. There were no patients who ceased the treatment due to adverse events. CONCLUSION: Adequate dose reduction of CF regimen would become more important in the era that only CF regimen can be a partner of immune-checkpoint inhibitor.

[A Case of Conversion Surgery after Chemotherapy for Unresectable Liver Metastasis of Rectal Cancer].

A 50s female was diagnosed as rectal cancer with multiple liver metastases after fecal occult blood scrutiny. Liver metastases were multiple in both lobes and involved the right Glisson's capsule. We determined that the liver metastases were unresectable and initiated FOLFOXIRI plus panitumumab treatment. After 6 courses of chemotherapy, rectal cancer resection was performed. After 12 courses of chemotherapy, the liver metastases which had extensively involved the right Glisson on imaging, shrank until the P7 root was visible. If S7 Glisson could be preserved, the radical resection was planned. If not, associated liver partition and portal vein ligation for staged hepatectomy(ALPPS)was planned. Intraoperatively, it was determined that preservation of S7 Glisson was possible and blood flow preservation in the S7 region was feasible, and an anterior segment hepatic resection(S5-6-8)and lateral segment hepatic partial resection(S2/3)were performed. She was discharged on the 18th day and has been under outpatient observation 12 months after hepatectomy.

A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes.

OBJECTIVES: Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy. METHODS: Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo. RESULTS: Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events. CONCLUSIONS: Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer.

Clinical Experience with Pancreas Graft Rescue From Severe Thrombus After Simultaneous Pancreas-Kidney Transplantation by Early Detection with Doppler Ultrasound: A Case Report.

BACKGROUND Graft thrombosis is the main cause of early graft loss after transplantation. In Japan, pancreases available for transplantation are frequently from marginal donors due to diverse backgrounds in the population. However, marginal tissues increase the risk of early thrombosis in the graft. CASE REPORT Here, we describe a 41-year-old woman with type 1 diabetes mellitus who underwent a simultaneous pancreas-kidney transplantation. The pancreas was retrieved from a 34-year-old man who had experienced severe hemodynamic instability. The pancreaticoduodenal graft was implanted in the recipient iliac fossa with enteric drainage. Although the patient had not shown any physical signs or alterations in substances that might indicate functional loss of the pancreas graft, a Doppler ultrasound analysis detected a major thrombus in the pancreas graft on day 7 after surgery. A thrombectomy was performed with a radiological emergent intervention. After percutaneous direct thrombolysis, the patient received adjuvant thrombolytic therapy. Thereafter, the postoperative course was uneventful and the pancreas graft remained functional. CONCLUSIONS Early detection and treatment of thromboses are required to avoid graft failure and graft pancreatectomy. This case study demonstrates that early detection of severe thrombus with Doppler ultrasound in a grafted pancreas did not increase the risk of graft failure.

[Long-Term Survival after Locally Advanced Pancreatic Ductal Adenocarcinoma Treated with Multidisciplinary Therapy - A Case Report].

A 60-year-old man visited a hospital with concerns about his physical health, including weight loss, thirst, and polyuria. He was diagnosed with acute onset of diabetes, and a pancreatic head tumor was observed on imaging studies. Computed tomography(CT)indicated that the tumor infiltrated the surrounding major vessels, portal vein(PV, 360 degrees), and superior mesenteric artery(SMA, <180 degrees). Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)was performed, and he was diagnosed with a borderline resectable(BR)clinical Stage IV a pancreatic ductal adenocarcinoma (PDAC). Chemoradiation therapy(CRT, S-1 plus gemcitabine [GEM] concurrent with 50.4 Gy radiation)followed by chemotherapy( GEM)was performed until a tumor response indicating sufficient reduction of SMA infiltration was observed on imaging studies. Twelve months after initiation of treatment, a pancreaticoduodenectomy and PV resection/reconstruction were performed. The pathological stage was ypT3N0M0(ypStage III ), and SMA infiltration was not detected in the resected specimen. He was discharged after an uneventful course following surgery, and adjuvant S-1 chemotherapy was continued from post-operative day 67 for 4 months. Now at post-operative 57 month, he has survived without recurrence. There have been some reports detailing long-term survival of patients with BR tumors who underwent multidisciplinary therapy as curative resection following preoperative CRT and postoperative adjuvant chemotherapy. During preoperative treatment, it is important to monitor the effects and determine the suitable timing to perform surgery to achieve long-term survival.

[A Case of Distal Bile Duct Cancer Occurring 38 Years after Cyst-to-Duct Anastomosis for a Congenital Biliary Dilatation].

A 41-year-old woman had undergone cyst-to-duct anastomosis for a congenital biliary dilatation when she was 3-yearold. After 38 years, she presented with a high fever, and laboratory findings showed elevation of liver and biliary enzyme levels. A CT scan showed a mass lesion in a choledochal cyst, and an adenocarcinoma was found in the anastomosis of the choledochal cyst and duodenum. We diagnosed distal bile duct cancer and performed SSPPD after neoadjuvant chemotherapy( gemcitabine plus cisplatin plus S-1). The resected tumor was pathologically diagnosed as papillary-infiltrating adenocarcinoma( ypT2N1M0, ypStage II B). Currently, 9 months after the second surgery, the patient is doing well without any signs of recurrence. The current case suggested the necessity of postoperative lifetime follow-up for patients with bile duct cancer who have undergone radical cyst excision for a congenital biliary dilatation.

[Three Resected Cases of Metachronous Pancreatic Cancer Successfully Treated with Repeated Pancreatectomy].

Repeated pancreatectomy for metachronous pancreatic cancer has rarely been reported. We report 3 cases with metachronous pancreatic ductal carcinoma that developed after pancreatectomy for the first pancreatic cancer. They were successfully resected by removal of the remnant pancreas. In all 3 cases, the cancers in the remnant pancreas were treated with repeated pancreatectomy. The histological margin of the first pancreatic resection was cancer-free in all the cases. Furthermore, the second cancer tissue contained carcinoma lesions in situ adjacent to invasive ductal carcinoma. Based on these findings, the 3 patients were diagnosed with metachronous pancreatic cancers.

Tissue factor predicts response to chemotherapy in esophageal cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) improves the prognosis of patients with esophageal cancer who respond, but it is not effective in nonresponders. Therefore, it is crucial to establish a reliable method of predicting response before initiation of chemotherapy. Hypercoagulability, which is thought to be because of upregulation of tissue factor (TF) in cancer cells, was reported to be associated with chemoresistance. The aim of this study was to investigate the association between TF expression and response to NACT in esophageal cancer. METHODS: In 67 patients with advanced esophageal cancer, TF expression in pretreatment biopsy samples was evaluated immunohistochemically and correlated with clinicopathologic factors and response to chemotherapy. RESULTS: TF was expressed by 43.3% of the tumors, but there were no correlations observed with any clinicopathologic parameters examined. Clinical and histologic responses to chemotherapy were significantly worse in TF-positive patients compared with TF-negative patients. Multivariate analysis revealed that TF expression was significantly associated with a poor clinical response (P = 0.0431). TF expression was also independently associated with poor progression-free survival (P = 0.0353). CONCLUSIONS: TF expression levels in pretreatment biopsy samples are useful for predicting response to NACT in advanced esophageal cancer. Further studies of mechanisms underlying the relationship between TF expression and chemosensitivity are needed.

[Hepatic metastasis from gastric GIST radically resected after imatinib mesylate therapy-a case report].

We report a case of hepatic metastasis from gastric gastrointestinal stromal tumor (GIST), which was safely resected with preoperative imatinib therapy. A 60-year-old woman was hospitalized and underwent a treatment for hepatic SOL at another hospital prior to gastric GIST resection. Computed tomography revealed a tumor compressing the right and middle hepatic vein. The tumor volume decreased after an initiation of imatinib therapy aimed at preserving the middle hepatic vein. Although tumor volume was further decreased over the course of twelve months, a new lesion appeared, suggesting a progressive disease. Our findings suggest that a radical resection of gastric GIST to preserve the middle hepatic vein is possible.

Talaporfin-mediated photodynamic therapy for peritoneal metastasis of gastric cancer in an in vivo mouse model: drug distribution and efficacy studies.

Photodynamic therapy (PDT) is a potential treatment for the peritoneal dissemination of gastric cancer, because its cytotoxicity is limited to superficial lesions. We examined the accumulation of talaporfin in peritoneal metastatic nodules and determined the optimal laser condition for these nodules. We also evaluated the pathological response after therapy. We created a peritoneal metastasis model in nude mice using the MKN-45 EGFP cell line. We evaluated the accumulation of talaporfin in peritoneal metastatic nodules and normal organs by spectrophotometric analysis 2-8 h after i.p. talaporfin. To determine optimal PDT conditions, we treated metastatic nodules and the small intestine using multiple laser doses (2, 5, and 10 J/cm2, respectively). Accumulation of talaporfin was detected in metastatic nodules in higher intensities than in the small intestine. The fluorescent intensity of the peritoneal metastatic nodules gradually decreased dependent on the time interval between the laser treatment and talaporfin administration. Fluorescent intensity in the small intestine decreased more than in the metastatic nodules. The pathological response rates by dose were 52.5% at 2 J/cm2, 43.2% at 5 J/cm2, and 64.4% at 10 J/cm2, respectively, when the laser treatment was used 2 h after talaporfin administration, whereas at 4 h, they were 20.8, 25.5, and 26.2%, respectively. Finally, the recommended treatment conditions were considered to be a 2 J/cm2 laser dose and a 4-h interval in terms of toxicity. Talaporfin-mediated PDT may be an effective treatment modality for patients with advanced gastric adenocarcinoma and metastatic peritoneal nodules.

Presence of minute cancer cell dissemination in peritoneal lavage fluid detected by reverse transcription PCR is an independent prognostic factor in patients with resectable pancreatic cancer.

BACKGROUND: Presence of minute cancer cell dissemination in peritoneal lavage fluid detected by reverse transcription polymerase chain reaction (RT-PCR) has been reported to be a reliable predictor of the prognosis in several kinds of cancers, but has not been determined in pancreatic cancer. METHODS: Peritoneal lavage fluid was harvested just after a laparotomy in 83 patients with adenocarcinoma of the pancreas. Half of the fluid was examined by cytology and the remaining half was used to measure carcinoembryonic antigen/beta-2-microglobulin (beta2M) mRNA expression. Patients were followed after surgery to evaluate its clinical significance. RESULTS: Among 83 patients, 3 were cytologically positive (CY+), while 23 were positive by RT-PCR (PCR+). Seventy-one patients underwent a surgical resection whereas 12 were unresectable. Because 2 were CY+ among the 71 operated patients, the remaining 69 CY- patients were further investigated. Among those 69 patients, PCR+ was observed in 15 patients, whose incidence of postoperative peritoneal recurrence was significantly higher than that in PCR- patients (21% vs 4% at 3 years; P = .039). Moreover, both the recurrence-free rate in the abdominal cavity (peritoneal or local recurrence, excluding liver metastases) and the overall survival rate were better in PCR- patients than PCR+ patients (78% vs 33%, P = .0045 and 67% vs 46%, P = .0151). A multivariate analysis revealed positive lymph node metastases (hazard ratio; 5.18) and positive RT-PCR (hazard ratio; 3.65) were independent prognostic factors. CONCLUSION: The RT-PCR-based cancer cell detection was an independent prognostic factor in patients with resectable adenocarcinoma of the pancreas and had close association with local or peritoneal recurrence.

[A case of metastatic liver cancer from rectal cancer demonstrating a clinical CR with 3D-CRT].

The patient was a 62-year-old man who underwent a low anterior resection for rectal cancer. The tumor was a moderately differentiated adenocarcinoma, type 2 in the Japanese classification of colorectal carcinoma. The tumor was considered to be in stage I (mp, n (-), P0, H0, M (-)). He did not receive any adjuvant chemotherapy. After 6 months from the surgery, ultra sound sonography and an abdominal CT scan revealed a 30 mm hepatic nodule lesion. We diagnosed liver metastasis of the rectal cancer. The patient refused a surgery and chemotherapy. We chose radiotherapy for liver metastasis. He was given a total dose of 60 Gy/10 fractions/10 days with 3D-CRT. After 1 month from the radiotherapy, the tumor was reduced to 17 mm in size and regressed gradually. At 19 months from the radio therapy, the disease was diagnosed as CR because no tumors were detected. There has been no recurrence for 25 months since his irradiation. 3D-CRT appears to be effective for liver metastasis from the rectal cancer.

[A long-term survival case of advanced sigmoid colon cancer with massive metastases to the para-aortic lymph nodes].

We report a long-term survival case of advanced sigmoid colon cancer with massive metastases to the para-aortic lymph nodes. The patient was a 63-year-old male. He underwent sigmoidectomy with D3 + para-aortic lymphadenectomy for advanced sigmoid colon cancer. Histological examination showed a moderately differentiated adenocarcinoma, ss, ly2, v2, n4 (total 30/64, para-aortic lymph nodes 18/39). From 6 months to 4 years after the operation, tegafur/uracil (UFT) was performed as chemotherapy. After 8-year disease-free interval, CT showed solitary mediastinal lymph node metastases. He underwent thoracoscopic mediastinal lymphadenectomy. Histological examination revealed metastases from colon cancer.