Kenjiro Kimura

Background: Cancer-associated fibroblasts (CAFs) play an important role in cancer growth by interacting with cancer cells, but their effects differ depending on the type of cancer. This study investigated the role of CAFs in biliary tract cancers (BTCs), compared with pancreatic ductal adenocarcinoma (PDAC) as a comparison cohort. Methods: We retrospectively evaluated alpha-smooth muscle actin (αSMA) expression in CAFs from 114 cases of PDAC and 154 cases of BTCs who underwent surgical treatment at our institution from 1996 to 2017. CAFs were isolated from resected specimens of BTC and PDAC, and tested for the effects of their supernatants and cytokines on cancer cell proliferation. Results: PDAC patients with positive αSMA expression showed significantly shorter overall survival and recurrence-free survival than αSMA-negative patients (p = 0.003, p = 0.009, respectively). BTC patients with positive αSMA expression showed better recurrence-free survival than αSMA-negative patients (p = 0.03). CAF-conditioned medium suppressed the proliferation of cancer cells for only OCUCh-LM1 cells and not PDAC cells. Blockage of Interleukin-8 (IL-8) or its receptor C-X-C motif chemokine receptor 2 (CXCR2) by antibodies canceled the suppressive effect of the IL-8. Conclusions: CAFs are a good prognostic factor in BTC, but not for PDAC. Moreover, CAF-produced Interleukin-8 suppresses the proliferation of OCUCh-LM1 cell lines.

Background: We aimed to investigate the difference in engraftment rates depending on the transplant site for a patient-derived xenograft (PDX) of pancreatic ductal adenocarcinoma (PDAC) and the effects of the microenvironment on engraftment. Materials and Methods: Frozen cancer tissues from PDAC tumors were used, and tumor fragments were directly implanted into the subcutaneous, orthotopic pancreas, peritoneum, and liver of X-linked severe combined immunodeficiency (XSCID) rats. We assessed the success of engraftment in each organ. Additionally, to evaluate the effect of the microenvironment in each organ, we performed immunohistochemical analysis. Results: Subcutaneous transplantation was successful in 8 of 10 PDAC cases (16 of 30 rats). This was a higher rate than for other organ transplants. The vascular endothelial cells in the stroma were replaced with those from rats instead of humans. Vascular endothelial growth factor-A (VEGF-A) and cluster of differentiation-31 (CD31) was significantly more strongly expressed in the subcutaneous transplantation model (VEGF-A: p<0.001, CD31: p=0.0036). Conclusion: The engraftment rate was significantly higher for the subcutaneous PDX model than for the orthotopic pancreatic, peritoneal, and liver PDX models. Blood vessels of the PDX stroma had been replaced by rat-derived vessels instead of the original human vessels, suggesting that angiogenesis in the PDX microenvironment may be a major factor in engraftment.

Background The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. Methods Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. Results The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2–G4, presence of LNM, pT3–4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis–T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3–4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. Conclusions Histologic grade G2–G4, presence of LNM, pT3–T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis–T1a. Moreover, based on the high frequency of LNM in T3–4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3–4 DC at any site.

Background/Aim: There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as Ki-67, p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. Results: Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0.003 and p=0.007, respectively). Conclusion: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.

Background/Aim: This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8⁺ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8⁺ TILs in biliary tract cancers (BTCs). Patients and Methods: A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8⁺ TILs were identified by immunohistochemical staining. Results: The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8⁺ TILs were longer than those with low CD8⁺ TILs. Preoperative NLR and CD8⁺ TILs were negatively correlated. Conclusion: NLR and CD8⁺ TILs were associated with OS and RFS in BTCs. NLR can predict CD8⁺ TILs infiltrating the cancer microenvironment.

Growing evidence indicates that inflammation contributes to cancer progression, and several inflammatory markers have been reported to be associated with the clinical outcomes in patients with various types of cancer. Recently, the advanced lung cancer inflammation index (ALI) has been developed as a prognostic marker in patients with lung cancer. The difference between the ALI and the inflammatory markers reported in the previous studies is that the ALI contains not only indices related to inflammation but also the body mass index (BMI), which was reported to correlate with the sarcopenic status. The aim of this study was to evaluate the prognostic significance of the ALI in patients with unresectable metastatic colorectal cancer. We retrospectively reviewed a database of 159 patients who underwent combination chemotherapy for unresectable metastatic colorectal cancer between 2008 and 2016. The BMI was calculated by dividing the weight by height squared. The neutrophil-to-lymphocyte ratio (NLR) was calculated from a blood sample by dividing the absolute neutrophil count by the absolute lymphocyte count. The ALI was defined as follows: ALI=BMI × serum albumin concentration/NLR. The overall survival rate was significantly worse in the low-ALI group than in the high-ALI group (p < 0.0001). Furthermore, the ALI was an independent prognostic factor for the overall survival (hazard ratio: 2.773, 95% confidence interval: 1.773–4.335, p < 0.001). A newly developed prognostic marker, the ALI, was found to be a novel prognostic marker in patients with unresectable metastatic colorectal cancer as well as in patients with lung cancer.

Pancreatic injuries are rare, and no treatment plan has yet been established for grade III injuries. In many cases, pancreatic stent placement has resulted in saving patients. However, some cases of perforation of a pancreatic duct during the placement of a stent have been described, and there are also a few cases of delayed perforation by a pancreatic stent. A 62-year-old man had obstructive jaundice and pancreatitis due to locally advanced pancreatic head cancer. Both biliary and pancreatic stent were placed by endoscopy, after which chemoradiotherapy was performed. Four months later, he visited our hospital with severe abdominal pain. We performed enhanced CT and diagnosed the patient as having a perforation of a pancreatic duct by a pancreatic stent; therefore, we performed an emergency operation. Since we deemed pancreatectomy risky, we inserted pancreatic tubes into both sides of the perforated site and performed percutaneous transgastric drainage. The postoperative course was uneventful. We thereafter cut the tubes and switched to internal drainage. Many cases of pancreatic injuries have reported that pancreatic stent placement results in saving the patient, but there have been few cases in which a pancreatic stent causes perforation of a pancreatic duct. External drainage by pancreatic tubes is very effective in resolving perforation of a pancreatic duct.

Laparoscopic spleen-preserving distal pancreatectomy (LSPDP), a newly developed operative procedure, is indicated for benign and low-grade malignant disease of the pancreas. However, few studies have reported on postoperative splenic infarction after LSPDP. We report a case of complete splenic infarction and obliteration of the splenic artery and vein after LSPDP. The patient was a 69-year-old woman with a 35-mm cystic tumor of the pancreatic body who underwent LSPDP. Although the operation was completed with preservation of the splenic artery and vein, postoperative splenic infarction was revealed with left back pain and fluid collection around the stump of the pancreas on postoperative day 9. Fortunately, clinical symptoms disappeared within days and additional splenectomy was not needed. Splenic infarction was attributed to scattered micro-embolizations within the spleen after drawing strongly on the tape encircling the splenic vessels. Preserving splenic vessels in LSPDP is a demanding procedure. To prevent splenic infarction in LSPDP, we should carefully isolate the pancreatic parenchyma from the splenic vessels, and must avoid drawing tightly on the vessel loop encircling splenic vessels.

We studied 14 patients with anal squamous cell carcinoma(ASCC)who were treated in our hospital between 1994 and 2016. As initial therapies, surgeries were performed in 5 patients. Of these, disease recurrence appeared in 4 patients, and 3 patients died within 1 year after operation. Other 9 patients were treated with chemoradiotherapy. As a result, 9 of 6 patients were considered as complete response(CR), and 4 patients are still alive without recurrence. Although other 2 patients were recurred, recurrent lesions were removed and then, they are still alive. Of 3 patients who were considered as partial response (PR), 1 patient who was treated with local excision is still alive without recurrence, however, 2 patients were died for distant metastases. Chemoradiotherapy is considered to be effective and expected to cure without surgery, however, a careful surveillance should be needed for distant metastases.

Common complications of pelvic fractures include visceral injury, large-volume hemorrhage, genitourinary injury, rectal injury, and pulmonary embolism. On the other hand, traumatic hernia is a rare complication, especially in association with pelvic fractures. We report a case of bowel perforation due to traumatic hernia at a pelvic fracture site. A 65-year-old female was presented at our hospital for further examination and treatment of ileus. She was diagnosed with bowel perforation due to traumatic hernia at a pelvic fracture site, and an emergency operation was thus immediately performed. We performed segmental jejunum resection and constructed jejunostomy, and the iliac bone fracture was fixed with four pins. In the postoperative course, she received antibiotics and vasopressors for septic shock. However, there was no need for either a ventilator, dialysis or admission to the ICU. At seven days after the operation, a residual abscess was detected in the pouch of Douglas. We performed percutaneous drainage (Clavien-Dindo IIIa) and jejunostomy closedown 35 days after the first operation. The postoperative course was without complication, but she received rehabilitation until she was able to walk unaided. She was discharged 64 days after the first operation. The occurrence of traumatic hernia is rare, especially in association with pelvic fractures. Although its rarity, traumatic hernia follows a severe course. Thus, proper diagnosis and effective treatment are necessary. Surgeons treating patients with pelvic injuries should consider the possibility of any complications and perform a work-up examination in order to achieve an accurate diagnosis at an earlier time point.