Neoadjuvant therapy alters the collagen architecture of pancreatic cancer tissue via Ephrin-A5.

BACKGROUND: The treatment of pancreatic cancer (PDAC) remains clinically challenging, and neoadjuvant therapy (NAT) offers down staging and improved surgical resectability. Abundant fibrous stroma is involved in malignant characteristic of PDAC. We aimed to investigate tissue remodelling, particularly the alteration of the collagen architecture of the PDAC microenvironment by NAT. METHODS: We analysed the alteration of collagen and gene expression profiles in PDAC tissues after NAT. Additionally, we examined the biological role of Ephrin-A5 using primary cultured cancer-associated fibroblasts (CAFs). RESULTS: The expression of type I, III, IV, and V collagen was reduced in PDAC tissues after effective NAT. The bioinformatics approach provided comprehensive insights into NAT-induced matrix remodelling, which showed Ephrin-A signalling as a likely pathway and Ephrin-A5 (encoded by EFNA5) as a crucial ligand. Effective NAT reduced the number of Ephrin-A5+ cells, which were mainly CAFs; this inversely correlated with the clinical tumour shrinkage rate. Experimental exposure to radiation and chemotherapeutic agents suppressed proliferation, EFNA5 expression, and collagen synthesis in CAFs. Forced EFNA5 expression altered CAF collagen gene profiles similar to those found in PDAC tissues after NAT. CONCLUSION: These results suggest that effective NAT changes the extracellular matrix with collagen profiles through CAFs and their Ephrin-A5 expression.

[A case of advanced pancreatic cancer with oculomotor nerve palsy caused by herpes zoster after introduction of gemcitabine plus nab-paclitaxel].

A 76-year-old woman was admitted to our hospital due to diabetes and was diagnosed with advanced pancreatic cancer for which she received gemcitabine plus nab-paclitaxel. Fourteen days later, eruptions were observed in the first division of the right trigeminal nerve;she was then diagnosed with herpes zoster and was successfully treated with antiviral therapy. Seven days after the herpes zoster infection, right ophthalmoplegia appeared. Oculomotor nerve palsy secondary to herpes zoster ophthalmicus was suspected and she was treated with steroid pulse therapy. Her symptoms improved, and chemotherapy was able to be continued. Her ophthalmoplegia had almost fully resolved 41 days after the onset of herpes zoster infection.

Punctate Purpura Complicated with Immunoglobulin G4-related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition affecting multiple organs; however, the involvement of skin lesions is rare. We herein report a 65-year-old man who presented with pruritic punctate purpura on both legs and elevated liver enzyme levels. Computed tomography showed enlargement of the pancreas and thickening of the bile duct wall. Magnetic resonance cholangiopancreatography showed diffuse irregular constriction of the main pancreatic duct, stricture of the lower common bile duct, and dilation after confluent stricture. A histopathologic examination of the pancreas and his enlarged salivary gland showed infiltration of IgG4-positive plasma cells. Ultimately, the patient was diagnosed with IgG4-RD.

[A difficult case of a stent-stone complex removal with endoscopic lithotomy].

An 88-year-old patient had undergone endoscopic stenting for the treatment of acute cholangitis caused by choledocholithiasis. After a year and two months, he presented with cholangitis caused by common bile duct stones that formed a stent-stone complex. Another stent was observed adjacent to the old stent;however, the cholangitis relapsed in a short term. Thus, we planned to remove as many stones as possible. These stones were not free-floating and had affected the bile duct. Endoscopic mechanical lithotripsy was attempted;however, it failed. He was successfully treated using peroral cholangioscopy and electrohydraulic lithotripsy. After three months, he developed cholangitis because of the recurrence of choledocholithiasis. After removing as many stones as possible and performing endoscopic stenting, he was followed up as an outpatient. He had no symptoms for seven months after the procedure.

[Successful treatment of unresectable advanced gastric cancer with bladder metastasis using mFOLFOX6:a case report].

A 42-year-old woman was referred to our hospital for the treatment of pyloric stenosis. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) revealed the presence of type 4 advanced gastric cancer with bladder metastasis and peritoneal dissemination. Biopsy specimen examination revealed poorly differentiated adenocarcinoma with signet ring cell carcinoma. Thus, two cycles of chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin were administered. Subsequently, the gastric lesion and bladder metastasis reduced as detected using EGD and CT. Consequently, she achieved adequate oral intake. After changing the regimen to tegafur/gimeracil/oteracil and oxaliplatin, she was discharged. Currently, she continues to receive chemotherapy.

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients.

PURPOSE: To evaluate the efficacy and safety of nab paclitaxel (nab-P) plus gemcitabine (GEM) in elderly patients ≥ 75 years old with unresectable pancreatic cancer (PC) compared with younger patients. METHODS: The data of 27 unresectable PC patients treated with nab-P plus GEM as first-line chemotherapy were retrospectively analyzed. The patients were divided into two groups according to their age at inclusion: an elderly group (9 patients ≥ 75 years old) and a younger group (18 patients <75 years old). We compared the disease control rate, median overall survival (OS), and adverse events (AEs) between the two groups. Predictive factors for the OS were also evaluated. RESULTS: The clinical characteristics of patients of the two groups were not significantly different except for the age. The respective values for the disease control rate (66.7% vs. 77.8%, P = 0.542) and median OS (277 days vs. 312 days, P = 0.722) were also not significantly different between the elderly and younger group, although the relative dose intensity of GEM/nab-P in the elderly group (56.6%/53.1%) was significantly lower than that in the younger group (67.3%/63.1%) (P = 0.016/0.04). The absence of biliary drainage and CEA ≥ 6.5 were found to be poor prognostic factors in a multivariate analysis. The most common grade ≥ 3 AE was neutropenia (44% in both groups). No significant differences in the frequency of all AEs were observed between the two groups. CONCLUSIONS: Nab-P plus GEM appears effective and well-tolerated for elderly patients ≥ 75 years old with unresectable PC.

Prognostic Factors for Survival in Patients with Advanced Intrahepatic Cholangiocarcinoma Treated with Gemcitabine plus Cisplatin as First-Line Treatment.

OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. METHODS: A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. RESULTS: Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. CONCLUSIONS: Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials.

[Comparison of Response to Chemotherapy between Ovarian and Extraovarian Metastasis of Gastric Cancer].

BACKGROUND: Ovarian metastasis of gastric cancer is thought to be less sensitive to chemotherapy. METHODS: The subjects of this retrospective study were 15 gastric cancer patients with ovarian metastasis treated with first-line chemotherapy between January 1998 and April 2015. Response to chemotherapy was compared between ovarian metastasis and other measurable lesions; progression free survival(PFS), post progression survival(PPS), and overall survival(OS)were compared among the patients showing disease progression only at the ovary(group A), only at lesions other than the ovary(group B), and at both sites(group C). RESULTS: The patient characteristics were as follows: median age 58 years(range 34-79); performance status 0/1, 4/11; histology of diffuse/intestinal type, 15/0; unilateral/bilateral ovarian metastasis, 5/10; metastasis to the perito- neum/lymph node/bone/pleura, 15/5/2/1; and chemotherapy regimen with S-1+cisplatin/S-1/methotrexate+5-fluorour- acil(5-FU)/5-FU, 9/3/2/1. Partial response/stable disease/progressive disease were obtained in 1/11/3 patients, respectively. In 5 patients having measurable lesions in the ovary and lymph nodes, the median of the largest decrease in size after chemotherapy was 2.8%(range -8.2 to 31.7)at the ovary and 39.4%(range 5.4 to 75.4)at the lymph nodes(p=0.018). The number of patients in the groups A/B/C who experienced disease progression were 6/5/4, respectively; there were no differences in PFS(median 8.6/6.3/7.3months, respectively). Group A showed the longest PPS and OS compared to group B and C(median OS 19.0/9.1/13.8 months and PPS 11.4/4.3/2.5 months, respectively). CONCLUSION: Compared with other metastatic sites, our findings suggest that ovarian metastasis of gastric cancer may show less chemo-response; however, its progression may have a smaller impact on survival.