Hyperprogressive disease in lung metastases without target lesion progression after durvalumab consolidation therapy: A case report.

Hyperprogressive disease (HPD) is a novel progressive pattern that occurs after immune checkpoint inhibitor (ICI) administration. Here, a 74-year-old woman who had undergone right lower lobectomy for lung cancer received curative chemoradiotherapy followed by consolidation therapy with durvalumab for metastatic recurrence confined to the mediastinal lymph nodes. Three weeks later, multiple randomly distributed nodular shadows appeared on chest CT, and thoracoscopic lung biopsy led to the diagnosis of multiple pulmonary metastases. HPD may be suspected when multiple metastases appear in new organs early after the administration of ICIs. This phenomenon may occur not only with ICI monotherapy but also with the administration of ICIs after chemoradiotherapy. Therefore, patients who have received radiation therapy should also be given similar attention early after the administration of ICIs.

Dramatic response to alectinib in a patient with ALK-rearranged squamous cell lung cancer.

Lung cancers with anaplastic lymphoma kinase (ALK) rearrangements are highly sensitive to treatment with ALK tyrosine kinase inhibitors (TKIs). Due to the very low rate of patients with squamous cell carcinoma enrolled in clinical trials, the efficacy of ALK inhibitors in patients with ALK-rearranged squamous cell carcinoma in the lung remains unclear. Herein, we present the case of a 70-year-old female patient with squamous cell lung cancer harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. The patient was treated with the ALK-TKI alectinib as first-line regimen and achieved a dramatic response without severe adverse events, demonstrating alectinib as a therapeutic option for patients with ALK-positive squamous cell carcinoma.

Oxytocin/vasopressin-like peptide inotocin regulates cuticular hydrocarbon synthesis and water balancing in ants.

Oxytocin/vasopressin-like peptides are important regulators of physiology and social behavior in vertebrates. However, the function of inotocin, the homologous peptide in arthropods, remains largely unknown. Here, we show that the level of expression of inotocin and inotocin receptor are correlated with task allocation in the ant Camponotus fellah Both genes are up-regulated when workers age and switch tasks from nursing to foraging. in situ hybridization revealed that inotocin receptor is specifically expressed in oenocytes, which are specialized cells synthesizing cuticular hydrocarbons which function as desiccation barriers in insects and for social recognition in ants. dsRNA injection targeting inotocin receptor, together with pharmacological treatments using three identified antagonists blocking inotocin signaling, revealed that inotocin signaling regulates the expression of cytochrome P450 4G1 (CYP4G1) and the synthesis of cuticular hydrocarbons, which play an important role in desiccation resistance once workers initiate foraging.

First case report of bacteremia caused by Dysgonomonas mossii.

We here report a case of Dysgonomonas mossii bacteremia with cholangitis. An 85-year-old male patient with recurrent hepatitis B surface antigen-negative/anti-hepatitis C virus-negative hepatocellular carcinoma came to our hospital in poor physical condition. Two sets of blood cultures revealed a positive result for D. mossii. As matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed to identify D. mossii, analysis of 16S rRNA gene sequencing was performed; however, this gene is not specific enough to distinguish between D. mossii and D. oryzarvi. Finally, D. mossii infection was confirmed by gyrB and recA sequencing. To our knowledge, this is the first report of D. mossii causing human infection, which was identified in culture and confirmed using a combination of 16S rRNA, gyrB, and recA sequencing.

Elevated serum uric acid level was a notable adverse event during combination therapy with sofosbuvir and ribavirin.

AIM: Combination therapy with sofosbuvir and ribavirin (SOF/RBV) has been recently available for chronic hepatitis C patients with genotype 2 (CHG2) in Japan. The domestic phase III clinical trial showed a high antiviral effect with a relatively safe adverse event (AE) profile. Our aim was to report an important AE detected during treatment. METHODS: A prospective multi-institutional study of 12-week combination therapy with SOF/RBV for CHG2 was carried out to evaluate efficacy and safety. RESULTS: The eligible subjects included 142 patients. Out of 50 assessable patients, 16% of the patients were diagnosed with hyperuricemia. The proportions of subjects with grade 1, grade 3, and grade 4 hyperuricemia were 12, 2, and 2%, respectively. Serum uric acid (UA) levels at week 1 of the therapy (W1) were numerically the highest during therapy in patients with hyperuricemia, and the ratio of W1/baseline serum UA levels was significantly higher than that of post-treatment week 4 or 8/baseline serum UA levels in assessable patients. Serum UA levels at W1 were significantly correlated with body mass index. The difference between serum UA levels at W1 and baseline serum UA levels was significantly correlated with the difference between serum creatinine levels at W1 and baseline serum creatinine levels. CONCLUSIONS: Elevated serum UA level was a notable AE associated with SOF/RBV therapy for CHG2. However, because of the small number of subjects, the exact frequency of AEs should be re-evaluated with larger cohorts. We need to remember that elevated serum UA level might develop during the therapy, especially at W1.

New Method of Parent Catheter Advancement in the Balloon Anchor Technique during Balloon-Occluded Transarterial Chemoembolization for Hepatic Tumors.

Balloon-occluded transarterial chemoembolization (B-TACE) using a microballoon catheter is a promising method for improvement of lipiodol emulsion accumulation and local control relative to conventional transarterial chemoembolization. This method has been referred to as the balloon anchor technique in previous reports. We report a new technique for successful parent catheter advancement for achievement of stable backup for the selective insertion of a microballoon catheter during B-TACE using the microballoon as an anchor, even in patients with tortuous anatomy of the hepatic and celiac arteries. Deep cannulation of parent catheters was accomplished in all three cases and complications such as vascular injury were not observed in the postprocedure angiograms.

Transforming growth factor-α activates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation.

The role that transforming growth factor-α (TGF-α) has in chronic pancreatitis and pancreatic cancer has not been fully elucidated. We evaluated the effects of TGF-α on the human pancreatic stellate cell (PSC) line RLT-PSC and primary human PSCs, and the expression levels of TGF-α and metalloproteinase-1 (MMP-1) in human chronic pancreatitis and pancreatic cancer tissues. TGF-α stimulated the proliferation and migration of PSCs. Although the mRNA expression levels of tissue inhibitor of metalloproteinase-1 and α1(I) collagen were unchanged, the mRNA expression levels of MMP-1 increased concomitant with increases in MMP-1 protein levels and collagenase activity. TGF-α-stimulated migration of RLT-PSC cells was partially blocked by tissue inhibitor of metalloproteinase-1 protein and MMP-1 small interfering RNA. MMP-1 was also observed to stimulate the migration of PSCs. TGF-α-induced MMP-1 expression was completely blocked by gefitinib in PSCs. The Ras-ERK and PI3/Akt pathways appear to be involved in the activation of MMP-1 in PSCs. Immunohistochemical analyses showed that MMP-1 expression was significantly increased in the pancreatic interstitial tissues in case of chronic pancreatitis or pancreatic cancer compared with those in case of normal pancreas. In conclusion, TGF-α increased proliferation and migration of PSCs. TGF-α-induced migration of cells may be partly due to upregulation of MMP-1. TGF-α and MMP-1 upregulation may contribute to the pathogenesis of chronic pancreatitis and pancreatic cancer.

[A case of hepatitis E differentially diagnosed from drug-induced liver injury].

A woman in her seventies was admitted because of general fatigue and liver dysfunction (ALT 2565 IU/l). She was diabetic and, 2 months ago, began eating kikuimo (Jerusalem artichoke) containing inulin, which is thought to decrease blood sugar level. Although tests showed no evidence of acute infection of HAV, HBV, HCV, EBV and CMV, a drug-induced lymphocyte stimulation test using kikuimo extract was positive. She was first diagnosed with drug-induced liver injury according to the Japanese diagnostic criteria for the disease. After a non-eventful recovery, her serum was found to be positive for hepatitis E-antibody and RNA (genotype 3), indicating recent, autochthonous infection of HEV. The patient might have been misdiagnosed with drug-induced liver injury unless the serum test for HEV had been performed. We believe that HEV screening is mandatory for accurate diagnosis of hepatitis E and drug-induced liver injury.

A retrospective cohort study of partial splenic embolization for antiviral therapy in chronic hepatitis C with thrombocytopenia.

BACKGROUND: Although partial splenic embolization (PSE) is reportedly effective prior to interferon (IFN)-based therapy, the number of subjects in these studies is small, and the appropriate candidates and disease prognosis remain unknown. METHODS: PSE was performed in 30 patients with advanced hepatitis C who could not receive IFN-based therapy because of thrombocytopenia, platelet counts of ≤100,000/mm(3), and hypersplenism. Also, we compared 25 PSE-treated patients with 23 PSE-untreated patients with thrombocytopenia receiving pegylated IFN (PEG-IFN)-alpha 2b plus ribavirin over the same period. RESULTS: PSE significantly increased platelet and leukocyte counts. PSE was well tolerated with no severe complications. All the patients could receive IFN-based therapy. Discontinuation of therapy in the total cohort of PSE-treated patients was not due to thrombocytopenia. Although PSE did not significantly increase the sustained virological response (SVR) rate, it significantly maintained higher platelet counts throughout the observation period and increased the percentage of patients with 100% adherence to PEG-IFN in the total controlled study population and in subjects with genotype 2. In PSE-treated patients with genotype 2, a trend towards increased SVR was noted. Four patients developed hepatocellular carcinoma (HCC) at a median of 14.5 months after PSE, even though two of these patients had achieved an SVR. CONCLUSIONS: IFN-based therapy following PSE had an advantage in the maintenance of higher platelet counts, and PSE possibly caused an increase in adherence to PEG-IFN. Although patients with genotype 2 might be better candidates for PSE, further evaluation is needed. Careful follow-up of PSE-treated patients, even though they may have achieved an SVR, is needed to detect HCC.

Gastric yolk sac tumor complicated with beta-human chorionic gonadotropin-producing metastases.

This report describes the case of 74-year-old man who had a gastric yolk sac tumor complicated with beta human chorionic gonadotropin (beta hCG) producing metastases. He was a heavy drinker. He was admitted to the hospital for abdominal pain and fullness. Based on computed tomography and gastric endoscopy he was diagnosed to have gastric cancer that had metastasized to the liver, lung and lymph nodes. The level of serum alpha fetoprotein (AFP) was high at 523 ng/mL. He died of multiorgan failure six days after admission. The autopsy revealed the stomach tumor to be an AFP-positive yolk sac tumor. Lymph node metastases showed the same characteristics as the stomach tumor. However, the lesions on the liver and lung were negative for AFP and positive for hCG. The yolk sac tumor seemed to have retrodifferentiated to form an hCG-producing tumor in the metastatic lesions. A gastric yolk sac tumor is extremely rare and only eight cases of gastric yolk sac tumors have been previously reported in the literature. To avoid a misdiagnosis, careful attention should be paid to the above-mentioned morphological features and immunohistochemical findings, in addition to the clinical findings.

Systemic sclerosis after interferon alphacon-1 therapy for hepatitis C.

A 66-year-old woman developed systemic sclerosis (SSc) after receiving interferon alphacon-1 (IFNalphacon-1; consensus interferon) therapy for chronic hepatitis C. She suffered from Raynauds phenomenon about 1 year after a course of IFNalphacon-1 therapy. The combination of proximal scleroderma, Raynauds phenomenon, and ANA positivity led to a diagnosis of systemic sclerosis (SSc). IFN has multiple effects on the immune system and is known to trigger the development of autoantibodies, as well as the onset or exacerbation of autoimmune disease. We suspect that the immunomodulatory effects of IFNalphacon-1 triggered the clinical manifestations of SSc in this patient. To our knowledge this is only the third case of SSc after IFNalpha therapy, and it is the first case associated with IFNalphacon-1 therapy.