PD-L1 expression in keratinocyte and infiltration of CD4 + T lymphocyte can predict a severe type of erythema multiforme major induced by the anti-PD-1 antibody, pembrolizumab.

Unlabelled: Skin toxicity is the most common adverse event of treatment with immune check point inhibitors. Among them, erythema multiforme is a rare occurrence with a frequency of 4%, with most of the cases developing grade 1/2 disease. We experienced high grade erythema multiforme major developing with pembrolizumab treatment for anal canal cancer with extensive skin metastases.

Recent trends in bone metastasis treatments: A historical comparison using the new Katagiri score system.

Background: Bone metastasis has various negative impacts. Activities of daily living (ADL) and quality of life (QOL) can be significantly decreased, survival may be impacted, and medical expenses may increase. It is estimated that at least 5% cancer patients might be suffering from bone metastases.

A case of hereditary breast and ovarian cancer syndrome of initially presented as cancer of unknown primary with lymph node metastases unveiled by genetic analysis.

Cancer of unknown primary (CUP) is a heterogeneous disease concept involving various malignant tumors. Understanding its pathophysiology is often difficult, together with its treatment. Here, we present a case of CUP with abdominal lymph node enlargement and elevated carbohydrate antigen 125 levels.

Association between albumin-bilirubin grade and plasma trough concentrations of regorafenib and its metabolites M-2 and M-5 at steady-state in Japanese patients.

The aim of the present study was to determine whether the trough plasma concentrations (C) of regorafenib and its metabolites, the N-oxide metabolite (M-2) and the desmethyl N-oxide metabolite (M-5), in 21 patients receiving regorafenib therapy were affected by albumin-bilirubin (ALBI) grade. Regorafenib was administered at dosages ranging from 40 to 160 mg once daily on a 3-week-on, 1-week-off cycle. C values of regorafenib and its major metabolites were measured by high-performance liquid chromatography on day 8 after treatment initiation.

Clinical response of pancreatic cancer bearing a germline BRCA2 p.I3169M fs*48 variant for platinum-based drug and PARP inhibitor.

Pancreatic cancer is a malignancy with a high mortality rate, accounting for 37 000 people annually in Japan. It is rarely diagnosed in a resectable state, and effective medicines for its advanced stage are scarce. Some pancreatic cancer is hereditary, and ~10% have germline mutations of Breast cancer 1/2 (BRCA1/2).

Clinical Course of a Rare Epstein-Barr Virus-Associated Smooth Muscle Tumor and Its Genomic Analysis.

Epstein-Barr virus (EBV) can rarely induce smooth muscle tumors (SMTs). A 20-year-old female patient underwent kidney transplantation for renal failure. Since then, she has been treated with immunosuppressants, including a calcineurin inhibitor, tacrolimus, and prednisolone, owing to the immunological rejection.

Lymph-node metastasis from gastric adenocarcinoma in a patient bearing a germ line missense variant MSH2 c.1808A > T (Asp603Val) responds to the immune checkpoint inhibitor pembrolizumab.

We report the sensitivity of immune checkpoint inhibitors for tumors developing in a patient bearing the MSH2 c.1808A > T (Asp603Val) variant belonging to a pedigree of Lynch syndrome. This variant was previously thought to be of unknown significance, but we recently found that this missense mutation was likely pathogenic.

Two Cases of ALK-Altered Cancers of Unknown Primary Diagnosed by Immunohistochemistry.

Cancer of unknown primary (CUP) accounts for 5% of all malignancies. Patients with CUP may live averagely for 8 months after diagnosis, and thus, rapid and reasonable diagnosis is necessary. Among patients with CUP, anaplastic lymphoma kinase (ALK)-overexpressing CUPs, whose primary sites were confirmed to be the lungs (Lung-CUP) by using antibodies against cytokeratin 7, thyroid transcription factor-1, and Napsin A, along with clinical characteristics progressed rapidly and were very sensitive to the ALK inhibitor alectinib.

Sudden and severe cardiotoxicity induced with pembrolizumab, its clinical course, therapeutic intervention, and outcome.

Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte associated antigen-4 inhibitors, and inhibitors of programmed cell death 1 and its ligand, are widely used in the treatment of several malignant tumors. Immune-related adverse events occur in two-thirds of recipients. Among them, cardiotoxicities are very rare (about 1%), albeit fatal.

A novel Lynch syndrome pedigree bearing germ-line MSH2 missense mutation c.1808A>T (Asp603Val).

We report the first pedigree of Lynch syndrome bearing a germ-line MSH2 missense mutation c.1808A>T (Asp603Val). Until now, this missense mutation, in exon 12 of MSH2, was identified as a variant of unknown significance in the International Society for Gastrointestinal Hereditary Tumours database.

Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture.

Background: Angiogenesis inhibitors (AIs) combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer (CRC). Aflibercept (AFL) is an option for second-line treatment of CRC, according to the 'VELOUR' trial. Currently, we can choose from three AIs, including bevacizumab, ramucirumab, and AFL.

Outcome of colorectal cancer in Diamond-Blackfan syndrome with a ribosomal protein S19 mutation.

Diamond-Blackfan anemia is an autosomal dominant syndrome, characterized by anemia and a predisposition for malignancies. Ribosomal proteins are responsible for this syndrome, and the incidence of colorectal cancer in patients with this syndrome is higher than the general population. This patient's Diamond-Blackfan anemia was caused by a novel ribosomal protein S19 gene mutation, and he received chemotherapy for colorectal cancer caused by it.

Lung adenocarcinoma in a patient with Li-Fraumeni syndrome bearing a novel germ-line mutation, TP53R333Vfs*12.

Germline mutations of TP53 are responsible for Li-Fraumeni syndrome in its 60-80%. We found a novel germline mutation, TP53: c.997del:p.

Therapeutic drug monitoring of regorafenib and its metabolite M5 can predict treatment efficacy and the occurrence of skin toxicities.

Background: Regorafenib is a multiple tyrosine kinase inhibitor, and the use of this drug is approved for the treatment of cancers that are resistant to chemotherapy, which include advanced colorectal cancer, gastrointestinal stromal tumor, and hepatocellular carcinoma. However, the drug causes adverse events, including skin toxicities that require dose modification in approximately 75% of cases. At present, the blood concentration of regorafenib is not assessed in clinical settings; thus, we recently developed a method that can assess the blood concentration of the drug using high-performance liquid chromatography.

Guillain-Barré syndrome in a cancer patient treated with bevacizumab.

We describe a case of Guillain-Barré syndrome (GBS) in a patient treated with bevacizumab. Our case is a 60-year-old woman with Stewart-Treves syndrome (STS), and angiosarcoma of her left forearm, with onset 12 years after diagnosis with stage IIIA left breast cancer. She suffered from repeated distal metastases including skin, bone, and liver metastases.

Curcumin analog, GO-Y078, overcomes resistance to tumor angiogenesis inhibitors.

Tumor angiogenesis inhibition is one of the most potent strategies in cancer chemotherapy. From past clinical studies, inhibition of the vascular endothelial growth factor pathway successfully treats malignant tumors. However, vascular endothelial growth factor inhibitors alone cannot cure tumors.

Effect of anti-PD-1 antibody, nivolumab on early gastric cancer.

Immunomodulation treatment using anti-programmed cell death protein 1 antibody is a very promising treatment for various types of advanced cancers, including melanoma, non-small cell lung cancer, and renal cell carcinoma. However, the therapeutic effects on early cancers are still unknown. We experienced 2 cases of early gastric cancers coexisting advanced melanomas.

Incidence of hypophosphatemia in advanced cancer patients: a recent report from a single institution.

Background: Recent approval of molecular-targeted agents has contributed to improving the therapeutic outcomes of advanced cancer patients. However, they result in unusual adverse events that rarely occur with cytotoxic agents, such as hypertension, hypomagnesemia, and an acne-like rash. Although hypophosphatemia can be induced by various agents, some kinds of molecular-targeted agents are known to induce it.

High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis.

Aim: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.

Methods: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy.

A diarylpentanoid curcumin analog exhibits improved radioprotective potential in the intestinal mucosa.

Purpose: To best enhance the effects of radiotherapy, it is important to minimize adverse events, including free radical-induced intestinal cell damage. Given the threat of nuclear power plant accidents or nuclear terrorism, there is an urgent need for radioprotectants to counteract the radiation-induced toxicity and/or injuries. Curcumin exhibits protective effects against gamma irradiation; however, its in vivo efficacy is decreased due to the low bioavailability.

Proper muscle layer damage affects ulcer healing after gastric endoscopic submucosal dissection.

Background And Aim: Endoscopic submucosal dissection (ESD) is the established therapy for superficial gastrointestinal neoplasms. However, management of the artificial ulcers associated with ESD has become important and the relationship between ulcer healing factors and treatment is still unclear. We aimed to evaluate ESD-related artificial ulcer reduction ratio at 4 weeks to assess factors associating with ulcer healing after ESD that may lead to optimal treatment.

The niche component periostin is produced by cancer-associated fibroblasts, supporting growth of gastric cancer through ERK activation.

Overexpression of periostin (POSTN), an extracellular matrix protein, has been observed in several cancers. We investigated the importance of POSTN in gastric cancer. Genome-wide gene expression analysis using publicly available microarray data sets revealed significantly high POSTN expression in cancer tissues from stage II-IV gastric cancer, compared with background normal tissues.