Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability

Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI

Prevalence of hypertension at high altitude: cross-sectional survey in Ladakh, Northern India 2007-2011

Objective: Prevalence of hypertension was examined in a widely dispersed (45 110 km2) representative group of Ladakhi in Northern India. The influence of hypoxic environment of wide-ranged altitude (2600–4900 m) and lifestyle change on hypertension was studied. Methods: 2800 participants (age 20–94 years) were enrolled. Systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg and/or taking current anti-hypertensive medicine was defined as hypertension. Height and weight for body mass index and SpO2 were examined. The rural population comprised six subdivisions with a distinct altitude, dietary and occupational pattern. Participants in the urban area of Leh consist of two groups, that is, migrants settled in Leh from the Changthang nomadic area, and dwellers born in Leh. The prevalence of hypertension in the two groups was compared with that in the farmers and nomads in rural areas. The effects of ageing, hypoxia, dwelling at high altitude, obesity, modernised occupation, dwelling in an urban area, and rural-to-urban migration to hypertension were analysed by multiple logistic regression. Results: The prevalence of hypertension was 37.0% in all participants and highest in migrants settled in Leh (48.3%), followed by dwellers born in Leh town (41.1%) compared with those in rural areas (33.5). The prevalence of hypertension in nomads (all: 27.7%, Tibetan/Ladakhi: 19.7/31.9%)) living at higher altitude (4000–4900 m) was relatively low. The associated factors with hypertension were ageing, overweight, dwelling at higher altitude, engagement in modernised sedentary occupations, dwelling in urban areas, and rural-to-urban migration. The effects of lifestyle change and dwelling at high altitude were independently associated with hypertension by multivariate analysis adjusted with confounding factors. Conclusions: Socioeconomic and cultural factors play a big role with the effect of high altitude itself on high prevalence of hypertension in highlanders in Ladakh

関節炎で発症した高安動脈炎の1例

高安動脈炎は全身の大血管に炎症がおこる疾患の1つであり,大動脈及びその主要分枝や肺動脈,冠動脈に閉塞性あるいは拡張病変を来すのが特徴である.初期症状としては,発熱や全身倦怠感などを呈し,その他の症状は障害を受けた血管の部位により異なる.稀には,消化器症状や皮膚症状,関節症状を呈する事もある.我々は関節炎を主訴に当院を受診し,後に高安動脈炎と診断された症例を経験した.患者は40歳代女性.左膝及び左足関節痛があり,関節超音波で滑膜炎の所見が認められた.血清学的検査ではリウマトイド因子陰性,抗CCP抗体陰性であり,未分類型関節炎として少量プレドニゾロンで治療が開始された.メトトレキサートの併用により,関節症状は改善した.しかし,治療開始6ヶ月後,胸背部痛を訴えて受診し,血液検査ではCRP上昇を認めた.造影CT検査で,腕頭動脈,左総頚動脈,下行大動脈に壁肥厚と周囲脂肪織濃度の上昇が認められ,高安動脈炎と診断された.関節リウマチとしては非典型的な関節炎の症例に遭遇した場合には,常に高安動脈炎を含めた,他疾患の可能性を念頭に入れて診療を行う必要がある.Takayasu arteritis is an idiopathic large vessel vasculitis affecting the aorta and its major branches. Although systemic symptoms, such as malaise, weight loss and fever, are common in the early stages of this disease, joint manifestations are rarely seen. We report the case of a woman in her 40s, who complained of arthritis of left knee and left ankle. Both rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative. Treatment with low dose prednisolone and methotrexate resulted in improvement of polyarthritis. Six months later, however, she presented with chest and back pain, with an elevation of serum C-reactive protein levels. Enhanced computed tomography demonstrated significantly wall thickness in the brachiocephalic trunk, left common carotid artery and descending aorta. She was diagnosed with Takayasu arteritis. We should keep Takayasu arteritis in mind for patients with seronegative undifferentiated arthritis

Hepatic Arterial Infusion Chemotherapy Combined with Radiation Therapy for Advanced Hepatocellular Carcinoma with Tumor Thrombosis of the Main Trunk or Bilobar of the Portal Vein

博士(医学)Doctor of Philosophy in Medical Science広島大学Hiroshima Universit

Risk factors for Early onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma.

Introduction Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo+Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo+Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo+Bev for patients with unresectable HCC. Methods Sixty-four patients with Child-Pugh scores of 5–7, an eastern cooperative oncology group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein to creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated. Results The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio (HR), 3.807; 95% confidence interval (CI), 1.579–9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614–24.010; p = 0.008) and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133–6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP > 135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR > 2 g/g Cr). Conclusion Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo+Bev

A case of acute liver failure with echovirus infection diagnosed by a multi-virus real-time PCR system

Background: Multi-virus real-time polymerase chain reaction (PCR) system is able to simultaneously detect 163 viruses using a multiplex Taqman real-time PCR system. We present a case of acute liver failure (ALF) of unknown etiology diagnosed with　echovirus 30 infection via multi-virus real-time PCR. Case presentation: A previously healthy 66-year-old man had a persistent fever and developed ALF of unclear etiology. Although viral infection was suspected, serological screening showed no evidence of acute viral infections such as hepatitis A, B, C and E, Epstein-Barr virus, herpes simplex virus, and varicella zoster virus. Multi-virus real-time PCR revealed the presence of enterovirus and echovirus 30 genomes, and reverse transcription-PCR using enterovirus-specific primers confirmed the presence of enterovirus genome in serum samples at the time of admission. Anti-echovirus antibody titers showed an increase in paired sera. In spite of multimodality treatment, the patient died due to multiple organ failure. Histological analysis in autopsy revealed extensive coagulative necrosis of the hepatocytes and immunohistochemical analysis showed the expression of enterovirus antigens in necrotic hepatocytes. Conclusions: We present here a case of echovirus 30 associated with ALF. Multi-virus real-time PCR is useful for detection of virus for patients with ALF of unknown etiology suspected of harboring a viral infection

Analysis of Lenvatinib’s Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin–bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis

Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child–Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin–bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation