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Tumor response and disease progression are assessed using imaging technologies. However, these technologies fail to detect tumor responses at the molecular level and clonal evolution. A potential surrogate for such parameters is using circulating tumor DNA (ctDNA). This study aimed to examine the quantity and composition of the ctDNA results of 29 cancer patients before and after dendritic cell (DC) immunotherapy and develop criteria to evaluate the molecular response to treatment based on these results. We categorized the patients into four categories based on percent changes in the total ctDNA compared with the baseline ctDNA titers, and this response assessment was termed genomic response evaluation criteria in solid tumors or gRECIST. Even those who are clinically evaluated as having a good response might harbor unfavorable tumor responses at the molecular level. Newly formed ctDNA levels can be the most prognostic parameter in tumor progression or the treatment response, while ctDNA clearance and the decline or rise in existing ctDNA did not change significantly in genomic response categories (gRECIST). More research is needed to support the clinical use of ctDNA in precision oncology and personalized cancer treatment.

Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using neoantigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for neoantigen-based immunotherapy and the importance of tailoring neoantigen-based immunotherapy in accordance with the liquid biopsy result in each treatment stage.

The proliferation and activation of CD4+ T helper 1 (Th1) cells and CD8+ cytotoxic T lymphocytes (CTLs) that produce interferon‑γ (IFN‑γ) is an essential action of effective cancer vaccines. Recently, a novel Wilms' tumor 1 (WT1) helper peptide (WT1 HP34‑51; amino acid sequence, WAPVLDFAPPGASAYGSL) applicable for various human leukocyte antigen (HLA) subtypes (HLA‑DR, HLA‑DP and HLA‑DQ) was reported to increase peptide immunogenicity; however, the function of WT1 HP34‑51 remains unclear. In the present study, mature dendritic cells (mDCs) pulsed with WT1 HP34‑51 (mDC/WT1 HP34‑51) activated not only WT1‑specific CD4+ T cells but also CD8+ T cells that produced IFN‑γ following stimulation with immature dendritic cells (imDCs) pulsed with WT1 killer peptide (imDC/WT1 KP37‑45) in an HLA‑A*02:01‑ or HLA‑A*02:06‑restricted manner. Furthermore, the activated WT1‑reactive CD4+ Th1 cells were predominantly effector memory (EM) T cells. In 5 of 12 (41.7%) patients with cancer carrying the HLA‑A*02:01 or HLA‑A*02:06 allele, WT1‑reactive CD8+ T cells stimulated with mDC/WT1 HP34‑51 enhanced their levels of WT1 KP37‑45‑specific IFN‑γ production, with an increase >10%. Simultaneous activation of CD4+ and CD8+ T cells occurred more often when stimulation with mDC/WT1 HP34‑51 was combined with imDC/WT1 KP37‑45 restimulation. These results indicated that the novel mDC/WT1 HP34‑51 combination induced responses by WT1‑specific EM CD4+ Th1 cells and HLA‑A*02:01‑ or HLA‑A*02:06‑restricted CD8+ CTLs, suggesting its potential as a WT1‑targeting cancer vaccine.

We herein report the first case of a single-incision laparoscopic access (SILA) adrenalectomy in Japan. A 74-year-old woman who was a hepatitis B virus carrier was referred to our hospital because of an abnormal screening result during a routine health checkup. Abdominal computed tomography and an endocrinologic workup revealed a 2-cm left adrenal tumor with primary aldosteronism. We prioritized the safety of the SILA adrenalectomy by choosing a left lower abdominal approach. A SILS port was inserted through a 2.5-cm incision. An ultrasonic coagulator was the main tool used during the surgical procedure. The duration of the surgery was 105 min and the blood loss was 1 ml. This result was comparable to that of a conventional laparoscopic adrenalectomy. Based on our experience, an SILA adrenalectomy is thus considered to be feasible and safe, with better cosmetic results and a greater overall patient satisfaction than that of a conventional laparoscopic adrenalectomy. However, further studies will be necessary before the universal adoption of this new technique can be considered.

症例は67歳の女性で, 近医に高血圧, 糖尿病で通院中であった. 血糖コントロールの悪化と, 腹部超音波検査で膵腫瘍を指摘され紹介入院となる. 血液検査所見ではエラスターゼ1が900ng/dlと高値であった. 腹部超音波検査所見では主膵管の閉塞と末梢膵管の拡張を認めた. MRCP所見では膵体部にて膵管は途絶し, 末梢膵管は拡張していた. ERCP所見でも, 膵体部にて膵管は途絶していた. 腹部CT所見では明らかな腫瘤は同定できなかった. その他, 上部消化管内視鏡検査, 下部消化管造影検査にて, 異常所見はなかった. 以上より, 通常の膵管癌を疑い, 平成17年2月, 膵体尾部切除術を施行した. 術後の病理組織学的検査にて, 同腫瘍細胞は卵円形細胞が充実性結節状, 胞巣状に増殖し, chromogranin染色陽性であった. また, 各種ホルモンの染色ではserotoninのみ陽性であり, 膵内分泌腫瘍と診断した.

Irinotecan is an effective drug in the treatment of colorectal cancer. However, there are reports of an association between certain UGT1A1 genetic polymorphisms and the development of adverse reactions(such as neutropenia)related to irinotecan metabolism. We retrospectively investigated UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic polymorphisms in these patients yielded the following classifications: a wild-type group( *1/*1)comprising 13 patients(52%), a heterozygous group(*1/ *28, *1/*6)of 10 patients(40%), and a homozygous group(*28/*28, *6/*6)of 2 patients(8%). The frequency of neutropenia was 15.4%(2/13)in the wild-type group, 30%(3/10)in the heterozygous group, and 100%(2/2)in the homozygous group. Grade 4 neutropenia only occurred in the homozygous group. These results suggest that a dose reduction of irinotecan should be considered for patients who fall into the homozygous group upon analysis of their UGT1A1 genetic polymorphisms, as such patients might be susceptible to grade 4 neutropenia.

症例は77歳の女性で, 心窩部不快感を主訴に近医受診し, 上部消化管内視鏡検査にて胃体中部前壁に壁外からの圧迫所見を認め当院紹介受診となった. 腹部超音波検査にて, 肝左葉外側区域(S2)に39×30mmの等から高エコー腫瘤を認めた. 腹部造影CTでは, 同部の辺縁部から内部に向けて, 不均一な造影効果を認めた. 腹部MRIではT1強調像で低信号, T2強調像で高信号, dynamic studyにて内部が不均一に造影された. その他, 消化管精査で異常はなかった.第1に海綿状血管腫を疑ったが, 画像所見上, 肝内胆管癌, 転移性肝癌などとの鑑別は困難であった. 平成16年7月, 腹腔鏡補助下肝部分切除術を施行した. 病理組織学的検査では線維性結合組織と海綿状血管腫が混在し, 肝硬化性血管腫と診断した. 肝硬化性血管腫の報告はまれであり, 検索しえたかぎり9例を認めるのみであった.

症例は62歳,男性,数カ月前から続く下痢と体重減少で近医受診し,当院紹介となる. 48歳時,穿孔性十二指腸潰瘍に対し幽門側胃切除術, Billroth II法再建の既往あり.来院時,極度のるい瘻を認め,低栄養状態であった.血液検査成績では,ヘマトクリット31.0%,血色素10.4g/dlと軽度の貧血を呈し,血清総蛋白4.1g/dl,血清アルブミン2.2g/dlと低蛋白,低アルブミン血症を認めた.腫瘍マーカーはCEA7.8ng/ml, CA19-948U/mlと軽度上昇を認めた.悪性腫瘍を疑い,下部消化管内視鏡検査を施行したところ,横行結腸に狭窄部を認め,その口側が双口となり,小腸と瘻孔を形成していた.そこで上部消化管内視鏡検査を施行したところ,胃空腸吻合部に多発潰瘍を認め,一部横行結腸に穿通していた.胃空腸吻合部潰瘍の横行結腸穿通と診断し,残胃全摘,瘻孔を含む結腸右半切除術を施行した.胃切除後の吻合部潰瘍は比較的多く認められるが,横行結腸に穿通するのは稀である.さらに主訴が便通異常で診断に苦慮したため,興味深い症例と考え報告する.

Eighteen cases of resected cholangiocellular carcinoma of the liver were investigated to elucidate their clinical features in relation to the macroscopic classification. The tumors were classified int

We describe a rare complication and the treating experience of it after pedicled omental grafting for mediastinitis. The patient was diagnosed as an acute mediastinitis soon after the total arch replacement was performed. A two-staged strategy to treat postoperative mediastinitis was scheduled, i.e., the setting up of a vacuum-assisted closure system until the improvement of inflammation followed by wound closure with pedicled omental grafting. The treatment for acute mediastinitis was successful and the patient followed a favorable postoperative course. During the follow-up, chest X-ray film suggested the gradual enlargement of mediastinum and CT showed the herniation of transverse colon into mediastinum. Surgical correction for the hernia was scheduled and performed successfully by the laparoscopic procedure to prevent a possible cardiac and pulmonary dysfunction.

From April 1980 to April 1995 a total of 54 patients (53 women, 1 man) were hospitalized in our department for the surgical treatment of radiation enterocolitis. Two surgical protocols were applied for these patients: intestinal decompression procedures alone (intestinal bypass, colostomy, or both; n = 18) or an intestinal resection in addition to decompression ( n = 36). The clinical factors contributing to survival after irradiation were retrospectively reviewed by a multiple variate proportional hazards model. As a result, patients treated with decompression procedures alone had an 11 times higher risk for death than those treated with the addition of intestinal resection. In the former group, 5 of 18 patients died of bleeding from the remaining intestine after operation. We concluded that surgical resection of the diseased intestine is a useful procedure for treating radiation enterocolitis to reduce intestinal bleeding from the irradiated intestine.