北山 丈二

Patients with peritoneal dissemination (PD) caused by abdominal malignancies are often associated with massive ascites, which shows extremely dismal prognosis because of the discontinuation of systemic chemotherapy mostly due to poor performance status. Many treatment methods, such as simple drainage, peritoneovenous shunting (PVS) and cell-free and concentrated reinfusion therapy (CART), have been used for symptom relief. However, the clinical efficacies of these methods have not been fully investigated yet. Recently, we developed the Clinical Practice Guideline for PD caused by various malignancies according to "Minds Clinical Practice Guideline Development Guide 2017". In this guideline, we systematically reviewed information on clinical diagnosis and treatments for PD using PubMed databases (2000 - 2020), and clarified the degree of recommendation for clinical questions (CQ). The evidence level was divided into groups by study design and quality. The literature level and a body of evidence were evaluated in reference to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Based on the results of systematic review, the strength of the recommendations was evaluated at a consensus meeting of the Guideline Committee. This is the English synopsis of the part of treatment of malignant ascites in Clinical Practice Guideline for PD, 2021 in Japanese. The guidelines summarize the general aspect of the treatment of malignant ascites and statements with recommendation strengths, evidence levels, agreement rates and future perspective for four raised clinical questions.

Patients with pancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination have a dismal prognosis because discontinuation of systemic chemotherapy is required for massive ascites or poor performance status. The natural history, diagnosis and treatment of PDAC with peritoneal dissemination have not been fully investigated. We systematically reviewed published information on the clinical diagnosis and treatment of PDAC with peritoneal dissemination using the PubMed database (2000-2020) and provided recommendations in response to clinical questions. This guideline was created according to the "Minds Clinical Practice Guideline Development Guide 2017". The literature quality and body of evidence were evaluated with the GRADE System and classified into four levels ("strong", "medium", "weak", "very weak"). The strength of each final recommendation was decided by a vote of committee members based on the GRADE Grid method. These guidelines address three subjects: diagnostic, chemotherapeutic, and surgical approaches. They include nine clinical questions and statements with recommendation strengths, evidence levels, and agreement rates, in addition to one "column". This is the English synopsis of the 2021 Japanese clinical practice guideline for PDAC with peritoneal dissemination. It summarizes the clinical evidence for the diagnosis and treatment of PDAC with peritoneal dissemination and provides future perspectives.

膵全摘では周術期血糖・栄養管理が重要である.12年間の膵全摘32例の周術期血糖・栄養状態を検討した.一期的・二期的膵全摘は各々16例で計48病変の約80%を膵管内乳頭粘液性腫瘍と浸潤性膵管癌が占めた.5年生存率は60.2%,一期的・二期的膵全摘で差はなかった.HbA1cは術前6.7%,術後1年は7.7%と上昇,prognostic nutritional index(PNI)は術前47.8,術後1年は43.0と低下した.予後因子を単変量解析すると術後1年neutrophil-lymphocyte ratio,術前platelet-lymphocyte ratio,術後1年PNIが抽出され,多変量解析では術後1年PNIが有意な因子であった.術後1年PNI 40.5未満は予後不良で,高力価パンクレアチン製剤投与群は予後良好であった.膵全摘後は正しい病態把握のもとに内外分泌治療を行うことが重要である.(著者抄録)

The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.

Polyamines are important to the survival and activation of organs and tissues via a homeostatic cell-metabolic process, and the polyamine content in cytoplasm decreases with aging. Decreases in cellular polyamine have been known to augment mutagenesis and cell death. Thus, supplementary polyamine in food is important to the prevention of aging. Here we show the anti-aging effects of oral intake of polyamine using luciferase-transgenic rats. Healthy rats, 10-12 weeks old, were given foods containing 0.01% and 0.1% (w/w) of polyamine, as compared a control food without polyamine, for 4 weeks. Using a bioimaging system, the photon intensities seen in the whole bodies and livers of rats consuming 0.1% of polyamine in food were stronger than those in rats consuming 0.01% and 0% of polyamine. However, there were no differences between groups in other characteristics, such as liver damage and body weight. In conclusion, we found that polyamine intake can activate cells throughout the whole body, providing an anti-aging effect.

BACKGROUND/AIMS: Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor. METHODS: Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations. RESULTS: At the genus level, the RA of Fusobacterium and Streptococcus at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was Fusobacterium nucleatum and Streptococcus anginosus. The RAs of these species gradually decreased from locations B to E with a statistically significant difference in F. nucleatum. The genus Peptostreptococcus also showed a similar trend, and the RA of Peptostreptococcus stomatis in location A was significantly associated with depth of tumor invasion and tumor size. CONCLUSION: Although the clinical relevance is not clear yet, these results suggest that F. nucleatum, S. anginosus, and P. stomatis can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.

症例は48歳の男性で,約1ヵ月前に左手外傷に対して鼠径部より採皮,植皮術を施行され,退院後より腹部違和感を自覚していた.腹部症状が増悪し意識障害も出現したため前医を受診し,造影CTで広範な門脈血栓症を認め,入院となった.翌日,下部消化管出血を認め,当院転院となった.転院時造影CTで上腸間膜静脈血栓症と診断された.小腸壊死は明らかでなく,抗凝固療法を開始し,約40日の経過で血栓はほぼ消失した.経口摂取開始後に嘔吐が出現したため,小腸造影および小腸3D-CTを撮影したところ上部空腸の器質的狭窄を認めた.転院後第59病日に小腸部分切除術を施行した.病理学的には血栓形成を伴う虚血性腸炎の診断であった.術後20日目に退院し,現在も再発は認めていない.本症例では,3D-CTが遅発性小腸狭窄の範囲の推定と切除範囲の決定に有用であった.(著者抄録)

症例は48歳の男性で,約1ヵ月前に左手外傷に対して鼠径部より採皮,植皮術を施行され,退院後より腹部違和感を自覚していた.腹部症状が増悪し意識障害も出現したため前医を受診し,造影CTで広範な門脈血栓症を認め,入院となった.翌日,下部消化管出血を認め,当院転院となった.転院時造影CTで上腸間膜静脈血栓症と診断された.小腸壊死は明らかでなく,抗凝固療法を開始し,約40日の経過で血栓はほぼ消失した.経口摂取開始後に嘔吐が出現したため,小腸造影および小腸3D-CTを撮影したところ上部空腸の器質的狭窄を認めた.転院後第59病日に小腸部分切除術を施行した.病理学的には血栓形成を伴う虚血性腸炎の診断であった.術後20日目に退院し,現在も再発は認めていない.本症例では,3D-CTが遅発性小腸狭窄の範囲の推定と切除範囲の決定に有用であった.(著者抄録)

BACKGROUND: Leiomyosarcoma is a rare tumor that could originate from the gastrointestinal tract, uterus, kidney, retroperitoneum, and the soft tissues of the extremities. It accounts for only 1% of all gastrointestinal mesenchymal tumors and primary leiomyosarcoma of the stomach is extremely rare. Most cases reported as leiomyosarcoma of the stomach before the development of KIT immunohistochemistry might be gastrointestinal stromal tumors (GISTs) of the stomach and only 18 cases of leiomyosarcoma of the stomach have been reported since early 2000s. We report here a patient with leiomyosarcoma of the stomach treated by laparoscopic and endoscopic cooperative surgery (LECS). CASE PRESENTATION: A 59-year-old man was referred to our hospital for an early gastric cancer, which was initially treated by endoscopic submucosal dissection. Six months after his initial treatment, a follow-up esophagogastroduodenoscopy revealed a small polypoid lesion at the lesser curvature of the proximal stomach, which appeared to be a hyperplastic polyp. However, one and a half years later, the lesion grew and showed more irregular surface. Biopsy at the time revealed smooth muscle cell proliferation suggestive of leiomyoma. Three years later, the lesion grew even larger and biopsy showed pleomorphic spindle cells. Immunohistochemical study showed positive staining for alpha-smooth muscle actin and desmin, but negative for c-kit and CD34. Ki-67 labeling index was nearly 60%. Based on these findings, the diagnosis of leiomyosarcoma was established. The patient subsequently underwent a partial gastrectomy by LECS. The patient is currently in good condition without recurrence or metastasis at 12 months after surgery. CONCLUSIONS: Leiomyosarcoma of the stomach is extremely rare. This is the first report of leiomyosarcoma of the stomach treated by LECS. We could also follow its appearance change through endoscopic examination for 3 years.

Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies globally. We have previously explored the clinical efficacy of intraperitoneal (IP) paclitaxel therapy for patients with PDAC and peritoneal metastasis, which demonstrated favourable response and disease control rates. However, the real implications of conversion surgery after IP therapy remain unclear. Methods: We conducted two multicenter clinical trials of IP therapy with paclitaxel in patients with PDAC and peritoneal metastasis. We focused on patients who underwent conversion surgery and investigated the long-term outcomes, particularly, initial recurrence patterns and long-term survival. Results: Seventy-nine patients with PDAC and peritoneal metastasis were treated, and 33 (41.8%) patients received SP (intravenous IP paclitaxel with S-1) and 46 (58.3%) were administered GAP (intravenous gemcitabine + nab-paclitaxel combined with IP paclitaxel) combination therapy. Of the 79 patients, 16 (20.3%) underwent conversion surgery. The median time to surgery was 9.0 (range, 4.1-13.0) months after the initiation of chemotherapy. Finally, 13 (81.3%) patients underwent R0 resection. Evans grade was IIA in nine patients, IIB in four patients, III in two patients, and IV in one patient. The median overall survival time in patients who underwent conversion surgery was 32.5 (range, 13.5-66.9) months. Twelve (75.0%) patients were found to have experienced recurrence after conversion surgery. Especially, peritoneal recurrence was observed in 50% of patients as the initial recurrence pattern. The median recurrence-free survival time was 9.2 (range, 5.1-32.8) months, and three patients have survived without recurrence to date. Conclusions: Our IP therapy displays promising clinical efficacy with acceptable tolerability in patients with PDAC and peritoneal metastasis. Although we could observe some super-responders in the cohort, further improvements in IP therapy are warranted.