小西 孝宜

＜文献概要＞ポイント ◆局所進行膵癌症例では,しばしば上腸間膜動脈神経叢浸潤を認め,神経叢の半周もしくは全周郭清を要する.◆浸潤を認めない症例では,極力上腸間膜動脈神経叢の全周温存を心掛け,術後QOLを低下させずに術後補助療法を遂行することが肝要である.◆病理学的神経叢浸潤陽性症例では,生存期間はR0とR1切除で差を認めず,今後は浸潤傾向の強い膵癌に対する新規治療法の開発が期待される.

BACKGROUND: Phosphorylated mammalian target of rapamycin (p-mTOR) plays a crucial role in the process of cancer progression. Common gene mutations of colorectal cancer lead to the activation of the PI3k/Akt/mTOR pathway. In this study, we determined whether p-mTOR expression in colorectal liver metastases is a predictive marker of prognosis following liver resection. METHODS: Eighty-one patients with colorectal liver metastases who had undergone curative resection were evaluated using immunohistochemistry of p-mTOR. Data regarding clinicopathological features and patient survival were analyzed. RESULTS: The p-mTOR expression in colorectal liver metastases was detected in 55 (67.9%) patients. Patients whose metastases had high p-mTOR expression showed a significantly lower overall survival rate after resection as compared to patients with low p-mTOR expression (p = 0.016), while there was no significant difference in the disease-free survival between the two groups. Repeat resection for recurrence was performed more frequently in patients with p-mTOR positive than others (p = 0.024). Multivariate analysis showed that p-mTOR expression was an independent prognostic factor of overall survival after liver resection (p = 0.019). CONCLUSIONS: mTOR was frequently activated in colorectal liver metastases, and the p-mTOR expression was a biological marker for predicting the overall survival of patients with colorectal liver metastases following liver resection.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the brain; therefore, the features of brain metastasis of PDAC are still unknown. We encountered simultaneous metastases to the brain and lung in a PDAC patient after curative surgery. Case presentation A 68-year-old man with PDAC in the tail of the pancreas underwent distal pancreato-splenectomy. He received gemcitabine as adjuvant chemotherapy for 6 months. Two months later, brain and lung metastases occurred simultaneously. Considering the systemic condition, the patient received gamma knife treatment and an Ommaya reservoir was inserted for drainage. The patient's condition gradually worsened and he received the best supportive care. To the best of our knowledge, only 28 cases in which brain metastases of PDAC were identified at the time of ante-mortem have been reported to date, including the present case. Notably, the percentage of simultaneous brain and lung metastases was higher (32%) in a series of reviewed cohorts. Thus, lung metastasis might be one of the risk factors for the development of brain metastasis in patients with PDAC. As a systemic disease, it can be inferred that neoplastic cells will develop brain metastasis via hematogenous dissemination beyond the blood-brain barrier, even if local recurrence is controlled. In our case, immunohistochemical staining showed that the neoplastic cells were positive for carbonic anhydrase 9 (CAIX), mucin core protein 1 (MUC1), and MUC5AC in the resected primary PDAC. CONCLUSION: We describe a case of simultaneous brain and lung metastases of PDAC after curative pancreatectomy, review previous literature, and discuss the clinical features of brain metastasis of PDAC.

症例は60歳、男性。膵尾部癌に対して脾合併尾側膵切除、胃・空腸・左腎静脈合併切除術を施行した。術後補助化学療法としてS-1内服を1年間行った。術後1年8ヵ月目にCA19-9の上昇を認めたため、gemcitabine(GEM)による化学療法を開始した。以後GEMを継続していたが、術後3年10ヵ月目に腸閉塞で入院となった。保存的治療で改善せず、手術を施行したところ腹膜播種巣が小腸に浸潤していたため、バイパス術、播種巣の生検を施行した。術後FOLFIRINOX療法を開始したが、初回手術より4年8ヵ月目にCA19-9の上昇を認めGEM+nab-paclitaxel療法に変更し、初回手術後6年11ヵ月、腹膜播種再発確認後5年3ヵ月現在、明らかな増悪なく外来化学療法を継続中である。本症例ではいずれのレジメンも長い奏効期間を維持しただけではなく、特筆すべき副作用なく長期継続可能であったことも長期生存に寄与していると考えられた。(著者抄録)

症例は48歳、女性。食後の腹痛、腹部膨満感を主訴に前医を受診し、膵腫瘍を指摘され当科紹介となった。腹部dynamic CT検査で膵尾部に多房性嚢胞性病変を認め、胸部CT検査で右肺S10に3mm、5mm、左肺S8に10mmの小結節影を認めた。膵粘液性嚢胞腺癌(mucinous cystic carcinoma:MCC)、両側多発肺転移の診断で膵切除を先行し、二期的に肺転移巣を切除する方針とした。手術は尾側膵切除術を施行し、病理組織学的診断は膵MCCであった。術後経過は良好で術後第18病日に退院となった。膵切除から2ヵ月後、5ヵ月後にそれぞれ左肺S8+9区域切除、右肺S9+10区域切除を施行し、いずれも膵MCCの肺転移の診断であった。補助化学療法は施行せず経過観察中であり、膵切除後11ヵ月、肺切除後6ヵ月現在、無再発生存中である。(著者抄録)

A 60-year-old man underwent distal pancreatectomy with splenectomy and combined resection partially of the stomach, jejunum, and left renal vein. We administered S-1 adjuvant chemotherapy for 1 year. After its completion, the patient showed no evidence of recurrence. However, his carbohydrate antigen(CA)19-9 level was elevated for 1 year and 8 months postoperatively. We administered gemcitabine chemotherapy. He was admitted for bowel obstruction 3 years and 10 months postoperatively. Conservative treatment with an ileus tube did not improve the bowel obstruction. Therefore, we performed the surgery. Intraoperative findings revealed peritoneal nodules invading the small intestine. We performed a small bowel bypass. Pathological examination revealed the peritoneal nodule of pancreatic cancer. Although we administered FOLFIRINOX chemotherapy postoperatively, his CA19-9 level remained elevated for 4 years and 8 months after the first surgery. Therefore, chemotherapy was changed to gemcitabine and nab-paclitaxel. Six years and 11 months after the first surgery and 5 years and 3 months after the diagnosis of peritoneal dissemination, he survives with recurrence. Herein, there were 2 contributors to long-term survival; the patient not only showed positive responses to each chemotherapy regimen but could also continue chemotherapy without developing significant adverse effects.

A 48-year-old female visited former doctor with abdominal pain and bloating. She was suspected of having pancreatic tumor and referred to our hospital. Abdominal dynamic CT showed multilocular cystic tumor in the pancreatic tail, and chest CT showed multiple lung nodules. From these findings, the patient was diagnosed mucinous cystic carcinoma(MCC)with lung metastases. We performed distal pancreatectomy for the first and lung resection after pancreatectomy. After all, the pathological diagnosis was MCC and metastatic lung cancer from the MCC. The adjuvant chemotherapy was not performed. Eleven months after pancreatectomy and 6 months after lung resection, the patient is still alive without recurrence.

胆嚢癌(疑診例)に対する術中迅速組織診は、癌の存在診断と、深達度診断という二つの側面をもつ。とくに深達度に関しては術式決定にかかわる重要な要素であり、その正確性が常に求められている。しかしながら、術中迅速組織診断はホルマリン固定後標本と異なり、急速凍結された標本であるため、標本の質が固定後標本よりも低く、診断に難渋することも少なくない。われわれの施設では、胆嚢癌疑診例に対しては全例全層胆嚢摘出術に加え術中迅速組織診を施行しているが、癌であった症例の深達度の正診率は90.2%と比較的良好であるものの、他施設の迅速診断と最終診断の乖離例も含めて検討すると、標本の質の問題以外にも癌のRAS進展の問題やサンプリングエラーなどが重要な課題と考えられた。(著者抄録)

BACKGROUND: Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection. METHODS: We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed. RESULTS: A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration. CONCLUSIONS: Splenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.