小西 孝宜

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is commonly performed for enteral nutrition in patients with various diseases. However, there are few reports on abdominal surgeries for patients after PEG, and the tips for these procedures have not been established. Specifically, in laparoscopic surgeries of the upper abdomen, a gastrostomy can interfere with the surgical field. In addition, perioperative management of concomitant diseases that require PEG placement, including neuromuscular disorders, is required. CASE PRESENTATION: A 64-year-old man with a PEG due to malnutrition from myotonic dystrophy was diagnosed with acute cholangitis and choledocholithiasis. After lithotomy during endoscopic retrograde cholangiopancreatography, the patient was scheduled for laparoscopic cholecystectomy for the cholelithiasis. Although the patient had myotonic dystrophy and limited respiratory function, his general condition was deemed acceptable for surgery. Given the potential risk of gastrostomy injury and the need to ensure sufficient working space, the location of the gastrostomy tube was preoperatively confirmed via a computed tomography scan, and precautions were taken to prevent injuries caused by port insertion, forceps manipulation, and pneumoperitoneum during the procedure. Ultimately, the gastrostomy did not interfere with manipulation around the gallbladder, and the surgery was completed without any complications. To manage myotonic dystrophy, general intravenous anesthesia with propofol was administered, with minimal use of muscle relaxants during surgery. Postoperatively, the patient was managed with high nasal flow to reduce respiratory workload, epidural anesthesia to prevent respiratory depression due to pain, and early initiation of aggressive physical therapy. The patient was discharged on postoperative day 4 without complications. CONCLUSIONS: Using appropriate surgical strategies, laparoscopic cholecystectomy may be safely performed for patients with myotonic dystrophy after PEG.

Pancreatic ductal adenocarcinoma (PDAC) is a progressive cancer with a poor prognosis. It contains a complex tumor microenvironment (TME) that includes various stromal cell types. Comprehending cellular communications within the TME is difficult due to a lack of research models that can recapitulate human PDAC-TME. Previously, we recapitulated, in part, the PDAC-TME containing a diversity of cancer-associated fibroblasts (CAFs) in vitro. This was done by establishing a PDAC organoid by co-culturing patient-derived cancer cells with human induced pluripotent stem cell (hiPSC)-derived mesenchymal and endothelial cells, which was designated the fused pancreatic cancer organoid (FPCO). We further incorporated macrophages derived from the THP-1 cell line, which are the source of tumor-associated macrophages (TAMs), a major TME component, into FPCO, which was designated M0-FPCO. Bulk RNA sequencing (RNAseq) analysis revealed that macrophages in M0-FPCO (FPCO-Mac) lost their pro-inflammatory features but acquired pro-angiogenic features. Consistently, the formation of an endothelial cell network was enhanced in M0-FPCO. Single-cell RNA-seq (scRNA-seq) analysis revealed that M0-FPCO contained five TAM subpopulations similar to the corresponding TAM in human PDAC tissue in the integrated analysis, including SPP1⁺-TAM, which has been correlated with tumor angiogenesis and cell proliferation. Focusing on PDAC cells, we found that they could survive longer within the organoid in the presence of TAM. Consistent with the prolonged proliferation and survival of PDAC cells, PDAC subclusters were characterized by proliferative features, such as increased M0-FPCO. Therefore, by establishing a PDAC organoid with macrophages, we recapitulated the diversity of TAMs and identified the role of TAM in endothelial network formation as well as in the modulation of PDAC cell properties. SIGNIFICANCE: PDAC organoids, including macrophages using hiPSC, showed that PDAC-TAM has angiogenic features and contributes to PDAC cell survival.

膵癌は浸潤・転移をきたしやすく悪性度の高い代表的な悪性腫瘍であり,多くの治療に抵抗性を示す。その大きな要因として膵癌細胞を取り巻く微小環境があり,これまで盛んに基礎研究が行われてきている。膵癌微小環境内にはさまざまな癌進展機構にかかわる因子が内包され,膵癌細胞とそれらの因子の相互作用による癌進展機構のメカニズムが解明されつつある。重要な構成成分として成長因子やサイトカインなどの液性因子,癌関連線維芽細胞(CAFs),pancreatic stellate cells(PSCs),癌関連免疫担当細胞があり,また細胞外基質(ECM)を含む豊富な間質を有することが特徴である。現在はそれらを治療ターゲットとした臨床試験が行われており,今後の有望な膵癌新規治療の出現が期待されている。(著者抄録)

BACKGROUND: Although some clinical trials have demonstrated the benefits of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC), its optimal candidate has not been clarified. This study aimed to detect predictive prognostic factors for resectable PDAC patients who underwent upfront surgery and identify patient cohorts with long-term survival without neoadjuvant therapy. PATIENTS AND METHODS: A total of 232 patients with resectable PDAC who underwent upfront surgery between January 2008 and December 2019 were evaluated. RESULTS: The median overall survival (OS) time and 5-year OS rate of resectable PDAC with upfront surgery was 31.5 months and 33.3%, respectively. Multivariate analyses identified tumor diameter in computed tomography (CT) ≤ 19 mm [hazard ratio (HR) 0.40, p < 0.001], span-1 within the normal range (HR 0.54, p = 0.023), prognostic nutritional index (PNI) ≥ 44.31 (HR 0.51, p < 0.001), and lymphocyte-to-monocyte ratio (LMR) ≥ 3.79 (HR 0.51, p < 0.001) as prognostic factors that influence favorable prognoses after upfront surgery. According to the prognostic prediction model based on these four factors, patients with four favorable prognostic factors had a better prognosis with a 5-year OS rate of 82.4% compared to others (p < 0.001). These patients had a high R0 resection rate and a low frequency of tumor recurrence after upfront surgery. CONCLUSIONS: We identified patients with long-term survival after upfront surgery by prognostic prediction model consisting of tumor diameter in CT, span-1, PNI, and LMR. Evaluation of anatomical, biological, nutritional, and inflammatory factors may be valuable to introduce an optimal treatment strategy for resectable PDAC.

血行再建術を伴う肝門部領域胆管癌手術は,肝胆膵外科高度技能手術においてもっとも高難易度の手術であるが,一方で標準的な手技の一つとして安全に施行する技術を取得しておくことも胆道外科医にとって重要といえる。動脈再建時には,吻合血管の口径,長さ,再建時の屈曲の程度などを考慮して,再建動脈を選択する。原則としては端々吻合を行うが,再建距離が長く直接吻合が難しい場合や,吻合に緊張がかかる場合には,胃十二指腸動脈や右胃大網動脈などを用いて再建することもある。門脈再建においては,その切除長が長い場合にはグラフト間置による再建が必要になり,その種類には外腸骨静脈,外頸静脈,左腎静脈グラフトなどいくつかの種類がある。動脈再建などで協力をあおぐ他診療科(心臓血管外科,形成外科など)と再建方法のシミュレーションを十分に行っておくことも,安全な手術を完遂するために重要である。血管合併切除・再建術後の周術期対策として,ドップラーエコーによる定期的な血流の確認と,出血や血栓症を疑った場合の遅滞のないdynamic CT撮影が必要である。(著者抄録)

高齢者肝門部領域胆管癌に対する拡大肝切除は増加傾向にあり,手術を施行した高齢者(75歳以上)と非高齢者(75歳未満)でその短期成績,長期成績は同等である。ただ,高齢者肝門部領域胆管癌に対する拡大肝切除に関しては,そのリスク評価とそれに基づいた手術適応には定まったものはなく,また予後に関しても,既存の因子では測定しえない高齢者特有の問題があることが示唆されるため,引き続き検討していく必要がある。(著者抄録)

PURPOSE: Systemic chemotherapy is generally used for metastatic pancreatic cancer; however, pulmonary resection may be a treatment option for lung oligometastases from pancreatic cancer. The current study aimed to clarify the oncological outcomes and clinical benefits of pulmonary resection for lung metastases. METHODS: Of 510 patients who underwent pancreatic resection for pancreatic cancer, 44 patients with recurrence of isolated lung metastases and one patient with simultaneous lung metastases were evaluated. RESULTS: Of the 45 patients, 20 patients were selected as candidates for pulmonary resection based on clinical factors such as recurrence-free interval (RFI) from pancreatectomy to lung metastases, number of lung metastases, and serum CA19-9 level. The post-recurrent survival of patients with pulmonary resection was significantly better than that of patients without pulmonary resection. Fourteen of the 20 patients with pulmonary resection developed tumor recurrence with a median disease-free survival (DFS) of 15 months. Univariate analyses revealed that an RFI from pancreatectomy to lung metastases of ≥28 months was associated with better DFS after pulmonary resection. Of the 14 patients with an RFI of ≥28 months, pulmonary resection resulted in prolonged chemotherapy-free interval in 12 patients. Furthermore, repeat pulmonary resection for recurrent tumors after pulmonary resection led to further cancer-free interval in some cases. CONCLUSIONS: Although many patients had tumor recurrence after pulmonary resection, pulmonary resection for lung metastases from pancreatic cancer may provide prolonged cancer-free interval without the need for chemotherapy. Pulmonary resection should be performed for the patients with a long RFI from pancreatectomy to lung metastases.

BACKGROUND: The indication for surgical resection of intraductal papillary mucinous neoplasms (IPMNs) is defined by imaging features, such as mural nodules. Although carbohydrate antigen (CA) 19-9 was selected as a parameter for worrisome features, no serum biomarkers were considered when deciding on surgical indications in the latest international consensus guideline. In this study, we assessed whether clinical factors, imaging findings, and serum biomarkers are useful in predicting malignant IPMNs. METHODS: A total of 234 resected IPMN cases in Chiba University Hospital from July 2005 to December 2021 were retrospectively analyzed. RESULTS: Among the 234 patients with resected IPMNs diagnosed by preoperative imaging, 117 were diagnosed with malignant pathologies (high-grade dysplasia and invasive IPMNs) according to the histological classification. In the multivariate analysis, cyst diameter ≥30 mm; p = 0.035), enhancing mural nodules on multidetector computed tomography (≥5 mm; p = 0.018), and high serum elastase-1 (≥230 ng/dl; p = 0.0007) were identified as independent malignant predictors, while CA19-9 was not. Furthermore, based on the receiver operator characteristic curve analyses, elastase-1 was superior to CA19-9 for predicting malignant IPMNs. Additionally, high serum elastase-1 levels (≥230 ng/dl; p = 0.0093) were identified as independent predictors of malignant IPMNs in patients without mural nodules on multidetector computed tomography (MDCT) in multivariate analysis. CONCLUSION: The serum elastase-1 level was found to be a potentially useful biomarker for predicting malignant IPMNs.

A 73-year-old female was diagnosed with gallbladder cancer, but the future liver remnant volume was deemed insufficient for curative resection. Consequently, transileocolic portal vein embolization was performed. During laparotomy, multiple nodules were palpable on the peritoneal surface of the pelvic floor. Subsequently, staging laparoscopy confirmed the pathological diagnosis of adenocarcinoma in the resected nodules, indicating peritoneal dissemination of gall bladder cancer. Due to this peritoneal dissemination, surgical resection was deemed inappropriate, and the patient was initiated on systemic chemotherapy consisting of gemcitabine and cisplatin. Following 22 courses of chemotherapy, contrast-enhanced computed tomography demonstrated no significant changes in the size of the primary tumor or its location relative to the main vessels, although a small metastatic lesion was identified in the gallbladder bed. At the second staging laparoscopy, any nodules suggesting peritoneal dissemination were observed. Based on these findings, we decided to perform curative resection. The surgical procedure involved right hepatectomy plus segment 4a resection, extrahepatic bile duct resection, and hepaticojejunostomy. Pathological examination revealed ypT3bN0M1(HEP), ypStage ⅣB, with the achievement of R0 resection. The patient survived with no recurrences for 40 months after surgery. These results suggest that aggressive therapeutic strategies, including conversion surgery following systemic chemotherapy, may be beneficial for patients initially deemed unresectable due to gallbladder cancer.

Serial pancreatic juice aspiration cytological examination(SPACE)has been reported as a reliable preoperative diagnostic method for early pancreatic cancer, when combined with imaging findings suspecting early pancreatic cancer. Among 259 patients with suspected pancreatic cancer who underwent pancreatic resection at our hospital, SPACE was preoperatively performed in 14 cases(5.4%). Of these 14 cases, final pathological diagnosis was pancreatic cancer in 12 patients (86%), including 5 patients with Stage ⅠA pancreatic cancer(35.7%), all of whom had a mass on preoperative CT or EUS. On the other hand, in the other 2 cases(14.3%), CT/EUS detected no mass but focal pancreatic parenchymal atrophy and main pancreatic duct stenosis which were the imaging findings suspecting very early pancreatic cancer such as cancer in situ. Although preoperative SPACE results of these 2 cases were class Ⅳ, final pathological results of resected specimen were low-grade PanIN in both cases. SPACE was considered useful for preoperative diagnosis of pancreatic cancer in our study, however further study is needed to examine its diagnostic accuracy for early pancreatic cancer which does not appear as a mass in any imaging modality.

R0切除困難な局所進行肝門部領域胆管癌に対して,化学療法を施行し,化学療法が奏効した症例に対して外科切除を行う(conversion surgery)という治療戦略は,安全で有効な可能性がある。しかし,肝門部領域胆管癌をR0切除困難と判断する基準や,化学療法の効果判定基準,化学療法が奏効しR0切除可能となったと判断する基準には一定のものはなく,施設ごとに大きく異なると予想される。また,近年,胆道癌に対する新規レジメンや,新規抗癌剤,分子標的薬が登場したことから,局所進行肝門部領域胆管癌に対するconversion surgeryの安全性と有効性に関しては,引き続き検討していく必要がある。(著者抄録)