Tetsushi Nakajima

Urinary Polyamine Biomarker Panels with Machine-Learning Differentiated Colorectal Cancers, Benign Disease, and Healthy Controls

Colorectal cancer (CRC) is one of the most daunting diseases due to its increasing worldwide prevalence, which requires imperative development of minimally or non-invasive screening tests. Urinary polyamines have been reported as potential markers to detect CRC, and an accurate pattern recognition to differentiate CRC with early stage cases from healthy controls are needed. Here, we utilized liquid chromatography triple quadrupole mass spectrometry to profile seven kinds of polyamines, such as spermine and spermidine with their acetylated forms. Urinary samples from 201 CRCs and 31 non-CRCs revealed the N1,N12-diacetylspermine showing the highest area under the receiver operating characteristic curve (AUC), 0.794 (the 95% confidence interval (CI): 0.704–0.885, p < 0.0001), to differentiate CRC from the benign and healthy controls. Overall, 59 samples were analyzed to evaluate the reproducibility of quantified concentrations, acquired by collecting three times on three days each from each healthy control. We confirmed the stability of the observed quantified values. A machine learning method using combinations of polyamines showed a higher AUC value of 0.961 (95% CI: 0.937–0.984, p < 0.0001). Computational validations confirmed the generalization ability of the models. Taken together, polyamines and a machine-learning method showed potential as a screening tool of CRC.

Surgical Outcomes of Pancreaticoduodenectomy for Pancreatic Cancer with Proximal Dorsal Jejunal Vein Involvement

Background/PurposeThe proximal jejunal vein which branches from the dorsal side of the superior mesenteric vein (SMV) usually drains the inferior pancreatoduodenal veins (IPDVs) and contacts the uncinate process of the pancreas. We focused on this vein, termed the proximal dorsal jejunal vein (PDJV), and evaluated the anatomical classification of the PDJV and surgical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) with PDJV involvement (PDJVI).MethodsThe jejunal veins that branch from the dorsal side of the SMV above the inferior border of the duodenum are defined as PDJVs. We investigated 121 patients who underwent upfront pancreaticoduodenectomy for PDAC between 2011 and 2017; PDJVs were resected in all patients. The anatomical classification of PDJV was evaluated using multidetector computed tomography. Surgical and prognostic outcomes of pancreticoduodenectomy for PDAC with PDJVI were evaluated.ResultsThe PDJVs were classified into seven types depending on the position of the first and second jejunal veins relative to the superior mesenteric artery. In all patients, the morbidity and mortality rates were 15.7 and 0.8%, respectively. The rates for parameters including SMV resection, presence of pathological T3–4, R0 resection, and 3-year survival were 46.2, 92.3, 92.3, and 61.1%, respectively, when there was PDJVI (n = 13). When there was no PDJVI (n = 108), the rates were 60.2, 93.5, 86.1, and 58.3%, respectively. Overall, there were no significant differences.ConclusionsPancreaticoduodenectomy with PDJV resection is feasible for PDAC with PDJVI and satisfactory overall survival rates are achievable. It may be necessary to reconsider the resectability of PDAC with PDJVI.

Surgical resection of neuroendocrine tumors of the pancreas (pNETs) by minimally invasive surgery: the laparoscopic approach

Neuroendocrine tumors of the pancreas (pNETs) are a rare group of neoplasms that originate from the endocrine portion of the pancreas. Tumors that either secrete or do not secrete compounds, resulting in symptoms, can be classified as functioning and non-functioning pNETs, respectively. The prevalence of such tumors has recently increased due to the use of more sensitive imaging techniques, such as multidetector computed tomography, magnetic resonance imaging and endoscopic ultrasound. The biological behavior of pNETs varies widely from indolent, well-differentiated tumors to those that are far more aggressive. The most effective and radical treatment for pNETs is surgical resection. Over the last decade, minimally invasive surgery has been increasingly used in pancreatectomy, with laparoscopic pancreatic surgery (LPS) emerging as an alternative to open pancreatic surgery (OPS) in patients with pNETs. Non-comparative studies have shown that LPS is safe and effective. In well-selected groups of patients with pancreatic lesions, LPS was found to results in good perioperative outcomes, including reduced intraoperative blood loss, postoperative pain, time to recovery, and length of hospital stay. Despite the encouraging results of studies from highly specialized centers with extensive experience, no randomized trials to date have conclusively validated these findings. Indications for minimally invasive LPS for patients with pNETs remain unclear. This review presents the current state of LPS for pNETs.

Liver metastasis is established by metastasis of micro cell aggregates but not single cells

Cancer cell engraftment in the target organ is necessary to establish metastasis. Clinically, lymph node metastasis of single cells has been confirmed using cytokeratin staining. In the current study, a LacZ-labeled cancer cell line was used to visualize intrahepatic metastasis of single cells or liver micrometastasis. KM12SM-lacZ stably expressing LacZ was prepared with a highly metastatic colon cancer cell line, KM12SM. KM12SM-lacZ was injected into the spleen of nude mice and following 1 week the spleen was excised. The liver was then examined for metastasis following 1, 2 or 3 weeks. Confirmation of liver metastasis was completed by observing the grade of metastasis. Grade-1 metastasis (DNA level), human DNA in liver tissue was detected; Grade-2 metastasis (metastasis of single cells), confirmed by X-gal staining; Grade-3 metastasis (histopathological micrometastasis), diagnosed by light microscopy and Grade-4 metastasis (typical metastasis), easily detected macroscopically or by hematoxylin and eosin staining. The Grade-1 metastasis detection rates 1, 2 and 3 weeks following splenectomy were 50, 100 and 100%, respectively. Grade-2 metastasis was not detected by microscopy. The Grade-3 metastasis detection rates for 1, 2 and 3 weeks were 75, 100 and 100%, respectively. Micrometastasis was observed in the portal vein lumen and wall. The Grade-4 metastasis detection rates were 50, 100 and 100% for 1, 2 and 3 weeks respectively. Cancer cells were present in vessels surrounding the main tumor. In conclusion, a specific number of cancer cell aggregates may be necessary to establish hematogenous metastasis.

Laparoscopic distal pancreatectomy without needle aspiration before resection for giant mucinous cell neoplasms.

Laparoscopic resection of large mucinous cystic neoplasms (MCN) has recently been reported. However, in most reports, needle aspiration of the cyst contents was performed before resection and can cause dissemination. Here, we report two patients with giant MCN: a 26‐year‐old woman with a 23‐cm MCN and a 41‐year‐old woman with an 18‐cm MCN. The MCN were successfully resected without aspiration by laparoscopic surgery. CT revealed no tumor involvement of the origins of the splenic artery and vein in either case. In case 1, we performed hand‐assisted laparoscopic surgery while dissecting around the spleen, whereas case 2 underwent pure laparoscopic surgery. No postoperative complications occurred in either case, indicating that laparoscopic distal pancreatectomy for giant MCN is feasible without aspiration in patients without splenic artery and vein origin involvement.