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Background The efficacy of neoadjuvant therapy (NAT), including neoadjuvant chemotherapy (NAC) and neoadjuvant chemo-radiotherapy (NACRT), for patients with borderline resectable pancreatic cancer (BRPC) has not been elucidated. This study aimed to clarify the efficacy of NAC and NACRT for patients with BRPC. Methods The study analyzed the treatment outcomes of 884 patients treated for BRPC from 2011 to 2013. Treatment results were compared between upfront surgery and NAT and between NAC and NACRT using propensity score-matching analysis. Overall survival (OS) was calculated via intention-to-treat analyses. Results The overall resection rates for the patients who underwent NAT were significantly lower than for the patients who underwent upfront surgery (75.1% vs 93.3%; p  < 0.001). However, the R0 resection rate was significantly higher for NAT than for upfront surgery ( p  < 0.001). Additionally, the OS for the patients who received NAT was significantly longer than for those who underwent upfront surgery (median survival time [MST], 25.7 vs 19.0 months; p  = 0.015). The lymph node rate for the patients with NACRT was significantly lower than for those who underwent NAC ( p  < 0.001). However, the resection rate for the NACRT cases was significantly lower than for the NAC cases ( p  = 0.041). The local recurrence rate for the NACRT cases was significantly lower than for the NAC cases ( p  = 0.002). However, OS did not differ significantly between NAC and NACRT (MST, 29.2 vs 22.5 months; p  = 0.130). Conclusions The study showed that NAT has potential benefit for patients with BRPC. Compared with NAC, NACRT decreased the rates for lymph node metastasis and local recurrence but did not improve the prognosis.

Neoadjuvant therapy is increasingly used to control local tumor spread and micrometastasis of pancreatic ductal adenocarcinoma (PDAC). Pathology assessments of treatment effects might predict patient outcomes after surgery. However, there are conflicting reports regarding the reproducibility and prognostic performance of commonly used tumor regression grading systems, namely College of American Pathologists (CAP) and Evans’ grading system. Further, the M.D. Anderson Cancer Center group (MDA) and the Japan Pancreas Society (JPS) have introduced other grading systems, while we recently proposed a new, simple grading system based on the area of residual tumor (ART). Herein, we aimed to assess and compare the reproducibility and prognostic performance of the modified ART grading system with those of the four grading systems using a multicenter cohort. The study cohort consisted of 97 patients with PDAC who had undergone post-neoadjuvant pancreatectomy at four hospitals. All patients were treated with gemcitabine and S-1 (GS)-based chemotherapies with/without radiation. Two pathologists individually evaluated tumor regression in accordance with the CAP, Evans’, JPS, MDA and ART grading systems, and interobserver concordance was compared between the five systems. The ART grading system was a 5-tiered system based on a number of 40× microscopic fields equivalent to the surface area of the largest ART. Furthermore, the final grades, which were either the concordant grades of the two observers or the majority grades, including those given by the third observer, were correlated with patient outcomes in each system. The interobserver concordance (kappa value) for Evans’, CAP, MDA, JPS and ART grading systems were 0.34, 0.50, 0.65, 0.33, and 0.60, respectively. Univariate analysis showed that higher ART grades were significantly associated with shorter overall survival (p = 0.001) and recurrence-free survival (p = 0.005), while the other grading systems did not show significant association with patient outcomes. The present study revealed that the ART grading system that was designed to be simple and more objective has achieved high concordance and showed a prognostic value; thus it may be most practical for assessing tumor regression in post-neoadjuvant resections for PDAC.

Background Laparoscopic lymph node (LN) dissection along the distal splenic artery (Station No. 11d) and around the splenic hilum (Station No. 10) remains challenging even for skilled surgeons. The major reason for the difficulty is the complex, multifarious anatomy of the splenic vessels. The latest integrated three-dimensional (3D) simulations may facilitate this procedure. Methods Usefulness of 3D simulation was investigated during 20 laparoscopic total gastrectomies with splenic hilar LN dissection while preserving the spleen and pancreas (LTG + PSP) or with splenectomy (LTG + S). Clinical information acquired by 3D simulation and the consistency of the virtual and real images were evaluated. Furthermore, clinical data of these patients were compared with that of the patients who underwent the same surgery before the introduction of 3D simulation ( n  = 10), to clarify its efficacy. Results The vascular architecture and morphologic characteristics were clearly demonstrated in 3D simulation, with sufficient consistency. The median durations of 14 LTG + PSP and 6 LTG + S operations were 318 and 322 min, respectively. The estimated blood losses were 18 and 38 g, respectively. There were no deaths. One postoperative peritoneal abscess (grade II according to Clavien–Dindo) was recorded. A comparison of clinical parameters between surgeries without or with 3D simulation showed no differences in operation time, blood loss, or complication rate; however, the number of retrieved No. 10 LNs has significantly increased in cases with the use of 3D simulation ( p  = 0.006). Conclusions This kind of surgery is not easy to perform, but the latest 3D computed tomography simulation technology has made it possible to reduce the degree of difficulty and also to enhance the quality of surgery, potentially leading to widespread use of these techniques.

BackgroundAlthough the artery-first approach is widely used in open pancreaticoduodenectomy, it is difficult to laparoscopically expose the origin of the inferior pancreaticoduodenal artery (IPDA) from the left side of the superior mesenteric artery (SMA). By contrast, damaging the inferior pancreaticoduodenal veins (IPDVs) is possible when approaching the IPDA from the right side of the SMA. To facilitate the artery-first approach in laparoscopic pancreaticoduodenectomy (LPD), we focused on the proximal-dorsal jejunal vein (PDJV) that branched from the superior mesenteric vein (SMV) dorsal side and drained the IPDVs. This study aimed to clarify the usefulness of the right SMA approach using the PDJV preisolation method.MethodsThe PDJV was first isolated, and the IPDVs were divided along the PDJV on the right side of the SMA. Then, the IPDA was divided at the root without first separating the pancreatic head from the portal vein and the SMV. Overall, 21 patients underwent this approach, and the results were retrospectively compared with those of 21 patients who underwent the artery-first approach, which was performed on the left side of the SMA. Anatomical characteristics of the PDJV were evaluated using multidetector computed tomography for the two groups.ResultsOperative times and resection times were significantly lower for the PDJV preisolation group than for the conventional LPD group (489.3 vs. 541.7 min, respectively; p = 0.002). During anatomical evaluation, 41 patients (97.6%) had a PDJV that drained from the SMV dorsally and was in contact with the anterior aspect of the uncinate process. The PDJV was confirmed as the first jejunal vein in 31 patients (73.8%) and as the second jejunal vein in 10 patients (23.8%).ConclusionsThis approach facilitates dissection of the IPDA on the right side of the SMA, thereby reducing operative times.

Background Detection of early remnant gastric cancer (ERGC) is increasing as a result of the development of endoscopic technology and a surveillance program. The aim of this study was to evaluate the results of limited subtotal gastrectomy (SG) surgery for ERGC compared to total gastrectomy (TG). Methods We retrospectively reviewed a database of 72 consecutive patients with remnant gastric cancer who underwent laparotomy at the National Cancer Center Hospital East between January 1993 and December 2008. Thirty-five patients with a preoperative diagnosis of ERGC underwent curative resection: 13 SG and 22 conventional TG. Patients and tumor characteristics, operative results, and postoperative assessments 1 year after surgery were compared between the two groups. Results Operating time, blood transfusion, and hospital stay were similar in the two groups. In the SG group, blood loss and postoperative recovery of body weight tended to be better than in the TG group. There was no dumping syndrome in the SG group, while this occurred in three patients in the TG group. The levels of hemoglobin and total protein were higher 1 year after remnant gastrectomy in the SG group than in the TG group. No recurrence of gastric cancer was detected in the SG group during median follow-up of 99.2 months. Conclusion In comparison to TG, limited SG surgery for ERGC improved the postoperative course, with no recurrence of cancer. Therefore, SG is a safe and effective treatment for ERGC.

Certain cell lines exhibit metastatic ability (highly metastatic cell lines) while their parent cell lines have no metastatic ability. Differences in methylation, which are not derived from differences in the gene sequence between cell lines, were extensively analyzed. Using an established highly metastatic cell line, KM12SM, and its parent cell line, KM12C, differences in the frequency of methylation were analyzed in the promoter regions of ~480,000 gene sites using Infinium HumanMethylation450. The promoter region of the Rho GTPase-activating protein 28 (ARHGAP28) gene was the most markedly methylated region in KM12SM compared with KM12C. ARHGAP28 is a GTPase-activating protein (GAP), and it converts activated RhoA to inactivated RhoA via GTPase. RhoA activity was compared between these two cell lines. The activated RhoA level was compared using western blot analysis and G-LISA. The activated RhoA level was higher in KM12SM compared to KM12C for western blot analysis and G-LISA analysis. RhoA is a protein involved in cytoskeleton formation and cell motility. RhoA, for which ARHGAP28 acts as a GAP, is possibly a factor involved in the metastatic ability of cancer.

Purpose Chemoradiotherapy using intensity-modulated radiotherapy (IMRT) is expected to provide a powerful alternative to conventional chemotherapy with a low incidence of adverse events. This study evaluated the efficacy of intensity modulated radiotherapy in combination with gemcitabine and S-1 as neoadjuvant chemoradiotherapy (NACRT) for borderline-resectable pancreatic cancer with arterial involvement (BR-A). Methods A total of 27 patients with BR-A were enrolled in this study between February 2012 and September 2015. IMRT was administered at 50.4 Gy in 28 fractions with concurrent gemcitabine at a dose of 600 mg/m 2 and S-1 at a dose of 60 mg. Results Only one patient (3.5%) experienced gastrointestinal adverse events at grade 3 or higher. Nineteen patients (70.3%) underwent resection, and R0 resection was achieved in 18 patients (94.7%). Thirteen patients (68.4%) developed distant metastasis at the initial site of recurrence after resection. Local recurrence developed in only one of these patients (7.7%). The median overall survival and 1-year survival rates were 22.4 months and 81.3%, respectively. Conclusions Concurrent IMRT with gemcitabine and S-1 for patients is feasible as NACRT for BR-A with low gastrointestinal toxicity. IMRT can be employed as a standard radiotherapy to provide more effective NACRT with powerful chemotherapy drugs.

Background/Purpose The 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). Methods The 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. Results The 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. Conclusions Pancreaticoduodenectomy 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.

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.