Portal vein wedge resection and patch venoplasty with autologous vein grafts for hepatobiliary-pancreatic cancer.

BACKGROUND: Advanced hepatobiliary-pancreatic cancer often invades critical blood vessels, including the portal vein (PV) and hepatic artery. Resection with tumor-free resection margins is crucial to achieving a favorable prognosis in these patients. Herein, we present our cases and surgical techniques for PV wedge resection with patch venoplasty using autologous vein grafts during surgery for pancreatic ductal adenocarcinoma (PDAC) and perihilar cholangiocarcinoma (PhCC). CASE PRESENTATION: Case 1: 73-year-old female patient with PDAC; underwent subtotal stomach-preserving pancreatoduodenectomy, with superior mesenteric vein wedge resection and venoplasty with the right gonadal vein. Case 2: 67-year-old male patient with PDAC; underwent distal pancreatectomy and celiac axis resection, with PV wedge resection and venoplasty with the middle colic vein. Case 3: 51-year-old female patient with type IV PhCC; underwent left hepatectomy with caudate lobectomy and bile duct resection, with hilar PV wedge resection and venoplasty with the inferior mesenteric vein (IMV). Case 4: 69-year-old male patient with type IIIA PhCC; underwent right hepatopancreatoduodenectomy, with hilar PV resection and patch venoplasty with the IMV. All patients survived for over 12 months after the surgery, without local recurrence. CONCLUSIONS: PV wedge resection and patch venoplasty is a useful technique for obtaining tumor-free margins in surgeries for hepatobiliary-pancreatic cancer.

Prognostic value of a novel index combining the prognostic nutritional index and D-dimer levels for gastric cancer after gastrectomy.

INTRODUCTION: The prognostic nutritional index and D-dimer level are two useful measures for gastric cancer prognosis. Since they each comprise different factors, it is possible to employ a more useful combined indicator. This study therefore aimed to establish a prognostic nutritional index-D score-which combines the prognostic nutritional index and D-dimer level-and validate its usefulness as a prognostic marker. METHODS: We collected data from 1,218 patients with gastric cancer who had undergone radical gastrectomy (R0) between January 2004 and December 2015. Patients were divided into three prognostic nutritional index-D score groups based on the following criteria: score 2, low prognostic nutritional index (≤46) and high D-dimer levels (>1.0 µg/ml); score 1, either a low prognostic nutritional index or high D-dimer levels; and score 0, no abnormality. We then defined the PNI-D score as low (score 0 or 1) and high (score 2). RESULTS: The prognostic nutritional index-D score was significantly associated with overall, recurrence-free, and disease-specific survival (all log-rank P<0.0001). The 5-year overall survival rates of the patients with prognostic nutritional index-D scores of low and high were 88.1% and 64.7%, respectively; their 5-year recurrence-free survival rates were 86.7% and 61.3%, respectively; and their 5-year disease-specific survival rates were 99.3% and 76.5%, respectively. Cox multivariate analysis revealed that a high prognostic nutritional index-D score was an independent, statistically significant prognostic factor for poor overall (P=0.01) survival in the patients with gastric cancer. CONCLUSIONS: The prognostic nutritional index-D is an independent prognostic factor for patients with gastric cancer.

Adjuvant Chemotherapy With S-1 Plus Docetaxel Versus S-1 Plus Oxaliplatin in Stage III Gastric Cancer.

BACKGROUND/AIM: The Japanese Gastric Cancer Treatment Guidelines recommend doublet chemotherapy (S-1 plus another chemotherapy) over S-1 alone for patients with pStage III gastric cancer who underwent radical gastrectomy. However, no consensus exists on adjuvant regimens for patients with pStage III gastric cancer. Therefore, we conducted a comparative study to evaluate the tolerability, safety, and survival outcomes of docetaxel plus S-1 (DS) and S-1 plus oxaliplatin (SOX) therapies as adjuvant chemotherapy for patients with pStage III gastric cancer. PATIENTS AND METHODS: We retrospectively collected data from consecutive patients with gastric cancer who underwent gastrectomy and received DS or SOX therapies postoperatively at the Osaka International Cancer Institute between December 2016 and December 2021. We conducted a propensity score matching analysis to balance clinical backgrounds. RESULTS: Eighty patients who met the eligibility criteria were analyzed. After matching, 40 patients were included in the study (20 each in the DS and SOX groups). No significant adverse events were observed. The mean ratios of the delivered dose to the planned dose were 74.1% and 86.6% for S-1 and docetaxel in the DS group, respectively, and 75.8% and 76.9% for S-1 and oxaliplatin in the SOX group, respectively. No significant differences were found in recurrence-free and overall survival between the DS and SOX groups (p=0.688 and p=0.772, respectively). CONCLUSION: DS and SOX therapies as adjuvants were safe and manageable for patients with pStage III gastric cancer who underwent radical gastrectomy. No significant differences were found in prognosis between the two therapies.

Metastases and treatment-resistant lineages in patient-derived cancer cells of colorectal cancer.

Circulating tumor cells (CTCs) play an important role in metastasis and recurrence. However, which cells comprise the complex tumor lineages in recurrence and are key in metastasis are unknown in colorectal cancer (CRC). CRC with high expression of POU5F1 has a poor prognosis with a high incidence of liver metastatic recurrence. We aim to reveal the key cells promoting metastasis and identify treatment-resistant lineages with established EGFP-expressing organoids in two-dimensional culture (2DOs) under the POU5F1 promotor. POU5F1-expressing cells are highly present in relapsed clinical patients' blood as CTCs. Sorted POU5F1-expressing cells from 2DOs have cancer stem cell abilities and abundantly form liver metastases in vivo. Single-cell RNA sequencing of 2DOs identifies heterogeneous populations derived from POU5F1-expressing cells and the Wnt signaling pathway is enriched in POU5F1-expressing cells. Characteristic high expression of CTLA4 is observed in POU5F1-expressing cells and immunocytochemistry confirms the co-expression of POU5F1 and CTLA4. Demethylation in some CpG islands at the transcriptional start sites of POU5F1 and CTLA4 is observed. The Wnt/ß-catenin pathway inhibitor, XAV939, prevents the adhesion and survival of POU5F1-expressing cells in vitro. Early administration of XAV939 also completely inhibits liver metastasis induced by POU5F1-positive cells.

Clinicopathological characteristics and survival outcomes in patients with advanced esophageal squamous cell carcinoma who were intraoperatively diagnosed non-curative.

INTRODUCTION: Curative esophagectomy is not always possible in patients with locally advanced esophageal cancer. However, few studies have investigated patients who underwent non-curative surgery with intraoperative judgment. This study aimed to investigate patient characteristics and clinical outcomes for patients undergoing non-curative surgery and compare them between non-resectional and non-radical surgery. METHODS: Among 989 consecutive patients with thoracic esophageal squamous cell carcinoma (ESCC) who were preoperatively expected for curative esophagectomy, 66 who were eligible for non-curative surgery were included in this study. RESULTS: Intraoperative diagnosis of T4b accounted for 93% of the reasons for the failure of curative surgery. In those patients, esophageal cancer locally invaded into the aortobronchial constriction (70%), trachea (25%), or pulmonary vein (5%). LN metastasis mainly invaded into the trachea (50%), or bronchus (28%).The overall survival of patients with non-curative surgery was 51.5%, 25.7%, and 10.4% at 6, 12, and 24 months after surgery, respectively. Although there were no differences in preoperative patient characteristics between non-resectional and non-radical surgery, distant metastasis, especially pleural dissemination, was significantly observed in T4b patients due to esophageal cancer with non-radical surgery than those with non-resectional surgery (35% vs. 15%, P=0.002). Even in patients with non-curative surgery, R1 resection and postoperative CRT were identified as independent factors for survival 1 year after surgery (P=0.047, and 0.019). CONCLUSIONS: T4b tumor located in aortobronchial constriction or trachea/bronchus makes it difficult to diagnose whether it is resectable or unresectable. Moreover, surgical procedures and perioperative treatment were deeply associated with the clinical outcomes.

Robotic-assisted colectomy for right-sided colon cancer: Short-term surgical outcomes of a multi-institutional prospective cohort study in Japan.

Background: In Japan, there are no substantial reports on robotic-assisted colectomy because few institutions performed the procedure, as it was not covered by national insurance until March 2022. Aim: This study aimed to evaluate the safety and feasibility of robotic-assisted colectomy for patients with curatively resectable colon cancer in Japan. Methods: This multi-institutional, prospective, single-arm, observational study enrolled patients diagnosed with curatively resectable clinical stage I-IIIC colon adenocarcinoma with D2 or D3 lymph node dissection and treated with robotic-assisted colectomy. The primary endpoint was the conversion rate to laparotomy. The non-inferiority of outcomes for robotic-assisted colectomy versus laparoscopic colectomy, which was determined from historical data, was verified. Results: One hundred patients were registered between July 2019 and March 2022 and underwent robotic-assisted colectomy performed by seven expert surgeons at six institutions. Thirteen patients were excluded because their surgeons had insufficient experience performing robotic-assisted colectomy; therefore, 87 patients were eligible for the primary endpoint analysis. There was no conversion in these 87 patients, and robotic-assisted colectomy was non-inferior to laparoscopic colectomy in terms of conversion rate (90% confidence interval 0-3.38, p = 0.0006). No intraoperative adverse events occurred, and no mortality was observed in a total of 100 patients. The rate of patients with Clavien-Dindo complications grade III or higher was 4%. Conclusion: This study showed the non-inferiority of the conversion rates between robotic-assisted colectomy and laparoscopic colectomy. Favorable perioperative outcomes also suggest the safety and feasibility of robotic-assisted colectomy.

Preoperative D-dimer Value and Lower Limb Venous Ultrasound for Deep Venous Thrombosis Prevents Postoperative Symptomatic Venous Thromboembolism in Patients Undergoing Colorectal Surgery: A Retrospective Study.

Objectives: Preoperative deep venous thrombosis (DVT) can cause potentially life-threatening postoperative venous thromboembolism (VTE). Lower limb venous ultrasound (LLVU) is a modality that can detect DVT. However, the threshold for performing preoperative LLVU in the population undergoing colorectal resection is controversial. In this context, we evaluated whether a preoperative D-dimer value can identify patients who benefit from LLVU from the perspective of preventing postoperative symptomatic VTE. Methods: Patients undergoing colorectal resection in our institute from 2013 to 2020 were retrospectively enrolled (n=2071). We divided the patients into two groups: the clinical indication group (CG: including patients from 2013 to 2016, n=875) and the D-dimer-orientated group (DG: including patients from 2017 to 2020, n=1196). In the CG, LLVU was performed when DVT was clinically suspected; in the DG, preoperative LLVU was performed in patients with a preoperative D-dimer>1.0 µg/ml. Results: In the surveyed period, 277 LLVUs were performed, among which DVT was detected in 34 cases (12.3%). In the CG, DVT was detected in 0.7% of patients, whereas in the DG, it was detected in 2.3% of patients. Postoperative symptomatic VTE was significantly reduced in the DG at both 3 and 6 months after surgery (p=0.041 and 0.020, respectively). Moreover, Multivariate analysis showed that a past medical history of PE and treatment following the CG protocol were independent risk factors for postoperative symptomatic VTE within 6 months of surgery (p<0.0001 and =0.036, respectively). Conclusions: LLVU in patients with a preoperative D-dimer>1.0 µg/ml is a useful method to prevent postoperative symptomatic VTE.

Modified Collard technique is more effective than circular stapled for cervical esophagogastric anastomosis in prevention of anastomotic stricture: a propensity score-matched study.

The anastomotic technique after esophagectomy is of great interest in the prevention of anastomotic complications that adversely affect postoperative recovery. This study aimed to compare the clinical outcomes of modified Collard (MC) and circular stapled (CS) anastomoses after esophagectomy. A total of 504 consecutive patients with thoracic esophageal cancer who underwent esophagectomy and cervical esophagogastric CS or MC anastomosis from January 2013 to December 2019 were enrolled. Out of 504 patients, 134 and 370 underwent CS and MC anastomoses. The frequency of anastomotic leakage and stricture was significantly lesser in the MC group than in the CS group (3.0 vs. 10.5%, P = 0.0014 and 11.1 vs. 34.3%, P < 0.001, respectively). CS anastomosis was an independent risk factor for anastomotic stricture (odds ratio, 4.89; P < 0.001). Oral intake was significantly higher in the group without anastomotic stricture than in the group with anastomotic stricture at 2, 3, and 6 months postoperatively (P < 0.001, P = 0.013, and P < 0.001, respectively). The percentage body weight loss (%BWL) was -12.2% in the group with anastomotic stricture and -7.5% in the group without anastomotic stricture at 3 months postoperatively (P = 0.0012). Anastomotic stricture was an independent factor associated with %BWL (odds ratio, 4.86; P = 0.010). Propensity score-matched analysis, which included 88 pairs of patients, confirmed a significantly lower anastomotic stricture rate in the MC group than in the CS group (10.2 vs. 35.2%, P < 0.001). MC anastomosis is better than CS anastomosis for reducing the frequency of anastomotic stricture, which may be useful for maintaining early postoperative nutritional status.

Tumor Deposit Is an Independent Factor Predicting Early Recurrence and Poor Prognosis in Gastric Cancer.

BACKGROUND: Accurate prognostic estimation is crucial; however, the prognostic value of tumor deposits in gastric cancer remains controversial. This study aimed to investigate their prognostic significance. METHODS: Clinicopathological and prognostic data of 1012 gastric cancer patients who underwent R0 or R1 surgery from 2010 to 2017 at the Osaka International Cancer Institute were retrospectively reviewed. RESULTS: Overall, 6.3% patients had tumor deposits, which were associated with Borrmann type, surgical procedure, type of gastrectomy, extent of lymphadenectomy, tumor size, histology, pT, pN, pM, pStage, lymphatic invasion, vascular invasion, preoperative chemotherapy, and postoperative chemotherapy. Tumor deposit-positive patients had worse 5-year disease-free survival (32.60% vs. 92.45%) and overall survival (41.22% vs. 89.37%) than tumor deposit-negative patients. Subgroup analysis regarding pStage II-III also showed significant differences between patients with and without tumor deposits for 5-year disease-free survival (34.15% vs. 80.98%) and overall survival (43.17% vs. 75.78%). Multivariable analysis showed that older age, undifferentiated histology, deeper tumor invasion, lymph node metastasis, distant metastasis, and presence of tumor deposits were significantly correlated with early tumor recurrence and shorter survival time; these factors were identified as independent prognostic factors. The 5-year disease-free survival of tumor deposit-positive patients was significantly worse than that of patients in the pStage III group and comparable to that of patients in the pT4, pN3, and pM1 groups. The 5-year overall survival of tumor deposit-positive patients was comparable to that of the pT4, pN3, pM1, and pStage III groups. CONCLUSIONS: Tumor deposits are strong and independent predictors of tumor recurrence and poor survival.

Phase II dose titration study of regorafenib in progressive unresectable metastatic colorectal cancer.

Regorafenib has shown significant survival benefit as a salvage therapy for colorectal cancer; however, its starting dose has been controversial in recent studies. Therefore, we conducted a prospective study on the efficacy and safety of the dose reduction of regorafenib to 120 mg. Patients received 120 mg regorafenib once per day for 3 weeks, followed by a 1-week off-treatment period. The primary endpoint was the investigator-assessed disease control rate (DCR). Sixty patients were registered, and the DCR was 38.3% with a median progression-free survival of 2.5 months (95% confidence interval [CI] 1.9-3.7) and median overall survival of 10.0 months (95% CI 6.9-15.2). Common grade 3-4 adverse events were hand-foot skin reaction and hypertension (20.0% each). The results of administration of 120 mg regorafenib as the starting dose are consistent with reports from prior phase III trials, which used starting doses of 160 mg. This lower initiating dose of regorafenib may be beneficial to certain patient populations. This clinical trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR number UMIN000018968, registration date: 10/09/2015).

A phase II study of neoadjuvant capecitabine, oxaliplatin, and irinotecan (XELOXIRI) in patients with locally advanced rectal cancer.

Purpose: Addition of perioperative multi-agent chemotherapy to the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. We conducted a phase II study to evaluate the safety and efficacy of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as triplet neoadjuvant chemotherapy in patients with LARC. Methods: Patients received neoadjuvant irinotecan and oxaliplatin and capecitabine and then underwent total mesorectal excision. The primary study endpoint was the pathological complete response (pCR) rate. Results: Between June 2013 and December 2016, 55 patients were enrolled in the study. Forty-two (77.8%) of 54 completed the study protocol. The pCR rate was 7.7% (95% CI 3.0% to 18.2%). The 3-year local recurrence rate was 3.9%, the 3-year disease-free survival (DFS) rate was 77.3, and the 3-year overall survival rate was 96.0%. Conclusion: XELOXIRI neoadjuvant chemotherapy appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate, the local recurrence rate, 3-year DFS, and measures of safety met current standards.

DUPAN-II normalisation as a biological indicator during preoperative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19-9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT). METHODS: This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured. RESULTS: Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03-4.24, p = 0.042). Total normalisation ratio was 49% (n = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p = 0.039). CONCLUSION: Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis.

The utility of bile juice culture analysis for the management of postoperative infection after pancreaticoduodenectomy.

BACKGROUND: Surgical site infections are common after pancreaticoduodenectomy. Our institution routinely performs intraoperative bile culture with pancreaticoduodenectomy. Herein we examined whether antibiotic selection based on bile culture analysis reduced the surgical site infection risk after pancreaticoduodenectomy. METHODS: A total of 349 patients underwent pancreaticoduodenectomy with intraoperative bile cultures in our institution between 2008 and 2019. Patients were categorized into "group A" (196 patients who underwent pancreaticoduodenectomy between 2008 and 2013) or "group B" (153 patients who underwent pancreaticoduodenectomy between 2018 and 2019). Group A received cefazoline perioperatively and for 2 days postoperatively, whereas group B received piperacillin-tazobactam instead based on the bile culture findings in group A. RESULTS: In group A, 91 (46.4%) intraoperative bile cultures were positive, and surgical site infections occurred in 61 patients (31.1%). A total of 32 patients had both positive bile culture and surgical site infection, of whom 23 (71.9%) exhibited the same microorganisms in the biliary and surgical site infection cultures. Due to the common finding of cefazoline-resistant Enterococcus spp. and Enterobacter spp. in group A, group B received piperacillin-tazobactam. Surgical site infection incidence in group B was 18.3% (n = 28), which was significantly lower than in group A (P = .006). Cefazoline-resistant Enterococcus spp. and Enterobacter spp., respectively, were cultured in 69.8% and 24.3% of patients with preoperative biliary drainage, compared with 32.2% and 9.7% of patients without preoperative biliary drainage. CONCLUSION: The perioperative selection of antibiotics based on bile culture findings at pancreaticoduodenectomy can reduce the incidence of surgical site infection.

Safety and efficacy of preoperative indocyanine green fluorescence marking in laparoscopic gastrectomy for proximal gastric and esophagogastric junction adenocarcinoma (ICG MAP study).

PURPOSE: The incidence of adenocarcinoma of the esophagogastric junction (AEG) and proximal gastric cancer (PGC) is rising worldwide. Recently, the use of indocyanine green (ICG) tracer-guided surgery has been reported; however, its efficacy for total/proximal gastrectomy has not been clarified. We evaluated the feasibility and safety of ICG fluorescent marking for tumor localization in AEG/PGC treatment by laparoscopic surgery. METHODS: We enrolled patients with AEG/PGC from October 2016 to March 2019 from a prospectively registered database. On the day before surgery, ICG markings were made at four locations just at the edge of the tumor by gastrointestinal fiberscope examination. Surgery was performed while viewing the fluorescence image of ICG, and the proximal portions of the esophagus and the distal portion of the stomach were resected at the edge of the area where ICG had spread. RESULTS: We enrolled 130 patients with AEG/PGC. Overall, 107 patients were eventually included in the study: AEG n = 64 (60%) and PGC n = 43 (40%). ICG markings were detected intraoperatively in all cases, and cancer invasion into the resection lines of the esophagus and stomach, performed based on ICG fluorescence images, was negative in all cases. The median visible range of ICG fluorescence was 22.5 mm. ICG diffusion expanded 20 mm proximal for AEG. There were no adverse events associated with endoscopic ICG injection. CONCLUSION: ICG fluorescence imaging is feasible and safe and can potentially be used as a tumor-marking agent for determining the surgical resection line for total/proximal gastrectomy in AEG and PGC treatment.

Recurrence Pattern Comparing Preoperative Chemoradiotherapy and Preoperative Chemotherapy with Docetaxel plus 5-Fluorouracil and Cisplatin for Advanced Esophageal Cancer.

BACKGROUND: Preoperative chemoradiation therapy (CRT) or chemotherapy (CT) followed by surgery is currently being administered for advanced esophageal cancer. However, few studies have directly compared CRT and CT for treating locally advanced esophageal carcinoma. This study aimed to assess postoperative recurrence patterns and post-recurrence outcomes in patients with radical esophagectomy after CRT or triplet CT regimen with docetaxel, cisplatin, and 5-fluorouracil (DCF). METHODS: This study included 325 consecutive patients with thoracic esophageal cancer who received preoperative CRT or DCF followed by curative esophagectomy between January 2010 and December 2019. We compared recurrence patterns after surgery and post-recurrence treatments between CRT and DCF. Locoregional recurrence was defined as recurrences at the primary tumor site or regional lymph nodes. Distant recurrence was defined as non-regional lymph node recurrences, systemic metastases, malignant pleural effusions, or peritoneal metastases. RESULTS: Among 325 patients, 74 received preoperative CF + RT and 251 received preoperative DCF. A propensity score-matched cohort of 53 with CRT and 53 with DCF was included. CRT patients had tumors located in the upper esophagus and had more advanced cancer than DCF patients; however, no differences in patient characteristics were observed in the matched cohort. CRT patients had better histopathological responses and control of locoregional recurrence than DCF patients. On the other hand, distant recurrence, especially in the non-regional lymph node, lung, and pleural dissemination, significantly developed more frequently in CRT patients. Furthermore, CRT patients may have received insufficient post-recurrence treatment, owing to fewer treatment options. Therefore, although there was no difference in recurrence rate in the two groups, CRT patients had significantly poorer post-recurrence survival than DCF patients. CONCLUSIONS: Preoperative DCF could reduce distant recurrence after surgery compared to preoperative CRT. The differences in recurrence patterns can be related to the selection of post-recurrence treatment and their prognosis after recurrence.

Combined Inflammation and Nutrition Factors Reinforce the Prognostic Prediction for Stage III Colorectal Cancer Patients.

BACKGROUND/AIM: Previous studies have shown that postoperative adjuvant chemotherapy improves overall survival in patients with stage III colorectal cancer (CRC). However, adjuvant chemotherapy may not be necessary for some patients. This study aimed to develop a new nutritional-inflammation score, which would be useful in identifying a favorable prognosis group among stage III CRC patients. PATIENTS AND METHODS: This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and a new prognostic model was developed. RESULTS: Multivariate analyses in TS revealed that lymph node metastasis (N2) (p=0.002), low albumin (p=0.017), high monocyte counts (p=0.008), and low platelet counts (p=0.018) were independent risk factors for disease free survival (DFS). The Kansai prognostic score (KPS) was assessed by 1 point each for <3.5 g/dl albumin level, >450 monocyte counts, and <1.65×105 platelet counts. Using KPS, DFS and overall survival (OS) were validated in VS. The C-indices of KPS to predict DFS and OS in TS were 0.707 and 0.772. It was validated in VS that the C-indices of KPS to predict DFS and OS were 0.618 and 0.708, respectively. A high KPS was a significant predictor of DFS and OS. CONCLUSION: KPS serves as a new model for the prognosis of patients with stage III CRC.

The DOLFIN method: a novel laparoscopic Billroth-I gastroduodenostomy for gastric cancer with duodenal invasion.

BACKGROUND: Laparoscopic Billroth-I gastroduodenostomy using a delta-shaped anastomosis is safe and feasible. However, it is often difficult to perform in patients who have a short posterior wall of the duodenum. Thus, we have developed a new method named duodenal overlap functional anastomosis with linear stapler (DOLFIN). We hereby report the technical details of the new method and our preliminary experience performing it. METHODS: After the completion of lymphadenectomy, the duodenum was transected craniocaudally with an endoscopic linear stapler. The hepatoduodenal mesentery was dissected approximately 4 cm along the duodenal bulb, and the anastomosis between the posterior wall of the stomach and the lesser curvature of the duodenum was created. The common entry hole was then transected using an endoscopic linear stapler, and the anastomosis was finally completed. RESULTS: There were 36 patients with gastric cancer who underwent laparoscopic distal gastrectomy (LDG) or robotic distal gastrectomy (RDG) with B-I reconstruction using DOLFIN. There were no postoperative complications classified as C-D grade 3 or more and complications related to anastomosis, such as anastomotic leak or stenosis. CONCLUSIONS: Our DOLFIN gastroduodenostomy can be performed safely. In addition, it results in good postoperative outcomes. A long-term comparative study is required to further evaluate the clinical usefulness of this method.

PLXND1/SEMA3E Promotes Epithelial-Mesenchymal Transition Partly via the PI3K/AKT-Signaling Pathway and Induces Heterogenity in Colorectal Cancer.

Colorectal cancer (CRC) is a major cause of cancer-related deaths. Metastasis is enhanced through epithelial-mesenchymal transition (EMT), a process primarily induced by the transforming growth factor beta (TGF-ß)-mediated canonical Smad pathway. This study focused on plexin D1 (PLXND1), a chemoreceptor for the ligand SEMA3E to mechanosensory, showing that PLXND1 induces EMT via activation of the PI3K/AKT pathway in CRC cells. The findings showed that PLXND1-knockdown decreases cell migration and invasion significantly, and that the binding of p61-SEMA3E to the PLXND1 enhances the invasiveness and migration through EMT. Furin inhibitor suppresses EMT, decreasing cell migration and invasion. Furin cleaves full-length SEMA3E and converts it to p61-SEMA3E, suggesting that furin inhibitors block PLXND1 and p61-SEMA3E binding. Furin is a potential therapeutic target for the purpose of suppressing EMT by inhibiting the binding of p61-SEMA3E to PLXND1. In vivo experiments have shown that PLXND1-knockdown suppresses EMT. Mesenchymal cells labeled with ZEB1 showed heterogeneity depending on PLXND1 expression status. The high-expression group of PLXND1 in 182 CRC samples was significantly associated with poor overall survival compared with the low-expression group (P = 0.0352, median follow-up period of 60.7 months) using quantitative real-time polymerase chain reaction analysis. Further research is needed to determine whether cell fractions with a different expression of PLXND1 have different functions.

Laparoscopic Proximal Gastrectomy with Novel Valvuloplastic Esophagogastrostomy vs. Laparoscopic Total Gastrectomy for Stage I Gastric Cancer: a Propensity Score Matching Analysis.

BACKGROUND: Laparoscopic total gastrectomy for early proximal gastric cancer is widely performed. Recently, the number of laparoscopic proximal gastrectomies performed, a surgery limited to early proximal gastric cancer, has gradually increased. However, evidence for the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy is insufficient. Therefore, this study aimed to clarify and compare the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy with novel valvuloplastic esophagogastrostomy for treatment of clinical stage I proximal gastric cancer. METHODS: This study included 111 patients who underwent laparoscopic total gastrectomy or laparoscopic proximal gastrectomy for the treatment of upper third clinical stage I gastric cancer between April 2004 and December 2017. After adjusting for propensity score matching analysis, we compared the postoperative complications, nutritional status, and long-term outcomes between the two groups. RESULTS: After matching the inclusion criteria, 56 patients (28 in each group) were enrolled. No significant differences were noted in the postoperative complications between the two groups. While laparoscopic proximal gastrectomy was associated with lower albumin levels, lower body weight loss was seen by 1 year after surgery and higher hemoglobin levels by 1, 2, and 3 years after surgery. No significant differences were observed in the 3-year overall survival and 3-year recurrence-free survival between the laparoscopic total gastrectomy and laparoscopic proximal gastrectomy groups (P = 0.74 and 0.72, respectively). CONCLUSION: Laparoscopic proximal gastrectomy and laparoscopic total gastrectomy for patients with upper third clinical stage I gastric cancer are feasible as regards its safety and outcomes.