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To investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC).Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear.In total, 1260 patients who underwent pancreatectomy with PV/SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42).Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3 V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 months vs. 30.9 months. p = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery (p = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups.PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.

The treatment strategies for colorectal cancer (CRC) must ensure a radical cure of cancer and prevent over/under treatment. Biopsy specimens used for the definitive diagnosis of T1 CRC were analyzed using artificial intelligence (AI) to construct a risk index for lymph node metastasis.A total of 146 T1 CRC cases were analyzed. The specimens for analysis were mainly biopsy specimens, and in the absence of biopsy specimens, the mucosal layer of the surgical specimens was analyzed. The pathology slides for each case were digitally imaged, and the morphological features of cancer cell nuclei were extracted from the tissue images. First, statistical methods were used to analyze how well these features could predict lymph node metastasis risk. A lymph node metastasis risk model using AI was created based on these morphological features, and accuracy in test cases was verified.Each developed model could predict lymph node metastasis risk with a 90% accuracy in each region of interest of the training cases. Lymph node metastasis risk was predicted with 81.8-86.3% accuracy for randomly validated cases, using a learning model with biopsy data. Moreover, no case with lymph node metastasis or lymph node risk was judged to have no risk using the same model.AI models suggest an association between biopsy specimens and lymph node metastases in T1 CRC and may contribute to increased accuracy of preoperative diagnosis.

Recurrence of colon cancer is associated with time after curative surgery. This study aimed to construct novel nomograms to predict relapse-free survival (RFS) in stage II-III colon cancer, considering "time after surgery" and using various inflammatory and nutritional biomarkers.All 542 patients who underwent radical surgery for stage II-III colon cancer between January 2000 and August 2015 at our institute were retrospectively analyzed. Time-dependent receiver operating characteristic curves and cutoff values were obtained for neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio, platelet-lymphocyte ratio, Japanese modified Glasgow prognostic score (mGPS), C-reactive protein-albumin ratio (CAR), prognostic nutritional index, and controlling nutritional status (CONUT) for each postoperative period (1 - 5 years). We used Cox proportional hazard analyses to evaluate independent risk factors and to construct nomograms in each period.We obtained a good accuracy in NLR, CAR, mGPS, and CONUT (area under the curve0.5). NLR was the only preoperative independent risk factor, except age, in multivariate analysis. We constructed the nomograms and obtained a good discrimination value of the concordance index in each period (0.75).Using inflammatory and nutritional biomarkers, we established and calibrated novel nomograms for predicting time-dependent RFS for stage II-III colon cancer patients.

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) predict the effects of fluoropyrimidine. However, the effects of FOLFOX therapy from the perspective of fluorouracil plus leucovorin (FL) remain underexplored. Hence, the relationship between mFOLFOX6 therapy (mFOLFOX6) and therapeutic efficacy was evaluated in patients with advanced/recurrent colorectal cancer (CRC).Correlations between TS and DPD and primary and metastatic lesions in recurrent CRC were analyzed. Univariate and multivariate analyses of TS and DPD in combination with response rate (RR), progression-free survival (PFS), and overall survival (OS) were performed.A positive correlation between DPD and primary and metastatic lesions; correlations between TS and RR, DPD and RR, and PFS and OS; and significant differences for RR and DPD and TS, PFS and DPD, and OS and DPD were obtained.Nucleic acid metabolizing enzymes in primary lesions can be used to predict mFOLFOX6 efficacy in patients with recurrent CRC.

Background: Early detection is essential to improve the outcome of patients with pancreatic cancer. A noninvasive and cost-effective diagnostic test using plasma/serum biomarkers would facilitate the detection of pancreatic cancer at the early stage.Methods: Using a novel combination of hollow fiber membrane–based low-molecular-weight protein enrichment and LC-MS-based quantitative shotgun proteomics, we compared the plasma proteome between 24 patients with pancreatic cancer and 21 healthy controls (training cohort). An identified biomarker candidate was then subjected to a large blinded independent validation (n = 237, validation cohort) using a high-density reverse-phase protein microarray.Results: Among a total of 53,009 MS peaks, we identified a peptide derived from CXC chemokine ligand 7 (CXCL7) that was significantly reduced in pancreatic cancer patients, showing an area under curve (AUC) value of 0.84 and a P value of 0.00005 (Mann–Whitney U test). Reduction of the CXCL7 protein was consistently observed in pancreatic cancer patients including those with stage I and II disease in the validation cohort (P < 0.0001). The plasma level of CXCL7 was independent from that of CA19-9 (Pearson's r = 0.289), and combination with CXCL7 significantly improved the AUC value of CA19-9 to 0.961 (P = 0.002).Conclusions: We identified a significant decrease of the plasma CXCL7 level in patients with pancreatic cancer, and combination of CA19-9 with CXCL7 improved the discriminatory power of the former for pancreatic cancer.Impact: The present findings may provide a new diagnostic option for pancreatic cancer and facilitate early detection of the disease. Cancer Epidemiol Biomarkers Prev; 20(1); 160–71. ©2011 AACR.

Supplementary Material from Possible Prediction of Chemoradiosensitivity of Esophageal Cancer by Serum Protein Profiling

Supplementary Figures 1-3 from Reduced Plasma Level of CXC Chemokine Ligand 7 in Patients with Pancreatic Cancer

Supplementary Tables 1-2 from Reduced Plasma Level of CXC Chemokine Ligand 7 in Patients with Pancreatic Cancer

Purpose: An invasive growth pattern is one of the hallmarks of pancreatic ductal carcinoma. Actinin-4 is an actin-binding protein associated with enhanced cell motility, invasive growth, and lymph node metastasis. Actinin-4 might play an important role in the development and progression of pancreatic cancer.Experimental Design: The expression of actinin-4 was examined immunohistochemically in 173 cases of invasive pancreatic ductal carcinoma. The copy number of the actinin-4 (ACTN4) gene was calculated by fluorescence in situ hybridization. The expression of actinin-4 was stably knocked down by short hairpin RNA, and tumorigenicity was evaluated by orthotopic implantation into mice with severe combined immunodeficiency.Results: The expression level of actinin-4 was increased in 109 (63.0%) of 173 cases of pancreatic cancer. Kaplan-Meier survival curves revealed that patients with increased expression of actinin-4 had a significantly poorer outcome (P = 0.00001, log-rank test). Multivariate analysis by the Cox proportional hazard model showed that high expression of actinin-4 was the most significant independent negative predictor of survival (hazard ratio, 2.33; P = 0.000009). Amplification (defined as more than four copies per interphase nucleus) of the ACTN4 gene was detected in 11 (37.9%) of 29 cases showing increased expression of actinin-4. Knockdown of actinin-4 expression inhibited the destructive growth of cancer cells in the pancreatic parenchyma.Conclusion: Recurrent amplification of chromosome 19q13.1-2 has been reported in pancreatic cancer, but the exact target gene has not been identified. Actinin-4 contributes to the invasive growth of pancreatic ductal carcinoma, and ACTN4 is one of the candidate oncogenes in this chromosome locus.

Background: The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer.Methods: Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray.Results: From a total of 53,009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann–Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae.Conclusions: Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer.Impact: The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies. Cancer Epidemiol Biomarkers Prev; 20(10); 2195–203. ©2011 AACR.

Supplementary Data from Expression and Gene Amplification of Actinin-4 in Invasive Ductal Carcinoma of the Pancreas

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Purpose: Establishment of a reliable method of predicting the efficacy of chemotherapy and radiotherapy is necessary to provide the most suitable treatment for each cancer patient. We investigated whether proteomic profiles of serum samples obtained from untreated patients were capable of being used to predict the efficacy of combined preoperative chemoradiotherapy against esophageal cancer.Experimental Design: Proteomic spectra were obtained from a training set of 27 serum samples (15 pathologically diagnosed responders to preoperative chemoradiotherapy and 12 nonresponders) by surface-enhanced laser desorption and ionization coupled with hybrid quadrupole time-of-flight mass spectrometry. A proteomic pattern prediction model was constructed from the training set by machine learning algorithms, and it was then tested with an independent validation set consisting of serum samples from 15 esophageal cancer patients in a blinded manner.Results: We selected a set of four mass peaks, at 7,420, 9,112, 17,123, and 12,867 m/z, from a total of 859 protein peaks, as perfectly distinguishing responders from nonresponders in the training set with a support vector machine algorithm. This set of peaks (i.e., the classifier) correctly diagnosed chemoradiosensitivity in 93.3% (14 of 15) of the cases in the validation set.Conclusions: Recent mass spectrometric approaches have revealed that serum contains a large volume of information that reflects the microenvironment of diseased organs. Although a multi-institutional large-scale study will be necessary to confirm each component of the classifier, there is a subtle but definite difference in serum proteomic profile between responders and nonresponders to chemoradiotherapy.

Supplementary Table from Possible Prediction of Chemoradiosensitivity of Esophageal Cancer by Serum Protein Profiling

Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR.We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs).All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound.Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.

AIM: Anastomotic leakage (AL) in left-sided colorectal cancer is a serious complication, with an incidence rate of 6-18%. We developed a novel predictive model for AL in colorectal surgery with double-stapling technique (DST) anastomosis using auto-artificial intelligence (AI). PATIENTS AND METHODS: A total of 256 patients who underwent curative surgery for left-sided colorectal cancer between 2017 and 2021 were included. In addition to conventional clinicopathological factors, we included the type of circular stapler using DST, conventional double-row circular stapler (DCS) or EEA™ circular stapler with Tri-Staple™ technology, 28 mm Medium/Thick (Covidien, New Haven, CT, USA) which had triple-row circular stapler (TCS) as a covariate. Auto-AI software Prediction One (Sony Network Communications Inc.) was used to predict AL with 5-fold cross validation. Predictive accuracy was assessed using the area under the receiver operating characteristic curve. Prediction One also evaluated the 'importance of variables' (IOV) using a method based on permutation feature importance. RESULTS: The area under the curve of the AI model was 0.766. The type of circular stapler used was the most influential factor contributing to AL (IOV=0.551). CONCLUSION: This auto-AI predictive model demonstrated an improvement in accuracy compared to the conventional model. It was suggested that use of a TCS may contribute to a reduction in the AL rate.

Background/aim We aimed to investigate the prognosis of patients who received radiofrequency ablation (RFA) for liver metastases of unresectable colorectal cancer (CRC). Patients and methods We retrospectively compared 147 patients treated for CRC liver metastases, who underwent RFA (n=26), resection (n=92), and chemotherapy (n=29) between 2001 and 2021. Results RFA and chemotherapy were performed for unresectable or non-operable cases, and resection was performed for suitable cases. The median overall survival (OS) was 44.9, 49.5, and 11.6 months for patients who underwent RFA, resection, and chemotherapy, respectively. RFA led to a significantly shorter OS compared to resection (p=0.027) but to a longer OS compared to chemotherapy (p=0.003). The 5-year survival rates were 34.6% and 42.4% for patients who underwent RFA and resection, respectively (p=0.508). Conclusion RFA has the potential to achieve long-term survival or radical cure, even for unresectable or non-operable cases of CRC with liver metastasis.

A 83-year-old man was diagnosed with diffuse large B-cell lymphoma and scheduled for treatment. However, he developed abdominal pain, and computed tomography revealed a gastrointestinal perforation. Emergency surgery was performed, upon which we identified perforations in the small intestine, and we therefore performed resection of the small intestine. R-CHOP therapy was performed postoperatively, resulting in successful tumor shrinkage. Malignant lymphoma of the small intestine often causes intestinal perforations, and the prognosis of patients with perforations is unfavorable. We report a case of a patient with multiple intestinal perforations owing to malignant lymphoma of the small intestine, in whom minimal surgery was performed and intervention in the early postoperative period was successful.

AIM This study aimed to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in elderly patients with Stage I-III colon cancer for long-term oncologic outcomes. PATIENTS AND METHODS We retrospectively reviewed 175 patients aged >75 years who underwent radical surgery for Stage I-III colon cancer between 2000 and 2015 at our institute. Overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) were evaluated according to NLR values using propensity score analysis. Patients were allocated to the higher NLR (H-NLR) or the lower NLR (L-NLR) group with a cut-off value of 2.3, based on receiver operating characteristic curve. RESULTS Before case matching, there were significant differences between the two groups for CSS (p=0.023) and RFS (p

Introduction In recent years, a shortage of surgeons and anesthesiologists, particularly in regional hospitals, has become a social issue in Japan. In such hospitals, urgent surgery at night has been performed with difficulty. Therefore, we retrospectively assessed the outcomes of appendectomies for the patients visited at nighttime in our hospital categorized as a local university hospital. Methods A retrospective review was conducted on 82 patients of acute appendicitis presented to our hospital between 5:30 p.m. to 8:30 a.m., between January 2014 and April 2019. We compared patients who underwent urgent nighttime appendectomy (group A) and patients who underwent appendectomy during the daytime, or so-called short interval appendectomy (group B). The evaluated factors were preoperative characteristics (age, sex, body mass index, cardiopulmonary complications, laboratory data, body temperature, presence of the Blumberg sign, and CT findings), operation characteristics, and postoperative characteristics (surgical-site infection [SSI], complications, and length of hospital stay). Results Patients in group A were significantly younger than patients in group B. Patients in group A were significant more likely to experience an SSI. Discussion Patients diagnosed with acute appendicitis during the nighttime can undergo short interval appendectomy, which leads to a decreased risk of SSI, has no effect on length of hospital stay after surgery, and lessens medical staff burden.

Background: Noninferiority of the laparoscopic approach compared with open surgery for colon cancer treatment has remained controversial. In this study, we aimed to evaluate the long-term outcomes ...

Background This study assessed the efficacy and safety of biweekly trifluridine and tipiracil hydrochloride (TAS-102) with bevacizumab combination therapy for patients with metastatic colorectal cancer (mCRC). Patients and methods We included 19 patients with mCRC who received TAS-102 and bevacizumab combination therapy biweekly as third-line chemotherapy. The primary endpoint was progression-free survival. Results Patients had a median age of 73 years and most (73.4%) were men. The median progression-free and overall survival were 5.6 and 11.5 months, respectively. Five (26.3%) patients achieved a response and the disease control rate was 12/19 (63.1%). One patient (5.2%) experienced neutropenia grade 3 or more. The median time from baseline performance status 0/1 to worsening to 2 or more was 10.3 months. Conclusion Biweekly TAS-102 plus bevacizumab facilitates tumor shrinkage by reducing the incidence of grade 3 or more neutropenia, improving survival, and maintaining performance status. This combination may represent a treatment option for patients with late-stage mCRC receiving third- or later-line therapy.

BACKGROUND The Glissonean approach has been widely validated for both open and minimally invasive anatomic liver resection (MIALR). However, the possible advantages compared to the conventional hilar approach are still under debate. The aim of this systematic review was to evaluate the application of the Glissonean approach in MIALR. METHODS A systematic review of the literature was conducted on PubMed and Ichushi databases. Articles written in English or Japanese were included. From 2,390 English manuscripts evaluated by title and abstract, 43 were included. Additionally, 23 out of 463 Japanese manuscripts were selected. Duplicates were removed, including the most recent manuscript. RESULTS The Glissonean approach is reported for both major and minor MIALR. The 1st, 2nd and 3rd order divisions of both right and left portal pedicles can be reached following defined anatomical landmarks. Compared to the conventional hilar approach, the Glissonean approach is associated with shorter operative time, lower blood loss, and better peri-operative outcomes. CONCLUSIONS Glissonean approach is safe and feasible for MIALR with several reported advantages compared to the conventional hilar approach. Clear knowledge of Laennec's capsule anatomy is necessary and serves as a guide for the dissection. However, the best surgical approach to be performed depends on surgeon experience and patients' characteristics. Standardization of the Glissonean approach for MIALR is important.

Purpose In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). Methods A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). Results A total of 3,372 studies were obtained, and 59 were selected and reviewed. Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction of HV exposure, 32 articles focused on the techniques and advantages of exposing HVs from either the root or the periphery. Ten articles focused on the techniques to perform a segmentectomy 8 in particularly difficult cases of MIALR. In seven articles, bleeding control from HVs was also discussed. Conclusions This review may help experts reach a consensus regarding the best approach to the management of hepatic veins during MIALR.

BACKGROUND Minimally invasive distal pancreatectomy (MIDP) is increasingly performed worldwide; however, the surgical anatomy required to safely perform MIDP has not yet been fully considered. This review evaluated the literature concerning peripancreatic vascular anatomy, which is considered important to conduct safe MIDP. METHODS A database search of PubMed and Ichushi (Japanese) was conducted. Qualified studies investigating the anatomical variations of peripancreatic vessels related to MIDP were evaluated using SIGN methodology. RESULTS Of 701 articles yielded by our search strategy, 76 articles were assessed in this systematic review. The important vascular anatomy required to recognize MIDP included the pancreatic parenchymal coverage on the root and the running course of the splenic artery, branching patterns of the splenic artery, confluence positions of the left gastric vein and the inferior mesenteric vein, forms of pancreatic veins including the centro-inferior pancreatic vein, characteristics of the left renal vein, and collateral routes perfusing the spleen following Warshaw's technique. Very few articles evaluating the relationship between the anatomical variations and surgical outcomes of MIDP were found. CONCLUSIONS The precise knowledge of peripancreatic vessels is important to adequately complete MIDP. More detailed anatomic analyses and descriptions will benefit surgeons and their patients who are facing these operations.

Background In preparation for the upcoming consensus meeting in Tokyo in 2021, this systematic review aimed to analyze the current available evidence regarding surgical anatomy of the liver, focusing on useful landmarks, strategies and technical tools to perform precise anatomic liver resection (ALR). Methods A systematic review was conducted on MEDLINE/PubMed for English articles and on Ichushi database for Japanese articles until September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). Results A total of 3169 manuscripts were obtained, 1993 in English and 1176 in Japanese literature. Subsequently, 63 English and 20 Japanese articles were selected and reviewed. The quality assessment of comparative series and case series was revealed to be usually low; only six articles were qualified as high quality. Forty-two articles focused on analyzing intersegmental/sectional planes and their relationship with specific hepatic landmark veins. In 12 articles, the authors aimed to investigate liver surface anatomic structures, while 36 articles aimed to study technological tools and contrast agents for surgical segmentation during ALR. Although Couinaud's classification has remained the cornerstone in daily diagnostic/surgical practices, it does not always portray the realistic liver segmentation and there has been no standardization on which a single strategy should be followed to perform precise ALR. Conclusions A global consensus should be pursued in order to establish clear guidelines and proper recommendations to perform ALR in the era of minimally invasive surgery.

BACKGROUND/AIM To identify prognostic factors for patients with stage IV gastric cancer (GC) and a single stage IV factor before chemotherapy who underwent conversion surgery (R0 resection). PATIENTS AND METHODS This study retrospectively analysed 32 GC patients with a single stage IV factor before chemotherapy and who underwent conversion surgery (R0 resection) between January 2001 and September 2015. The univariate and multivariate analyses were performed to identify independent prognostic factors. RESULTS The five-year survival rate was 39.6%, and the median survival time was 47.0 months. In the univariate analysis, diffuse-type according to Lauren classification was significantly associated with worse overall survival (p

To assess the utility of the Glasgow Prognostic Score (GPS) obtained before curative resection for predicting outcomes in patients with advanced gastric cancer (GC). This study retrospectively analyzed the outcomes of 337 consecutive patients with GC who underwent curative surgery for locally advanced gastric cancer between January 2003 and June 2014. GPS was assessed within 4 days prior to surgery. The number of patients with GPS scores of 0, 1, and 2 was 302, 26, and 9, respectively. There was significantly more blood loss during surgery and more postoperative complications in the GPS 1/2 group than in the GPS 0 group. Patients in the GPS 1/2 group had significantly poorer overall survival than those in the GPS 0 group (p = 0.001). On multivariate analysis, GPS 1/2 was identified as an independent factor for poor survival (p = 0.019). GPS before curative resection might be a useful predictive factor for perioperative complications and survival in locally advanced GC.