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Background: Survival in patients with retroperitoneal liposarcoma (RPLS) depends on the surgical management of the dedifferentiated foci. The present study investigated the diagnostic yield of contrast-enhanced CT, 18F-fluorodeoxyglucose positron emission tomography (PET), and diffusion-weighted MRI in terms of dedifferentiated foci within the RPLS. Methods: Patients treated with primary or recurrent RPLS who underwent the above imaging between January 2010 and December 2021 were retrospectively reviewed. The diagnostic accuracy of the three modalities for histologic subtype of dedifferentiated liposarcoma (DDLS) and French Federation of Cancer Center (FNCLCC) grade 2/3 were compared using receiver operating characteristic curves and areas under the curves (AUCs). Results: The cohort involved 32 patients with 53 tumors; 30 of which exhibited DDLS and 31 of which did FNCLCC grades 2/3. The optimal thresholds for predicting DDLS were mean CT value of 31 Hounsfield Unit (HU) (AUC = 0.880, 95% CI 0.775–0.984; p

The aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status.Seventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0-1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately.The rates of traditional R0 (RM 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005).Narrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM.

Background Tranexamic acid (TXA) may reduce intraoperative blood loss, but it has not been investigated in pancreaticoduodenectomy (PD). Methods A pragmatic, multicentre, randomized, blinded, placebo-controlled trial was conducted. Adult patients undergoing planned PD for biliary, duodenal, or pancreatic diseases were randomly assigned to TXA or placebo groups. Patients in the TXA group were administered 1 g TXA before incision, followed by a maintenance infusion of 125 mg/h TXA. Patients in the placebo group were administered the same volume of saline as those in the placebo group. The primary outcome was blood loss during PD. The secondary outcomes included perioperative blood transfusions, operating time, morbidity, and mortality. Results Between September 2019 and May 2021, 218 patients were randomly assigned and underwent surgery (108 in the TXA group and 110 in the placebo group). Mean intraoperative blood loss was 659 ml in the TXA group and 701 ml in the placebo group (mean difference −42 ml, 95 per cent c.i. −191 to 106). Of the 218 patients, 202 received the intervention and underwent PD, and the mean blood loss during PD was 667 ml in the TXA group and 744 ml in the placebo group (mean difference −77 ml, 95 per cent c.i. −226 to 72). The secondary outcomes were comparable between the two groups. Conclusion Perioperative TXA use did not reduce blood loss during PD. Registration number jRCTs041190062 (https://jrct.niph.go.jp).

This study sought to define the impact of skeletal muscle mass and quality on postoperative outcomes in patients with perihilar cholangiocarcinoma.Patients who underwent major hepatectomy for perihilar cholangiocarcinoma were included. The normalized total psoas area (TPA) (psoas muscle index [PMI]) and average Hounsfield units of the TPA (psoas muscle density [PMD]) were measured using preoperative computed tomography images. The cohort was dichotomized using the following indices: sex-specific lowest tertile (low PMI and low PMD) and other (normal PMI and normal PMD). Intraoperative and postoperative outcomes were compared, focusing on PMI and PMD.A total of 456 patients were analyzed. The intraoperative blood loss (IBL) was 21.3 ml/kg in the low PMI group and 17.2 ml/kg in the normal PMI group (P = .008). Patients in the low PMI or PMD group experienced postoperative infectious complications more frequently than those in the other groups. The median survival time was 37.8 months in the low PMI group and 54.2 months in the normal PMI group (P = .027).PMI and PMD were closely associated with IBL and postoperative infectious complications. Additionally, PMI impacted long-term survival. These results suggest an importance of improving muscle mass and quality before surgery.

Standardized criteria for drain removal in hepatobiliary resection are lacking. Here, we evaluated the outcomes of delayed removal policy in this extended surgery.Patients undergoing hepatectomy with biliary reconstruction between 2012 and 2018 were retrospectively reviewed. The drains were removed on postoperative day (POD) 7 when the drainage fluid was grossly serous, biochemically normal, and negative for bacterial contamination as assessed by Gram staining; additionally, no abnormal fluid collection was confirmed by computed tomography. Clinically relevant abdominal complications (CRACs), including biliary leakage, pancreatic fistula or intra-abdominal abscess, served as the primary outcome measure.Among 374 study patients, surgical drains were removed in 166 (44.3%) patients who met the criteria. Of these patients, 16 (9.6%) patients subsequently required additional drainage due to CRAC. Drains were retained and exchanged in 208 (55.6%) patients who did not meet the criteria. Of these, exchanged drains were soon removed in 34 patients due to no signs of CRAC. The diagnostic ability of the criteria revealed 0.916 sensitivity, 0.815 specificity, and 0.866 accuracy.The four findings on POD 7 worked well as criteria for drain removal, and these criteria may be helpful in drain management after hepatobiliary resection.

Objective: Given the frequent adverse events with multidrug chemotherapy, not only the survival benefit but also the feasibility of using neoadjuvant chemotherapy to treat pancreatic cancer need to be clarified. Summary of Background Data: Although the development of multidrug chemotherapy regimens has improved the survival outcomes of patients with unresectable pancreatic cancer, the benefits of these treatments in the neo-adjuvant setting remain controversial. Methods: Patients with borderline-resectable pancreatic cancer were enrolled and randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX or gemcitabine with nab-paclitaxel (GEM/nab-PTX). After the completion of chemotherapy, patients underwent surgical resection when feasible. This study (NUPAT-01) was a randomized phase II trial, and the primary endpoint was the R0 resection rate. Results: Fifty-one patients were enrolled in this study [FOLFIRINOX (n = 26) and GEM/nab-PTX (n = 25)]. A total of 84.3% (n = 43/51) of the patients eventually underwent surgery, and R0 resection was achieved in 67.4% (n = 33/ 51) of the patients. Adverse events (grade >3) due to neoadjuvant treatment were observed in 45.1% of the patients (n = 23/51), and major surgical complications occurred in 30.0% (n = 13/43), with no mortality noted. The intention-to-treat analysis showed that the 3-year overall survival rate was 54.7%, with a median survival time of 39.4 months, and a significant difference in overall survival was not observed between the FOLFIRINOX and GEM/nab-PTX groups. Conclusions: These results indicate that neoadjuvant chemotherapy with FOLFIRINOX or GEM/nab-PTX is feasible and well tolerated, achieving an R0 resection rate of 67.4%. The survival of patients was even found to be favorable in the intention-to-treat analysis.

Purpose.Anastomotic leakage (AL) is one of the most critical postoperative complications after subtotal esophagectomy in patients with esophageal cancer. This study attempted to develop an optimal scoring system for stratifying the risk for AL. Methods. The study included 171 patients who underwent subtotal esophagectomy for esophageal cancer followed by esophagogastrostomy in the cervical region from January 2011 to April 2021 at Nagoya University Hospital. AL was defined by radiologic or endoscopic evidence of anastomotic breakdown using some modalities. A risk scoring system for early diagnosis of AL was established using factors determined in the multivariate analysis. A score was calculated for each patient, and the patients were classified into three categories according to the risk for AL: low-, intermediate-, and high-risk. The trend of the risk for AL among the categories was evaluated. Results. Twenty-nine patients (17%) developed AL. Multivariate analysisdemonstrated that sinistrous gross features of drain fluid (P Conclusions. The present AL-risk scoring system may be useful in postoperative patientcare after subtotal esophagectomy.

The recurrence risk of estrogen receptor (ER)-positive breast cancer remains high for a long period of time, unlike other types of cancer. Late recurrence reflects the ability of cancer cells to remain dormant through various events, including cancer stemness acquisition, but the detailed mechanism is unknown. ESR1 locus enhancing and activating noncoding RNAs (ELEANORS) are a cluster of nuclear noncoding RNAs originally identified in a recurrent breast cancer cell model. Although their functions as chromatin regulators in vitro are well characterized, their roles in vivo remain elusive. In this study, we evaluated the clinicopathologic features of ELEANORS, using primary and corresponding metastatic breast cancer tissues. The ELEANOR expression was restricted to ER-positive cases and well-correlated with the ER and progesterone receptor expression levels, especially at the metastatic sites. ELEANORS were detected in both primary and metastatic tumors (32% and 29%, respectively), and frequently in postmenopausal cases. Interestingly, after surgery, patients with ELEANOR-positive primary tumors showed increased relapse rates after, but not within, 5 years. Multivariate analysis showed that ELEANORS are an independent recurrence risk factor. Consistently, analyses with cell lines, mouse xenografts, and patient tissues revealed that ELEANORS upregulate a breast cancer stemness gene, CD44, and maintain the cancer stem cell population, which could facilitate tumor dormancy. Our findings highlight a new role of nuclear long noncoding RNAs and their clinical potential as predictive biomarkers and therapeutic targets for late recurrence of ER-positive breast cancer.

Background Although surgical resection for liver or lung metastases of colorectal cancer has been widely accepted, the use of this approach for extrahepatopulmonary metastases remains debatable due to the systemic nature of the disease. The aim of this study was to clarify the utility of resection along with perioperative chemotherapy for patients with extrahepatopulmonary metastases of colon cancer. Methods This is a retrospective single-arm study at a single institution. Forty-two patients with resectable extrahepatopulmonary metastases who underwent metastasectomy with curative intent between 2009 and 2018 at Nagoya University Hospital were retrospectively analyzed. The primary outcomes measured were overall and relapse-free survival. Results The most common metastatic site was the peritoneum (n = 31), followed by the distant lymph nodes (n = 10), ovary (n = 1) and spleen (n = 1), with overlaps. Preoperative and postoperative chemotherapies were administered to 22 and 8 patients, respectively; the remaining 14 patients received surgery alone. R0 resection was achieved in 36 patients (85.7%). The 5-year overall survival and 3-year relapse-free survival rates were 58.6% and 33.8%, respectively. In the univariate analysis, R1 resection was associated with a poor relapse-free survival rate (P = 0.02). In the multivariate analysis, the absence of perioperative chemotherapy was an independent risk factor for poor overall survival rates (P = 0.02). Conclusions Surgical resection benefited selected patients with extrahepatopulmonary metastases with favorable long-term survival outcomes. Surgery alone without systemic chemotherapy is likely to bring poor outcome; therefore, preoperative induction might be promising to keep up with chemotherapy.

Although gemcitabine-based chemotherapy is the standard of care for advanced biliary tract cancers (BTCs), adjuvant phase III studies (BCAT in Japan, PRODIGE 12 in France) failed to show benefit, possibly owing to fewer patients (n = 225 and n = 194) compared with the adjuvant capecitabine BILCAP trial (n = 447). We performed a combined analysis of both gemcitabine-based chemotherapy adjuvant studies.We performed individual patient data meta-analysis of all patients included in BCAT and PRODIGE 12. BCAT study randomised patients with extrahepatic cholangiocarcinoma to single-agent gemcitabine or observation. PRODIGE 12 randomised patients with all BTC subtypes to gemcitabine-oxaliplatin combination or observation. Combined analysis was performed using Kaplan-Meier curves and a Cox regression model stratified on the trial.Two hundred and twelve versus 207 patients were randomised in the gemcitabine-based chemotherapy versus observation arms. Baseline characteristics were balanced between arms. The median follow-up was 5.5 years. After 258 relapse-free survival (RFS) events, there was no difference in RFS (log-rank p = 0.45; hazard ratio [HR] = 0.91 [95% confidence interval [CI] 0.71-1.16]; p = 0.46). RFS rates at five years were 40.8% (95%CI: 33.9%-47.5%) for gemcitabine-based chemotherapy versus 36.6% (95%CI: 29.8%-43.4%) for observation. After 201 deaths, there was no difference in overall survival (OS) (log-rank p = 0.83; HR = 1.03 [95%CI: 0.78-1.35]; p = 0.85). OS rates at five years were 50.5% (95%CI: 43.1%-57.4%) for gemcitabine-based chemotherapy versus 49.3% (95%CI: 41.6%-56.5%) for observation.With 419 patients included, this analysis did not show significant improvement in RFS and no trend in improvement in OS. Gemcitabine-based chemotherapy should not be used as an adjuvant treatment for BTC.

Background & aims: To elucidate the impact of synbiotics on bacterial translocation and subsequent bacteremia during neoadjuvant chemotherapy for esophageal cancer. Methods: Patients requiring neoadjuvant chemotherapy for esophageal cancer were randomized to receive synbiotics (synbiotics group) or no synbiotics (control group) during chemotherapy. Blood and fecal samples were taken before and after every chemotherapy cycle, and 1 day before surgery. Mesenteric lymph nodes (MLNs) were harvested at laparotomy (MLN-1) and after resection of the tumor (MLN-2). Bacteria in each sample were detected. Fecal microbiota and organic acid concentrations were also determined. The primary endpoint was the detection of bacteria in the blood samples, as well as the incidence of side effects during chemotherapy. The secondary endpoint was the detection rate of bacteria in the MLN samples collected during surgery. Results: The study recruited a total of 42 patients (22 in the control group, 20 in the synbiotics group). Bacteria were detected in 16 of 101 blood samples in the control group, whereas those were detected only 2 of 100 blood samples in the synbiotics group (p < 0.001) during neoadjuvant chemotherapy. Additionally, bacteria were detected in 12 of 34 MLN samples in the control group, whereas no bacteria were detected in 38 MLN samples in the synbiotics group (p < 0.001). Suppression of bacterial translocation was at least partly associated with an increased fecal acetic acid concentration as well as a lowered fecal pH by synbiotics. The incidence rate of grade 3 gastrointestinal toxicity during chemotherapy was lower in the synbiotics group compared to the control group (8/22 vs. 1/20, p = 0.022). Conclusions: Neoadjuvant chemotherapy for esophageal cancer may induce bacterial translocation and subsequent bacteremia, which can be prevented by synbiotics administration. Trial registration: The University Hospital Medical Information Network (http://www.umin.ac.jp; registration number ID 000007651).

To clarify the influence of additional internal iliac artery (IIA) resection on the loss of the gluteus muscle volume after pelvic exenteration (PE).The subjects of this retrospective analysis were 78 patients who underwent PE with or without IIA resection (n = 44 and n = 34, respectively) between 2006 and 2018. The areas of gluteal muscles (GMs) and psoas muscles (PSMs) were calculated using CT images before and 6 months after PE, and the difference was compared.The volumes of the GMs and PSMs were significantly reduced after PE (P 0.001 and P = 0.005, respectively). In the IIA resection group, the GMs were significantly reduced after surgery, but the PSMs were not. The maximum GM (Gmax) was the most atrophied among the GMs. Multivariable analysis revealed that complete IIA resection was an independent promotor of the loss of volume of the Gmax (P = 0.044). In 18 patients with unilateral IIA resection, the downsizing rate of the Gmax was significantly greater on the resected side than on the non-resected side (P = 0.008).The GMs and PSMs were significantly smaller after PE. Complete IIA resection reduced the Gmax area remarkably. Preservation of the superior gluteus artery is likely to help maintain Gmax size, suggesting a potential preventative measure against secondary sarcopenia.

BACKGROUND Clinical tumor staging is essential information for making a therapeutic decision in cancer. This study aimed to identify the optimal tumor classification system for predicting resectability and survival probability in perihilar cholangiocarcinoma. METHODS Patients who were treated for perihilar cholangiocarcinoma between 2009 and 2018 were enrolled. Local tumor extension was staged radiologically according to a diameter-based classification system in addition to the AJCC, Blumgart, and Bismuth systems. Survival and resectability were compared between T subgroups, and the discriminability of the four systems was assessed with Harrell's concordance index (C-index). RESULTS Among 702 study patients, 559 (80.0%) underwent laparotomy, 489 (70.0%) of whom underwent resection. The resectability significantly decreased for more advanced tumors in all systems (P

The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure.In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH).Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures.Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% (P = 0.432) and 24% versus 0% in advanced tumors (P = 0.011). Tumor size ≥18 mm (P = 0.041), portal vein invasion (P = 0.009), and conventional LH (P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years (P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group (P0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor (P = 0.009) along with ductal margin status (P = 0.030).The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors.

The necessity of a specific T classification for extrahepatic intraductal papillary neoplasm of the bile duct (IPNB) type 2, one of the precursors of cholangiocarcinoma (CC), remains unclear.Patients who underwent resection for extrahepatic biliary tumors were reviewed. Relapse-free survival (RFS) was compared between IPNB type 2 and CC, stratified by T classification.The cohort involved 443 patients with IPNB type 2 (n = 57) and CC (n = 386). In 342 patients with perihilar tumors, 5-year RFS of IPNB type 2 and CC group was 49.8% versus 34.5% (p = .012), respectively. The RFS was 54.6% versus 47.2% (p = .110) for pT1-2 tumors and 28.6% versus 22.7% (p = .436) for pT3-4 tumors, respectively. In 92 patients with distal tumors, 5-year RFS was 47.4% versus 42.1% (p = .678). The RFS was 68.2% versus 49.6% (p = .422) for pT1 tumors and 18.8% versus 38.3% (p = .626) for pT2-3 tumors, respectively. Multivariate analysis identified that poor histologic grade (HR, 2.105; p .001), microscopic venous invasion (HR, 1.568; p = .002), and nodal metastasis (HR, 1.547; p .001) were independent prognostic deteriorators, while tumor type (IPNB type 2 vs. CC) was not.Prognostic impact of IPNB type 2 was limited, suggesting unnecessity of a specific T classification for IPNB type 2 with invasive carcinoma.

OBJECTIVE To visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. BACKGROUND Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. METHODS Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. RESULTS A total of 4230 complications occurred in the 484 study patients (CDC grade I, n=27; II, n=132; IIIa, n=290; IIIb, n=4; IVa, n=21; IVb, n=1; and V, n=9). The trajectory was categorized into 3 patterns: mild (n=209), moderate (n=235), and severe (n=40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P

BACKGROUND The efficacy of adjuvant chemotherapy for biliary cancers remains controversial because of conflicting results from previous phase 3 studies that used different key drugs and enrolled patients with heterogeneous tumor sites and disease stages. Fluoropyrimidine seems more beneficial than gemcitabine (GEM) combination regimens in the adjuvant setting; however, data comparing the survival benefit between GEM- and fluoropyrimidine-based regimens are lacking. METHODS Patients who underwent resection for node-positive perihilar cholangiocarcinoma were included. The patients who underwent adjuvant chemotherapy were divided into the S-1 and GEM groups according to the regimen. The recurrence-free survival (RFS) and the overall survival (OS) were compared between the groups and adjusted with propensity scores generated from 14 potentially confounding clinicopathological factors. RESULTS In total, 186 patients (Surgery alone, n = 71; S-1, n = 60; GEM, n = 55) were included. The S-1 and GEM completion rates were 75% and 65%, respectively. Among the patients who underwent adjuvant therapy, the RFS was longer in the S-1 group patients than the GEM group patients (median, 24.4 months vs 14.9 months; P = .044) whereas the OS was not significantly different between the groups (median, 48.5 months vs 35.0 months; P = .324). After propensity score adjustment, the differences in RFS and OS between the groups were more evident (HR: 2.696, 95% CI: 1.739-4.180 P

Background: Nutritional status and tumor markers are important prognostic indicators for surgical decisions in pancreatic carcinoma. This study aimed to stratify the probability of surviving pancreatic carcinoma based on systematically chosen nonanatomic biomarkers. Methods: We included 187 consecutive patients that underwent surgical resections for pancreatic carcinoma. We performed multivariable analyses to evaluate prognostic indicators, including 4 blood-test indexes: the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index, and the modified Glasgow prognostic score; and 4 body-composition indexes: the normalized total psoas muscle area, the normalized total elector spine muscle area, the psoas muscle computed tomography value, and the elector spine muscle computed tomography value. Results: Poor survival was associated with 2 independent risk factors: neutrophil-to-lymphocyte ratio ≥3.0 (hazard ratio, 1.54) and prognostic nutritional index

Introduction The oncological benefit of neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to clarify the clinical risk factors for poor prognosis before and after NAC for decision making regarding additional treatment in patients with LARC. Materials and methods We examined a total of 96 patients with MRI-defined poor-risk locally advanced mid-low rectal cancer treated by NAC alone between 2006 and 2018. Survival outcomes and clinical risk factors for poor prognosis before and after NAC were analyzed. Results In the median follow-up duration after surgery of 60 months (3–120), the rates of 5-year overall survival (OS), relapse-free survival (RFS), and local recurrence (LR) were 83.6%, 78.4%, and 8.2%, respectively. In the multivariate analyses, patients with cT4 disease had a significantly higher risk of poor OS (HR; 6.10, 95% CI; 1.32–28.15, P = 0.021) than those with cT3 disease. After NAC, ycN+ was significantly associated with a higher risk of poor OS (HR; 5.92, 95% CI; 1.27–27.62, P = 0.024) and RFS (HR; 2.55, 95% CI; 1.01–6.48, P = 0.048) than ycN-. In addition, patients with CEA after NAC (post-CEA) ≥ 5 ng/ml had a significantly higher risk LR (HR; 5.63, 95% CI; 1.06–29.93, P = 0.043). Conclusion NAC alone had an insufficient survival effect on patients with cT4 disease, ycN+, or an elevated post-CEA level. In contrast, NAC alone is a potential treatment for other patients with LARC.

The carcinoembryonic antigen (CEA) “value” itself is often useless in patients with a normal CEA level at initial presentation and those with tumor-irrelevant elevated CEA. Although the unified marker using CEA has been desirable for recurrent tumor staging as well as for primary tumor staging, little is known concerning its relationship with the survival of patients with recurrent colorectal cancer in particular. This retrospective historical study included patients who experienced disease relapse after curative surgery for stage I–III colorectal cancer between 2006 and 2018. A total of 129 patients with recurrent disease after curative surgery for colorectal cancer were included. We focused on the CEA “ratio” (CEA-R: the ratio of the CEA level at the time of recurrence to that measured 3 months before recurrence) and aimed to evaluate the correlation between CEA-R and survival in recurrent colorectal cancer. Patients with a high CEA-R (≥ 2) exhibited significantly worse 2 year survival than those with a low CEA-R (

Recent findings suggest that the dissemination of tumor cells occurs at the early stage of breast and pancreatic carcinogenesis, which is known as early dissemination. The evidence of early dissemination has been demonstrated predominantly in the bloodstream and bone marrow; however, limited evidence has revealed the existence and behavior of disseminated cells in distant organs. Here, we show that premalignant pancreatic cells seed distant stealth metastasis that eventually develops into manifest metastasis. By analyzing lineage-labeled pancreatic cancer mouse models (KPCT/TFF1KO; Pdx1-Cre/LSL-KRASG12D/LSL-p53R172H/LSL-tdTomato/TFF1KO), we found that premalignant pancreatic cells, rather than mature malignant cells, were prone to enter the bloodstream and reside in the bone marrow, liver, and lung. While these metastatic cells exhibited the characteristics of the cells of host organs and did not behave as malignant cells, they underwent malignant transformation and formed distinct tumors. Surprisingly, the manifestation of distant metastasis occurred even before tumor development in the primary site. Our data revealed that disseminated premalignant cells reside stealthily in distant organs and evolve in parallel with the progression of the primary tumor. These observations suggest that we must rebuild a therapeutic strategy for metastatic pancreatic cancer.

The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014.In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded.This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.