Peritumoral Fat Content Identified Using Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-squares Estimation (IDEAL) Correlates with Breast Cancer Prognosis.

PURPOSE: Adipocytes around aggressive breast cancer (BC) are less lipid different from naive adipocytes (cancer-associated adipocytes, CAAs), and peritumoral edema caused by the release of cytokines from CAAs can conduce to decrease the peritumoral fat proportion. The purpose of this study was to correlate peritumoral fat content identified by using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with lymph node metastasis (LNM) and recurrence-free survival (RFS) in BC patients and to compare with T2-weighted (T2WI) and diffusion-weighted images (DWI) analyses. METHODS: This retrospective study consisted of 85 patients who were diagnosed with invasive carcinoma of breast and underwent breast MRI, including IDEAL before surgery. The scan time of fat fraction (FF) map imaging using IDEAL was 33s. Four regions of interest (ROIs), which are 5 mm from the tumor edge, and one ROI in the mammary fat of the healthy side were set on the FF map. Then average peritumoral FF values (TFF), average FF values on the healthy side (HFF), and peritumoral fat ratio (PTFR, which is defined as TFF/HFF) were calculated. Tumor apparent diffusion coefficient (ADC) values were measured on ADC map obtained by DWI. Peritumoral edema was classified into three grades based on the degree of signal intensity around the tumor on T2WI (T2 edema). RESULTS: The results of stepwise logistic regression analysis for four variables (TFF, PTFR, T2 edema, and ADC value) indicated that TFF and T2 edema were significant factors of LNM (p < 0.01). RFS was significantly associated with TFF (p = 0.016), and 47 of 49 (95.9%) patients with TFF more than 85.5% were alive without recurrence. CONCLUSION: Peritumoral fat content identified by using IDEAL is associated with LNM and RFS and may therefore be a useful prognostic biomarker for BC.

Laparoscopic approach for port site mass diagnosed as a Schloffer tumor following surgery of ascending colon cancer.

Schloffer tumor is a foreign body granuloma that develops in the subcutaneous layer of the abdomen over several months to several years after surgery due to sutures. Here, we performed a laparoscopic resection for a benign Schloffer tumor that showed positive F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) at the port site of a laparoscopic right hemicolectomy for advanced colon cancer. We report a case in which systemic chemotherapy was avoided as a result of the histological examination following the laparoscopic approach. A 66-year-old female, who underwent laparoscopic right hemi colectomy for stage IIIA ascending colon cancer, was revealed an enhanced mass at the right side of the abdominal subcutaneous layer. PET examination showed a high accumulation of FDG. Laparoscopic tumor resection was performed. Pathological findings reported the formation identical to the Schloffer tumor. Schloffer tumor, which is rare, should be considered as one of the differential diagnoses for tumor with FDG-PET positivity at the port site during the postoperative surveillance period of colorectal cancer.

Clinical features and distribution of the APC variant in duodenal and ampullary polyps in patients with familial adenomatous polyposis: a multicenter retrospective cohort study in Japan.

BACKGROUND: Management of duodenal or ampullary adenomas in patients with familial adenomatous polyposis (FAP) is a major challenge for clinicians. Insufficient data are available to evaluate the clinical manifestations and distribution of adenomatous polyposis coli (APC) variants in these patients. METHODS: We enrolled 451 patients with data regarding duodenal or ampullary polyps from 632 patients with FAP retrospectively registered in a nationwide Japanese multicenter study. Clinicopathological features and distribution of APC variants were compared between patients with and without duodenal or ampullary polyps. RESULTS: Duodenal and ampullary polyps were found in 59% and 18% of patients with FAP, respectively. The incidence of duodenal cancer was 4.7% in patients with duodenal polyps, and that of ampullary cancer was 18% in patients with ampullary polyps. Duodenal polyps were significantly associated with the presence of ampullary polyps and jejunal/ileal polyps. Duodenal polyps progressed in 35% of patients with a median follow-up of 776 days, mostly in those with early Spigelman stage lesions. Ampullary polyps progressed in 50% of patients with a follow-up of 1484 days. However, only one patient developed a malignancy. The proportion of patients with duodenal polyps was significantly higher among those with intermediate- or profuse-type APC variants than attenuated-type APC variants. The presence of duodenal polyps was significantly associated with ampullary and jejunal/ileal polyps in patients with intermediate- or profuse-type APC variants. CONCLUSIONS: Periodic endoscopic surveillance of the papilla of Vater and small intestine should be planned for patients with FAP with duodenal polyps.

Short-term outcomes of pancreatoduodenectomy in older individuals over a 9-year period using real-world data: A multilevel analysis based on a nationwide administrative database in Japan.

BACKGROUND: We aimed to evaluate the short-term outcomes of pancreatoduodenectomy (PD) in older individuals. METHODS: Data from the Japanese Diagnosis Procedure Combination database on 62 275 patients who underwent PD from 1 April 2012 to 31 March 2020 were analyzed. Patients were divided into five age groups: <70, 70-74, 75-79, 80-84, and ≥85 years. The associations between postoperative outcomes and age were investigated using multilevel analysis. The mean differences in length of hospital stay and cost were also compared. RESULTS: The rate of PD in older individuals increased annually. Compared with the youngest age group (< 70 years), the incidence rate ratios for in-hospital mortality were 1.52 (95% confidence interval [CI]: 1.30-1.76), 2.07 (1.82-2.37), 2.29 (1.94-2.71), and 2.92 (2.20-3.87) in the 70-74, 75-79, 80-84, and ≥ 85-year-old age groups, respectively (all p < .001). Postoperative complications, length of postoperative hospital stay, and cost increased significantly with increasing age. CONCLUSIONS: These real-world data emphasize the higher levels of morbidity, mortality, and cost in older patients. Careful attention should be paid when considering the indication for PD in older individuals.

Management of Patients Receiving Antiplatelet Therapy During Gastroenterological Surgery: A Multicenter Prospective Cohort Study (GSATT).

OBJECTIVE: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). SUMMARY BACKGROUND DATA: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. METHODS: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1,170) were assigned to the continued APT group, discontinued APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. RESULTS: The rate of thromboembolic complications in the continued APT group was substantially lower than that in the non-APT or discontinued APT groups (0.5% vs. 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P<0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued APT groups (0.6% vs. 3.3%; P=0.012). CONCLUSIONS: APT discontinuation following elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery.

Mechanical and oral antibiotics bowel preparation for elective rectal cancer surgery: A propensity score matching analysis using a nationwide inpatient database in Japan.

Aim: The best bowel preparation method for rectal surgery remains controversial. In this study we compared the efficacy and safety of mechanical bowel preparation (MBP) alone and MOABP (MBP combined with oral antibiotic bowel preparation [OABP]) for rectal cancer surgery. Methods: In this retrospective study we analyzed data from the Japanese Diagnosis Procedure Combination (DPC) database on 37 291 patients who had undergone low anterior resection for rectal cancer from 2014 to 2017. Propensity score matching analysis was used to compare postoperative outcomes between MBP alone and MOABP. Results: A total of 37 291 patients were divided into four groups: MBP alone: 77.7%, no bowel preparation (NBP): 16.9%, MOABP: 4.7%, and OABP alone: 0.7%. In propensity score matching analysis with 1756 pairs, anastomotic leakage (4.84% vs 7.86%, P < 0.001), small bowel obstruction (1.54% vs 3.08%, P = 0.002) and reoperation (3.76% vs 5.98%, P = 0.002) were less in the MOABP group than in the MBP group. The mean duration of postoperative antibiotics medication was shorter in the MOABP group (5.2 d vs 7.5 d, P < 0.001) than in the MBP group. There was no significant difference between the two groups in the incidence of Clostridium difficile (CD) colitis (0.40% vs 0.68%, P = 0.250) and methicillin-resistant Staphylococcus aureus (MRSA) colitis (0.11% vs 0.17%, P = 0.654). There was no significant difference in in-hospital mortality between the two groups (0.00% vs 0.11% respectively, P = 0.157). Conclusion: MOABP for rectal surgery is associated with a decreased incidence of postoperative complications without increasing the incidence of CD colitis and MRSA colitis.

Changes in operative trends and short-term outcomes of surgery for congenital biliary dilatation in adults using real-world data: A multilevel analysis based on a nationwide administrative database in Japan.

Aim: We aimed to evaluate the operative trends and compare the short-term outcomes between open and laparoscopic surgery for congenital biliary dilatation (CBD) in adults using real-world data from Japan. Methods: Data from the Japanese Diagnosis Procedure Combination database on 941 patients undergoing surgery for CBD at 357 hospitals from April 1, 2016, to March 31, 2021, were analyzed. The patients were divided into two groups: open surgery (n = 764) and laparoscopic surgery (n = 177). We performed a retrospective analysis via a multilevel analysis of the short-term surgical outcomes and costs between open and laparoscopic surgery. Results: The rate of laparoscopic surgery has been increasing annually and had almost doubled to 25% by 2021. There were no significant differences in the in-hospital mortality rate or postoperative morbidity between the two groups. The length of anesthesia was significantly longer in the laparoscopic than open surgery group (8.80 vs 6.16 hours, p < .001). The time to removal of the abdominal drain and length of hospital stay were significantly shorter in the laparoscopic than open surgery group (6.12 vs 8.35 days, p = .001 and 13.57 vs 15.79 days, p < .001, respectively). The coefficient for cost was 463 235 yen (95% confidence interval, 289 679-636 792) higher in laparoscopic than open surgery (p < .001). Conclusion: The short-term results were comparable between laparoscopic and open surgery for CBD. Further investigation is needed to validate our findings and long-term outcomes.

Clinical Guidelines for Diagnosis and Management of Juvenile Polyposis Syndrome in Children and Adults-Secondary Publication.

Juvenile polyposis syndrome (JPS) is a rare disease characterized by multiple hamartomatous polyps within the gastrointestinal tract. SMAD4 or BMPR1A is known as a causative gene of JPS. Approximately 75% of newly diagnosed cases have an autosomal-dominantly inherited condition, whereas 25% are sporadic without previous history of polyposis in the family pedigree. Some patients with JPS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood. JPS is classified into three categories according to phenotypic features of polyp distributions, including generalized juvenile polyposis, juvenile polyposis coli, and juvenile polyposis of the stomach. Juvenile polyposis of the stomach is caused by germline pathogenic variants of SMAD4 with a high risk leading to gastric cancer. Pathogenic variants of SMAD4 are also associated with hereditary hemorrhagic telangiectasia-JPS complex, inducing regular cardiovascular survey. Despite growing concerns regarding the managing JPS in Japan, there are no practical guidelines. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labor and Welfare involving specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of JPS with three clinical questions and corresponding recommendations based on a careful review of the evidence and involve incorporating the concept of the Grading of Recommendations, Assessment, Development, and Evaluation system. Herein, we present the clinical practice guidelines of JPS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with JPS.

Clinical Guidelines for Diagnosis and Management of Juvenile Polyposis Syndrome in Children and Adults­Secondary Publication

Juvenile polyposis syndrome (JPS) is a rare disease characterized by multiple hamartomatous polyps within the gastrointestinal tract. SMAD4 or BMPR1A is known as a causative gene of JPS. Approximately 75% of newly diagnosed cases have an autosomal-dominantly inherited condition, whereas 25% are sporadic without previous history of polyposis in the family pedigree. Some patients with JPS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood. JPS is classified into three categories according to phenotypic features of polyp distributions, including generalized juvenile polyposis, juvenile polyposis coli, and juvenile polyposis of the stomach. Juvenile polyposis of the stomach is caused by germline pathogenic variants of SMAD4 with a high risk leading to gastric cancer. Pathogenic variants of SMAD4 are also associated with hereditary hemorrhagic telangiectasia-JPS complex, inducing regular cardiovascular survey. Despite growing concerns regarding the managing JPS in Japan, there are no practical guidelines. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labor and Welfare involving specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of JPS with three clinical questions and corresponding recommendations based on a careful review of the evidence and involve incorporating the concept of the Grading of Recommendations, Assessment, Development, and Evaluation system. Herein, we present the clinical practice guidelines of JPS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with JPS.

The Effects of Hospital Volume on Short-Term Outcomes of Laparoscopic Surgery for Rectal Cancer: A Large-Scale Analysis of 37,821 Cases on a Nationwide Administrative Database.

INTRODUCTION: Laparoscopic low anterior resection (L-LAR) has become widely accepted for the treatment of rectal cancer. However, little is known about the superiority of L-LAR in a real-world setting (including low-volume hospitals) and the association between the short-term outcomes and hospital volume focusing on L-LAR. METHODS: This is a retrospective cohort study. A total of 37,821 patients who underwent LAR for rectal cancer were analyzed using the Diagnosis Procedure Combination (DPC) database from January 2014 to December 2017. The short-term surgical outcomes were analyzed using a multilevel analysis. Hospital volumes were divided into quartiles, including low (1-31), middle (32-55), high (56-91), and very-high volume (92-444 resections per 4 years). The effects of hospital volume on the outcomes were investigated. RESULTS: The study population included 8,335 patients (22%) who underwent open low anterior resection (O-LAR) and 29,486 patients (78%) who underwent L-LAR. The in-hospital mortality and morbidity were consistent with previous reports. In patients who underwent L-LAR, the in-hospital mortality (0.12% vs. 0.41%; OR: 0.33; p = 0.005), the rate of reoperation (3.76% vs. 6.48%; OR: 0.67; p < 0.001), and the perioperative transfusion rate (3.81% vs. 5.90%; OR: 0.66; p < 0.001) were significantly lower in very-high-volume hospitals than in low-volume hospitals. These effects of hospital volume were not observed in O-LAR. CONCLUSIONS: Our present study demonstrates that high volume improves outcomes in patients who underwent L-LAR in a real-world setting.

Receptor for Hyaluronic Acid-mediated Motility (RHAMM) Is Associated With Prostate Cancer Migration and Poor Prognosis.

BACKGROUND/AIM: Hyaluronic acid (HA) is a large glycosaminoglycan composed of an extracellular matrix. The HA-rich microenvironment and receptors of HA have been suggested to play roles in cancer progression. The biological and clinical significance of receptor for HA-mediated motility (RHAMM), known as CD168 in prostate cancer (PC) remains unknown. This study aimed to investigate the expression of RHAMM, as well as its functional and clinical relevance in PC. MATERIALS AND METHODS: HA concentration and RHAMM mRNA expression were examined in 3 PC cell lines (LNCaP, PC3 and DU145). We investigated the effect of HA and RHAMM on the migratory ability of PC cells using a transwell migration assay. Immunohistochemistry was also used to evaluate the RHAMM expression pattern in pre-treatment tissue samples from 99 patients with metastatic hormone-sensitive PC (HSPC) who received androgen deprivation therapy (ADT). RESULTS: HA was secreted in all cultured PC cell lines. Among the total HA, low-molecular-weight HA (LMW-HA) (<100 kDa) was detected all examined cell lines. The number of migration cells was significantly increased by adding LMW-HA. RHAMM mRNA expression was increased in DU145 cells. Knockdown of RHAMM using small-interfering RNA resulted in decreased cell migration. Immunohistochemical analysis revealed strong RHAMM expression in 31 (31.3%) patients with metastatic HSPC. A strong RHAMM expression was significantly associated with short ADT duration and poor survival in univariate and multivariate analyses. CONCLUSION: The size of HA is important in terms of PC progression. LMW-HA and RHAMM enhanced PC cell migration. RHAMM could be used as a novel prognostic marker in patients with metastatic HSPC.

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial.

INTRODUCTION: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. METHOD: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. RESULTS: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. CONCLUSION: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer.

Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II-IV resectable CRC (n = 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49-24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P < 0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P < 0.001). Furthermore, postsurgical ctDNA positivity identified patients with stage II or III CRC who derived benefit from ACT (HR 6.59, P < 0.0001). The results of our study, a large and comprehensive prospective analysis of ctDNA in resectable CRC, support the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.

Current practice of colonoscopy surveillance in patients with lynch syndrome: A multicenter retrospective cohort study in Japan.

Objectives: Colonoscopy surveillance reduces the incidence of colorectal cancer through the detection and endoscopic removal of adenomas. Current guidelines recommend that patients with Lynch syndrome should have colonoscopy surveillance every 1-2 years starting at the age of 20-25. However, insufficient data are available to evaluate the quality and safety of colonoscopy surveillance for patients with Lynch syndrome nationwide in Japan. Methods: Patients with Lynch syndrome (n = 309) from 13 institutions who underwent one or more colonoscopy procedures were enrolled in this retrospective analysis. Colonoscopy completion rate, colonoscopy-related complication rate, proportion with an adequate colonoscopy interval, and adenoma detection rate were reviewed. Results: The colonoscopy completion rate was 98.8% and a history of previous colorectal cancer surgery was significantly associated with a higher completion rate. All complications were associated with endoscopic treatment and the rate of bleeding needing hemostasis and perforation needing surgical repair were both 0.16% after colonoscopy with polypectomy. The adenoma detection rate at the first colonoscopy was 25%. Although there was no difference in the completion and complication rates based on differences in the colonoscopy experience of the endoscopist, the detection rate of adenomas and intramucosal cancers was significantly higher with more experienced endoscopists. The proportion of patients developing cancer was significantly higher with a >24 months than a ≤24 months interval. Conclusion: High-volume experienced endoscopists and appropriate surveillance intervals may minimize the risk of developing colorectal cancers in patients with Lynch syndrome.

Concurrent Overexpression of Two Hyaluronidases, KIAA1199 and TMEM2, Strongly Predicts Shorter Survival After Resection in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated hyaluronan metabolism. Our previous studies have shown increased expression of 2 newly identified hyaluronidases, KIAA1199 and transmembrane protein 2 (TMEM2), in PDAC. However, the relationship between these 2 hyaluronidases is unknown. In the present study, we investigated the correlation between KIAA1199 and TMEM2 expression in PDAC. METHODS: Using quantitative real-time reverse transcription polymerase chain reaction, we analyzed KIAA1199 and TMEM2 mRNA expression in 11 PDAC cell lines and frozen tissues from 12 patients with PDAC. We used immunohistochemistry to investigate expression patterns of KIAA1199 and TMEM2 in archival tissues obtained from 92 patients with PDAC who underwent surgical resection. We compared survival between 4 groups according to expression patterns of KIAA1199 and TMEM2. RESULTS: We found a significantly positive correlation between KIAA1199 and TMEM2 mRNA in PDAC cell lines and tissues. Immunohistochemical analysis found that median overall survival was 30.2 months in patients with low expression of KIAA1199 and TMEM2 and 12.5 months in those with high expression of both. Patients with high expression of KIAA1199 and TMEM2 had significantly shorter survival than other patient groups. CONCLUSIONS: Concurrent overexpression of these 2 hyaluronidases could be a strong prognostic marker in PDAC.

Biweekly TAS-102 and bevacizumab as third-line chemotherapy for advanced or recurrent colorectal cancer: a phase II, multicenter, clinical trial (TAS-CC4 study).

BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.

An advanced bipolar device helps reduce the rate of postoperative pancreatic fistula in laparoscopic gastrectomy for gastric cancer patients: a propensity score-matched analysis.

BACKGROUND: Advanced bipolar devices (ABD; e.g., LigaSure™) have a lower blade temperature than ultrasonically activated devices (USAD; e.g., Harmonic® and Sonicision™) during activation, potentially enabling accurate lymph node dissection with less risk of postoperative pancreatic fistula (POPF) due to pancreatic thermal injury in laparoscopic gastrectomy. Therefore, we compared the efficacy and safety of ABD and USAD in laparoscopic gastrectomy for gastric cancer patients. METHODS: A retrospective cohort study was conducted on patients who underwent laparoscopic distal gastrectomy (LDG) between August 2008 and September 2020. A total of 371 patients were enrolled, and short-term surgical outcomes, including the incidence of ISGPF grades B and C POPF, were compared between ABD and USAD. The risk factors for POPF in LDG were investigated by univariate and multivariate analyses. RESULTS: A propensity score-matching algorithm was used to select 120 patients for each group. The POPF rate was significantly lower (0.8 vs. 9.2%, p < 0.001), the morbidity rate was lower (13.3 vs. 28.3%, p < 0.001), the length of postoperative hospitalization was shorter (14 vs. 19 days, p < 0.001), and the lymph node retrieval rate was higher (34 vs. 26, p < 0.001) with an ABD than with a USAD. There were no mortalities in either group. A multivariate analysis showed that a USAD was the only independent risk factor with a considerably high odds ratio for the occurrence of POPF (USAD/ABD, odds ratio 8.38, p = 0.0466). CONCLUSION: An ABD may improve the safety of laparoscopic gastrectomy for gastric cancer patients.

Clinical impact of laparoscopic surgery and adhesion prevention material for prevention of small bowel obstruction.

Aim: Adhesive small bowel obstructions (SBO) are one of the most common complications following abdominal surgery, and they decrease patient quality of life. Since 2000, laparoscopic surgery has been employed with increasing frequency, as has adhesion prevention material (APM). In this study we tried to evaluate whether laparoscopic surgery and APM reduce the incidence of SBO. Methods: In Cohort 1, we included patients who developed SBO and received inpatient treatment between 2015 and 2018. We evaluated the elapsed time between precedent surgery and the onset of SBO, and what kind of surgery most often causes SBO. In Cohort 2, we included patients who underwent digestive surgery between 2012 and 2014 and evaluated SBO incidence within 5 y after the precedent surgery. Results: In all, 2058 patients were included in Cohort 1. Of these, 164 had experienced no precedent surgery. Among patients with a history of abdominal surgery, 29.7% experienced SBO within 1 y after the precedent surgery and 48.1% within 3 y. Altogether, 18798 patients were analyzed in Cohort 2. The incidence of SBO after laparoscopic colorectal surgery was lower than that of open colorectal surgery (P < .001), and laparoscopic gastroduodenal surgery was also lower (P = .02). However, there were no differences between laparoscopic and open surgery for other types of surgery. The use of APM had no effect on SBO incidence in any type of abdominal surgery. Conclusions: Laparoscopic surgery helps to reduce SBO incidence only in colorectal surgery, and possibly in gastroduodenal surgery. APM does not reduce SBO after abdominal surgery.

Prognostic and functional role of hyaluronan-binding protein 1 in pancreatic ductal adenocarcinoma.

Hyaluronan-binding protein 1 (HABP1) is among the molecules known to bind to hyaluronan and is involved in a variety of cellular processes, including cell proliferation and migration. HABP1 has been implicated in the progression of various cancers; however, there have been (to the best of our knowledge) few studies on the expression and function of HABP1 in pancreatic ductal adenocarcinoma (PDAC), a topic that is examined in the present study. Immunohistochemical analysis of HABP1 protein was conducted in archival tissues from 105 patients with PDAC. Furthermore, the functional effect of HABP1 on proliferation, colony formation, and migration in PDAC cells was examined by knockdown of HABP1. It was revealed that HABP1 was overexpressed in 49 (46.2%) out of 105 patients with PDAC. Overall survival was significantly shorter in patients with high HABP1 expression than in those with low HABP1 expression (median survival time of 12.8 months vs. 28.5 months; log-rank test, P=0.004). Knockdown of HABP1 expression in PDAC cells resulted in decreased cell proliferation, colony formation, and cell migration activity. Thus, HABP1 may serve as a prognostic factor in PDAC and may be of use as a novel therapeutic target.

Multicenter, single-arm, phase II study of the continuous use of panitumumab in combination with FOLFIRI after FOLFOX for RAS wild-type metastatic colorectal cancer: Exploratory sequential examination of acquired mutations in circulating cell-free DNA.

This multicenter single-arm, phase II study evaluated the efficacy and safety of uninterrupted panitumumab usage combined with cytotoxic doublets for unresectable/metastatic colorectal cancer (mCRC). Additionally, clinical value of the RAS/BRAF mutation status in circulating cell-free DNA (ccfDNA) was evaluated; this evaluation was measured independently of the protocol treatment. Eligible patients with RAS wild-type mCRC who had received the first-line panitumumab plus FOLFOX treatment were recruited and administered continuous panitumumab combined with FOLFIRI. Progression-free survival (PFS) at 6 months was the primary endpoint, with threshold and expected values of 35% and 50%, respectively. In total, 54 patients were enrolled between October 2017 and October 2019. The crude 6-month PFS rate was 37.0%, with a 4.8-month median PFS. The response rate and disease control rate were 16.7% and 50.0%, respectively. Notably, of the 54 participants, 17 showed RAS/BRAF mutations until the end of the protocol treatment and of the 22 patients with progressive disease as their best response, 10 possessed RAS/BRAF mutations in their plasma ccfDNA at baseline. The median PFS significantly differed among patients harboring tumors with BRAF and RAS mutations and those with wild-type tumors. In conclusion, our study failed to show the expected efficacy of the continuous panitumumab use in the second-line treatment. Liquid biopsy discriminated the duration of PFS according to the mutation status. The effectiveness of continuous treatment with panitumumab should be evaluated in patients with RAS/BRAF wild-type mCRC determined by liquid biopsy at the start of the second-line treatment.