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Background: Defecation status is an important determinant of quality of life. Previous studies showed that postoperative defecation disorders occurred after open surgery for ulcerative colitis (UC)...

Early detection of surgical site infection (SSI) allows for appropriate management after Crohn's disease (CD) surgery. The aim of this study was to evaluate the usefulness of bacterial culture of postoperative drainage fluid after CD surgery.This study included 110 patients with CD who underwent surgery with bowel resection between January 2010 and March 2020 at Osaka University Hospital. Patients with only perianal surgery or incomplete records were excluded. Risk factors for SSI were evaluated in the context of clinical findings, including bacterial culture of postoperative drainage fluid, and bacterial species related to SSI were also examined.Of 110 patients, 18 (16.4%) developed SSI. Organ/space SSI developed in six, and a positive bacterial culture of drainage fluid (D-Posi) was found in five (83.3%). Of 104 patients without organ/space SSI, 31 (29.8%) were D-Posi (This study suggests the usefulness of postoperative drainage fluid bacterial culture for early diagnosis of SSI after CD surgery.

The incidence of fecal incontinence is ~2%, and the associated symptoms significantly impact daily life. New treatment methods including electrical stimulation and regenerative therapy using stem cells for fecal incontinence have been reported. We explored the usefulness of an anal sphincter injury mouse model by means of a balloon catheter and focused on the defecation status of mice as a novel method for evaluating anal function. We examined the utility of the mouse model of anal sphincter injury and the efficacy of electrical stimulation as a treatment modality using this model.A 10-mm balloon catheter was used to create an anal sphincter injury model in mice. Sphincter function was evaluated in the noninjured (n = 4), injured (n = 4), noninjured electrical stimulation (n = 4), and injured electrical stimulation (n = 4) groups. Defecation status (defecation frequency in 24 h and fecal weight per stool) and pathological evaluation were used for comparison.The defecation frequency increased and the fecal weight per stool decreased significantly in the anal sphincter injury model. Pathological evaluation revealed that anal sphincter tears occurred the day after the injury. Meanwhile, the defecation frequency improved on d 7, and the fecal weight per stool gradually normalized to that of the control group and exhibited significant sphincter muscle hypertrophy in the electrical stimulation group.Anal sphincter injury using a balloon catheter in mice allowed us to create a uniform model. The evaluation of defecation status in mice is a useful method for comparatively evaluating anal function.

Stoma outlet obstruction (SOO) is much more common after total proctocolectomy (TPC) and ileal-pouch anal anastomosis (IPAA) for ulcerative colitis (UC) compared to after rectal surgery for cancer. Few prior reports have evaluated anatomical risk factors for SOO. In this study we aimed to clarify the risk factors for SOO after IPAA, focusing on the anatomical perspective.This study included 68 UC patients who underwent IPAA with diverting ileostomy. These cases were analyzed based on clinicopathological factors and computed tomography (CT)-based anatomical factors.SOO was identified in 18 patients (26.5%). We compared this SOO group with the non-SOO group. The two groups significantly differed in sex distribution, and patients in the SOO group tended to have a longer postoperative hospital stay. Regarding surgery-related factors, patients who underwent two-stage surgery and experienced high-output syndrome tended to develop SOO. Analysis of anatomical risk factors revealed that SOO was more common in patients with a longer distance between the root of their superior mesenteric artery and the bottom of the external anal sphincter (rSMA-bEAS). This tendency remained significant even with adjustment for patient height. In multivariate analyses, adjusted rSMA-bEAS (191.0 mm/m) and male sex were independent risk factors associated with SOO.A long rSMA-bEAS distance suggests that the mesentery is likely to be under tension. In such cases, surgeons should endeavor to avoid tension in the mesentery as much as possible.

Background The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. Aims This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. Methods In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. Results The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. Conclusion Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed.

Although common cancer therapies, such as chemotherapy and radiation therapy, have recently improved and yielded good results, evaluated as tumor shrinkage, disease recurrence is still a common event for most cancer patients. This is termed refractory cancer. This tumor regrowth following therapy is generally thought to be caused by a small, specific population of tumor cells called cancer stem cells (CSCs). Similar to other stem cells, CSCs have the capacity for self-renewal and multipotent differentiation, and they have been identified in many tumor types based on cell surface protein expression. This specific cell population has stemness characteristics as examined by serial transplantation in animal models. Previous studies have developed a specific signature of cell surface markers and biological functions that can identify CSCs in many solid tumors. In this review, we summarize the characterization of CSCs using new techniques for identifying and quantifying them in situ. These techniques and concepts could be valuable for evaluating the effects of therapies on this cell population. Finally, we conclude by discussing several unique preclinical treatment strategies to targets CSCs, such as reprogramming CSCs or inducing attack by immune cells. Therapeutic and diagnostic methodologies that can target and quantify CSCs will be valuable tools for eradicating refractory cancer.

It is highly controversial whether a lymphadenectomy for treating distant lymph nodes, such as the para-aortic lymph node, provides clinical benefit in colorectal cancer (CRC). This study aimed to investigate the benefit of a lymphadenectomy for para-aortic lymph node metastasis (PALM) in CRC, by evaluating the extent of dissection. This retrospective cohort study included 28 consecutive patients with pathologically positive PALMs in CRC that underwent lymphadenectomies from October 2001 to March 2018 at our institute. We analyzed the rates of 3-year recurrence-free survival (RFS), postoperative complications, and peri-operative death. We examined RFS in two groups with different operation types. One group received radical resections (radical group), defined as a systematic dissection of para-aortic lymph nodes, which removed the area under the renal vein and above the aortic bifurcation. The other group (targeted group) received targeted dissections, which removed specific swollen para-aortic lymph nodes. The radical group had a significantly better RFS than the targeted group. In addition, females had significantly better RFS prognoses than males. Univariate and multivariate Cox regression analyses identified two clinical factors significantly associated with RFS: sex (P = 0.0100) and surgical procedure (P = 0.0033). Postoperative complications after PALM resections occurred in 35.7% of patients. There was no postoperative mortality. Our study suggested that a radical lymphadenectomy for treating PALMs in CRC could be performed safely and could prolong the RFS. More studies are necessary to strengthen the evidence in support of this conclusion.

Lessons Learned The 3-year disease-free survival rate of the twice-daily regimen was not inferior to that of the conventional three-times-daily regimen, and the twice-daily regimen did not lead to an increase in adverse events. The effectiveness of the twice-daily regimen highlights an increased number of treatment options for patients. This will facilitate personalized medicine, particularly for elderly or frail patients who may experience more severe side effects from the combination therapy. Background Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. Methods Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The primary endpoint was 3-year disease-free survival. Results In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6–84.4–74.5–85.9), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). Conclusion Group B outcomes were not inferior to group A outcomes, and adverse events did not increase.

BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation of the digestive tract. Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD, their low sensitivity and high variability characteristics limit clinical efficacy. Thus, the establishment of better biomarkers is expected. Fucosylation is one of the most important glycosylation modifications of proteins. Fucosylated haptoglobin (Fuc-Hpt) is used as a biomarker for several cancers and inflammation-related diseases. We recently established a novel glycan monoclonal antibody (mAb), designated 10-7G, which recognizes Fuc-Hpt. We developed an enzyme-linked immunosorbent assay (ELISA) to measure serum levels of Fuc-Hpt (10-7G values). AIM To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD. METHODS This was a case control study. Intestinal tissues of IBD patients (n = 10) were examined immunohistochemically using the 10-7G mAb. We determined 10-7G values using serum from patients with ulcerative colitis (UC, n = 110), Crohn’s disease (n = 45), acute enteritis (AE, n = 11), and healthy volunteers (HVs) who exhibited normal (n = 20) or high (n = 79) C-reactive protein (CRP) levels at medical check-up. We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers. RESULTS In the immunohistochemical analysis, positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles. The 10-7G values were significantly higher in patients with IBD (P < 0.001) and AE (P < 0.05) compared with HVs. In addition, 10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC, particularly the CRP level (rs = 0.525, P = 0.003) and clinical activity index score (rs = 0.435, P = 0.038). However, there was no correlation between 10-7G values and CRP in HVs with high CRP levels, suggesting that the 10-7G values is not the same as a general inflammation biomarker. ROC curve analysis showed that area under the curve (AUC) value of 10-7G values for the diagnosis of endoscopic remission was higher than other biomarkers (AUC value = 0.699). CONCLUSION The serum 10-7G value is a novel biomarker for evaluating intestinal inflammation and endoscopic mucosal healing in UC.

A left ventricular assist device (LVAD) is used for patients with severe heart failure. We present a case of a 35-year-old man who had undergone LVAD implantation 2 years ago for dilated phase of hypertrophic cardiomyopathy. He had right lower abdominal pain and was diagnosed with acute appendicitis. Single-incision laparoscopic surgery for appendicitis was performed. We incised approximately 3 cm of the umbilicus carefully because the driveline of LVAD was passing just caudal to the umbilicus. LVAD is only available for patients waiting for cardiac transplantation in Japan, and the number of patients with LVAD has been increasing. Adequate anticoagulant therapy is necessary because device thrombosis often causes fatal complications, but during emergency cases, the surgeons have to be cautious of bleeding and injury to the driveline of LVAD.

Purpose The purpose of this clinical study was to be the first to explore whether ART-123, a recombinant human soluble thrombomodulin, prevents oxaliplatin-induced peripheral neuropathy (OIPN). Methods This randomized, phase IIa trial enrolled stage II/III colon cancer patients who received adjuvant mFOLFOX6 chemotherapy. Participants were randomly allocated to 3 arms in a double-blind manner: placebo (placebo: days 1–3); 1-day ART (ART-123: day 1, placebo: days 2–3); and 3-day ART (ART-123: days 1–3). ART-123 (380 U/kg/day) or placebo was infused intravenously before each 2-week cycle of mFOLFOX6. OIPN was assessed with the Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity-12 (FACT/GOG-Ntx-12) score by participants and the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) by investigators. Results Seventy-nine participants (placebo n = 28, 1-day ART n = 27, 3-day ART n = 24) received study drugs. The least-squares mean FACT/GOG-Ntx-12 scores at cycle 12 from the mixed effect model for repeated measures were 28.9 with placebo, 36.3 with 1-day ART (vs. placebo: 7.3 [95% CI 1.9 to12.8, p = 0.009]), and 32.3 with 3-day ART (vs. placebo: 3.4 [95% CI −.1 to 9.0, p = 0.222]). The cumulative incidence of NCI-CTCAE grade ≥ 2 sensory neuropathy at cycle 12 was 64.3% with placebo, 40.7% with 1-day ART (vs. placebo: −23.5 [95% CI −48.4 to 4.0], p = 0.108), and 45.8% with 3-day ART (vs. placebo: −18.5 [95% CI −44.2 to 9.4], p = 0.264). Common adverse events were consistent with those reported with mFOLFOX6; no severe bleeding adverse events occurred. Conclusion ART-123 showed a potential preventive effect against OIPN with good tolerability. A larger study with 1-day ART is warranted. NCT02792842, registration date: June 8, 2016

Highlights • Pain in the anus or presented with red, flat, elevated lesions in the anus needs to suspecte anal canal cancer. • To differentiate between extramammary Paget’s disease (EMPD) and Anorectal cancer with pagetoid spread (PS) is difficult. • A two-stage operation, a local excision followed by pathological diagnosis and an additional excision,can be useful in PS., Introduction Paget’s disease is an intraepithelial invasion by a malignant tumour and is characterised by erythema and inflammation. It can manifest as mammary or extramammary Paget’s disease (EMPD), with the latter often developing in the perianal area. Anorectal cancer can cause transepithelial invasion into the epidermis, resulting in an appearance similar to that of EMPD. This is called pagetoid spread (PS), which is completely different from EMPD. These two conditions are difficult to differentiate because of the nature of intricacy and requirements of histopathology. Presentation of case We present a case in which differential diagnosis between these two conditions was not possible during the preoperative examination, resulting in difficulties in treatment. The patient was a 70-year-old woman who experienced pain in the anus since the previous month and presented with red, flat and elevated lesions. Discussion Treatment for dermatitis was ineffective, and endoscopic examination did not indicate rectal or anal cancer. However, immunohistochemical examination of the biopsy specimen suggested PS. Thus, two-stage operation was planned. Transanal surgery was performed to confirm the diagnosis of PS and intersphincteric resection was allowed as a radical surgery. Conclusion Thus, when differentiation between EMPD and PS is intricacy, two-stage operation is useful in selecting an appropriate radical surgery method, leading to preservation of anal function.

It remains unclear whether Helicobacter pylori (H. pylori), a major cause of gastric cancer (GC), is involved in other intestinal cancers. In our previous study, ICOS+ Foxp3+ CD4+ T cells (ICOS+ Tregs) in GC tumors were identified as effector Tregs and associated with H. pylori. In the present study, the impact of ICOS+ Tregs on not only GC, but also colorectal cancer (CRC) and their prognosis was investigated in association with H. pylori. Tissue-infiltrating lymphocytes (TILs) purified from fresh tumor and sera were obtained from GC and CRC patients prospectively. % ICOS+ Tregs were analyzed by flow cytometry and their production of anti-H. pylori antibody (Hp-Ab) in sera was detected by ELISA. % ICOS+ Tregs were higher in GC and CRC patients with Hp-Ab than in those without Hp-Ab, including eradicated patients. ICOS+ Tregs purified had higher potential to produce IL-10 than ICOS- Tregs. For prognostic analysis, immunohistochemical analysis and ELISA were performed using archival fixed specimens and frozen sera, respectively, obtained from GC and CRC patients. Overall survival was longer in patients with low % ICOS+ Tregs than in those with high % ICOS+ Tregs, and patients with Hp-Ab showed shorter recurrence-free survival than those without Hp-Ab. These results suggested that ICOS+ Tregs in GC and CRC patients were closely associated with H. pylori in gastric epithelium and their prognosis, and that pre-operative H. pylori eradication has potential as a novel immunotherapy for GC and CRC patients.

Objectives The efficacy of negative pressure wound therapy (NPWT) and its application to severely contaminated wounds sustained during surgery remain to be established. Here, we evaluated the efficacy of utilizing NPWT until delayed primary closure (DPC) by assessing the infection rates in patients with lower gastrointestinal perforations. Methods This prospective multicenter cohort study included 56 patients that underwent abdominal surgery for lower gastrointestinal perforations in eight institutions, from February 2016 to May 2017. All patients received NPWT after surgery before attempting DPC. The extent of peritonitis was categorized according to Hinchey's classification. Patients in stages II-IV were included. Results Five patients had surgical site infections (SSIs) during NPWT and did not receive a DPC (9%). Of the 51 patients that received DPCs, 44 had no infection (91%) and 7 developed SSIs after the DPC (13.7%). For stages II, III, and IV, the SSI rates were 0%, 22.6%, and 35.7%, respectively; the median (range) times to wound healing were 15 (10-36), 19 (11-99), and 19 (10-53) days, respectively. There were no significant differences between the stages. Conclusions NPWT followed by DPC resulted in low infection rates in each peritonitis stage. This approach appears promising as an alternative to traditional DPC alone for treating lower gastrointestinal perforations.

Objectives We previously reported the feasibility of neoadjuvant capecitabine and oxaliplatin plus bevacizumab as a treatment for locally advanced rectal cancer (UMIN000003219). The aim of this study is to investigate the prognostic relevance of neoadjuvant chemotherapy followed by total mesorectal resection (TME). Methods Twenty-five patients of our prior multicenter prospective study of neoadjuvant chemotherapy followed by TME enrolled to this study. We analyzed the adjuvant chemotherapy regimen, and the duration between surgery and initial chemotherapy treatment. Five-year progression-free survival and overall survival were estimated using the Kaplan-Meier method. Results Among survivors, the median follow-up time was 66 months. Recurrence occurred in six patients, all of whom had suboptimal tumor regression after neoadjuvant chemotherapy. Five patients died from other causes. The rate of local recurrence and distant metastasis was 17.4% and 8.7%, respectively. Five-year progression-free survival was 70.0%, and 5 year overall survival was 84.0%. Conclusions We report the long-term survival of patients who received neoadjuvant chemotherapy without radiation followed by TME, revealing a generally favorable prognosis.

Malnutrition has been considered to be associated with the prognosis of cancer. The Geriatric Nutritional Risk Index (GNRI), based on serum albumin levels, present body weight, and ideal body weight, is a simple screening tool to predict the risk of nutrition-related morbidity and mortality in elderly patients. We aimed to evaluate whether preoperative GNRI was associated with postoperative complications and prognosis in elderly patients with colorectal cancer (CRC). We retrospectively enrolled 313 CRC patients aged ≥65 years after curative surgery and classified them into an all-risk GNRI (≤98) group and a no-risk GNRI (>98) group. Kaplan-Meier analysis showed overall survival was significantly worse in the all-risk GNRI group than in the no-risk GNRI group (P = 0.009). Multivariable analyses showed low GNRI (≤98) was an independent risk factor for postoperative complications (P = 0.048) and overall survival (P = 0.001) in the patients. Among the complications, the incidence of surgical site infection, in particular, was significantly higher in the all-risk GNRI group (P = 0.008). In conclusion, low preoperative GNRI (≤98) was associated with increased postoperative complications and poor prognosis. Preoperative GNRI can be used as an identifier for potential high-risk group of morbidity and mortality in elderly CRC patients.

This review outlines current topics on the surgical treatment of benign colorectal diseases, with a focus on inflammatory bowel disease (IBD) and diverticulitis. Treatment options for IBD and diverticulitis have evolved in the last few years as a result of medical advances in technology and new clinical trials. Therefore, treatment options and strategies need to be updated to provide optimal care for patients. The purpose of this review is to elucidate recent global trends and update the surgical treatment strategy for IBD and diverticulitis based on literature published in the past 2 years. Prevalence of IBD, including ulcerative colitis and Crohn's disease, has increased over the last few decades. During this period, many new medical therapies were introduced for the treatment of IBD, including biological therapy, immunomodulators, and leukocyte apheresis therapy. As a result, new surgical strategies for IBD are required. In order to improve surgical outcomes in IBD patients, the influence of preoperative treatment on postoperative complications needs to be considered. The incidence of diverticulitis is also increasing with lifestyle changes and increasing numbers of older people. For diverticulitis with perforation and generalized peritonitis, surgery is the gold standard. Elective surgery after conservative treatment of diverticulitis is also an option because of high recurrence rates. With an increase in diverticulitis, systematic strategies are essential for an appropriate approach to diverticulitis, taking into account various factors, including the patient's background.

Background Locally recurrent rectal cancer (LRRC) remains a major problem after curative resection of primary rectal cancer. A noninvasive, prognostic biomarker with which to accurately evaluate disease status and assess the treatment response is critically needed to optimize treatment plans. This study assesses the effectiveness of PET/CT evaluation of preoperative chemoradiation therapy (CRT) in patients with LRRC. Methods Since 2004, we have been performing preoperative CRT to improve local tumor control and survival. Between 2004 and 2013, 40 patients with LRRC underwent preoperative CRT (radiation: 50 Gy/25 fractions; chemotherapy: irinotecan plus UFT [tegafur and uracil]/leucovorin) and radical surgery, and underwent 18F-FDG-PET/CT before and 3 weeks after the completion of CRT. The maximum standardized uptake values (SUVmax) of the pre-CRT scan (Pre-SUV) and the post-CRT scan (Post-SUV) were measured. The predictive value of the 18F-FDG-PET and CT/MRI response assessments was evaluated. Results The mean Pre-SUV was significantly higher than the Post-SUV (8.2 ± 6.1, vs. 3.8 ± 4.0; P P = 0.0038). Pathological response was not correlated with the response as evaluated by CT (P > 0.9999) or MRI (P > 0.9999). Multivariate regression analysis identified Post-SUV as an independent predictor of local re-recurrence-free survival (P = 0.0383) and for overall survival (P = 0.0195). Conclusions PET/CT is useful in assessing tumor response to preoperative CRT for LRRC and predicting prognosis after surgery.

Background The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. Methods This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. Results A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30–0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

Chemotherapy with panitumumab is expected to be well tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). However, skin toxicities are its most common adverse events. The aim of this trial was to evaluate the efficacy and safety of pre-emptive antibiotic treatment with clarithromycin (CAM) to prevent panitumumab skin toxicities.We conducted a phase lll, multicenter, open-label, randomized clinical trial on mCRC patients treated with panitumumab. Eligible patients were randomly assigned 1:1 to pre-emptive antibiotic and control groups. In the pre-emptive group, CAM administration (200 mg twice per day) continued daily through the panitumumab treatment period. The control regimen consisted of skin care only. The primary end point was the incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period.Of 156 enrolled patients, 78 received pre-emptive antibiotic treatment, and 78 received reactive treatment. The number and incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period were 16 (21.3%) and 41 (54.7%) for the pre-emptive and control groups, respectively (HR, 0.32; 95% CI, 0.17-0.56). There was almost no difference in the rate of other adverse events between the two groups, but the incidence of grade ≥ 3 diarrhea in the pre-emptive group was high, at 8% vs. 1.3% in the control group. There were no treatment-related deaths.Prophylactic oral CAM together with relatively simple skin care was found to be effective in suppressing the development of grade ≥ 2 skin toxicities induced by panitumumab.UMIN000011485 DATE OF REGISTRATION: Sep 1st, 2013.

Simple Summary The screening methods and therapeutic strategies for gastrointestinal cancer (GIC) have improved, but mortality in GIC patients remains high. Early detection and precise evaluation of GIC are required to further improve treatment outcomes in GIC patients. MicroRNAs (miRNAs), which do not encode proteins, have attracted attention as biomarkers of various diseases. Since the first report revealing the strong correlation between miRNAs and cancer in 2002, numerous studies have illustrated the changes in the expression and the biological and oncological effects of miRNAs in GIC. Furthermore, miRNAs circulating in the blood are reported to be associated with GIC status. These miRNAs are thought to be useful as noninvasive biomarkers because of their stability in blood. Herein, we discuss the potential of miRNAs as noninvasive biomarkers for each type of GIC on the basis of previous reports and describe perspectives for their future application. Abstract Gastrointestinal cancer (GIC) is a common disease and is considered to be the leading cause of cancer-related death worldwide; thus, new diagnostic and therapeutic strategies for GIC are urgently required. Noncoding RNAs (ncRNAs) are functional RNAs that are transcribed from the genome but do not encode proteins. MicroRNAs (miRNAs) are short ncRNAs that are reported to function as both oncogenes and tumor suppressors. Moreover, several miRNA-based drugs are currently proceeding to clinical trials for various diseases, including cancer. In recent years, the stability of circulating miRNAs in blood has been demonstrated. This is of interest because these miRNAs could be potential noninvasive biomarkers of cancer. In this review, we focus on circulating miRNAs associated with GIC and discuss their potential as novel biomarkers.

Background Perianal fistula (PAF) is a disabling complication of Crohn’s disease (CD) which greatly impacts the quality of life. To address a scarcity of data in Asian populations, we determined the prevalence of CD-associated PAF in Japan, the order of diagnosis, and medical history of patients. Methods A retrospective, longitudinal, observational cohort study was conducted, using an employer-based health insurance claims database. The study included patients diagnosed with CD and/or PAF from October 2013 to September 2019. Results The age- and gender-adjusted prevalence rates of CD-associated PAF increased from 10.33 per 100 000 in 2014, to 13.68 per 100 000 in 2019. Among patients with CD-associated PAF, 15.7% were diagnosed with PAF after diagnosis of CD, 68.6% were diagnosed with PAF before diagnosis with CD, and 15.7% were diagnosed with CD and PAF within the same month. Of the patients diagnosed with CD after PAF, approximately 30% were diagnosed with PAF by the age of 20 years, whereas less than 10% of PAF patients without CD were diagnosed with PAF by the age of 20 years. Conclusions The study reveals the prevalence of CD-associated PAF in Japan and that most individuals were diagnosed with CD after the diagnosis of PAF. Crohn’s disease may be underdiagnosed in patients with PAF; patients diagnosed with PAF at a young age should be monitored to allow timely diagnosis of CD.

Doublecortin-like kinase 1 (DCLK1) promotes tumour proliferation in human colorectal cancer (CRC). To elucidate the mechanism and clinical relevance of this association, we performed expression analysis using commercially available colon carcinoma cell lines (SW480, HCT116, CaCO2, SW48 and SKCO1) and immunohistochemical analysis of 200 resected CRC samples for correlation with clinical features. DCLK1 showed a high level of expression, especially in SW480 and HCT116 cells. Silencing DCLK1 expression using short hairpin DCLK1 (shDCLK1) RNA inhibited the growth and invasion capacities of these cell lines, which showed signs of entering into the mesenchymal–epithelial transition (MET). We found evidence of a strong correlation of DCLK1 expression with that of Tribbles homolog 3 (TRIB3), and silencing TRIB3 also led to the MET phenotype in these cells. In the clinical samples, compared with samples showing low expression of DCLK1, high expression was associated with poor prognosis in terms of overall and recurrence-free survival (P < 0.0001). The results of univariate and multivariate analysis suggested that high expression of DCLK1 in clinical colon cancer samples was tied to poor prognosis, cancer invasion depth and lymph node metastasis. DCLK1 expression correlates with malignant grade of colon cancer and offers a potential treatment target.

Aim Visceral obesity (VO) reportedly has a stronger association with complications after colorectal surgery than does body mass index. Here, we retrospectively assessed VO as a risk factor for postoperative ileus (POI) after colorectal resection in patients with colorectal cancer. Methods This study included 417 consecutive patients with colorectal cancer who underwent elective surgery at our institute from January 2010 to December 2012. Visceral fat area (VFA) was calculated by image analysis software. VO was defined as VFA ≥100 cm2. We assessed 49 factors, including VO, comorbidities, surgical procedure, and postoperative complications. Data were analyzed using a propensity score‐matching strategy. Results Postoperative ileus occurred in 18 patients (4.3%) from the entire cohort, and in 14 (5.5%) of the 256 matched patients. Multivariate analysis (n = 417 patients) showed that significant risk factors for POI included VO (OR 7.9, 95% confidence interval [CI] 1.9‐32.1, P = .004), open surgery (OR 6.4, 95% CI 1.6‐26.7, P = .010), and pelvic/intra‐abdominal abscess (OR 11.0, 95% CI 1.1‐110.2, P = .041). Propensity score matching showed two independent risk factors in the multivariate analysis: VO (OR 6.2, 95% CI 1.3‐30.4, P = .025) and open surgery (OR 9.1, 95% CI 2.0‐40.5, P = .004). Conclusion Visceral obesity may be an independent risk factor for POI in patients with colorectal cancer., Visceral obesity reportedly has a stronger association with complications after colorectal surgery than does body mass index. We retrospectively assessed visceral obesity as a risk factor for postoperative ileus (POI) after colorectal resection in patients with colorectal cancer. Visceral obesity may be an independent risk factor for POI in patients with colorectal cancer.

We assessed the feasibility and safety of single-site laparoscopic surgery for patients with colorectal cancer who required perioperative heparinization. This retrospective study reviewed the medical records of 390 patients who underwent single-site laparoscopic surgery for colorectal cancer from January 2010 to December 2016. Antithrombotic drugs were stopped preoperatively and heparin was administered according to the operative risk of each patient, based on consultation with the cardiologist physician or neurosurgeon. Propensity score modeling was utilized to adjust for baseline characteristics. Of 390 patients, 29 were treated with standard bridging intravenous heparin therapy. Propensity matching identified 119 patients: 22 patients in the heparinization group and 97 in the control group. The matched groups were not significantly different in operation times, bleeding volumes, or conversion rate. The mean postoperative hospital stay was 17.9 days in the heparinization group and 9.5 days in the control group (p = 0.034). Postoperative bleeding was observed in 4 patients (18.2%) in the heparinization group and 11 patients (11.4%) in the control group (p = 0.646), while other complications were similar in the two study groups (p = 0.502). Of these other complications, thromboembolic events were observed in two patients in the heparinization group and one patient in the control group. We found that single-site laparoscopic surgery for colorectal cancer with heparinization was feasible and safe. Heparinization did not increase the risk of postoperative bleeding complications, but postoperative hospital stay was prolonged.

Paroxysmal nocturnal hemoglobinuria is a rare and life-threatening disorder of acquired hemolytic anemia. Surgery is one of the major clinical situations that trigger hemolytic attack. Eculizumab is a humanized monoclonal antibody that binds the complement protein C5 and prevents complement-mediated hemolysis via inhibition of the terminal complement cascade. A 76-year-old woman received a diagnosis of ascending colon cancer during the search for the cause of right lower abdominal pain. She had received a diagnosis of paroxysmal nocturnal hemoglobinuria and been followed for 26 years at our hospital. We planned to start eculizumab for perioperative management in order to reduce the risk of the patient developing hemolytic crisis as a result of surgery. We administered 600 mg of eculizumab on the 15th, 8th, and 1st preoperative days. The levels of serum complement and lactate dehydrogenase decreased with the first administration of eculizumab. Laparoscopic right hemicolectomy was performed successfully. The patient had good postoperative progress. We administered 600 mg of eculizumab on the 6th postoperative day and 900 mg of eculizumab on the 13th postoperative day. She was discharged from hospital on the 16th postoperative day. We started use of eculizumab before surgery for safety in the management of the operation and during the perioperative period. When we enforce the elective operation for patients with paroxysmal nocturnal hemoglobinuria who do not start treatment of eculizumab, we recommend the use of eculizumab for perioperative management of patients with paroxysmal nocturnal hemoglobinuria.

We aimed to evaluate the short-term outcome of colorectal resection in very elderly patients, aged 85 years or older. As the population ages, the number of elderly patients with colorectal cancer (CRC) is increasing in Japan. At this time, it is unclear whether or not laparoscopic colorectal resection is safe for this very elderly patient population. From January 2005 to November 2014, a total of 20 patients aged 85 years or older underwent laparoscopic colorectal resection at Osaka University Hospital. Pre- and postoperative clinical data and outcomes were collected retrospectively. There were no intraoperative or postoperative deaths. In 2 cases, the laparoscopic procedure was converted to open surgery. Postoperative complications occurred in 6 patients. Two patients developed an infection at the surgical site. Among the 4 patients who underwent low anterior resection (LAR), 2 experienced postoperative anastomotic leakage. Two other patients developed a lung infection and urinary tract infection, respectively. Laparoscopic colectomy for very elderly patients with CRC appears to involve tolerable risk. However, special caution is advisable for patients who may undergo LAR.

Introduction Intestinal obstruction in pregnancy is very rare, but the maternal mortality rate and the fetal loss rate are high. Therefore, an early diagnosis and appropriate treatments for small bowel obstructions (SBOs) during pregnancy are crucial for the mothers and fetuses. On the other hand, laparoscopic surgeries are widely used in pregnant patients, although laparoscopic surgeries for SBOs can have higher risks of complications. Then, reduced port surgery (RPS) can reduce the risk of intestinal injury by minimizing the number of ports the operator could not control alone. There is no previous report of RPS for SBOs in pregnant patients. We report on a pregnant patient with a strangulated SBO treated with RPS without complications. Case presentation A 37-year-old Japanese pregnant woman complaining of severe abdominal pain was admitted by ambulance. Her gestational age was 9 weeks. Her medical history included surgery for acute perforated appendicitis and deep vein thrombosis due to anti-thrombin III deficiency. Abdominal computed tomography revealed a strangulated SBO. We performed RPS and the cause of strangulated SBO was a string at the postoperative site of the appendectomy. The ischemic region of the small bowel recovered after we cut the string and released the adhesion. The patient's postoperative course was uneventful and the fetus was not harmed. Conclusion This is the first report of RPS performed for the pregnant patient with the strangulated SBO. Our findings indicate that RPS is a feasible treatment for strangulated SBOs in pregnant women.

Unlike cancer cell lines, tumors and primary cultured cells exhibit phenotypic heterogeneity. Although methods for establishing organoids within three-dimensional (3D) gels are well-known, the growth is slower than that of two-dimensional (2D) cultured cells and many niche factors need to be added. In this study, we established primary cultured organoid in 2D culture (2D organoid; 2DO) in a reproducible manner and with clinical phenotypic heterogeneity. The 2DO contained cancer stem cells (CSCs) expressing CD44 and CD133. The addition of basic fibroblast growth factor and transforming growth factor-β as niche factors was necessary to establish the 2DO and maintain the CSC population. The established 2DO showed sufficient proliferation, and the culture could be transferred to the 3D culture. Morphological analysis of the xenograft induced by 2DO reflected parental tumor differentiation, and gene expression in the 2DO was similar to that in the parental tumor. In vitro drug sensitivity analysis using the 2DO reflected individual clinical courses. The 2DO is an in vitro personal cancer model, and the results of the drug sensitivity assessment may be useful for introducing clinical chemotherapy agents in personalized medicine.

ADP-ribosylation factor-like 4c (ARL4C) is identified as a small GTP-binding protein, which is expressed by Wnt and EGF signaling and plays an important role in tubulogenesis of cultured cells and the ureters. ARL4C is little expressed in adult tissues, but it is highly expressed in lung cancer and colorectal cancer and shown to represent a molecular target for cancer therapy based on siRNA experiments. This study revealed that ARL4C is highly expressed in primary hepatocellular carcinoma (HCC) tumors and colorectal cancer liver metastases, and that ARL4C expression is associated with poor prognosis for these cancers. Chemically modified antisense oligonucleotides (ASO) against ARL4C effectively reduced ARL4C expression in both HCC and colorectal cancer cells and inhibited proliferation and migration of these cancer cells in vitro. ARL4C ASOs decreased the PIK3CD mRNA levels and inhibited the activity of AKT in HCC cells, suggesting that the downstream signaling of ARL4C in HCC cells is different from that in lung and colon cancer cells. In addition, subcutaneous injection of ARL4C ASO was effective in reducing the growth of primary HCC and metastatic colorectal cancer in the liver of immunodeficient mice. ARL4C ASO accumulated in cancer cells more efficiently than the surrounding normal cells in the liver and decreased ARL4C expression in the tumor. These results suggest that ARL4C ASO represents a novel targeted nucleic acid medicine for the treatment of primary and metastatic liver cancers.

Aim Appendiceal mucinous neoplasms are rare, and thus the literature is sparse with regard to histological types, staging, and prognosis. In particular, it is unclear how long‐term outcome may differ between mucinous adenocarcinomas and other adenocarcinomas. In the present study, we aimed to investigate the histological types and stages of appendiceal neoplasms, and to evaluate the prognostic impacts of these factors in patients with mucinous adenocarcinomas and non‐mucinous adenocarcinomas. Methods Patients with appendiceal tumors diagnosed between 2007 and 2016 were retrospectively identified from the databases of 19 institutions in the Clinical Study Group of Osaka University, Colorectal Group. Results A total of 266 patients with appendiceal tumors were identified, of whom 130 had pathologically diagnosed adenocarcinomas, including 57 with mucinous adenocarcinomas and 73 with non‐mucinous adenocarcinomas. Five‐year overall survival (OS) rates were 64.5% for mucinous adenocarcinomas, and 49.0% for non‐mucinous adenocarcinomas. OS was significantly shorter among patients with non‐mucinous adenocarcinomas compared to mucinous adenocarcinomas. Among patients with mucinous adenocarcinomas, 5‐year OS rates were 53.6% for stage 0/I, 82.6% for II/III, and 48.4% for IV. Among patients with non‐mucinous adenocarcinomas, 5‐year OS rates were 90.9% for stage 0/I, 68.8% for II/III, and 7.1% for IV. Analysis of patients with stage IV disease revealed significantly shorter OS among patients with non‐mucinous adenocarcinomas compared to mucinous adenocarcinomas. Conclusion Our present findings showed a better prognosis in patients with mucinous adenocarcinomas compared to non‐mucinous adenocarcinomas. In this setting, Union for International Cancer Control staging was associated with prognosis for non‐mucinous adenocarcinomas, but not for mucinous adenocarcinomas.

To determine the effectiveness of surveillance colonoscopy (SC) and optimize its use by assessing real-world surgically resected cases of ulcerative colitis (UC)-associated colorectal cancer (CRC) and dysplasia.Clinicopathological data of 406 (238 CRC and 168 dysplasia) patients who underwent surgical resection in 10 UC specialized institutions were retrospectively reviewed. The overall survival (OS) rates were compared between the SC and non-SC groups. The incidence of and risk factors for early-onset CRC (8 years after UC onset) were identified. The distribution of CRC lesions was also assessed.Cancer stages were significantly more advanced in the non-SC group than in the SC group (P0.001). The patients in the SC group showed significantly better OS than those in the non-SC group (5-year OS: 89% vs 70%; log-rank test: P = 0.001). Seventeen percent of patients developed CRC within 8 years after UC onset. The age at UC onset was a risk factor and a good predictor of early-onset CRC (8 years) (P0.01; AUC: 0.85). The most common sites of CRC were the rectum (51%) and sigmoid colon (20%). Multiple CRC was identified in 16% of patients.Surveillance colonoscopy was effective and improved the OS in patients with UC. We recommend that patients with late-onset UC (40 years) undergo SCs earlier because of the high incidence of CRC within 8 years of UC onset. Moreover, the rectum and sigmoid colon should be more thoroughly examined.

Purpose Surgical site infection (SSI) is the most frequently occurring nosocomial infection. Remarkable surgical progress has recently been made in laparoscopic surgery. Therefore, our objective was to investigate the association between increased rates of laparoscopic colon surgery and SSI. Methods We retrospectively investigated SSI surveillance data from July 2003 to December 2015. Two university hospitals and 25 university-affiliated hospitals participated in prospective SSI surveillance. Univariate and multivariate analyses were performed to detect significant associations. Results We investigated 9655 colon surgeries. The year in which surgery was performed was significantly associated with the SSI rate (p = 0.0381). The rate of laparoscopic surgery gradually increased during the study period, and by 2012 it was routinely used for > 50% of colon surgeries. Laparoscopic surgery became a significant factor associated with reduced SSI rates compared with conventional open surgery once the performance rate of laparoscopic surgery reached > 50%. Conclusions Increasing rates of laparoscopic colon surgery tended to be associated with a reduction in the SSI risk after surgical treatment of colonic disease. The results of this study might encourage surgeons to view laparoscopic surgical techniques as an evidence-based approach for reducing the risk of SSI. Electronic supplementary material The online version of this article (10.1007/s00595-019-1760-1) contains supplementary material, which is available to authorized users.

Background/Aims: Endoscopic recurrence (ER) after intestinal resection for Crohn’s disease (CD) precedes the clinical recurrence, and the severity of ER correlates with the severity of the subsequent clinical recurrence. This study aimed to identify risk factors related to early ER after intestinal resection for CD and to create a prediction model. Methods: The patients who underwent intestinal resection for CD between April 2008 and April 2017 and took endoscopic evaluation between 6 and 12 months after surgery were retrospectively analyzed. Results: A total of 15 out of 52 (29%) patients developed early ER. A univariate analysis demonstrated that early ER was significantly correlated with history of prior intestinal resections for CD (p = 0.005), low preoperative albumin levels (p = 0.035), and excessive perioperative inflammation (i.e., high C-reactive protein levels in both preoperative and postoperative periods; p = 0.034). Based on these clinical factors, a nomogram for predicting early ER was created with the area under the curve 0.808. Conclusion: We developed a novel predictive nomogram for early ER after intestinal resection for CD. This prediction model might assist clinicians in managing patients with CD after an intestinal resection. Additional validation studies are currently being developed.

Objectives: The aim of this study was to determine the recommended dose (RD) of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as a neoadjuvant chemotherapy in patients with locally advanced rectal cancer. Method: Patients received irinotecan and oxaliplatin (85 mg/m2) on day 1, and capecitabine (1,000 mg/m2 orally twice daily) on days 1–7 of a biweekly schedule. Three dose levels, ranging from 100 to 150 mg/m2, were explored for irinotecan in sequential cohorts of 6 patients. Dose-limiting toxicities (DLTs) were assessed in the first cycle to determine the RD. Results: Six patients were enrolled. The DLT was grade 3 febrile neutropenia, which was observed in 2 of the 6 patients at dose level 1. The RD of irinotecan was defined as 150 mg/m2. Toxicity was manageable: the most common grade ≥3 toxicities were neutropenia (2 patients), anemia (1 patient), and anorexia (1 patient). Nodal downstaging (cN+ to ypN0) was detected in 2 patients and the T stage was downstaged in 3 patients. Conclusions: XELOXIRI is a feasible and active regimen for patients with locally advanced rectal cancer. Febrile neutropenia was the DLT, and the RD of irinotecan is 150 mg/m2.

Background Local recurrence is common after curative resections for rectal cancer. Surgical intervention is among the best treatment choices. However, achieving a negative resection margin often requires extensive pelvic organ resections; thus, the postoperative complication rate is quite high. Recent studies have reported that the inflammatory index could predict postoperative complications. This study aimed to validate the correlation between clinical factors, including inflammatory markers, and severe complications after surgery for local recurrent rectal cancer. Methods This retrospective study included 99 patients that underwent radical resections for local recurrences of rectal cancer. Postoperative complications were graded according to the Clavien-Dindo classification. Grades ≥3 were defined as severe complications. Risk factors for severe complications were identified with univariate and multivariate logistic regression models and assessed with receiver-operating characteristic curves. Results Severe postoperative complications occurred in 38 patients (38.4%). Analyses of correlations between inflammatory markers and severe postoperative complications revealed that the strongest correlation was found between the prognostic nutrition index and severe postoperative complications. The receiver-operating characteristic analysis showed that the optimal prognostic nutrition index cut-off value was 42.2 (sensitivity: 0.790, specificity: 0.508). In univariate and multivariate analyses, a prognostic nutrition index ≤44.2 (Odds ratio: 3.007, 95%CI:1.171–8.255, p = 0.02) and a blood loss ≥2850 mL (Odds ratio: 2.545, 95%CI: 1.044–6.367, p = 0.04) were associated with a significantly higher incidence of severe postoperative complications. Conclusions We found that a low preoperative prognostic nutrition index and excessive intraoperative blood loss were risk factors for severe complications after surgery for local recurrent rectal cancer.

POU5F1-expressing cells can self-renew and differentiate, contributing to metastasis formation in colorectal cancer (CRC), but it plays an important role in normal pluripotent stem cells. Here, we identified the CRC-specific gene, HNF1A, which is the downstream of POU5F1. HNF1A associates with fatty acid and glucose metabolism, and CRC cells highly expressed it. In 198 CRC patients, high HNF1A expression was an independent predictor of disease-free (P = 0.031) and overall (P = 0.007) survival. HNF1A-knockdown showed significantly reduced cell growth, increased apoptosis, and improved anticancer drug sensitivity. We revealed that HNF1A regulated controlled GLUT1 expression via HIF1A and multidrug resistance protein function to suppress SRI. HNF1A expression was elevated in persister cells after exposure to anticancer drugs, and anticancer drug sensitivity was also improved in persister cells via the inhibition of HNF1A. In conclusion, HNF1A expression can reflect resistance to anticancer drug treatment, and its suppression improves anticancer drug sensitivity as a new therapeutic target.

Background Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated. This study aimed to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS. Methods This randomized phase II, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled. Results Overall response rates were 59.1 and 43.5% (p = 0.29) and disease control rates were 90.9 and 91.3% (p = 0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR = 0.607, p = 0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR = 0.558, p = 0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p = 0.032 and p = 0.003, respectively). Conclusions The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen. Trial registration UMIN Clinical Trials Registry (UMIN000006706). Date of registration: NOV/11/2011. URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920

Castleman's disease (CD) is a rare atypical lymphoproliferation disorder first reported in 1954. Clinically, CD is classified as unicentric or multicentric CD based on anatomical distribution. Unicentric CD primarily affects the mediastinum, and rarely affects the retroperitoneal location. The standard treatment for unicentric CD is complete surgical resection; however, this can be complicated by a high degree of attachment with other organs or hypervascularity. Preoperative angiography and embolization of the arteries that feed the problematic mass can reduce intraoperative bleeding in cases of CD with hypervascularity. In the present case report, a 44-year-old man who was found to have a pelvic retroperitoneal mass with calcification based on abdominal imaging results is discussed. Due to the hypervascularity of the mass, preoperative embolization was performed. The mass was completely resected without any complications. Additionally, a review of the literature on pelvic CD and preoperative embolization of CD was performed to provide an up-to-date reference on the management and outcomes of patients with CD.

Background The presence of lateral pelvic lymph node (LLN) metastasis is an essential prognostic factor in rectal cancer patients. Thus, preoperative diagnosis of LLN metastasis is clinically important to determine the therapeutic strategy. The aim of this study was to evaluate the efficacy of preoperative positron emission tomography/computed tomography (PET/CT) in the diagnosis of LLN metastasis. Methods Eighty-four patients with rectal cancer who underwent LLN dissection at Osaka University were included in this study. The maximum standardized uptake value (SUVmax) of the primary tumor and LLN were preoperatively calculated using PET/CT. Simultaneously, the short axis of the lymph node was measured using multi-detector row computed tomography (MDCT). The presence of metastases was evaluated by postoperative pathological examination. Results Of the 84 patients, LLN metastases developed in the left, right, and both LLN regions in 6, 7, and 2 patients, respectively. The diagnosis of the metastases was predicted with a sensitivity of 82%, specificity of 93%, positive predictive value of 58%, negative predictive value of 98%, false positive value of 7%, and false negative value of 18% when the cutoff value of the LLN SUVmax was set at 1.5. The cutoff value of the short axis set at 7 mm on MDCT was most useful in diagnosing LLN metastases, but SUVmax was even more useful in terms of specificity. Conclusions The cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients.

Histological examination of the lymph nodes (LNs) is crucial to determine the colorectal cancer (CRC) stage. We previously reported a new fat-dissociation method (FM) to detect LNs from surgically resected mesentery. This study aimed to examine the effectiveness of FM compared with that of conventional palpation method (PM) in CRC. This single-center, open-label, randomized controlled study was performed at Osaka International Cancer Institute in Japan in 2014. Randomization was performed using a computer-generated permuted-block sequence. Patients were stratified by surgical procedures and the LN dissection area. The primary endpoint was the time required for LN identification. The secondary endpoint was the number of LNs and 5-year cancer-specific survival. The 130 enrolled patients were randomly assigned in a 1:1 ratio to the FM and the PM groups. LN identification times were 45 (range 15–80) and 15 (range 7–30) minutes in the PM and the FM groups, respectively (P P = 0.047). The number of LN which could be examined pathologically was 16 (range 2–48) and 18 (range 4–95) in the PM and FM groups, respectively (P = 0.546). In right-sided CRC, the number of LNs was higher in the FM group than in the PM group (P = 0.031). Relapse-free survival rates and cancer-specific survival rates did not differ between the groups. In conclusion, FM reduced the time required for LN detection without reducing the number of detected LNs, making it is a useful method to detect LNs in surgical specimens.

We report the case of a 71-year-old man who complained of abdominal distension, pedal edema, respiratory discomfort, and weight gain. Computed tomography revealed a giant, poorly enhancing tumor occupying the entire abdomen, with abdominal ascites. The tumor was causing hydronephrosis, compression of the inferior vena cava, and elevation of the diaphragm. The patient exhibited deterioration of performance status (PS3 on the ECOG scale) and required oxygen; therefore, emergency surgery was performed. Operative findings included bloody abdominal ascites and peritoneal dissemination. The large tumor arose from the small bowel mesentery, and infiltrated into the cecum and sigmoid colon. Tumor excision with ileocecal resection and sigmoidectomy was performed. Histopathological examination revealed dedifferentiated liposarcoma. The patient was discharged on postoperative day 22, but pre-discharge CT revealed a recurrent liposarcoma in the retroperitoneum. Therefore, chemotherapy was initiated and the treatment has been continued for over 6 months after surgery. Due to the rarity of this disease, there is no consensus regarding treatment strategies for DDLPS with peritoneal dissemination or in patients with a poor general condition, especially in the setting of oncologic emergency. In this case, multimodal treatment was used to successfully manage this life-threatening state and obtain satisfactory therapeutic results.

Introduction: Recently, “low-grade appendiceal mucinous neoplasms” (LAMNs) have been proposed as one subtype of appendiceal mucinous neoplasms, characterized by a villous or flat proliferation of mucinous epithelium with low-grade cytologic atypia. The aim of this study was to clarify the clinicopathological characteristics of LAMN. Methods: In this multi-institutional cohort study, we retrospectively analyzed the clinicopathological characteristics in appendiceal neoplasms patients who underwent treatment from 2000 to 2017. Results: In total, 922 patients were enrolled, with 279 (30.3%) cases of LAMN, and 93 (10.1%) cases of non-LAMN disease. In comparison with patients with non-LAMN disease, those with LAMN had significantly lower levels of CA19-9 (p = 0.045), a lower frequency of T4 tumors (p < 0.0001), a lower frequency of lymph node metastasis (p < 0.0001), and a lower frequency of distant metastasis (p < 0.0001). Survival analysis revealed that patients with LAMN had a significantly better prognosis than did those with non-LAMN disease (p < 0.001). Among the patients with distant metastasis, those with LAMN had a significantly better prognosis than did those with non-LAMN disease (p = 0.0020), but among the patients without distant metastasis, the difference between the 2 groups was not significant (p = 0.26). However, among patients who underwent complete resection, the difference in prognosis between the 2 groups was not significant (p = 0.10). Conclusions: A multicenter retrospective study revealed that the clinicopathological characteristics of LAMN was different from those of non-LAMN.

BACKGROUND Appendiceal tumor has recently been treated differently from colorectal cancer. However, obtaining knowledge of this disease is difficult because of its rareness. OBJECTIVE This study aimed to investigate the clinicopathological characteristics of appendiceal tumors in a Japanese cohort. DESIGN This was a nationwide multi-institution retrospective observational study. SETTING This study was conducted at the participating tertiary referral hospitals. PATIENTS Patients with appendiceal tumor who were diagnosed between 2000 and 2017 were included. MAIN OUTCOME MEASURES The primary outcome measured was the total survivability. RESULTS A total of 922 patients from the 43 facilities that participated were identified. Of these, 114 patients were diagnosed with cancer other than adenocarcinomas. The remaining 760 patients, with the exception of 48 patients with unknown survival data, were eligible for the final cohort analysis. Of these 760 patients, 515 (67.8%) had mucinous adenocarcinomas and 245 (32.2%) had nonmucinous adenocarcinomas. Within the mucinous adenocarcinoma group, 267 patients (35.1%) were diagnosed as having low-grade appendiceal mucinous neoplasm. The 5-year survival rate of mucinous adenocarcinoma (83.1%) was superior to that of nonmucinous adenocarcinoma (62.0%; p < 0.01). Regarding mucinous adenocarcinoma, multivariate analysis revealed that high differentiation grade (American Joint Committee on Cancer grade 2/3), distant metastases, and R2 operation were significantly associated with a higher 5-year mortality rate. The 5-year survival rate was significantly better for low-grade appendiceal mucinous neoplasms (93.3%) than for other mucinous adenocarcinomas (72.1%; p < 0.01). LIMITATIONS This study was limited by its retrospective study design. CONCLUSIONS We cumulatively investigated appendiceal tumors in a multicenter retrospective study; this is the first such report from Asia. Grouping the grades as per the American Joint Committee on Cancer was useful as a prognostic indicator of appendiceal mucinous adenocarcinomas, including low-grade appendiceal mucinous neoplasm. See Video Abstract at http://links.lww.com/DCR/B282. ANALISIS DE LAS CARACTERISTICAS CLINICOPATOLOGICAS DE LOS TUMORES APENDICULARES EN JAPON: UN ESTUDIO CLINICO RETROSPECTIVO COLABORATIVO MULTICENTRICO: UNA ENCUESTA NACIONAL JAPONESA: El tumor apendicular recientemente se ha tratado de manera diferente al cancer colorrectal. Sin embargo, obtener conocimiento de esta enfermedad es dificil debido a su rareza.Este estudio tuvo como objetivo investigar las caracteristicas clinicopatologicas de los tumores apendiculares en una cohorte Japonesa.Este fue un estudio observacional retrospectivo de multiples instituciones a nivel nacional.Este estudio se realizo en los hospitales de referencia terciarios participantes.se incluyeron pacientes con tumor apendicular que fueron diagnosticados entre el 2000 y 2017.El resultado primario medido fue la supervivencia total.Se identificaron un total de 922 pacientes de las 43 instalaciones que participaron. De estos, 114 pacientes fueron diagnosticados con cancer distinto de adenocarcinomas. Los 760 pacientes restantes, excepto 48 pacientes con datos de supervivencia desconocidos, fueron elegibles para el analisis de cohorte final. De estos 760 pacientes, 515 (67,8%) tenian adenocarcinomas mucinosos y 245 (32,2%) tenian adenocarcinomas no mucinosos. Dentro del grupo de adenocarcinoma mucinoso, 267 pacientes (35,1%) fueron diagnosticados con neoplasia mucinica apendicular de bajo grado (LAMN). La tasa de supervivencia a 5 anos del adenocarcinoma mucinoso (83.1%) fue superior a la del adenocarcinoma no mucinoso (62,0%) (p

Recently developed molecularly targeted therapies such as EGFR inhibitors have notably improved the prognosis of patients with cancer. However, patients with KRAS and BRAF mutations do not currently benefit from these therapies. Here, we aimed to examine potential effects of crenolanib as a new molecularly targeted therapy in colorectal cancer. We used multiple colorectal cancer cell lines to investigate the growth-inhibitory effect of crenolanib and its effect in combination with other cytotoxic agents. Primary cultures of patient-derived organoids (PDO), a model that reflects the heterogeneity of clinical colorectal cancer, were used to further validate the effects of crenolanib. Unlike cetuximab, crenolanib remarkably suppressed ERK and AKT/mTOR pathways in HT29 cells with BRAF mutation and in HCT116 cells with KRAS mutation with corresponding growth-suppressing effects. Additive or synergistic effects were observed in treatments with combination of crenolanib and other cytotoxic drugs. Moreover, crenolanib suppressed the expression of stem cell markers, such as OCT4, NANOG, and SOX2. These observations were substantiated in seven PDOs with KRAS mutation and two PDOs without KRAS/BRAF mutations, with crenolanib suppressing the growth of all PDOs regardless of their KRAS mutation status. Furthermore, crenolanib abrogated PDGF- and TGFβ-induced increase of OCT4-positive cells in PDOs. Together, these findings suggest that crenolanib may have clinical utility for patients with colorectal cancer, especially patients with KRAS/BRAF mutations. Implications: These findings indicate that crenolanib can be a useful target agent for patients with colorectal cancer, especially patients with KRAS/BRAF mutations.

In cases of lower rectum-located tumor or severe disease, surgical resection is currently the effective management; however, it also carries increased risks of function loss. The interdisciplinary field of regenerative medicine offers strategies that can potentially restore severely diseased and injured tissues and organs. Adipose-derived stromal cells (ASCs) are an abundant and accessible source of adult stem cells and hold great promise as therapeutic agents for tissue regeneration. In this work, we transplanted cells isolated from human stromal tissues, including a 6%–7% ASC population, into heat-damaged femoral muscles of non-obese diabetic immunodeficient mice. The movement of the limbs was observed to determine the functional recovery 3 months after transplantation. Among the mice that did not receive cell transplantation, 20% were able to walk with the injured limb touching the ground, while all of the mice in the ASC-treatment group were able to walk. Furthermore, all ASC-treated mice were able to stand on both back paws, in contrast to the control group mice. The human stromal cell population containing ASCs was able to differentiate and engraft the injured muscle tissues successfully. Our results indicate that stromal material/ASC-based therapies are a promising strategy for the regeneration of tissues and function restoration after severe injury due to surgery.

In recent years, systemic chemotherapy has significantly improved the prognosis of metastatic colorectal cancer (CRC); however, different patients have different responses to chemotherapeutics. Dipeptidyl peptidase 9 (DPP9) is an enzyme in the dipeptidyl peptidase IV family that has been reported to increase drug sensitivity in acute myeloid leukemia. In this study, we examined the relationship between DPP9 expression and the prognosis of patients with CRC, as well as the role of DPP9 in anticancer drug resistance. Moreover, the effects of the DPP9 inhibitors talabostat and vildagliptin in CRC cell lines and primary cultured cells were assessed. High expression of DPP9 was associated with worse prognosis in 196 patients with CRC. Cell viability was markedly inhibited in CRC cell lines transfected with DPP9 small interfering RNA or small hairpin RNA. Talabostat suppressed proliferation in CRC cell lines and primary cultured cells, and increased their sensitivity to chemotherapy. Vildagliptin, a DPP family inhibitor currently administered for diabetes, also increased the sensitivity of CRC cells to anticancer drugs. DPP9 was a poor prognostic factor for CRC and could be a new therapeutic target, while vildagliptin could be used as a repositioned drug for CRC treatment.