Examination of colorectal cancer cases with metal allergy.

PURPOSE: To report our initiatives and treatment results for patients with colorectal cancer with metal allergy. METHODS: A total of 27 patients (2.6%) with a history of metal contact dermatitis were identified among 1027 patients who underwent curative resection of colorectal cancer from 2014 to 2020. The results of the patch test, perioperative results, and postoperative colonoscopy findings were also investigated. RESULTS: The patch test for metal allergens and staples was performed in 21 patients (77.8%), and 13 of them (61.9%) tested positive for at least one metal allergen. Ni (38.1%), Co (28.6%), and Pd (19.0%) showed higher positive rates than other metals, and 1 patient (4.8%) tested positive for staples. Stapled anastomosis/suturing was performed as planned in 15 of 27 patients. In 10 patients, the anastomosis method was changed from stapled to hand-sewn according to the no-patch test results (60%), positivity for multiple metals (20%), positivity for staples (10%), and surgeon's judgment (10%). No complications and abnormal colonoscopy findings were found to be associated with stapled anastomosis/suturing. CONCLUSION: The patch test is useful for selecting an optimal anastomosis method for patients with suspected metal allergy.

[A Case of Cecum Cancer with Lymph Node Metastasis and Invasion in the Superior Mesenteric Vein Treated with Combined SMV Resection and Reconstruction].

The patient was a 77-year-old woman. She visited her family doctor with a complaint of bloody stools, and was pointed out a Type 3 colon cancer in the cecum with a colonoscopy. In addition, an enlarged lymph node(#203)was found on the right side of the superior mesenteric vein(SMV). Laparoscopic surgery was initiated, and when the patient was moved to vascular processing, a firm adhesion of the lymph node(#203)was observed on the right side of the SMV. A small laparotomy was added, and a partial combined resection of the SMV was performed en bloc to complete the ileal resection. Histopathological findings showed T4b(transverse colon)N3M0, pStage Ⅲc, and metastatic lymph node(#203)showed evidence of invasion to the SMV. Adjuvant chemotherapy was administered, but lung metastases appeared 4 months and liver metastasis appeared 29 months after surgery. The patient was transferred to a different hospital for best supportive care(BSC)at 34 months after surgery.

Significance of postoperative adjuvant chemotherapy with an oxaliplatin-based regimen after simultaneous curative resection for colorectal cancer and synchronous colorectal liver metastasis: a propensity score matching analysis.

BACKGROUND: Expansion of the indication for liver resection and new regimens for systemic chemotherapy have improved postoperative outcomes for synchronous colorectal liver metastases (CRLM). However, such cases can still have a high recurrence rate, even after curative resection. Therefore, there is a need for postoperative adjuvant chemotherapy (POAC) after liver resection in patients with CRLM. There are few studies of the efficacy of POAC with an oxaliplatin-based regimen after simultaneous resection for colorectal cancer and CRLM with curative intent. The goal of the study was to compare POAC with oxaliplatin-based and fluoropyrimidine regimens using propensity score (PS) matching analysis. METHODS: The subjects were 94 patients who received POAC after simultaneous resection for colorectal cancer and synchronous CRLM, and were enrolled retrospectively. The patients were placed in a L-OHP (+) group (POAC with an oxaliplatin-based regimen, n = 47) and a L-OHP (-) group (POAC with a fluoropyrimidine regimen, n = 47). Recurrence-free (RFS), cancer-specific (CSS), unresectable recurrence-free (URRFS), remnant liver recurrence-free (RLRFS), and extrahepatic recurrence-free (EHRFS) survival were analyzed. RESULTS: Before PS matching, the L-OHP (+) and (-) groups had no significant differences in RFS, CSS, URRFS, RLRFS, and EHRFS. Univariate analysis indicated significant differences in age, preoperative serum CEA (≤ 30.0 ng/mL/ > 30.0 ng/mL), differentiation of primary tumor (differentiated/undifferentiated), T classification (T1-3/T4), number of hepatic lesions and maximum diameter of the hepatic lesion between the L-OHP (+) and (-) groups. After PS matching using these confounders, RFS was significantly better among patients in the L-OHP (+) group compared with the L-OHP (-) group (HR 0.40, 95% CI 0.17-0.96, p = 0.04). In addition, there was a trend towards better RLRFS among patients in the L-OHP (+) group compared with the L-OHP (-) group (HR 0.42, 95% CI 0.17-1.02, p = 0.055). However, there were no significant differences in CSS, URRFS and EHRFS between the L-OHP (+) and (-) groups. CONCLUSIONS: PS matching analysis demonstrated the efficacy of POAC with an oxaliplatin-based regimen in RFS and RLRFS.

Creatine kinase elevation after robotic surgery for rectal cancer due to a prolonged lithotomy position.

BACKGROUND: Robotic surgery for rectal cancer, which is now performed worldwide, can be associated with elevated creatine kinase levels postoperatively. In this study, we compared postoperative complications between patients undergoing robotic surgery and laparoscopic surgery. METHODS: We identified 66 consecutive patients who underwent curative resection for rectal cancer at Juntendo University Hospital between January 2016 and February 2019. Patients were divided into a conventional laparoscopic surgery (CLS) group (n = 38) and a robotic-assisted laparoscopic surgery (RALS) group (n = 28) before comparing various clinicodemographic factors between the groups. RESULTS: Patient age and gender, surgical approach (CLS/RALS), pathological T factor, pathological stage, duration of postoperative hospital stay, and postoperative complications were not significantly different between the RALS and CLS groups. However, the operation time was significantly longer in the RALS group (407 min) than in the CLS group (295 min; p < 0.001). Notably, the serum level of creatine kinase on postoperative day 1 was significantly higher in the CLS group (154 IU/L) than in the RALS group (525 IU/L; p < 0.001), despite there being no significant differences in the incidence of rhabdomyolysis. The multivariate analysis showed that RALS/CLS (HR 6.0 95% CI 1.3-27.5, p = 0.02) and operation time (HR 15.9 95% CI 3.79-67.4, p = 0.001) remained independent factors of CK elevation on postoperative day 1. CONCLUSIONS: Clinically relevant positioning injuries and rhabdomyolysis may occur in patients who are subjected to a prolonged and extreme Trendelenburg position or who have extra force applied to the abdominal wall because of remote center displacement. The creatine kinase value should therefore be measured after RALS to monitor for the sequelae of these potential positioning injuries.

Pharmacological targeting of plasmin prevents lethality in a murine model of macrophage activation syndrome.

Macrophage activation syndrome (MAS) is a life-threatening disorder characterized by a cytokine storm and multiorgan dysfunction due to excessive immune activation. Although abnormalities of coagulation and fibrinolysis are major components of MAS, the role of the fibrinolytic system and its key player, plasmin, in the development of MAS remains to be solved. We established a murine model of fulminant MAS by repeated injections of Toll-like receptor-9 (TLR-9) agonist and d-galactosamine (DG) in immunocompetent mice. We found plasmin was excessively activated during the progression of fulminant MAS in mice. Genetic and pharmacological inhibition of plasmin counteracted MAS-associated lethality and other related symptoms. We show that plasmin regulates the influx of inflammatory cells and the production of inflammatory cytokines/chemokines. Collectively, our findings identify plasmin as a decisive checkpoint in the inflammatory response during MAS and a potential novel therapeutic target for MAS.

Effects of Receptor for Advanced Glycation End-Products (RAGE) Signaling on Intestinal Ischemic Damage in Mice.

OBJECTIVE: Superior mesenteric artery ischemia and nonocclusive mesenteric ischemia are representative diseases of the vascular emergency known as irreversible transmural intestinal necrosis (ITIN). The receptor for advanced glycation end-products (RAGE) belongs to the immunoglobulin superfamily of extracellular ligands, which also includes high-mobility group box 1 (HMGB-1) and proteins of the S100 family. The HMGB-1 ligands have been implicated in the pathogenesis of various inflammatory disorders. This study was designed to investigate the relation between RAGE and ITIN in a murine acute intestinal ischemic model. MATERIALS AND METHODS: ITIN was induced by clipping the cranial mesenteric artery and the peripheral blood vessels. Mucosal and blood samples were collected and analyzed by reverse-transcription PCR and immunohistochemistry for mucosal inflammation and levels of RAGE-related proteins. The influence of RAGE signaling on intestinal cell reproduction was investigated using the cell scratch test, an in vitro wound-healing assay. Finally, RAGE-related proteins and their respective inhibitors were administered intraperitoneally to ITIN model mice to determine their effects. RESULTS: RAGE-expressing cells were located at the base of the intestinal crypts at day 0. As ITIN progressed, most of the damaged intestinal cells expressed RAGE, and ligands of RAGE such as HMGB-1, S100 A8/A9, and S100ß were present in the crypt cells from the bottom to the top. The quantities of S100 A8/A9 and S100ß were particularly high, above the levels found in other diseases. When S100 A8/A9 and S100ß were applied to small intestinal epithelial cells in vitro, regeneration was significantly impeded. Inflammatory Gr1+ neutrophils and F4/80+ macrophages are involved in tissue ischemia. S100 A8/A9 enhances inflammatory myeloid cell influx. CONCLUSIONS: RAGE-related proteins are elevated in ITIN model mice and impede intestinal regeneration in vitro. RAGE-related proteins may be a new therapeutic target or a new marker for ITIN.

[A Case of Systemic Chemotherapy Combined with Molecular Drug Treatment Following Biliary Stent Implantation for Obstructive Jaundice Due to Metastases of Liver Gland Lymph Node after Colorectal Cancer Surgery].

We report a case of systemic chemotherapy after biliary stent placement for obstructive jaundice due to hepatic portal lymph node metastasis after colorectal cancer surgery. The patient was a 40s woman. Laparoscopic anterior resection for rectosigmoidRS cancer was performed. The pathological diagnosis was T3N0M0PUL0R0, pStage Ⅱ according to the 8th edition of colorectal cancer handling regulations. Because multiple liver metastases were observed 8 months after the surgery, partial resection of the posterior region of the liver was performed. Multiple lung metastases were observed 1 year after hepatectomy, but she wantedto undergo follow-up observation. Jaundice was observed 1 year after the diagnosis of lung metastasis, and obstructive jaundice due to hepatic portal lymph node metastasis was diagnosed. Endoscopic retrograde biliary drainage(ERBD)was performed, and a bile duct stent was placed. After improving jaundice, 12 courses of mFOLFOX6 plus cetuximab therapy were performed. Currently, because of the exacerbation of lung metastasis, FOLFIRI plus bevacizumab therapy is being administered. Systemic chemotherapy containing a molecular-targeted drug is being administered in our case, but complications relatedto the biliary stent have not been observed. There are few reports on similar cases, andfollow - up observation with careful attention to long-term safety is necessary.

Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells.

Tissue plasminogen activator (tPA), aside from its vascular fibrinolytic action, exerts various effects within the body, ranging from synaptic plasticity to control of cell fate. Here, we observed that by activating plasminogen and matrix metalloproteinase-9, tPA expands murine bone marrow-derived CD45(-)TER119(-)Sca-1(+)PDGFRα(+) mesenchymal stromal cells (PαS-MSCs) in vivo through a crosstalk between PαS-MSCs and endothelial cells. Mechanistically, tPA induces the release of Kit ligand from PαS-MSCs, which activates c-Kit(+) endothelial cells to secrete MSC growth factors: platelet-derived growth factor-BB (PDGF-BB) and fibroblast growth factor 2 (FGF2). In synergy, FGF2 and PDGF-BB upregulate PDGFRα expression in PαS-MSCs, which ultimately leads to PαS-MSC expansion. These data show a novel mechanism by which the fibrinolytic system expands PαS-MSCs through a cytokine crosstalk between niche cells.

Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice.

Adhesive small bowel obstruction remains a common problem for surgeons. After surgery, platelet aggregation contributes to coagulation cascade and fibrin clot formation. With clotting, fibrin degradation is simultaneously enhanced, driven by tissue plasminogen activator-mediated cleavage of plasminogen to form plasmin. The aim of this study was to investigate the cellular events and proteolytic responses that surround plasminogen activator inhibitor (PAI-1; Serpine1) inhibition of postoperative adhesion. Peritoneal adhesion was induced by gauze deposition in the abdominal cavity in C57BL/6 mice and those that were deficient in fibrinolytic factors, such as Plat-/- and Serpine1-/- In addition, C57BL/6 mice were treated with the novel PAI-1 inhibitor, TM5275. Some animals were treated with clodronate to deplete macrophages. Epidermal growth factor (EGF) experiments were performed to understand the role of macrophages and how EGF contributes to adhesion. In the early phase of adhesive small bowel obstruction, increased PAI-1 activity was observed in the peritoneal cavity. Genetic and pharmacologic PAI-1 inhibition prevented progression of adhesion and increased circulating plasmin. Whereas Serpine1-/- mice showed intra-abdominal bleeding, mice that were treated with TM5275 did not. Mechanistically, PAI-1, in combination with tissue plasminogen activator, served as a chemoattractant for macrophages that, in turn, secreted EGF and up-regulated the receptor, HER1, on peritoneal mesothelial cells, which led to PAI-1 secretion, further fueling the vicious cycle of impaired fibrinolysis at the adhesive site. Controlled inhibition of PAI-1 not only enhanced activation of the fibrinolytic system, but also prevented recruitment of EGF-secreting macrophages. Pharmacologic PAI-1 inhibition ameliorated adhesion formation in a macrophage-dependent manner.-Honjo, K., Munakata, S., Tashiro, Y., Salama, Y., Shimazu, H., Eiamboonsert, S., Dhahri, D., Ichimura, A., Dan, T., Miyata, T., Takeda, K., Sakamoto, K., Hattori, K., Heissig, B. Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice.

Inhibition of plasmin protects against colitis in mice by suppressing matrix metalloproteinase 9-mediated cytokine release from myeloid cells.

BACKGROUND & AIMS: Activated proteases such as plasmin and matrix metalloproteinases (MMPs) are activated in intestinal tissues of patients with active inflammatory bowel diseases. We investigated the effect of plasmin on the progression of acute colitis. METHODS: Colitis was induced in Mmp9(-/-), Plg(-/-), and C57BL/6 (control) mice by the administration of dextran sulfate sodium, trinitrobenzene sulfonic acid, or CD40 antibody. Plasmin was inhibited in control mice by intraperitoneal injection of YO-2, which blocks its active site. Mucosal and blood samples were collected and analyzed by reverse-transcription polymerase chain reaction and immunohistochemical analyses, as well as for mucosal inflammation and levels of cytokines and chemokines. RESULTS: Circulating levels of plasmin were increased in mice with colitis, compared with controls. Colitis did not develop in control mice injected with YO-2 or in Plg(-/-) mice. Colons from these mice had reduced infiltration of Gr1+ neutrophils and F4/80+ macrophages, and reduced levels of inflammatory cytokines and chemokines. Colonic inflammation and colitis induction required activation of endogenous MMP9. After colitis induction, mice given YO-2, Plg(-/-) mice, and Mmp9(-/-) mice had reduced serum levels of tumor necrosis factor and C-X-C motif chemokine ligand 5, compared with control mice. CONCLUSIONS: In mice, plasmin induces a feedback mechanism in which activation of the fibrinolytic system promotes the development of colitis via activation of MMP9 or proteolytic enzymes. The proteolytic environment stimulates the influx of myeloid cells into the colonic epithelium and the production of tumor necrosis factor and C-X-C motif chemokine ligand 5. In turn, myeloid CD11b+ cells release the urokinase plasminogen activator, which accelerates plasmin production. Disruption of the plasmin-induced chronic inflammatory circuit therefore might be a strategy for colitis treatment.

Role of mesenchymal stem cell-derived fibrinolytic factor in tissue regeneration and cancer progression.

Tissue regeneration during wound healing or cancer growth and progression depends on the establishment of a cellular microenvironment. Mesenchymal stem cells (MSC) are part of this cellular microenvironment, where they functionally modulate cell homing, angiogenesis, and immune modulation. MSC recruitment involves detachment of these cells from their niche, and finally MSC migration into their preferred niches; the wounded area, the tumor bed, and the BM, just to name a few. During this recruitment phase, focal proteolysis disrupts the extracellular matrix (ECM) architecture, breaks cell-matrix interactions with receptors, and integrins, and causes the release of bioactive fragments from ECM molecules. MSC produce a broad array of proteases, promoting remodeling of the surrounding ECM through proteolytic mechanisms. The fibrinolytic system, with its main player plasmin, plays a crucial role in cell migration, growth factor bioavailability, and the regulation of other protease systems during inflammation, tissue regeneration, and cancer. Key components of the fibrinolytic cascade, including the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are expressed in MSC. This review will introduce general functional properties of the fibrinolytic system, which go beyond its known function of fibrin clot dissolution (fibrinolysis). We will focus on the role of the fibrinolytic system for MSC biology, summarizing our current understanding of the role of the fibrinolytic system for MSC recruitment and the functional consequences for tissue regeneration and cancer. Aspects of MSC origin, maintenance, and the mechanisms by which these cells contribute to altered protease activity in the microenvironment under normal and pathological conditions will also be discussed.

Clinical pathway to discharge 3 days after colorectal endoscopic submucosal dissection.

BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) is a useful treatment method; however, no index has been established for time for patient to start food ingestion or be discharged after ESD. We investigated the potential of a clinical pathway in which patients started food ingestion on day 2 after ESD and were discharged on day 3. METHODS: A total of 382 patients underwent colorectal ESD between 2006 and 2012. A flow chart of a clinical pathway was prepared based on the data obtained, with the aim of shortening hospital stay after ESD. RESULTS: Mean duration of postoperative hospital stay in the 382 patients was 5.3 ± 1.8 days. The most common cause of extended hospital stay was abnormal blood test finding, as detected in 50 patients in group C (n = 131; 38.2%), followed by careful course observations, as noted in 48 patients in group C (n = 131; 36.6%). Regarding procedural accidents as a result of ESD, intraoperative perforation occurred in 15 patients (3.9%) and post-ESD bleeding in seven patients (1.8%), which extended the hospital stay. Food ingestion was started on day 2 when no abnormality was noted during ESD or in physical and imaging findings or blood tests on day 1. In the 86 patients who underwent the prepared clinical pathway as a validation study, 68 (79.0%) were discharged on day 3. Duration of postoperative hospital stay was 3.4 ± 1.2 days. CONCLUSION: Discharge may be possible 3 days after ESD when no abnormalities are noted during ESD or on post-ESD day 1.

Heparin-binding EGF-like growth factor via miR-126 controls tumor formation/growth and the proteolytic niche in murine models of colorectal and colitis-associated cancers.

MicroRNAs, including the tumor-suppressor miR-126 and the oncogene miR-221, regulate tumor formation and growth in colitis-associated cancer (CAC) and colorectal cancer (CRC). This study explores the impact of the epithelial cytokine heparin-binding epidermal growth factor (HB-EGF) and its receptor epidermal growth factor receptor (EGFR) on the pathogenesis of CAC and CRC, particularly in the regulation of microRNA-driven tumor growth and protease expression. In murine models of CRC and CAC, lack of miR-126 and elevated miR-221 expression in colonic tissues enhanced tumor formation and growth. MiR-126 downregulation in colon cells established a pro-tumorigenic proteolytic niche by targeting HB-EGF-active metalloproteinase-7, -9 (MMP7/MMP9), disintegrin, and metalloproteinase domain-containing protein 9, and modulating chemokine-mediated recruitment of HB-EGF-loaded inflammatory cells. Mechanistically, downregulation of HB-EGF and EGFR in the colon suppressed miR-221 and enhanced miR-126 expression via activating enhancer-binding protein 2 alpha. Reintroducing miR-126 reduced tumor development and HB-EGF expression. Combining miR-126 reintroduction, which targets specific HB-EGF-active proteases but not ADAM17, with MMP inhibitors like Batimastat or Marimastat effectively suppressed tumor growth. This combination normalized protease expression and balanced miR-126 and miR-221 levels in developing and growing tumors. These findings demonstrate that suppressing HB-EGF and EGFR1 shifts the balance from oncogenic miR-221 to tumor-suppressive miR-126 action. Consequently, normalizing miR-126 expression could open new avenues for treating patients with CAC and CRC, and this normalization is intertwined with the anticancer efficacy of MMP inhibitors.

CHFR-Promoter-Methylation Status Is Predictive of Response to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal Cancer.

BACKGROUND/AIM: We investigated whether promoter methylation of the checkpoint-with-forkhead-and-ring-finger-domains (CHFR) gene is a predictor of the efficacy of irinotecan-based systemic chemotherapy for advanced colorectal cancer (CRC) patients. MATERIALS AND METHODS: CHFR-promoter methylation was measured by quantitative methylation-specific PCR (qMSP). The histoculture drug response assay (HDRA) was used in vitro to analyze the correlation between CHFR-promoter methylation and the efficacy of the irinotecan-active-metabolite SN38 in colorectal-cancer tissues from 44 CRC patients. CHFR promoter-methylation was also analyzed for its correlation with clinical response to irinotecan-based systemic chemotherapy of 49 CRC patients. RESULTS: CHFR-promoter methylation significantly-positively correlated with inhibition of colon cancer by SN38 in the HDRA (p=0.002). CHFR-promoter methylation also significantly-positively correlated with clinical response to irinotecan-based systemic chemotherapy (p=0.04 for disease control). CHFR-promoter methylation also significantly-positively correlated (p=0.01) with increased progression-free survival for patients treated with irinotecan-containing FLOFIRI in combination with bevacizumab, the most-frequent regimen in the cohort. CONCLUSION: Sensitivity of advanced CRC patients to irinotecan-based systemic chemotherapy can be predicted by the extent of CHFR-promoter methylation.

Benefits and risks of diverting stoma creation during rectal cancer surgery.

Purpose: A consensus has been reached regarding diverting stoma (DS) construction in rectal cancer surgery to avoid reoperation related to anastomotic leakage. However, the incidence of stoma-related complications (SRCs) remains high. In this study, we examined the perioperative outcomes of DS construction in patients who underwent sphincter-preserving surgery for rectal cancer. Methods: We included 400 participants who underwent radical sphincter-preserving surgery for rectal cancer between 2005 and 2017. These participants were divided into the DS (+) and DS (-) groups, and the outcomes, including postoperative complications, were compared. Results: The incidence of ileus was higher in the DS (+) group than in the DS (-) group (P<0.01); however, no patients in the DS (+) group showed grade 3 anastomotic leakage. Furthermore, early SRCs were observed in 33 patients (21.6%) and bowel obstruction-related stoma outlet syndrome occurred in 19 patients (12.4%). There was no significant intergroup difference in the incidence of grade 3b postoperative complications. However, the most common reason for reoperation was different in the 2 groups: anastomotic leakage in 91.7% of patients with grade 3b postoperative complications in the DS (-) group, and SRCs in 85.7% of patients with grade 3b postoperative complications in the DS (+) group. Conclusion: Patients with DS showed higher incidence rates of overall postoperative complications, severe postoperative complications (grade 3), and bowel obstruction, including stoma outlet syndrome, than patients without DS. Therefore, it is important to construct an appropriate DS to avoid SRCs and to be more selective in assigning patients for DS construction.

Safety, efficacy, and operability of a newly developed absorbable adhesion barrier (GM142) in patients with primary rectal cancer scheduled for diverting ileostomy during laparoscopic surgery: Randomized controlled trial.

Aim: The aim of this study was to compare the outcomes of GM142, a newly developed gelatin film with a concave and convex structure to a commercially available conventional film, hyaluronate-carboxymethylcellulose. Methods: Patients with primary rectal cancer who were scheduled for diverting ileostomy during laparoscopic surgery were eligible for this study. Patients were randomized before surgery and an antiadhesion film was applied under the umbilical incision. The primary outcome was the incidence of adhesion under the midline incision confirmed by second-look surgery for diverting ileostomy closure. The secondary outcomes were the adhesion severity score, the extent of adhesion score, the presence of intestinal obstruction, and the success of all patching. Results: A total of 146 patients were enrolled. A total of 123 patients were included in the full analysis set. The primary outcome of "no adhesion" was observed in 66.1% in the GM142 group and 55.7% in the conventional film group. The noninferiority of GM142 to conventional film was confirmed (P = .0005). The secondary outcomes were similar between the groups. For the safety evaluation, there were no safety concerns regarding allergic reactions to gelatin or increased gelatin-specific IgE antibody titers. Conclusions: The noninferiority of GM142 to conventional film was shown. GM142 showed no major safety issues. The clinical safety profiles of GM142 suggested certain physiological benefits of the gelatin film as an adhesion barrier.

Rectal metastasis from bladder urothelial carcinoma: a case report.

BACKGROUND: Urothelial carcinoma arises from transitional cells in the urothelial tract. In advanced cases, it can metastasize locally to surrounding organs or distally to organs such as the lungs, bones, or liver. Here we describe a case of rectal metastasis from urothelial carcinoma treated with multiple sessions of transurethral resection of bladder tumor (TURBT). CASE PRESENTATION: A 72-year-old woman presented to our department with abdominal bloating andobstructed defecation. She had undergone two sessions of TURBT for early urothelial carcinoma in another hospital at 64 and 65 months ago, respectively. Cystoscopy at 3 months after the second TURBT session had indicated disease recurrence, and thus, she had been referred to our hospital for further examination, followed by TURBT for the third time at 59 months ago and for the fourth time at 48 months ago; thereafter, she had been followed up with cystoscopy every 6 months without any recurrence. However, she returned to our hospital, complaining of difficult defecation. Subsequent colonoscopy demonstrated an obstructive tumor in the rectum, which was pathologically diagnosed as metastatic urothelial carcinoma of the bladder. Laparoscopic examination revealed two small areas of peritoneal dissemination in the pelvis. A sigmoid colostomy was performed without rectal tumor resection. She has been receiving chemotherapy and is still alive 10 months after surgery. CONCLUSIONS: Rectal metastasis is a rare site of metastasis for urothelial carcinomas. It is important to consider the possibility of annular rectal constriction caused by infiltrating or metastasizing urothelial carcinoma when managing patients with urothelial carcinoma and with difficult defecation.

Analysis of ileostomy stool samples reveals dysbiosis in patients with high-output stomas.

Construction of a diverting stoma can significantly reduce the onset of severe anastomotic leakage in patients with rectal cancer. High-output stoma is one of the most important potential surgical complications after anal function-preserving surgery with ileostomy. Culture-independent techniques have revealed the interaction of the complex intestinal bacterial ecology with various diseases. Our objective was to evaluate the differences in patient characteristics and gut microbiota distribution features in patients with high-output stomas. The cases of 24 consecutive patients who underwent curative resection for rectal cancer at our hospital between November 2016 and June 2018 were reviewed, and the patients were categorized into high-output and low-output groups. Their microbiota were analyzed using next-generation sequencing of ileostomy stool samples collected on postoperative day 7. There was a significant difference in the percentage of Bacteroidetes between the high-output and low-output groups (14.8% vs 0.5%; p=0.01). The percentage of Clostridium butyricum was increased in the low-output group (p=0.01). After the exclusion of those treated with the probiotic Miya-BM, whose principal component is C. butyricum, analyses revealed no significant differences between the high-output and low-output groups. This pilot study provides the first evidence correlating gut microbiota with the pathogenesis of high- output stoma compared with low-output stoma.

Analysis of appendectomy samples identified dysbiosis in acute appendicitis.

Appendicitis is the most common cause of sudden-onset abdominal pain requiring surgery. Culture-independent techniques have revealed that the complex intestinal bacterial ecology is associated with various diseases. To evaluate differences in patient characteristics and gut microbiota distribution in patients with appendicitis, we enrolled 12 patients who underwent appendectomy for appendicitis (appendicitis group) and 13 patients who underwent ileocecal resection or right hemicolectomy for colon cancer (control group). Microbiota were analyzed using next-generation sequencing of surgical specimens from appendix swab samples collected postoperatively. Overall differences in the structure of the gut microbiota were evaluated using the α- and ß-diversity indices, which were calculated using the weighted or unweighted UniFrac distance. Changes in the gut microbial distribution were taxonomically evaluated at the phylum and genus levels. The α-diversity of observed species was significantly different between patients with and without inflammation of the appendix. The appendiceal microbiome of patients with appendicitis exhibited the highest unweighted UniFrac distances. There were no significant differences at the phylum level. Ruminococcus (p=0.02) and f_erysipelotrichaceae_g_clostridium (p=0.005) were increased in the control group compared with the appendicitis group. This pilot study provides the first report of the correlation of the gut microbiota with the pathogenesis of appendicitis evaluated using mucus-origin sampling.