Downregulation of ABCC3 activates MAPK signaling through accumulation of deoxycholic acid in colorectal cancer cells.

ABCC3 (also known as MRP3) is an ATP binding cassette transporter for bile acids, whose expression is downregulated in colorectal cancer through the Wnt/ß-catenin signaling pathway. However, it remained unclear how downregulation of ABCC3 expression contributes to colorectal carcinogenesis. We explored the role of ABCC3 in the progression of colorectal cancer-in particular, focusing on the regulation of bile acid export. Gene expression analysis of colorectal adenoma isolated from familial adenomatous polyposis patients revealed that genes related to bile acid secretion including ABCC3 were downregulated as early as at the stage of adenoma formation. Knockdown or overexpression of ABCC3 increased or decreased intracellular concentration of deoxycholic acid, a secondary bile acid, respectively, in colorectal cancer cells. Forced expression of ABCC3 suppressed deoxycholic acid-induced activation of MAPK signaling. Finally, we found that nonsteroidal anti-inflammatory drugs increased ABCC3 expression in colorectal cancer cells, suggesting that ABCC3 could be one of the targets for therapeutic intervention of familial adenomatous polyposis. Our data thus suggest that downregulation of ABCC3 expression contributes to colorectal carcinogenesis through the regulation of intracellular accumulation of bile acids and activity of MAPK signaling.

Dickkopf 1 is expressed in normal fibroblasts during early stages of colorectal tumorigenesis.

BACKGROUND AND PURPOSE: Colorectal cancer progression from adenoma to cancer is a time-intensive process; however, the interaction between normal fibroblasts (NFs) with early colorectal tumors, such as adenomas, remains unclear. Here, we analyzed the response of the microenvironment during early tumorigenesis using co-cultures of organoids and NFs. MATERIALS AND METHODS: Colon normal epithelium, adenoma, cancer organoid, and NFs were established and co-cultured using Transwell inserts. Microarray analysis of NFs was performed to identify factors expressed early in tumor growth. Immunostaining of clinical specimens was performed to localize the identified factor. Functional analysis was performed using HCT116 cells. Serum DKK1 levels were measured in patients with colorectal cancer and adenoma. RESULTS: Colorectal organoid-NF co-culture resulted in increased organoid diameter and cell viability in normal epithelial and adenomatous organoids but not in cancer organoids. Microarray analysis of NFs revealed 18 genes with increased expression when co-cultured with adenoma and cancer organoids. Immunohistochemical staining revealed DKK1 expression in the tumor stroma from early tumor growth. DKK1 stimulation reduced HCT116 cell proliferation, while DKK1 silencing by siRNA transfection increased cell proliferation. Serum DKK1 level was significantly higher in patients with advanced cancer and adenoma than in controls. Serum DKK1 level revealed area-under-the-curve values of 0.78 and 0.64 for cancer and adenoma, respectively. CONCLUSION: These findings contribute valuable insights into the early stages of colorectal tumorigenesis and suggest DKK1 as a tumor suppressor. Additionally, serum DKK1 levels could serve as a biomarker to identify both cancer and adenoma, offering diagnostic possibilities for early-stage colon tumors. The present study has a few limitations. We considered using DKK1 as a candidate gene for gene transfer to organoids and NFs; however, it was difficult due to technical problems and the slow growth rate of NFs. Therefore, we used cancer cell lines instead. In addition, immunostaining and ELISA were based on the short-term collection at a single institution, and further accumulation of such data is desirable. As described above, most previous reports were related to advanced cancers, but in this study, new findings were obtained by conducting experiments on endoscopically curable early-stage tumors, such as adenomas.

Syndrome of inappropriate secretion of antidiuretic hormone after total proctocolectomy for ulcerative colitis.

We report a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after total proctocolectomy followed with ileal pouch-anal anastomosis (TPC-IPAA) for ulcerative colitis (UC). The patient was a 46-year-old woman. She was diagnosed with UC of pancolitis in 2000. High grade dysplasia was detected in the transverse colon after a surveillance colonoscopy in 2021. She underwent laparoscopy-assisted TPC-IPAA. On the sixth postoperative day, she had a decreased level of consciousness that worsened on the following day. Her laboratory data showed a serum sodium level of 108 mEq/L and the plasma osmolality was 234 mOsm/kg. We did not find any other abnormalities in the laboratory examination that could cause hyponatremia. Computed tomography scan showed no central nervous system disturbances such as a pituitary tumor, antidiuretic hormone-producing tumors, or pulmonary diseases. The patient was diagnosed with Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) caused by surgical invasion. We started to administer 3% sodium chloride slowly to improve the hyponatremia. Her serum sodium level became normal and stable. Although it is rare for SIADH to be caused by abdominal surgery, if hyponatremia is observed after surgery, the possibility of postoperative SIADH should be considered.

A case of intestinal malrotation apparent after laparoscopically total proctocolectomy followed by ileal-pouch-anal anastomosis for ulcerative colitis.

Intestinal malrotation (IM) is an abnormality due to a failure of the normal midgut rotation and fixation. We report a case of 46-year-old man with ulcerative colitis whose IM was apparent after laparoscopically total proctocolectomy (TPC) followed by ileal-pouch-anal anastomosis (IPAA) and ileostomy. There was no abnormal anatomy except for mobile cecum/ascending colon during the initial operation. Intestinal obstruction occurred after ileostomy closure. The computed tomography scan showed the duodeno-jejunal transition was located in right abdomen, the superior mesenteric vein was located left of the superior mesenteric artery (SMA) and the obstruction point was the distal ileum near the pouch. We performed an ileo-ileo bypass across the ventral side of the SMA to relieve the intestinal obstruction. The patient would have incomplete IM preoperatively, which became apparent by TPC. In case of TPC for mobile colon, anatomy of small intestine should be checked before IPAA.

The Mucus Binding Factor Is Not Necessary for Lacticaseibacillus rhamnosus CRL1505 to Exert Its Immunomodulatory Activities in Local and Distal Mucosal Sites.

Both viable and non-viable orally administered Lacticaseibacillus rhamnosus CRL1505 modulate immunity in local (intestine) and distal (respiratory) mucosal sites. So, intestinal adhesion and colonization are not necessary for this probiotic strain to exert its immunomodulatory effects. In this work, a mucus-binding factor knockout CRL1505 strain (ΔmbfCRL1505) was obtained and the lack of binding ability to both intestinal epithelial cells and mucin was demonstrated in vitro. In addition, two sets of in vivo experiments in 6-week-old Balb/c mice were performed to evaluate ΔmbfCRL1505 immunomodulatory activities. (A) Orally administered ΔmbfCRL1505 prior to intraperitoneal injection of the Toll-like receptor 3 (TLR3) agonist poly(I:C) significantly reduced intraepithelial lymphocytes (CD3+NK1.1+CD8αα+) and pro-inflammatory mediators (TNF-α, IL-6 and IL-15) in the intestinal mucosa. (B) Orally administered ΔmbfCRL1505 prior to nasal stimulation with poly(I:C) significantly decreased the levels of the biochemical markers of lung tissue damage. In addition, reduced recruitment of neutrophils and levels of pro-inflammatory mediators (TNF-α, IL-6 and IL-8) as well as increased IFN-ß and IFN-γ in the respiratory mucosa were observed in ΔmbfCRL1505-treated mice when compared to untreated control mice. The immunological changes induced by the ΔmbfCRL1505 strain were not different from those observed for the wild-type CRL1505 strain. Although it is generally accepted that the expression of adhesion factors is necessary for immunobiotics to induce their beneficial effects, it was demonstrated here that the mbf protein is not required for L. rhamnosus CRL1505 to exert its immunomodulatory activities in local and distal mucosal sites. These results are a step forward towards understanding the mechanisms involved in the immunomodulatory capabilities of L. rhamnosus CRL1505.

[A Case of Laparoscopic Abdominoperineal Resection and Perineal Reconstruction for Signet-Ring Cell Carcinoma with Skin Invasion Derived from the Anal Gland].

A 56-year-old man was referred to our hospital with an awareness of anal tumor. The tumor extended from the anal verge to the back of left testicle. Colonoscopy showed no tumor in the rectum and the anal canal. Biopsy showed mucus- producing adenocarcinoma(sig), and we diagnosed anal canal adenocarcinoma with immunostaining. Laparoscopic abdominoperineal rectal resection and perineal reconstruction with the V-Y fasciocutaneous flap closure technique. The patient had no major postoperative complications, and was discharged on 23rd postoperative day. Pathological examination revealed that the tumor was pT3N0M0, pStage ⅡB. The patient received adjuvant chemotherapy with CAPOX and has survived 12 months without recurrence. Immunostaining may be used to diagnose the signet-ring cell carcinoma without tumor of anal canal. In addition, reconstruction of the perineum for large anal tumors is useful.

[A Case of Robot-Assisted Abdominoperineal Resection with Prostatectomy for Locally Advanced Rectal Cancer].

The patient was referred to our hospital because of bloody stool and anorectal pain, and a colonoscopy revealed a tumor in the lower rectum. Although no distant metastasis was found, the tumor was suspected to have invaded the distal prostate. Neoadjuvant chemoradiotherapy(45 Gy/25 Fr with S-1)resulted in tumor shrinkage and symptomatic improvement, however, the primary tumor remained in close proximity to the prostate and urethra. Thus, we performed a robot-assisted abdominoperineal resection and Retzius-sparing prostatectomy in collaboration with the urology department. The surgical margins were negative and radical resection was achieved. Although minor vesicourethral anastomotic leakage was observed, it recovered conservatively. The patient has been alive 1 year postoperatively without recurrence. The patient initially had urinary incontinence, but it gradually improved. Although a total pelvic resection could have been considered, the robot-assisted surgery made it possible to preserve the urinary tract. The future application of robot-assisted surgery in extended surgery is expected.

A Phenylfurocoumarin Derivative Reverses ABCG2-Mediated Multidrug Resistance In Vitro and In Vivo.

The ATP-binding cassette subfamily G member 2 (ABCG2) transporter is involved in the development of multidrug resistance in cancer patients. Many inhibitors of ABCG2 have been reported to enhance the chemosensitivity of cancer cells. However, none of these inhibitors are being used clinically. The aim of this study was to identify novel ABCG2 inhibitors by high-throughput screening of a chemical library. Among the 5812 compounds in the library, 23 compounds were selected in the first screening, using a fluorescent plate reader-based pheophorbide a (PhA) efflux assay. Thereafter, to validate these compounds, a flow cytometry-based PhA efflux assay was performed and 16 compounds were identified as potential inhibitors. A cytotoxic assay was then performed to assess the effect these 16 compounds had on ABCG2-mediated chemosensitivity. We found that the phenylfurocoumarin derivative (R)-9-(3,4-dimethoxyphenyl)-4-((3,3-dimethyloxiran-2-yl)methoxy)-7H-furo [3,2-g]chromen-7-one (PFC) significantly decreased the IC50 of SN-38 in HCT-116/BCRP colon cancer cells. In addition, PFC stimulated ABCG2-mediated ATP hydrolysis, suggesting that this compound interacts with the substrate-binding site of ABCG2. Furthermore, PFC reversed the resistance to irinotecan without causing toxicity in the ABCG2-overexpressing HCT-116/BCRP cell xenograft mouse model. In conclusion, PFC is a novel inhibitor of ABCG2 and has promise as a therapeutic to overcome ABCG2-mediated MDR, to improve the efficiency of cancer chemotherapy.

Antimesenteric cutback end-to-end isoperistaltic anastomosis (Sasaki-Watanabe anastomosis) for Crohn's disease: Novel surgical technique and early results of surgical anastomotic recurrence.

BACKGROUND: Antimesenteric cutback end-to-end isoperistaltic anastomosis (Sasaki-Watanabe anastomosis; Sasaki-W anastomosis), which was developed in our department, is a novel hand-sewn anastomotic technique for Crohn's disease intended to prevent anastomotic stenosis and preserve the peripheral circulation. AIM: The aim of the present study is to present the surgical technique of Sasaki-W anastomosis and to assess the safety and the early results of the surgical anastomotic recurrence of Sasaki-W anastomosis. PATIENTS AND METHODS: The present study was a single-center retrospective cohort study. As an early-period group, 13 patients with Crohn's disease, who were mainly selected from cases considered to be at high risk of recurrence, underwent 15 Sasaki-W anastomoses from August 2009 to January 2012. As a late-period group, 36 patients with Crohn's disease, who were selected regardless of risk factors, underwent 37 Sasaki-W anastomoses from September 2016 to March 2020. The medical data including patient characteristics, surgical records, postoperative details, and surgical recurrences were assessed. RESULTS: There were no intraoperative complications. With a median follow-up of 107 mo, surgical recurrence occurred in one patient at 106 mo after surgery in the early-period group. The cumulative surgical recurrence-free rate in the early-period group was 100% at 5 y and 86% at 10 y after surgery. No patients required reoperation in the late-period group. CONCLUSION: Sasaki-W anastomosis is safe and feasible. Although long-term study is needed, this anastomotic technique can be a reasonable operative option for Crohn's disease.

Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer.

The splicing of microexons (very small exons) is frequently dysregulated in the brain of individuals with autism spectrum disorder. However, little is known of the patterns, regulatory mechanisms and roles of microexon splicing in cancer. We here examined the transcriptome-wide profile of microexon splicing in matched colorectal cancer (CRC) and normal tissue specimens. Out of 1492 microexons comprising 3 to 15 nucleotides, 21 (1%) manifested differential splicing between CRC and normal tissue. The 21 genes harboring the differentially spliced microexons were enriched in gene ontology terms related to cell adhesion and migration. RNA interference-mediated knockdown experiments identified two splicing factors, RBFOX2 and PTBP1, as regulators of microexon splicing in CRC cells. RBFOX2 and PTBP1 were found to directly bind to microexon-containing pre-mRNAs and to control their splicing in such cells. Differential microexon splicing was shown to be due, at least in part, to altered expression of RBFOX2 and PTBP1 in CRC tissue compared to matched normal tissue. Finally, we found that changes in the pattern of microexon splicing were associated with CRC metastasis. Our data thus suggest that altered expression of RBFOX2 and PTBP1 might influence CRC metastasis through the regulation of microexon splicing.

A long-term survivor of metachronous liver metastases of pancreatic serous cystic neoplasm associated with von Hippel-Lindau disease.

BACKGROUND: Pancreatic serous cystic neoplasm (SCN) is an uncommon exocrine neoplasm, which is believed to be a benign entity. However, some of these neoplasms may occasionally attain metastatic ability. Von Hippel-Lindau disease (VHL) manifests a dominantly inherited systemic syndrome accompanied by several benign or malignant tumors, including cystic tumors, in various organs. We describe here a long-term survival case who underwent surgical resection for metachronous liver metastases of pancreatic SCN associated with VHL disease. CASE PRESENTATION: A 35-year-old woman with VHL underwent total pancreatectomy and right nephrectomy for pancreatic SCN and renal cell carcinoma, respectively. At the 4th year follow-up examination after the resection, contrast-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) showed arterially hyper-enhanced neoplastic lesions in the segment VI and VIII of the liver. Partial resections of the liver were performed 53 months after the initial surgery. At the 6th month follow-up examination from the second surgery, one and two tumors located in the liver segment III, and VIII, respectively, were detected by contrast-enhanced CT and Gd-EOB-DTPA-enhanced MRI. Anterior segmentectomy and partial resection of the segment III were performed 66 months after the initial surgery and 13 months after the second, respectively. The tumors were pathologically diagnosed as liver metastases of pancreatic SCN synonymous with serous cystadenocarcinoma. She remains disease-free without recurrence 6.5 years after the last operation. CONCLUSIONS: This is the first report of a case of metastatic SCN associated with VHL. Surgical resection might confer a favorable prognosis in patients of pancreatic SCN with liver metastases.

Wnt5a in cancer-associated fibroblasts promotes colorectal cancer progression.

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and have been shown to promote cancer aggressiveness. In our previous study, analysis of expression profiles obtained from paired CAFs and normal fibroblasts from colorectal cancer (CRC) tissue revealed that gene sets related to the Wnt signaling pathway were highly enriched in colorectal CAFs. Furthermore, among the components of the ß-catenin-independent Wnt pathway, Wnt5a was highly expressed in CAFs. Since Wnt5a is considered to be a regulator of CRC progression in CAFs, we performed immunohistochemical analysis on Wnt5a in 171 patients who underwent surgery for CRC. Positive staining for Wnt5a was often found in cancer stroma, particularly in fibromatous areas, although the immunoreactivity for Wnt5a was weak in cancer cells. Wnt5a status in CAFs was significantly associated with tumor size, depth of invasion, lymphatic and vascular invasion, lymph node metastasis, TNM stage, and recurrence. Subsequent in vitro analyses using human recombinant Wnt5a protein revealed that cancer cell proliferation and migration were significantly increased by stimulation with Wnt5a. Our findings suggest that Wnt5a-derived CAFs play a crucial role in CRC progression and have potential as a target of anti-cancer therapies.

The association between ERK inhibitor sensitivity and molecular characteristics in colorectal cancer.

The mitogen-activated protein kinase (MAPK) pathway plays an important role in the colorectal cancer (CRC) progression, being supposed to be activated by the gene mutations, such as BRAF or KRAS. Although the inhibitors of extracellular signal-regulated kinase (ERK) have demonstrated efficacy in the cells with the BRAF or KRAS mutations, a clinical response is not always associated with the molecular signature. The patient-derived organoids (PDO) have emerged as a powerful in vitro model system to study cancer, and it has been widely applied for the drug screening. The present study aims to analyze the association between the molecular characteristics which analyzed by next-generation sequencing (NGS) and sensitivity to the ERK inhibitor (i.e., SCH772984) in PDO derived from CRC specimens. A drug sensitivity test for the SCH772984 was conducted using 14 CRC cell lines, and the results demonstrated that the sensitivity was in agreement with the BRAF mutation, but was not completely consistent with the KRAS status. In the drug sensitivity test for PDO, 6 out of 7 cases with either BRAF or KRAS mutations showed sensitivity to the SCH772984, while 5 out of 6 cases of both BRAF and KRAS wild-types were resistant. The results of this study suggested that the molecular status of the clinical specimens are likely to represent the sensitivity in the PDOs but is not necessarily absolutely overlapping. PDO might be able to complement the limitations of the gene panel and have the potential to provide a novel precision medicine.

Comprehensive Analysis of microRNA Profiles in Organoids Derived from Human Colorectal Adenoma and Cancer.

INTRODUCTION: Exosomes are membrane-enclosed nanovesicles, which are increasingly being recognized as important cell communication components for their role in transmitting microRNAs (miRNAs). No previous study has addressed the exosomal miRNA profile in colorectal adenomas (CRAs) because the long-term culture of CRA is challenging. This study aimed to identify the miRNA signature in organoid exosomes derived from human CRA and colorectal cancer (CRC) samples. METHODS: Organoid cultures were developed from resected colorectal tissues of patients with CRA or CRC undergoing surgery or endoscopic mucosal resection. Exosomes were prepared from the conditioned medium of the organoids. miRNAs were prepared from the exosomes and their source organoids. The miRNA expression profiles were compared using microarray analysis. The impact of alteration of miRNA expression on cell proliferation was examined using miRNA mimics or inhibitors in HT-29 human CRC cells. RESULTS: We established 6 organoid lines from CRC and 8 organoid lines from CRA. Exosomal miRNA signatures were different between the organoids derived from CRA and CRC. Both exosomal and cellular miR-1246 expressions were upregulated in CRC-derived organoids compared to their expression in CRA-derived organoids. Alteration of miR-1246 expression by the miR-1246 mimic or inhibitor increased or decreased cell proliferation in HT-29 cells, respectively. CONCLUSIONS: We report for the first time the miRNA profiles of exosomes in CRA- and CRC-derived organoids. The upregulation of miR-1246 might play a role in increased cell proliferation in the process of CRA-carcinoma transition.

[A Case of Rectal Cancer with Disseminated Intravascular Coagulation Successfully Treated with Emergent Chemotherapy].

A 70's woman complaining blood stool and lower abdominal pain visited a local doctor and was given the diagnosis of rectal cancer by colonoscopy. CT, MRI, and bone scintigraphy revealed multiple lymph node and bone metastasis and peritoneal dissemination. She had developed disseminated intravascular coagulation(DIC)during hospitalization, and the cause was considered to be disseminated carcinomatosis of the bone marrow. Thus, we emergently started chemotherapy with mFOLFOX6, in conjunction with anticoagulation therapy, and the DIC was resolved 11 days after the introduction. Partial response was achieved and the chemotherapy has been continued after 5 months from the onset of the DIC. Since the prognosis of solid tumor patients who developed DIC has been reported to be extremely poor, prompt introduction of chemotherapy should be considered.

[A Case of Curative Resection after Neoadjuvant Chemotherapy for Locally-Advanced Sigmoid Colon Carcinoma with Urinary Bladder Invasion].

A 56-year-old man was referred to our hospital for multidisciplinary treatment of advanced sigmoid colon carcinoma with a suspected bladder invasion. The patient received 8 courses of modified Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6)plus panitumumab as neoadjuvant chemotherapy for reliable and safe radical resection after ileostomy construction. There was a significant reduction in the tumor size following chemotherapy; hence, low anterior resection was performed. In addition, since preoperative and intraoperative findings suggested bladder invasion, a total cystectomy with ileal conduit urinary diversion was performed. The pathological diagnosis was ypT4b, N0, M0, and ypStage Ⅱc, with all surgical margins being negative. Subsequently, the patient received adjuvant chemotherapy with 4 courses of mFOLFOX6, and his condition improved with no incidence of cancer recurrence following 8 months after the operation. Neoadjuvant chemotherapy for locally advanced colon cancer is one of the effective treatments for reliable and safe radical resection.

Resection rate curves by location along the small intestine provide perspectives on characteristics of Crohn's disease.

AIM: Crohn's disease (CD) can affect any part of the gastrointestinal tract; however, the frequency of CD lesions differs by location. This work aimed to examine resection rates by location to clarify locational characteristics of the small intestine in surgical CD cases. METHOD: This was a single-centre retrospective case note review of patients who had undergone resection for CD affecting the small intestine between January 2014 and February 2020. Operative details, including length of the small intestine, location and extent of the resection, identified the pattern of disease. By normalizing these data the resection rate along the length of the intestine was calculated to create resection rate curves. RESULTS: One hundred and twenty six surgical cases were identified. The resection rate curves could be divided into two types: exponential and bimodal. For primary surgery, this depended on whether or not surgery was limited to an ileocolic resection. At subsequent surgery, a previous ileocaecal resection influenced the pattern of disease. The peaks of the bimodal curve were located at the proximal and distal ileum. CONCLUSION: CD patients requiring resection of the small intestine can be divided into terminal ileum type (exponential type) and proximal ileum type (bimodal type). In the future this analytical method may help predict the site of any recurrent disease but also provides a new perspective on the disease.

Laparoscopic right hemicolectomy for an ascending colon cancer patient with an implantable left ventricular assist device: a case report.

BACKGROUND: Left ventricular assist devices (LVADs) currently play an important role in the treatment of patients with end-stage heart failure who require a bridge to heart transplantation or destination therapy. With the development and improvement of the LVADs, the morbidity and mortality rates are declining and life expectancies increasing, and the number of patients with LVADs requiring non-cardiac surgery is likely to increase. We present the case of a patient with implantable LVAD who underwent laparoscopic right hemicolectomy for ascending colon cancer. CASE DESCRIPTION: The patient was a 66-year-old man who underwent LVAD implantation as a BTT 3 years prior. He suffered from severe anemia at follow-up, and a colonoscopy revealed ascending colon cancer. The LVAD pump was implanted in the epigastrium. The long C-shaped subfascial driveline tunnel was made, and driveline exit site was located on the left lateral abdominal wall. We assessed the positional relationship between the tumor and the driveline using X-ray and three-dimensional computed tomography (3D CT) images. 3D CT image allowed us to easily identify the location of the driveline, and we determined to perform laparoscopic right hemicolectomy. The port sites were decided upon carefully to avoid the driveline injury, and the driveline was marked on the skin before surgery. There were no adhesions in the abdominal cavity, and both the LVAD and the driveline were observable. The trocars were in nearly the same positions as in a standard laparoscopic right hemicolectomy. During the operation, the LVAD and the driveline did not interfere with the trocars. We successfully completed a standard laparoscopic right hemicolectomy despite hemorrhagic tendency. The patient was discharged without any bleeding complications during the postoperative course. CONCLUSION: Laparoscopic surgery is feasible and safe for patients with LVADs with intensive preoperative simulation and perioperative prevention of infection.

[Bladder-Sparing Surgery with Preoperative Chemotherapy for Rectal Cancer with Urinary Bladder Involvement-A Case Report].

A 65-year-old male was diagnosed with rectal cancer invading the urinary bladder, swollen para-aorticlymph nodes, and multiple liver metastases in abdominal CT. After 8 courses of mFOLFOX6 plus panitumumab, the rectal cancer, para-aortic lymph nodes metastasis, and liver metastases decreased significantly in size. Rectal cancer and liver metastases were considered resectable, hence low anterior resection of the rectum was performed. Intraoperative frozen section analysis showed negative metastaticinvolvement of the para-aorticlymph nodes and surgical margins of the urinary bladder; therefore, the urinary bladder was completely preserved. Partial resection of the liver was performed 2 months later. In conclusion, the patient showed good surgical and quality of life results. Thus, the bladder-sparing strategy with preoperative chemotherapy could be considered for appropriately selected rectal cancer patients with urinary bladder involvement.