CRISPR-Cas9 for selective targeting of somatic mutations in pancreatic cancers.

Somatic mutations are desirable targets for selective elimination of cancer, yet most are found within noncoding regions. We have adapted the CRISPR-Cas9 gene editing tool as a novel, cancer-specific killing strategy by targeting the subset of somatic mutations that create protospacer adjacent motifs (PAMs), which have evolutionally allowed bacterial cells to distinguish between self and non-self DNA for Cas9-induced double strand breaks. Whole genome sequencing (WGS) of paired tumor minus normal (T-N) samples from three pancreatic cancer patients (Panc480, Panc504, and Panc1002) showed an average of 417 somatic PAMs per tumor produced from single base substitutions.

CRISPR-Cas9 for selective targeting of somatic mutations in pancreatic cancers.

Somatic mutations are desirable targets for selective elimination of cancer, yet most are found within the noncoding regions. We propose a novel, cancer-specific killing approach using CRISPR-Cas9 which exploits the requirement of a protospacer adjacent motif (PAM) for Cas9 activity. Through whole genome sequencing (WGS) of paired tumor minus normal (T-N) samples from three pancreatic cancer patients (Panc480, Panc504, and Panc1002), we identified an average of 417 somatic PAMs per tumor produced from single base substitutions.

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.

The Pre-treatment Lymphocyte-to-Monocyte Ratio Predicts Efficacy in Metastatic Colorectal Cancer Treated With TAS-102 and Bevacizumab.

Background/aim: Our multicenter phase II TAS-CC3 study demonstrated favorable median progression-free survival (PFS) and overall survival (OS) of 32 metastatic colorectal cancer (mCRC) patients treated with TAS-102 + bevacizumab as 3-line treatment.

Patients And Methods: We investigated the predictive and prognostic values of pre-treatment blood inflammation-based scores, including the neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte ratio (LMR) on disease-control (DC), PFS and OS by a post-hoc analysis.

Results: Receiver operating characteristic curve analyses of the 3 inflammation-based scores versus DC showed the best predictive performance for LMR, followed by NLR and PLR.

Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study.

Background: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment.

A Progressive Huge Accessory Spleen in the Greater Omentum.

Huge accessory spleen (AS) is a rare condition difficult to diagnose. We recently treated a Japanese woman with a progressive huge AS. She had a history of aortic valve replacement for aortic stenosis 1 month prior.

Biphenotypic Differentiation of Pancreatic Cancer in 3-Dimensional Culture.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer death in the United States. Improved characterized models of PDAC are needed for drug screening.

Methods: We grew 4 established pancreatic cancer cell lines in hanging drop cultures to produce spheroids.

Current status of venous thromboembolism development during the perioperative period for colorectal cancer, its prevention with enoxaparin, and monitoring methods.

There is a high incidence of venous thromboembolism (VTE) during the perioperative period for cancer. Therefore, there is an urgent need to elucidate the perioperative onset and appropriate prophylaxis for VTE. VTE during the perioperative period for colorectal cancer was evaluated by lower limb venous ultrasonic examinations (lower limb echo) under enoxaparin prophylaxis.

Colorectal Perforation in Patients with Connective Tissue Disease.

Purpose: The goal of this retrospective study was to identify prognostic factors associated with mortality after surgery for colorectal perforation among patients with connective tissue disease (CTD) and to review postoperative outcomes based on these prognostic factors.

Methods: The subjects were 105 patients (CTD group: n=26, 24.8%; non-CTD group: n=79, 75.

[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.

[A Case of Good Quality of Life(QOL)and Favorable Response to Transarterial Chemoembolization(TACE)against Synchronous Multiple Liver Metastases].

We report a case of good quality of life(QOL)and favorable response to transarterial chemoembolization(TACE)against synchronous multiple liver metastases. An 85-year-old man was admitted to our hospital because of melena. Colonoscopy showed multiple type 2 tumors in the sigmoid colon and upper rectum.

Circulating Tumor DNA as a Clinical Test in Resected Pancreatic Cancer.

Purpose: In research settings, circulating tumor DNA (ctDNA) shows promise as a tumor-specific biomarker for pancreatic ductal adenocarcinoma (PDAC). This study aims to perform analytical and clinical validation of a ctDNA assay in a Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathology-certified clinical laboratory.

Experimental Design: Digital-droplet PCR was used to detect the major PDAC-associated somatic mutations (G12D, G12V, G12R, and Q61H) in liquid biopsies.

[A Case of Pelvic Metastasis of Rectal Cancer That Developed Ten Years after Curative Resection].

We report a case of pelvic metastasis of rectal cancer that developed 10 years after curative resection. An 81-year-old woman underwent intersphincteric resection for lower rectal cancer 10 years previously. The tumor was pathologically diagnosed as T2N0M0, Stage Ⅰ.

[A Study of Treatment for Pathological T1(SM)Colorectal Cancer Patients after Endoscopic Resection at Our Department].

Approximately 10% of pathological T1(SM)colorectal cancer patients develop lymph node metastases. Therefore additional colectomy with lymph node dissection is recommended when it applies to the specific criteria in the current JSCCR guidelines. However, additional colectomy would not be done in some cases, because surgery is too invasive for some patients.

Histological characteristics of eosinophilic myenteric ganglionitis: an under-recognised cause of chronic intestinal pseudo-obstruction.

Eosinophilic myenteric ganglionitis (EMG) is characterised by eosinophilic infiltration of the myenteric plexus. EMG has been rarely reported as a cause of chronic intestinal pseudo-obstruction (CIPO), and its histopathological features are not fully elucidated. We analysed seven patients with CIPO.

Repeated laparoscopic resection of extra-regional lymph node metastasis after laparoscopic radical resection for rectal cancer.

Here, we report a case of repeated laparoscopic resection of extra-regional lymph node metastases in a patient after laparoscopic surgery for rectal cancer. A 72-year-old woman was diagnosed with upper rectal cancer and underwent laparoscopic low anterior resection and D3 dissection. The pathological stage was considered as T3, N2b, M0, Stage IIIC.

Case of idiopathic and complete appendiceal intussusception.

Appendiceal intussusception is a rare disease in which the appendix invaginates into the cecum. It is often caused by organic diseases. The present case involved an appendiceal intussusception without an organic disease, and laparoscopic resection of part of the cecum was performed.

Case report of perineal hernia after laparoscopic abdominoperineal resection.

Perineal hernia (PH) is a rare complication following laparoscopic abdominoperineal resection (APR) for rectal cancer. We present a case report of perineal hernia after laparoscopic APR and discuss its management. The patient was a 77-year-old man who was diagnosed with lower rectal cancer.

Two Cases of Rectal Neuroendocrine Tumor Resection Combined with Dissection of the Circular Muscle Layer Using the Endoscopic Submucosal Dissection Technique.

Generally, lesions of rectal neuroendocrine tumors (NETs) 10 mm or smaller are less malignant and are indicated for endoscopic therapy. However, the vertical margin may remain positive after conventional endoscopic mucosal resection (EMR) because NETs develop in a way similar to submucosal tumors (SMTs). The usefulness of EMR with a ligation device, which is modified EMR, and endoscopic submucosal dissection (ESD) was reported, but no standard treatment has been established.

Ascending Colon Cancer Associated with Dermatomyositis Which Was Cured after Colon Resection.

A 76-year-old woman with muscle ache, weakness of the extremities, and skin rash was diagnosed with dermatomyositis (DM). Upon the diagnosis of DM, a systemic survey of malignancy revealed an advanced carcinoma of the ascending colon. The patient underwent right hemicolectomy approximately 2 months after the onset of DM.

Unusual False-Positive Mesenteric Lymph Nodes Detected by PET/CT in a Metastatic Survey of Lung Cancer.

Positron emission tomography/computed tomography (PET/CT) is a credible diagnostic modality for detecting primary and metastatic malignancy. PET/CT sometimes shows false positives and negatives, which make clinical diagnosis difficult. A 42-year-old man who had undergone right upper lobectomy for lung cancer 1 year previously had PET/CT for a metastatic survey of the lung.

Combined laparoscopic abdominoperineal resection and robotic-assisted prostatectomy for synchronous double cancer of the rectum and the prostate.

Here we report a combined laparoscopic abdominoperineal resection and robotic-assisted prostatectomy. A 74-year-old man was diagnosed with T4b low rectal and prostate cancer. The operation was performed after neoadjuvant chemotherapy for the rectal cancer.

Complete Endoscopic Submucosal Dissection of a Giant Rectal Villous Adenocarcinoma with Electrolyte Depletion Syndrome.

An 81-year-old female consulted a local physician due to diarrhea. Since general fatigue and body weight loss were observed, she was admitted for detailed examination and treatment. Colonoscopy revealed a circumferential giant tumor with a maximum diameter of 10 cm in the rectum, and biopsy findings indicated villous adenoma.

Transflip mutations produce deletions in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is driven by the inactivation of the tumor suppressor genes (TSGs), CDKN2A (P16) and SMAD4 (DPC4), commonly by homozygous deletions (HDs). Using a combination of high density single-nucleotide polymorphism (SNP) microarray and whole genome sequencing (WGS), we fine-mapped novel breakpoints surrounding deletions of CDKN2A and SMAD4 and characterized them by their underlying structural variants (SVs). Only one third of CDKN2A and SMAD4 deletions (6 of 18) were simple interstitial deletions, rather, the majority of deletions were caused by complex rearrangements, specifically, a translocation on one side of the TSG in combination with an inversion on the other side.