Long-term prognosis after stapled and hand-sewn ileal pouch-anal anastomoses for familial adenomatous polyposis: a multicenter retrospective study.

PURPOSE: The long-term prognosis of stapled and hand-sewn ileal pouch-anal anastomoses in familial adenomatous polyposis patients in Japan remains unknown. This study aimed to compare the overall survival in familial adenomatous polyposis patients who underwent stapled or hand-sewn ileal pouch-anal anastomosis. METHODS: This multicenter retrospective study was conducted at 12 institutions in Shizuoka Prefecture, Japan. The clinical outcomes of 53 eligible familial adenomatous polyposis patients who underwent stapled (n = 24) and hand-sewn (n = 29) ileal pouch-anal anastomosis were compared. RESULTS: The median follow-up duration was 171.5 months. The incidence of adenoma in the remnant rectum or anal transitional zone and metachronous rectal cancer was significantly more common in stapled ileal pouch-anal anastomosis (adenoma: stapled, 45.8%, vs. hand-sewn, 10.3%, p = 0.005; metachronous rectal cancer: 29.2%, vs. none, p = 0.002). The number of deaths was remarkably higher in stapled ileal pouch-anal anastomosis (p = 0.002). Metachronous rectal cancer was the most common cause of death. Overall survival was worse in stapled ileal pouch-anal anastomosis than in hand-sewn ileal pouch-anal anastomosis (120 months, 90.7% vs. 96.6%; 240 months, 63.7% vs. 96.6%; p = 0.044). Cox regression analysis revealed the independent effects of preoperative advanced colorectal cancer and stapled ileal pouch-anal anastomosis on overall survival. CONCLUSION: Stapled ileal pouch-anal anastomosis negatively affected the overall survival of familial adenomatous polyposis patients. Therefore, hand-sewn ileal pouch-anal anastomosis is recommended for better prognosis in these patients.

Using a multistep approach with multidisciplinary team to increase the diagnosis rate of Lynch syndrome-associated colorectal cancer after universal screening: a single-center study in Japan.

BACKGROUNDS: This study aimed to evaluate the changes in the rates of genetic counseling and genetic testing as well as the diagnosis rate of Lynch syndrome (LS)-associated colorectal cancer before and after multistep approach with multidisciplinary team in Japanese. METHODS: In September 2016, we started universal screening for LS by mismatch repair protein immunohistochemistry and prospectively collected the records. Following patient interviews, we started multistep approach with multidisciplinary team (MA) in January 2020. MA consists of six surgeons, one genetic counselor, one medical geneticist, and six pathologists. MA is set up to compensate for patients' lack of knowledge about genetic diseases and make case selection for elderly colorectal cancer patients with deficient mismatch repair (dMMR). MA is designed as a system that could be performed by a small number of medical genetic specialists. A total of 522 patients were included during the study duration, 323 and 199 patients in the pre-MA (P-MA) and MA groups, respectively. RESULTS: The frequency of dMMR in all patients was 10.0%. The patient interview results indicated a significant lack of patient education regarding genetic diseases. The rates of genetic counseling and genetic testing was significantly higher in MA group than in P-MA group (genetic counseling: MA 34.6% vs. P-MA 7.7%, p = 0.04; genetic testing: MA 30.8% vs. P-MA 3.8%, p = 0.02). Moreover, the diagnosis rate of LS-associated colorectal cancer was significantly higher in MA group (2.5%) than in P-MA group (0.3%) (P = 0.03). In addition, MA could be performed without problems despite the small number of medical and human genetics specialists. CONCLUSIONS: MA has achieved appropriate pickup of suspected hereditary colorectal cancer patients and complemented the lack of knowledge about genetic diseases. The introduction of MA increased LS-associated colorectal cancer after universal screening. MA is an appropriate LS screening protocol for Japanese patients who lag behind in medical and human genetics education.

Analysis of external pressure on the left calf in the Lloyd-Davies position during colorectal surgery.

PURPOSE: Well-leg compartment syndrome (WLCS) is a potentially life-threatening postoperative complication related to the Lloyd-Davies surgical position, which can place increased external pressure on the calf region. We conducted this study to analyze external pressure changes, by applying a leg holder system to the left calf region of patients placed in the Lloyd-Davies position during laparoscopic surgery. METHODS: The study participants were 50 patients who underwent laparoscopic surgery for colorectal cancer in the Lloyd-Davies position. We assessed the maximum external pressure (MEP) on the left calf region using a pressure-distribution measurement system. Intraoperative measurements were taken continuously, and the MEP was evaluated with the patient horizontal and every 30 min during surgery in the head and right-down tilt position. RESULTS: The intraoperative MEP increased gradually when the patient was in the head and right-down tilt position and decreased when the patient was returned to the horizontal position. The MEP was higher in patients aged < 60 years, those who were obese, and those with a thick calf circumference. Both body mass index (BMI) and the maximum left calf circumference (MLCC) were found to correlate with the MEP. CONCLUSIONS: In addition to a high BMI, which is a well-known risk factor for WLCS, a high MLCC should be considered another risk factor, especially for patients under 60 years.

Long-term prognosis of familial adenomatous polyposis with or without mucosectomy.

PURPOSE: This study primarily aimed to compare the long-term prognosis of patients who underwent total colectomy/proctocolectomy with or without mucosectomy to the dentate line for the diagnosis of familial adenomatous polyposis (FAP). METHODS: Patients who underwent total colectomy/proctocolectomy for FAP between January 1979 and December 2020 and were followed up at Hamamatsu University Hospital were included in this study. Those who underwent total proctocolectomy with hand-sewn ileal pouch-anal anastomosis were defined as the mucosectomy group. Those who underwent total colectomy or total proctocolectomy using the stapled ileal pouch-anal anastomosis approach were defined as the no mucosectomy group. RESULTS: A total of 61 individuals (37 families) were diagnosed during the surveillance period (median, 191 months). Between the mucosectomy (n = 24) and no mucosectomy groups (n = 34), metachronous rectal cancer was significantly more common in the no mucosectomy group (21% in no mucosectomy vs. 0% in mucosectomy, P = 0.02). Overall survival in the no mucosectomy group was worse than that in the mucosectomy group (84.5% in no mucosectomy vs. 100% in mucosectomy at 120 months, 81.1% vs. 90.0% at 240 months, 50.6% vs. 75.0% at 360 months, P = 0.09). Cox regression analysis revealed an independent effect of not performing mucosectomy on overall survival (P = 0.03). CONCLUSION: Long-term surveillance revealed that colectomy or total proctocolectomy without mucosectomy had a negative impact on the overall survival of patients with FAP. Therefore, we recommend total proctocolectomy with mucosectomy, i.e., hand-sewn ileal pouch-anal anastomosis, for FAP.

Usefulness of a finger-mounted tissue oximeter with near-infrared spectroscopy for evaluating the intestinal oxygenation and viability in rats.

PURPOSE: To investigate the utility of the device for evaluating intestinal oxygenation and viability using an animal model. METHODS: Sprague-Dawley rats underwent laparotomy under general anesthesia, and the blood vessels in the terminal ileum were clamped to create ischemia. We measured the regional tissue oxygenation saturation (rSO2) using an oximeter after 1, 3, and 6 h of vessel clamping. Ischemic tissue damage was assessed using a histological score. The intestine was reperfused after each clamping period, and intestinal rSO2 and survival rate were evaluated. RESULTS: When reperfusion was performed at 1 and 3 h after ischemia, rSO2 increased after 10 min, and it improved to the same level as for normal intestine after 1 h; all rats survived for 1 week. In contrast, after 6 h of ischemia, rSO2 did not increase after reperfusion, and all animals died within 2 days. The histological scores increased after 1 h of reperfusion, with longer clamping periods. CONCLUSION: A finger-mounted tissue oximeter could evaluate intestinal ischemia and the viability, which is thus considered to be a promising result for future clinical application.

[Clinical Complete Response to Definitive Chemoradiotherapy for Advanced Lower Rectal Cancer-A Case Report].

A man in his 80s was admitted to our hospital with a chief complaint of bloody stools. He was diagnosed with cT2N0M0, cStage Ⅰ rectal cancer. As the patient was of advanced age and had multiple comorbidities, definitive chemoradiotherapy was administered. Immediately after treatment, the patient achieved a complete clinical response, and recurrence has not been detected for 2 years and 3 months since treatment.

Prevalence of laparoscopic surgical treatment and its clinical outcomes in patients with familial adenomatous polyposis in Japan.

BACKGROUND: Laparoscopic surgery is becoming the preferred technique for most colorectal interventions. This study aimed to clarify the time trend of surgical treatment for familial adenomatous polyposis (FAP) and its relevance to clinical outcomes in Japan over a 13-year period. METHODS: This was a multicenter retrospective cohort study comprising 23 specialist institutions for colorectal disease and a cohort of 282 FAP patients who underwent total colectomy or proctocolectomy during 2000-2012. Patient clinical backgrounds and surgical outcomes were compared between the first and second halves of the study period. RESULTS: The proportion of surgical types adopted over the entire study period was 46, 21, 30, and 3 % for ileoanal anastomosis (IAA), ileoanal canal anastomosis, ileorectal anastomosis, and permanent ileostomy, respectively. FAP patients undergoing laparoscopic surgery have increased since 2008 and reached 74 % in the past 3 years. In particular, the number of patients undergoing laparoscopic proctocolectomy with IAA increased approximately four-fold from the first to the second half of the study period. A laparoscopic approach was increasingly used in patients with coexisting colorectal malignancies. Despite this trend, surgical results of the laparoscopic approach between the two study periods showed similar morbidity, pouch operation and stoma closure completion rates. No postoperative mortality was observed in this series, and laparoscopic surgery was comparable to open surgery in terms of stoma closure rate, incidence of intra-abdominal/abdominal desmoid tumors, and postoperative survival rate in both study periods. CONCLUSION: Laparoscopic approach is increasingly being adopted for prophylactic FAP surgery in Japan and may provide clinically acceptable practical outcomes.

Has widespread use of biologic and immunosuppressant therapy for ulcerative colitis affected surgical trends? Results of a questionnaire survey of surgical institutions in Japan.

PURPOSE: The aim of the study is to assess the relationship between the introduction of biologic and immunosuppressant therapy and the number of patients undergoing surgery for ulcerative colitis (UC). METHODS: A questionnaire survey about patients undergoing surgery for UC was sent to 26 teaching hospitals throughout Japan. The questionnaire period spanned from 2008 to 2013, to account for the introduction of tacrolimus (2009) and infliximab (2010). RESULTS: The total number of patients who underwent surgery was 297, 291, 273, 255, 300, and 305 in 2008, 2009, 2010, 2011 2012, and 2013, respectively. The emergency surgery rate remained stable at 32-34 % each year. The proportion of patients who underwent surgery for cancer increased from 13.8 % in 2008 to 20 % in 2013. In 2013, 41, 38, and 6 % of patients who underwent surgery had received treatment with a biologic, tacrolimus, and cyclosporine, respectively. No institution reported an increase in postoperative complications among patients treated with immunosuppressive drugs. CONCLUSIONS: The number of patients undergoing surgery decreased temporarily soon after infliximab and tacrolimus first became widely available, but subsequently increased again. The emergency surgery rate remained unchanged throughout the study period. These data show that immunosuppressive drugs have had little effect on the risk of postoperative complications.

RSPO fusion transcripts in colorectal cancer in Japanese population.

R-spondin (RSPO) gene fusions have recently been discovered in a subset of human colorectal cancer (CRC) in the U.S. population; however, whether the fusion is recurrent in CRC arising in patients from the other demographic areas and whether it is specific for CRC remain uncertain. In this study, we examined 75 primary CRCs and 121 primary lung cancers in the Japanese population for EIF3E-RSPO2 and PTPRK-RSPO3 fusion transcripts using RT-PCR and subsequent sequencing analyses. Although the expression of EIF3E-RSPO2 and PTPRK-RSPO3 was not detected in any of the lung carcinomas, RSPO fusions were detected in three (4%) of the 75 CRCs. Two CRCs contained EIF3E-RSPO2 fusion transcripts, and another CRC contained PTPRK-RSPO3 fusion transcripts. Interestingly, in one of the two EIF3E-RSPO2 fusion-positive CRCs, a novel fusion variant form of EIF3E-RSPO2 was identified: exon 1 of EIF3E was connected to exon 2 of RSPO2 by a 351-bp insertion. A quantitative RT-PCR analysis revealed that RSPO mRNA expression was upregulated in the three CRCs containing RSPO fusion transcripts, while it was downregulated in nearly all of the other CRCs. An immunohistochemical analysis and a mutational analysis revealed that the RSPO fusion-containing CRC had a CDX2 cell lineage, was positive for mismatch repair protein expression, and had the wild-type APC allele. Finally, the forced expression of RSPO fusion proteins were shown to endow colorectal cells with an increased growth ability. These results suggest that the expression of RSPO fusion transcripts is related to a subset of CRCs arising in the Japanese population.

Impact of shear stress on sacral pressure injury from table rotation during laparoscopic colorectal surgery performed in the lithotomy position.

This study aimed to evaluate the impact of shear stress on surgery-related sacral pressure injury (PI) after laparoscopic colorectal surgery performed in the lithotomy position. We included 37 patients who underwent this procedure between November 2021 and October 2022. The primary outcome was average horizontal shear stress caused by the rotation of the operating table during the operation, and the secondary outcome was interface pressure over time. Sensors were used to measure shear stress and interface pressure in the sacral region. Patients were divided into two groups according to the presence or absence of PI. PI had an incidence of 32.4%, and the primary outcome, average horizontal shear stress, was significantly higher in the PI group than in the no-PI group. The interface pressure increased over time in both groups. At 120 min, the interface pressure was two times higher in the PI group than in the no-PI group (PI group, 221.5 mmHg; no-PI group, 86.0 mmHg; p < 0.01). This study suggested that shear stress resulting from rotation of the operating table in the sacral region by laparoscopic colorectal surgery performed in the lithotomy position is the cause of PI. These results should contribute to the prevention of PI.

Effects of povidone-iodine wound irrigation on surgical site infection in gastroenterological surgery: A randomized controlled trial.

BACKGROUND: The irrigation efficacy of a povidone-iodine solution to prevent surgical site infection is still controversial. We assessed the irrigation effect with a povidone-iodine solution on the incidence of surgical site infection after gastroenterological surgery. METHODS: This study is a single-center, prospective, randomized, blinded-end point superiority trial for surgical wound irrigation. Patients undergoing gastroenterological surgery were randomly assigned in a 1:1 replacement ratio using computer-generated randomization. Patients were grouped according to their surgical wound treatment into the control group using the normal sterile saline and the povidone-iodine group using 10% povidone-iodine solution after the NS solution. The main finding was 30-day surgical site infections assessed in the full analysis set. RESULTS: From November 2020 to December 2022, 697 of 894 patients were eligible for the study, among which 347 were in the povidone-iodine group and 350 in the control group. Thirty-day surgical site infections occurred in 100 (14%) patients-54 (16%) in the povidone-iodine group and 46 (13%) in the control group (odds ratio, 1.229; 95% CI, 0.800-1.889; P = .406). Superficial incisional surgical site infections occurred in 30 (9%) and 15 (4%) patients, respectively (odds ratio, 2.154; 95% CI, 1.134-4.090; P = .026). Only 3 patients (1%) in the control group developed adverse skin reactions. CONCLUSION: This study examined the irrigation efficacy of povidone-iodine for surgical site infection prevention compared to control in gastroenterological surgery. Povidone-iodine wound irrigation has shown no additional beneficial effect on the occurrence of surgical site infections.

Accumulated phosphatidylcholine (16:0/16:1) in human colorectal cancer; possible involvement of LPCAT4.

The identification of cancer biomarkers is critical for target-linked cancer therapy. The overall level of phosphatidylcholine (PC) is elevated in colorectal cancer (CRC). To investigate which species of PC is overexpressed in colorectal cancer, an imaging mass spectrometry was performed using a panel of non-neoplastic mucosal and CRC tissues. In the present study, we identified a novel biomarker, PC(16:0/16:1), in CRC using imaging mass spectrometry. Specifically, elevated levels of PC(16:0/16:1) expression were observed in the more advanced stage of CRC. Our data further showed that PC(16:0/16:1) was specifically localized in the cancer region when examined using imaging mass spectrometry. Notably, because the ratio of PC(16:0/16:1) to lyso-PC(16:0) was higher in CRC, we postulated that lyso-PC acyltransferase (LPCAT) activity is elevated in CRC. In an in vitro analysis, we showed that LPCAT4 is involved in the deregulation of PC(16:0/16:1) in CRC. In an immunohistochemical analysis, LPCAT4 was shown to be overexpressed in CRC. These data indicate the potential usefulness of PC(16:0/16:1) for the clinical diagnosis of CRC and implicate LPCAT4 in the elevated expression of PC(16:0/16:1) in CRC.

Methylation of CpG island promoters at ZNF625, LONRF2, SDC2 and WDR17 in a patient with numerous non-granular type laterally spreading tumors and colorectal cancer: A case report.

Patients with adenomatous polyposis syndromes such as familial adenomatous polyposis are at higher risk of colorectal cancer, hence continuous management is necessary. However, little is known about the etiology of patients with numerous laterally spreading tumors (LSTs), or how genetic alterations uniquely influence LSTs in colorectal carcinogenesis. The present case report investigated a woman with >150 non-granular type LSTs (LST-NG) and one sigmoid colon cancer. After subtotal colectomy via ileorectal anastomosis, genetic and epigenetic analyses were conducted by comparing the profiles of the patient's normal colonic mucosa, four LST-NG lesions and a cancer lesion. Using customized multigene panel testing, no pathogenic germline mutations were detected, including APC regulator of WNT signaling pathway, but identified a somatic pathogenic variant of APC in one LST-NG lesion, and both TP53 and F-box and WD repeat domain containing 7 somatic mutations in the cancer. Comprehensive genome-wide methylation analysis showed that CpG island promoters at zinc finger protein 625, LON peptidase N-terminal domain and ring finger 2, WD repeat domain 17 and syndecan 2 were methylated in both LST-NG and cancer, which may contribute to colorectal tumorigenesis as early as the LST-NG phase.

Thyroid transcription factor-1 expression in rectal adenocarcinoma metastatic to the lung.

Distinguishing metastatic lung tumors from primary lung cancer is essential for planning the appropriate treatment strategy. Thyroid transcription factor-1 (TTF-1) is a reliable immunohistochemistry (IHC) marker for differentiating between primary lung adenocarcinomas and metastatic lung tumors originating from colorectal adenocarcinomas. Herein, we report a rare case of TTF-1 expression in both the metastatic lung tumor and primary rectal adenocarcinoma. Aside from the similar histological characteristics of both tumors when stained with hematoxylin-eosin, the IHC patterns, including negative results for alveolar epithelium markers (napsin A and CK7) and positive results for intestinal markers (CK20, CDX2, SATB2, and ß-catenin), of the lung tumor and the primary rectal adenocarcinoma strongly supported the final diagnosis. Considering the non-negligible frequency of TTF-1 positivity in colorectal adenocarcinomas, applying the IHC panel including multiple markers for alveolar epithelium and intestinal differentiation, would be helpful to support the diagnosis of metastatic lung tumor from a rectal adenocarcinoma.

Long-term Prognostic Impact of Metachronous Rectal Cancer in Patients With Familial Adenomatous Polyposis: A Single-center Retrospective Study.

AIM: To evaluate the risk factors and long-term prognosis of metachronous rectal cancer in the remnant rectum of patients with familial adenomatous polyposis (FAP). PATIENTS AND METHODS: Sixty-five patients (49 families) who underwent prophylactic surgery, including bowel resection, for FAP between January 1976 and August 2022 at Hamamatsu University Hospital were included and divided into two groups based on the presence of metachronous rectal cancer. Risk factors for metachronous rectal cancer development were analysed in cases treated with total colectomy with ileorectal anastomosis (IRA) and stapled total proctocolectomy with ileal pouch anal anastomosis (IPAA) (IRA, n=22; stapled IPAA n=20; total, n=42). RESULTS: The median surveillance period was 169 months. Twelve patients developed metachronous rectal cancer (IRA, n=5; stapled IPAA, n=7), of which six with advanced cancer died. Patients who temporarily dropped out of surveillance were significantly more likely to have metachronous rectal cancer (metachronous vs. non-metachronous rectal cancer: 33.3% vs. 1.9%, p<0.01). The mean duration of surveillance suspension was 87.8 months. Cox regression analysis revealed that temporary surveillance drop-out independently affected the risk (p=0.04). The overall survival associated with metachronous rectal cancer was 83.3% at 1 year and 41.7% at 5 years. Overall survival was significantly worse in advanced cancer than in early cancer cases (p<0.01). CONCLUSION: Temporary drop-out from surveillance was a risk factor for metachronous rectal cancer development, and advanced cancer had a poor prognosis. Continuous surveillance of patients with FAP, without temporary drop-out, is strongly recommended.

Prevention of ureteral injury during laparoscopic colorectal cancer surgery with horseshoe kidney using fluorescent ureteral catheters: a case report.

BACKGROUND: Horseshoe kidney is one of the most common congenital renal fusion anomalies and is characterized by abnormalities in the position, rotation, vascular supply, and ureteral anatomy of the kidney. When performing surgery for colorectal cancer in patients with horseshoe kidneys, anatomical identification is important to avoid organ injuries. Several reports on surgery for colorectal cancer with horseshoe kidneys have described the usefulness of three-dimensional (3D) computed tomography (CT) angiography for detecting abnormalities in vascular supply. However, few reports have focused on the prevention of ureteral injury in surgery for colorectal cancer with horseshoe kidney, despite abnormalities in the ureteral anatomy. Here, we report a case in which laparoscopic sigmoid colon resection for sigmoid colon cancer with a horseshoe kidney was safely performed using fluorescent ureteral catheters. CASE PRESENTATION: A 60-year-old Japanese man presented to our hospital testing positive for fecal occult blood. Colonoscopy revealed sigmoid colon cancer, and CT confirmed a horseshoe kidney. The 3D-CT angiography showed aberrant renal arteries from the aorta and right common iliac artery, and the left ureter passed across the front of the renal isthmus. A fluorescent ureteral catheter was placed in the left ureter before the surgery to prevent ureteral injury. Laparoscopic sigmoid colon resection with D3 lymph node dissection was performed. The fluorescent ureteral catheter enabled the identification of the left ureter that passed across the front of the renal isthmus and the safe mobilization of the descending and sigmoid colon from the retroperitoneum. The operative time was 214 min, with intraoperative bleeding of 25 mL. The patient's postoperative course was good: no complications arose and she was discharged on the seventh postoperative day. CONCLUSION: In patients with horseshoe kidney, the use of fluorescent ureteral catheters and 3D-CT angiography enables safer laparoscopic surgery for colorectal cancer. We recommend the placement of fluorescent ureteral catheters in such surgeries to prevent ureteral injury.

Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study.

Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression.

Role of Corticosterone in Lipid Metabolism in Broiler Chick White Adipose Tissue.

Excessive accumulation of body fat in broiler chickens has become a serious problem in the poultry industry. However, the molecular mechanism of triglyceride accumulation in chicken white adipose tissue (WAT) has not been elucidated. In the present study, we investigated the physiological importance of the catabolic hormone corticosterone, the major glucocorticoid in chickens, in the regulation of chicken WAT lipid metabolism. We first examined the effects of fasting on the mRNA levels of lipid metabolism-related genes associated with WAT, plasma corticosterone, and non-esterified fatty acid (NEFA). We then examined the effects of corticosterone on the expression of these genes in vivo and in vitro. In 10-day-old chicks, 3 h of fasting significantly decreased mRNA levels of lipoprotein lipase (LPL) in WAT and significantly elevated plasma concentrations of NEFA. Six hours of fasting significantly increased mRNA levels of adipose triglyceride lipase (ATGL) in WAT and significantly elevated plasma concentrations of corticosterone. On the other hand, fasting significantly reduced mRNA levels of LPL in WAT and elevated plasma concentrations of NEFA in 29-day-old chicks without affecting mRNA levels of ATGL in WAT or plasma corticosterone concentrations. Oral administration of corticosterone significantly reduced mRNA levels of LPL and significantly increased the mRNA levels of ATGL in WAT in 29-day-old chicks without affecting plasma NEFA concentrations. The addition of corticosterone to primary chicken adipocytes significantly increased mRNA levels of ATGL, whereas mRNA levels of LPL tended to decrease. NEFA concentrations in the culture medium were not influenced by corticosterone levels. These results suggest that plasma corticosterone partly regulates the gene expression of lipid metabolism-related genes in chicken WAT and this regulation is different from the acute elevation of plasma NEFA due to short-term fasting.

Precision cancer genome testing needs proficiency testing involving all stakeholders.

To implement precision oncology, analytical validity as well as clinical validity and utility are important. However, proficiency testing (PT) to assess validity has not yet been systematically performed in Japan. To investigate the quality of next-generation sequencing (NGS) platforms and cancer genome testing prevalent in laboratories, we performed pilot PT using patient samples. We prepared genomic DNA from the cancer tissue and peripheral blood of 5 cancer patients and distributed these to 15 laboratories. Most participating laboratories successfully identified the pathogenic variants, except for two closely located KRAS variants and 25 bp delins in EGFR. Conversely, the EGFR L858R variant was successfully identified, and the allele frequency was similar for all the laboratories. A high DNA integrity number led to excellent depth and reliable NGS results. By conducting this pilot study using patient samples, we were able to obtain a glimpse of the current status of cancer genome testing at participating laboratories. To enhance domestic cancer genome testing, it is important to conduct local PT and to involve the parties concerned as organizers and participants.

Mismatch repair proteins immunohistochemical null phenotype in colon medullary carcinoma.

INTRODUCTION: In mismatch repair (MMR) immunohistochemistry, four MMR proteins' staining pattern reveals which particular gene may be defective. However, in the null phenotype, four MMR proteins are lost; consequently, it will be challenging to assume the target gene by immunohistochemistry and to determine whether deficient MMR was sporadic or germline. CASE REPORT: A 70-year-old man underwent right hemicolectomy with the diagnosis of ascending colon cancer. The postoperative histopathology revealed the diagnosis of medullary carcinoma and the loss of all four MMR expressions in immunohistochemistry. The mutation analysis using a peripheral blood sample showed no germline mutations in the four genes. DISCUSSION: This clinical case presents an unusual colon carcinoma that showed a MMR protein immunohistochemistry null phenotype. The cause of expression loss of MMR proteins can be explained by the loss of MLH1 and MSH2 functions associated with somatic loss of function mutations, functional loss in all four MMR proteins associated with somatic loss of function mutations, or Lynch-like syndrome. Correct interpretation and accumulation of relevant cases are necessary to unveil unusual cases in the era of universal screening.