Lymph node harvesting after laparoscopic complete mesocolic excision colectomy in colon cancer with practical application of glacial acid, absolute ethanol, water, and formaldehyde solution: A prospective cohort study.

Objectives: Quality of surgery has recently become an essential topic in the prognosis of colon cancer. Complete mesocolic excision for colon cancer has recently gained popularity with high-quality surgery. Patient specimens after complete mesocolic excision with central vessel ligation procedures have an integrity of the mesocolon and the yield of three fields of lymph node harvest. We apply the glacial acid, absolute ethanol, water, and formaldehyde solution to each specimen based on the Japanese classification of lymph node groups and station numbers. We aim to identify the distribution and status of lymph node metastasis according to each tumor site and some pathological characteristics related to this disease. Methods: A prospective cohort study was performed on 45 laparoscopic complete mesocolic excision surgery patients. Results: 2791 lymph nodes were harvested after complete mesocolic excision surgery. The average number was 62.0 ± 22.3 nodes. The mean tumor size (in the largest dimension) was 4.2 ± 1.8 cm. The average length of the resected bowel segments was 29.1 ± 7.7 cm. There are 63 (2.3%) node metastases in 2791 lymph nodes, in which 17/45 (37.8%) patients had pN(+). The minimum positive node size was 1 mm. The positive pericolic lymph nodes (station 1) accounted for the highest rate, with 53 nodes (1.9%). The number of lymph nodes in young age ⩽60 is more significant than in older. The results were similar, with a more significant node retrieval in the group with a tumor size >4.5 cm and specimen length >25 cm. The number of lymph nodes in lower tumor invasive (pT1,3) was smaller than pT4. Our research shows that the cecum, ascending, and descending colon had greater nodes than others, with a mean number of 78.6, 74.2, and 71.3, respectively. Conclusions: The metastasis and harvested lymph nodes accounted for the highest rate of colon cancer in station 1 and the lowest rate in station 3. The number of retrieved lymph nodes was significantly associated with tumor location, size, specimen length, and patient age.

Splenic lymphangioma in adult patient treated with laparoscopic splenectomy: A rare case report.

Splenic lymphangioma is a benign cystic tumor that develops as a result of lymphatic vessels' congenital abnormalities. It is a rare condition that mostly occurs in children and young adults. Due to the lack of typical symptoms and signs, splenic lymphangioma is difficult to diagnose and often incidentally revealed during radiological examinations. We report a case of a 55-year-old Asian female, who presented with left upper quadrant abdominal pain in the past 3 days. She had mild upper abdominal tenderness, with no other specific findings. Abdominal contrast material-enhanced computed tomography revealed three hypodense lesions arising from a normal-sized spleen. The histologic findings after laparoscopic splenectomy demonstrated a 3-cm-diameter yellowish-white tumor made up of multiple cystic structures. Primary benign splenic tumors are exceedingly rare, especially in adults over 20. While small lesions are mostly asymptomatic, bigger lesions can cause organ compression or even rupture. Therefore, even in adults with pain in the left upper quadrant abdomen or enlarged spleen, splenic lymphangioma should be taken into account in the differential diagnosis. The case serves as an example of a rare congenital splenic tumor. Treatment of this benign splenic abnormality with laparoscopic splenectomy is a good, safe approach.

Long non-coding RNA PCAT19 safeguards DNA in quiescent endothelial cells by preventing uncontrolled phosphorylation of RPA2.

In healthy vessels, endothelial cells maintain a stable, differentiated, and growth-arrested phenotype for years. Upon injury, a rapid phenotypic switch facilitates proliferation to restore tissue perfusion. Here we report the identification of the endothelial cell-enriched long non-coding RNA (lncRNA) PCAT19, which contributes to the proliferative switch and acts as a safeguard for the endothelial genome. PCAT19 is enriched in confluent, quiescent endothelial cells and binds to the full replication protein A (RPA) complex in a DNA damage- and cell-cycle-related manner. Our results suggest that PCAT19 limits the phosphorylation of RPA2, primarily on the serine 33 (S33) residue, and thereby facilitates an appropriate DNA damage response while slowing cell cycle progression. Reduction in PCAT19 levels in response to either loss of cell contacts or knockdown promotes endothelial proliferation and angiogenesis. Collectively, PCAT19 acts as a dynamic guardian of the endothelial genome and facilitates rapid switching from quiescence to proliferation.

Heterotopic Pancreas in the Duodenum Diagnosed after Laparoscopic Biopsy.

Heterotopic pancreas is defined as the presence of ectopic pancreatic tissue outside boundaries of the pancreas without vascular and duct system connection with the pancreas. Ectopic locations are mostly found anywhere in the gastrointestinal tract such as the stomach (24-38%), the duodenum (9-36%), and the jejunum (0.5-27%). Clinical manifestations are not specific, vague, and misdiagnosed another digestive disease. Most cases are incidentally detected by histological examination of specimens resected for different pathologies during endoscopy, surgery, or even autopsy. We report a case of a 31-year-old man who admitted to the hospital with the reason of epigastric pain for 3 days. Clinical examination showed mild epigastric tenderness. The past medical history of patient was unremarkable. A submucosal lesion was observed in the first part of the duodenum during endoscopy. Computed tomography and endoscopic ultrasonography findings were suspected to be heterotopic pancreatic tissue. After laparoscopic surgery for biopsy, it was histologically confirmed duodenal ectopic pancreas. It is difficult to differentiate gastrointestinal pancreatic heterotopia from gastrointestinal stromal tumors, leiomyoma, or lymphomas by using endoscopy because ectopic tissue is mostly located in the submucosal layer. In addition, rare cases of ectopic pancreatic tissue transform malignancy. Surgical treatment should be considered to take adequate tissue samples for biopsy or resect the lesions in symptomatic patients. Duodenal pancreatic heterotopia is an uncommon congenital malformation and most patients are asymptomatic. Histological examination is essential to exclude malignant lesions and to have an appropriate treatment.

Mitochondrial-cell cycle cross-talk drives endoreplication in heart disease.

Endoreplication, duplication of the nuclear genome without cell division, occurs in disease to drive morphologic growth, cell fate, and function. Despite its criticality, the metabolic underpinnings of disease-induced endoreplication and its link to morphologic growth are unknown. Heart disease is characterized by endoreplication preceding cardiac hypertrophy. We identify ATP synthase as a central control node and determinant of cardiac endoreplication and hypertrophy by rechanneling free mitochondrial ADP to methylenetetrahydrofolate dehydrogenase 1 L (MTHFD1L), a mitochondrial localized rate-limiting enzyme of formate and de novo nucleotide biosynthesis. Concomitant activation of the adenosine monophosphate­activated protein kinase (AMPK)­retinoblastoma protein (Rb)-E2F axis co-opts metabolic products of MTHFD1L function to support DNA endoreplication and pathologic growth. Gain- and loss-of-function studies in genetic and surgical mouse heart disease models and correlation in individuals confirm direct coupling of deregulated energetics with endoreplication and pathologic overgrowth. Together, we identify cardiometabolic endoreplication as a hitherto unknown mechanism dictating pathologic growth progression in the failing myocardium.

Ileal mucosa-associated lymphoid tissue lymphoma diagnosed after emergency surgery: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, also called MALT lymphoma, is one of the entities of marginal zone lymphomas. These lymphomas are originated from indolent B-cell lymphomas and involve many organs such as the gastrointestinal tract, salivary gland, skin, lung, thyroid or breast. Ileal MALT lymphoma is relatively rare and clinical symptoms are usually atypical. CASE PRESENTATION: We report a case of a 99-year-old man who admitted to the emergency department with increasing and colicky periumbilical pain, vomiting and constipation. Non-contrast-enhanced computed tomography suggested small bowel obstruction due to phytobezoar. Intraoperatively, surgeon discovered the tumor at the site of phytobezoar. Histologically, there was a diffuse infiltration comprised of small to medium sized lymphocytes with monocytoid features. Immunohistochemical result confirmed CD20 positive B-lymphocytes and the Ki-67 proliferation index was 10%. Ileal mucosa-associated lymphoid tissue lymphoma was diagnosed based on histological findings and immunohistochemistry. DISCUSSION: MALToma of the gastrointestinal tract is related to chronic antigenic, inflammatory bowel disease and malabsorption syndromes. However, the etiology of ileal MALToma is unclear. Moreover, symptom of ileal MALToma is really not typical and overleaped in the context of small intestinal obstruction. It should be differentiated small intestinal MALToma from immunoproliferative small intestinal disease and an alpha heavy chain disease. CONCLUSION: Ileal MALT lymphoma remains little known in many previous studies. It is really difficult to preoperatively diagnose. The combination of clinical presentation, postoperative histology and immunohistochemistry contribute to diagnosis and carry out appropriate management.

A rare congenital anomaly of the duodenal shape incidentally found at duodenopancreatectomy: A case report and literature review.

INTRODUCTION: An anomaly of the duodenal shape is one of the rare congenital anomalies and remains poorly known in many previous studies and the literature. The duodenum is formed by developing the terminal foregut and proximal midgut through four stages in the embryonic period. According to the anatomy, the duodenum is typically described as C-shaped, U-shaped, or even horseshoe-shaped. PRESENTATION OF CASE: The patient was hospitalized for abdominal pain and jaundice and diagnosed with ampullary carcinoma. During surgery, we incidentally discovered that the duodenum was not a C-shape. The first part of the duodenum and proximal half of the second part descended the head of the pancreas. However, the distal half of the second part bent to the right and ascended upwards to the upper-right margin of the pancreatic head. After that, the third part ran slantingly downward to the left and posterior of the pancreas and portal vein. DISCUSSION: During the fifth week, the ventral pancreatic bud moves around the duodenum's posterior side and unites the dorsal pancreatic bud at the sixth week. The place of the distal half of D2 migrated abnormally after ventral pancreatic bud rotation finished. The rapid and premature elongation of the proximal midgut, the influence of a very fast enlarged liver, or the early return of the umbilical loop combine with insufficiently developed abdominal space. These reasons may have led to the abnormal folding of the D2 position. CONCLUSION: Knowledge about this anomaly helps clinicians know the duodenal-anatomical abnormalities.

SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes.

AIMS: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality. It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection. METHODS AND RESULTS: Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression. Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections. SARS-CoV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Coronavirus particles were further observed in cardiomyocytes of a patient with coronavirus disease 2019. Infection of induced pluripotent stem cell-derived cardiomyocytes was dependent on cathepsins and angiotensin-converting enzyme 2, and was blocked by remdesivir. CONCLUSION: This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an angiotensin-converting enzyme 2- and cathepsin-dependent manner. SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.

Inhibition of the Hypoxia-Inducible Factor 1α-Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease.

BACKGROUND: Enhancers are genomic regulatory elements conferring spatiotemporal and signal-dependent control of gene expression. Recent evidence suggests that enhancers can generate noncoding enhancer RNAs, but their (patho)biological functions remain largely elusive. METHODS: We performed chromatin immunoprecipitation-coupled sequencing of histone marks combined with RNA sequencing of left ventricular biopsies from experimental and genetic mouse models of human cardiac hypertrophy to identify transcripts revealing enhancer localization, conservation with the human genome, and hypoxia-inducible factor 1α dependence. The most promising candidate, hypoxia-inducible enhancer RNA ( HERNA)1, was further examined by investigating its capacity to modulate neighboring coding gene expression by binding to their gene promoters by using chromatin isolation by RNA purification and λN-BoxB tethering-based reporter assays. The role of HERNA1 and its neighboring genes for pathological stress-induced growth and contractile dysfunction, and the therapeutic potential of HERNA1 inhibition was studied in gapmer-mediated loss-of-function studies in vitro using human induced pluripotent stem cell-derived cardiomyocytes and various in vivo models of human pathological cardiac hypertrophy. RESULTS: HERNA1 is robustly induced on pathological stress. Production of HERNA1 is initiated by direct hypoxia-inducible factor 1α binding to a hypoxia-response element in the histoneH3-lysine27acetylation marks-enriched promoter of the enhancer and confers hypoxia responsiveness to nearby genes including synaptotagmin XVII, a member of the family of membrane-trafficking and Ca2+-sensing proteins and SMG1, encoding a phosphatidylinositol 3-kinase-related kinase. Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. In vitro and in vivo inactivation of SMG1 and SYT17 revealed overlapping and distinct roles in modulating cardiac hypertrophy. Finally, in vivo administration of antisense oligonucleotides targeting HERNA1 protected mice from stress-induced pathological hypertrophy. The inhibition of HERNA1 postdisease development reversed left ventricular growth and dysfunction, resulting in increased overall survival. CONCLUSIONS: HERNA1 is a novel heart-specific noncoding RNA with key regulatory functions in modulating the growth, metabolic, and contractile gene program in disease, and reveals a molecular target amenable to therapeutic exploitation.