Cadaveric and CT angiography study of vessels around the transverse colon mesentery.

BACKGROUND: Laparoscopic and robotic surgery for transverse colon cancer are difficult due to complex fusion of the foregut and midgut and variation of the vessels of the transverse colon. Although the vessels of the right colon have been investigated, middle colic artery (MCA) variation and the relationship with vessels around the transvers colon are unknown. We investigated variation of the MCA using computed tomography angiography (CTA) and cadaver specimen and the relationship between the superior mesenteric vein (SMV) and MCA using CTA. The classification of vessels around the transverse colon may lead to safer and reliable surgery. METHODS: This study included 505 consecutive patients who underwent CTA in our institution from 2014 to 2020 and 44 cadaver specimens. Vascular anatomical classifications and relationships were analyzed using CT images. RESULTS: The MCA was defined as the arteries arising from the superior mesenteric artery (SMA) that flowed into the transverse colon at the distal ends. The classifications were as follows: type I, branching right and left from common trunk; type II, the right and left branches bifurcated separately from the SMA; and type III, the MCA branched from a vessel other than the SMA. Type II was subclassified into two subtypes, type IIa with one left branch and type IIb with two or more left branches from SMA. In the CTA and cadaver studies, respectively, the classifications were as follows: type I, n = 290 and n = 31; type IIa, n = 211 and n = 13; type IIb, n = 3 and n = 0; and type III, n = 1 and n = 0. We classified the relationship between the MCA and left side of the SMV into three types: type A, a common trunk runs along the left edge of the SMV (n = 173; 59.7%); type B, a right branch of the MCA runs along the left edge of the SMV (n = 116; 40.0%); and type C, the MCA runs dorsal of the SMV (n = 1; 0.3%). CONCLUSIONS: This study revealed that The MCA branching classifications and relationship between the SMV and MCA. Preoperative CT angiography may be able to reliably identify vessel variation, which may be useful in clinical practice.

Long-term prognosis of laparoscopic gastrectomy for patients on antithrombotic therapy: a retrospective cohort study.

PURPOSE: Few studies have reported on the interactions between gastrectomy and antithrombotic therapy, especially the long-term prognosis. We aimed to clarify the short- and long-term prognosis of gastrectomy for patients on antithrombotic therapy. METHODS: We reviewed the perioperative data and survival rate of patients who underwent laparoscopic distal gastrectomy (LDG) at our institute between 2010 and 2013. RESULTS: There were 119 patients enrolled in this retrospective study: 31 who were taking antithrombotic drugs (antithrombotic therapy (ATT) group), and 88 who were not (non-ATT group). The mean age was significantly higher in the ATT group than in the non-ATT group. No significant differences were observed in the amount of intraoperative bleeding or blood hemoglobin level after surgery between the groups. Bleeding complications occurred in only one patient from the ATT group, and the postoperative complication rate was comparable between the groups. During follow-up, cerebrovascular or cardiovascular events developed in 19.4% of the ATT group patients and 4.5% of the non-ATT group patients; however, there were no significant differences in the 5-year overall survival rates between the groups (ATT group, 76.9%; non-ATT group, 82.9%). CONCLUSIONS: Antithrombotic therapy did not affect the short-term or long-term prognosis of patients after LDG.

Fast reconstruction of an original continuous series from a recurrence plot.

We propose an algorithm to refine the reconstruction of an original time series given a recurrence plot, which is also referred to as a contact map. The refinement process calculates the local distances based on the Jaccard coefficients with the neighbors in the previous resolution for each point and takes their weighted average using local distances. We demonstrate the utility of our method using two examples.

Usefulness of laparoscopic subtotal cholecystectomy with operative cholangiography for severe cholecystitis.

PURPOSE: Cholecystectomy can become hazardous when inflammation develops, leading to anatomical changes in Calot's triangle. We attempted to study the safety and efficacy of laparoscopic subtotal cholecystectomy (LSC) to decrease the incidence of complications and the rate of conversion to open surgery. METHODS: Patients who underwent LSC between January 2005 and December 2008 were evaluated retrospectively. The operations were performed laparoscopically irrespective of the grade of inflammation estimated preoperatively. However, patients with severe inflammation of the gallbladder underwent LSC involving resection of the anterior wall of the gallbladder, removal of all stones and placement of an infrahepatic drainage tube. To prevent intraoperative complications, including bile duct injury, intraoperative cholangiography was performed. RESULTS: LSC was performed in 26 elective procedures among 26 patients (eight females, 18 males). The median patient age was 69 years (range 43-82 years). The median operative time was 125 min (range 60-215 min) and the median postoperative inpatient stay was 6 days (range 3-21 days). Cholangiography was performed during surgery in 24 patients. One patient underwent postoperative endoscopic sphincterotomy for a retained common bile duct stone that was found on cholangiography during surgery. Neither complications nor conversion to open surgery were encountered in this study. CONCLUSIONS: LSC with the aid of intraoperative cholangiography is a safe and effective treatment for severe cholecystitis.

Crosstalk within and beyond the Polycomb repressive system.

The development of multicellular organisms depends on spatiotemporally controlled differentiation of numerous cell types and their maintenance. To generate such diversity based on the invariant genetic information stored in DNA, epigenetic mechanisms, which are heritable changes in gene function that do not involve alterations to the underlying DNA sequence, are required to establish and maintain unique gene expression programs. Polycomb repressive complexes represent a paradigm of epigenetic regulation of developmentally regulated genes, and the roles of these complexes as well as the epigenetic marks they deposit, namely H3K27me3 and H2AK119ub, have been extensively studied. However, an emerging theme from recent studies is that not only the autonomous functions of the Polycomb repressive system, but also crosstalks of Polycomb with other epigenetic modifications, are important for gene regulation. In this review, we summarize how these crosstalk mechanisms have improved our understanding of Polycomb biology and how such knowledge could help with the design of cancer treatments that target the dysregulated epigenome.

A case of MCA arising from ICA: a case report.

BACKGROUND: Complete mesocolic excision (CME) and central vascular detachment are very important procedures in surgery for colorectal cancer. Preoperative and intraoperative assessments of the anatomy of major colorectal vessels are necessary to avoid massive bleeding, especially in endoscopic surgery. A case with a rare anomaly in which the middle colic artery (MCA) and ileocolic artery (ICA) had a common trunk is reported. CASE PRESENTATION: The patient was a 73-year-old woman diagnosed with ascending colon cancer on colonoscopy. Preoperative abdominal contrast-enhanced computed tomography confirmed that the MCA and ICA had a common trunk. She underwent laparoscopic ileocecal resection for the ascending colon cancer with D3 lymph node dissection. Intraoperative indocyanine green fluorescence imaging was conducted. After confirming vessel bifurcation, the ICA was dissected at the distal end of the MCA bifurcation. The patient has been followed as an outpatient, with no signs of recurrence as of 2 years postoperatively. CONCLUSION: A case of an ascending colon cancer with a unique vascular bifurcation pattern was presented. Preoperative and intraoperative evaluations of the major colorectal vessels are very important for preventing perioperative and postoperative complications.

A case of robot-assisted resection for cecum cancer with anomalous venous confluence.

There are many reports on the positional relationship between the ileocolic artery and superior mesenteric vein (SMV). However, there have been no reports of anomalous venous confluence in the ileocecal vessel area. A 69-year-old man was diagnosed with cecal cancer on a preoperative examination of a lung tumor. We planned to perform surgery for the cecal cancer. Computed tomography angiography revealed an anomalous vein confluence in the ileocolic region. We performed robot-assisted ileocecal resection. Although the small intestinal vein was misidentified as the SMV at first, we confirmed the misidentification, identified the SMV on the dorsal side of the ileocolic artery, and ligated the ileocolic vessels with precise forceps manipulation during robotic surgery. Especially for cases with vascular anomalies revealed by preoperative computed tomography angiography, robotic surgery may be useful, as flexible forceps manipulation prevents vascular injury.

C16, a PKR inhibitor, suppresses cell proliferation by regulating the cell cycle via p21 in colorectal cancer.

Double-stranded RNA-activated protein kinase R (PKR) is highly expressed in colorectal cancer (CRC). However, the role of PKR in CRC remains unclear. The aim of this study was to clarify whether C16 (a PKR inhibitor) exhibits antitumor effects and to identify its target pathway in CRC. We evaluated the effects of C16 on CRC cell lines using the MTS assay. Enrichment analysis was performed to identify the target pathway of C16. The cell cycle was analyzed using flow cytometry. Finally, we used immunohistochemistry to examine human CRC specimens. C16 suppressed the proliferation of CRC cells. Gene Ontology (GO) analysis revealed that the cell cycle-related GO category was substantially enriched in CRC cells treated with C16. C16 treatment resulted in G1 arrest and increased p21 protein and mRNA expression. Moreover, p21 expression was associated with CRC development as observed using immunohistochemical analysis of human CRC tissues. C16 upregulates p21 expression in CRC cells to regulate cell cycle and suppress tumor growth. Thus, PKR inhibitors may serve as a new treatment option for patients with CRC.

Early Laparoscopic Colostomy in Advanced Cancer Patients with Rectovaginal Fistula: Results of Seven Patients.

A rectovaginal fistula (RVF) is an abnormal tract between the rectum and vagina, which requires surgical intervention in many cases. Although there are many different therapeutic approaches for RVF depending on the patient's' condition, there are no established guidelines for the care of RVF. This study aimed to evaluate the results of laparoscopic colostomy in advanced cancer patients with RVF, and the safety and efficacy of this surgery. In this study, seven female advanced cancer patients with RVF were hospitalized and successfully treated with laparoscopic colostomy from 2015 to 2018 at our university hospital. Their data were retrospectively evaluated from their medical records. The early use of diverting stomas facilitated timely resumption of cancer treatment and enabled early treatment with chemotherapy or radiotherapy. Although vaginal stool leakage affected three patients, all patients recovered, experiencing neither pain nor infection during their cancer treatment. While colostomy was physically and mentally taxing for the patients, it improved the infection and pain caused by the RVF. We conclude that the early use of diverting stomas had two effects: a significant improvement in infection management and facilitation of the rapid resumption of cancer treatment.

A double-helical S,C-bridged tetraphenyl-para-phenylenediamine and its persistent radical cation.

A structurally constrained, double-helical S,C-bridged tetraphenyl-para-phenylenediamine (TPPD) has been synthesized. The stable radical cation of the S,C-bridged TPPD was generated by chemical oxidation, and the electron spin was found to be delocalized over the entire π-conjugated framework. The excellent conformational stability of the neutral molecule facilitated the separation of its enantiomers.

Tumor local chemohyperthermia using docetaxel-embedded magnetoliposomes: Interaction of chemotherapy and hyperthermia.

BACKGROUND AND AIM: We have studied and reported the usefulness of tumor local chemohyperthermia at a low-grade temperature below 43°C with docetaxel-embedded magnetoliposome (DML) and an applied alternating current magnetic field. However, the mechanisms of this treatment and the dynamics of the injected docetaxel were not investigated in our previous study. Thus, we investigated the interaction of chemotherapy and hyperthermia in the treated tumor. METHODS: Human MKN45 gastric cancer cells were implanted in the hind limbs of Balb-c/nu/nu mice. DML, magnetite-loaded liposome, and docetaxel were injected into the tumors with or without being exposed to an alternating current magnetic field. Docetaxel and tumor necrosis factor-α concentrations, the cell cycle, and cell death rates in the tumor were examined. RESULTS: Docetaxel concentrations were significantly higher in the DML-injected group than in the docetaxel-injected group 3 days after injection. A G2/M peak was observed 1 day after treatment in the DML-injected and exposed group and the docetaxel-injected group, while it was observed 3 days after treatment in the DML-injected without heating group and the magnetite-loaded liposome group. The tumor cell death rate gradually increased in the DML-injected group, with or without being exposed, while it gradually decreased after its peak in other groups. The tumor necrosis factor-α concentration in the tumor treated with DML with heating remained at a high level on the 7th day after treatment, while it decreased after its peak in other groups. CONCLUSION: The antitumor effect of this treatment derives from a combination of hyperthermia and chemotherapy locally in the tumor.

Establishment of mouse stem cells that can recapitulate the developmental potential of primitive endoderm.

The mammalian blastocyst consists of three distinct cell types: epiblast, trophoblast (TB), and primitive endoderm (PrE). Although embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) retain the functional properties of epiblast and TB, respectively, stem cells that fully recapitulate the developmental potential of PrE have not been established. Here, we report derivation of primitive endoderm stem cells (PrESCs) in mice. PrESCs recapitulate properties of embryonic day 4.5 founder PrE, are efficiently incorporated into PrE upon blastocyst injection, generate functionally competent PrE-derived tissues, and support fetal development of PrE-depleted blastocysts in chimeras. Furthermore, PrESCs can establish interactions with ESCs and TSCs and generate descendants with yolk sac-like structures in utero. Establishment of PrESCs will enable the elucidation of the mechanisms for PrE specification and subsequent pre- and postimplantation development.

The arrival time of indocyanine green in tissues can be a quantitative index because of its correlation with tissue oxygen saturation: A clinical pilot study.

Indocyanine green (ICG) fluorescence angiography has recently been reported useful as a method for predicting intestinal blood flow and may reduce anastomotic leakage. However, the quantification method for ICG fluorescence angiography has not been established. We usually measure the tissue oxygen saturation (StO2 ) in the intestinal tract via near-infrared spectroscopy, as it is able to measure the oxygen concentration accurately and immediately shows objective data. In this study, we propose that the time to reach the anastomotic site after intravenous ICG injection is an effective parameter for quantifying ICG fluorescence angiography from the comparison to the data of StO2 in the intestinal tract.

Acute respiratory distress syndrome after gastrointestinal surgery.

BACKGROUND/AIMS: Acute respiratory distress syndrome (ARDS) occasionally occurs after gastrointestinal surgery involving severe inflammation such as diffuse peritonitis. Management of this condition has been difficult and effective therapies have not yet been established. In the present study the management for ARDS after gastrointestinal surgery was evaluated. METHODOLOGY: A total of 15 patients developed ARDS after gastrointestinal operations performed in our institution. The mean patient age was 75.4±11.1 years. Onset of ARDS occurred ≤24 hours postoperatively in 12 patients and 3- 11 days postoperatively in 3 patients. Treatment for ARDS comprised continuous hemodiafiltration (CHDF), high-dose glucocorticoid therapy or administration of a neutrophil elastase inhibitor (sivelestat). RESULTS: Four patients died 3-45 days after onset of ARDS (mortality rate, 26.6%). CHDF was performed in 12 patients, 8 patients received highdose glucocorticoid therapy and 11 patients received sivelestat. No differences in severity scores and clinical data were noted between survivors and non-survivors. PaO2/FiO2 ratio was significantly lower in non-survivors than in survivors from 5 days after starting treatment, whereas no difference was apparent at the onset of ARDS. CONCLUSIONS: Multimodal therapies for ARDS were effective. Longitudinal fluctuation in PaO2/ FiO2 ratio after starting treatment appears to offer a prognostic factor for ARDS.

[Polycomb Group Proteins Establish a Morphogen-Mediated Spatial Map During Early-Stage Brain Development].

The first step for development of a functionally and structurally intricate organ, the brain, involves precise control of the neural stem cell (NSC) fate. NSCs produce a variety of neurons and glial cells according to the developmental time and 3-dimensional (3D) position within the brain. Morphogens play a key role in determining the 3D positional information of NSCs and thus regulating brain arealization along the rostrocaudal and dorsoventral axes. In this review article, we summarize recent studies that described essential roles of Polycomb group proteins in the establishment of the 3D atlas of the brain, in part through suppressing brain area-specific genes such as morphogens.

Preparation of optimized concanavalin A-conjugated Dynabeads® magnetic beads for CUT&Tag.

Epigenome research has employed various methods to identify the genomic location of proteins of interest, such as transcription factors and histone modifications. A recently established method called CUT&Tag uses a Protein-A Tn5 transposase fusion protein, which cuts the genome and inserts adapter sequences nearby the target protein. Throughout most of the CUT&Tag procedure, cells are held on concanavalin A (con A)-conjugated magnetic beads. Proper holding of cells would be decisive for the accessibility of Tn5 to the chromatin, and efficacy of the procedure of washing cells. However, BioMag®Plus ConA magnetic beads, used in the original CUT&Tag protocol, often exhibit poor suspendability and severe aggregation. Here, we compared the BioMag beads and Dynabeads® magnetic particles of which conjugation of con A was done by our hands, and examined the performance of these magnetic beads in CUT&Tag. Among tested, one of the Dynabeads, MyOne-T1, kept excessive suspendability in a buffer even after overnight incubation. Furthermore, the MyOne-T1 beads notably improved the sensitivity in CUT&Tag assay for H3K4me3. In conclusion, the arrangement and the selection of MyOne-T1 refine the suspendability of beads, which improves the association of chromatin with Tn5, which enhances the sensitivity in CUT&Tag assay.

Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target genes.

Polycomb repressive complexes-1 and -2 (PRC1 and 2) silence developmental genes in a spatiotemporal manner during embryogenesis. How Polycomb group (PcG) proteins orchestrate down-regulation of target genes upon differentiation, however, remains elusive. Here, by differentiating embryonic stem cells into embryoid bodies, we reveal a crucial role for the PCGF1-containing variant PRC1 complex (PCGF1-PRC1) to mediate differentiation-associated down-regulation of a group of genes. Upon differentiation cues, transcription is down-regulated at these genes, in association with PCGF1-PRC1-mediated deposition of histone H2AK119 mono-ubiquitination (H2AK119ub1) and PRC2 recruitment. In the absence of PCGF1-PRC1, both H2AK119ub1 deposition and PRC2 recruitment are disrupted, leading to aberrant expression of target genes. PCGF1-PRC1 is, therefore, required for initiation and consolidation of PcG-mediated gene repression during differentiation.

Feasibility of chemohyperthermia with docetaxel-embedded magnetoliposomes as minimally invasive local treatment for cancer.

Hyperthermia is a minimally invasive approach to cancer treatment, but it is difficult to heat only the tumor without damaging surrounding tissue. To solve this problem, we studied the effectiveness of chemohyperthermia with docetaxel-embedded magnetoliposomes (DMLs) and an applied alternating current (AC) magnetic field. Human MKN45 gastric cancer cells were implanted in the hind limb of Balb-c/nu/nu mice. Various concentrations of docetaxel-embedded DMLs were injected into the tumors and exposed to an AC magnetic field (n = 6, each). For comparison with hyperthermia alone, magnetite-loaded liposome (ML)-injected tumors were exposed to an AC magnetic field. Furthermore, the results of DML without AC treatment and docetaxel diluted into PBS with AC treatment were also compared (n = 10, each). Tumor surface temperature was maintained between 42 and 43 degrees C. Tumor volume was reduced in the DML group with a docetaxel concentration > 56.8 microg/ml, while a docetaxel concentration > 568.5 microg/ml was required for tumor reduction without hyperthermia. Statistically significant differences in tumor volume and survival rate were observed between the DML group exposed to the magnetic field and the other groups. The tumor disappeared in 3 mice in the DML group exposed to the magnetic field; 2 mice survived over 6 months after treatment, whereas all mice of the other groups died by 15 weeks. Histologically, hyperthermia with DML damaged tumor cells and DML diffused homogeneously. To the best of our knowledge, this is the first report to show that hyperthermia using chemotherapeutic agent-embedded magnetoliposomes has an anticancer effect.

Continuous irrigation with gabexate mesilate around pancreaticojejunostomy after pancreaticoduodenectomy.

UNLABELLED: BACKGOUND/AIMS: The aim of this study is to present the new method of continuously irrigated around the pancreaticojejunostomy to reduce postoperative complications after pancreaticoduodenectomy. METHODOLOGY: Twenty-seven patients underwent pancreaticoduodenectomy in our institution between 2002 and 2007. Pancreaticojejunostomy was performed with the external pancreatic duct stent tube, and continuous irrigation around the pancreaticojejunostomy was started on the operative day with physiological saline solution containing gabexate mesilate. RESULTS: Mean duration of irrigation was 7.1 +/- 4.4 days, mean duration of drainage tube placement was 14.2 +/- 9 days, and mean duration of pancreatic duct drainage tube placement was 24.9 +/- 4.7 days. Pancreatic fistula was diagnosed in 8 patients. Three cases were classified as grade A and 5 cases were grade B. These pancreatic fistulae were closed by non-invasive treatment and the in-hospital death rate was 0%. CONCLUSIONS: External total drainage of the main pancreatic duct and continuous irrigation around pancreaticojejunostomy appears to avoid severe postoperative complications.

Metachronous intraductal papillary mucinous neoplasm with carcinoma in situ of the pancreas arising within a short interval: report of a case.

A 61-year-old man with an intraductal papillary mucinous neoplasm (IPMN) and carcinoma in situ (CIS) of the pancreatic body initially underwent a distal pancreatectomy. Postoperative follow-up included computed tomography (CT) and ultrasonography (US) every 6 months. Intraductal papillary mucinous neoplasm of the pancreatic head was diagnosed 17 months later using peroral pancreatoscopy (POPS) including a biopsy, revealing IPMN with highly dysplastic changes. A total pancreatectomy was therefore performed. The pathological examination revealed IPMN with CIS. The patient was discharged from the hospital and is doing well as of 1 year postoperatively. Although cautious surveillance seems mandatory, consensus has not yet been reached regarding postoperative surveillance. This report presents an unreported case of metachronously arising IPMN with CIS within a relatively early interval, thus suggesting that surveillance every 6 months is preferable to > or = 1 year. In addition, endoscopic US, endoscopic retrograde cholangiopancreatography, intraductal US, or POPS should be included in pathological examinations to avoid missing opportunities to treat lesions such as noninvasive IPMN with a good prognosis. Surgically indicated patients with noninvasive recurrence should therefore be strongly considered to undergo a total pancreatectomy.