Endoscopic Submucosal Dissection (ESD) Offers a Safer and More Cost-effective Alternative to Transanal Endoscopic Microsurgery (TEM): An International Collaborative Study.

BACKGROUND: Endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) are minimally invasive procedures that treat early rectal cancer (ERC). Both are effective treatments, yet there are very few studies comparing them. The aim of our study was to identify ideal candidates for each procedure. MATERIALS AND METHODS: Between January 2016 and November 2019, 204 ERC patients were managed with either ESD (n=101) or TEM (n=103) at 7 international centers. Data analyzed included clinical success, tumor characteristics, procedure info, and recurrence rates. RESULTS: Median tumor size was 40 mm±23.9 in the ESD group and 56 mm±27.9 in the TEM group, significantly larger in the latter ( P <0.00001). Average procedure time was 131.5±67.9 minutes in ESD group and 104.9±28.4 minutes in TEM group ( P =0.000347). Average hospital stay was 3.3±2.6 days in the ESD group and 4.7±0.7 days in the TEM group ( P <0.00001). Adverse event rate was 6.8% in the ESD group and 24% in the TEM group. There were no significant difference in the rate of en bloc resection, technical success, tumor location, necessity of additional procedures, and tumor recurrence rates. CONCLUSION: Compared with TEM, ESD is a safer procedure with shorter hospital stay and should be offered for patients who have ERC.

Gastric per-oral endoscopic myotomy versus pyloromyotomy for gastroparesis: An international comparative study.

BACKGROUND AND AIM: Gastroparesis is a potentially debilitating gastric motility disorder with limited treatment options. Highest efficacy treatments include gastric per-oral endoscopic myotomy (GPOEM) and surgical pyloromyotomy. This study compares the efficacy and safety of GPOEM versus laparoscopic pyloromyotomy for refractory gastroparesis. METHODS: Patients who underwent GPOEM or laparoscopic pyloromyotomy for refractory gastroparesis from four centers across the USA and Latin America were included in a dedicated registry. Data collected included patient demographics, imaging, laboratory values, clinical success, gastroparesis cardinal symptom index, procedure time, pre-op and post-op gastric emptying times, adverse events, and hospital length of stay. RESULTS: A total of 102 patients were included (mean age 47; 32.4% male): GPOEM n = 39, surgical pyloromyotomy n = 63.Technical success was 100% in both groups. Clinical success was 92.3% in the GPOEM group and 82.5% in the surgery group (P = 0.164). The GPOEM group had a significantly higher post-op GSCI score reduction by 1.3 units (P < 0.00001), post-op retention reduction at 2 h by 18% (P < 0.00001), post-op retention reduction at 4 h by 25% (P < 0.00001) and a lower procedure time by 20 min (P < 0.00001) as compared with surgery. GPOEM also had a lower hospital length of stay by 2.8 days (P < 0.00001). Adverse events were significantly fewer in the GPOEM group (13%) compared with surgery group (33.3%; P = 0.021). Mean blood loss in the GPOEM group was only 3.6 mL compared with 866 mL in the surgery group. CONCLUSIONS: The GPOEM may be a less invasive, safer, and more efficacious procedural treatment for refractory gastroparesis as compared with surgical pyloromyotomy.

Mammary-like Carcinoma of the vulva: A diagnostic challenge.

Mammary-like carcinoma of the vulva is incredibly rare with less than 30 cases published since 1935, and the similarities of such pathology between breast cancer metastases, squamous adenocarcinoma, Bartholin gland carcinomas, etc, make an accurate diagnosis challenging. A diagnosis can be made utilizing immunohistochemical staining and patient history to rule out more likely causes such as metastases to ensure a correct diagnosis.

MDM2 Derived from Dedifferentiated Liposarcoma Extracellular Vesicles Induces MMP2 Production from Preadipocytes.

Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the MDM2 gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects. Overall, these findings indicate that MDM2 plays a crucial role in DDLPS by enabling cross-talk between tumor cells and the surrounding microenvironment and that targeting vesicular MDM2 could represent a therapeutic option for treating DDLPS. SIGNIFICANCE: Extracellular vesicles derived from dedifferentiated liposarcoma cells induce oncogenic properties in preadipocytes.

Detection of Protease Activity by Fluorescent Peptide Zymography.

The purpose of this method is to measure the proteolytic activity of complex biological samples. The samples are separated by molecular weight using electrophoresis through a resolving gel embedded with a degradable substrate. This method differs from traditional gel zymography in that a quenched fluorogenic peptide is covalently incorporated into the resolving gel instead of full length proteins, such as gelatin or casein. Use of the fluorogenic peptides enables direct detection of proteolytic activity without additional staining steps. Enzymes within the biological samples cleave the quenched fluorogenic peptide, resulting in an increase in fluorescence. The fluorescent signal in the gels is then imaged with a standard fluorescent gel scanner and quantified using densitometry. The use of peptides as the degradable substrate greatly expands the possible proteases detectable with zymographic techniques.

Detection of proteolytic activity by covalent tethering of fluorogenic substrates in zymogram gels.

Current zymographic techniques detect only a subset of known proteases due to the limited number of native proteins that have been optimized for incorporation into polyacrylamide gels. To address this limitation, we have developed a technique to covalently incorporate fluorescently labeled, protease-sensitive peptides using an azido-PEG3-maleimide crosslinker. Peptides incorporated into gels enabled measurement of MMP-2, -9, -14, and bacterial collagenase. Sensitivity analysis demonstrated that use of peptide functionalized gels could surpass detection limits of current techniques. Finally, electrophoresis of conditioned media from cultured cells resulted in the appearance of several proteolytic bands, some of which were undetectable by gelatin zymography. Taken together, these results demonstrate that covalent incorporation of fluorescent substrates can greatly expand the library of detectable proteases using zymographic techniques.