The Impact of Preoperative Sarcopenia on Survival Prognosis in Patients Receiving Neoadjuvant Therapy for Esophageal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Sarcopenia is a poor prognostic factor in patients with esophageal cancer (EC). It can be aggravated by neoadjuvant therapy (NAT) that improves the prognosis of patients with EC. Until now, the impact of preoperative sarcopenia on survival prognosis in patients receiving NAT for EC remains unclear. METHODS: We systematically researched relevant studies in the PubMed, EMBASE, Web of Science, the Cochrane Library databases up to March 8, 2020. Prevalence of sarcopenia before and after NAT, overall survival (OS) and disease-free survival (DFS) were collected for analysis. Finally, eleven cohort studies were included. RESULTS: Pooled analysis indicated that preoperative sarcopenia was negatively associated with OS. (HR = 1.290; 95% CI [1.078-1.543]; P = 0.005; I 2 = 0.0%) and DFS (HR = 1.554; 95% CI [1.177-2.052]; P = 0.002; I 2 = 0.0%) in the patients with EC receiving NAT. The prevalence of sarcopenia increased by 15.4% following NAT (95%CI [12.9%-17.9%]). Further subgroup analysis indicated that sarcopenia diagnosed following NAT (HR = 1.359; 95% CI [1.036-1.739]; P = 0.015; I 2 = 6.9%) and age >65 years (HR = 1.381; 95% CI [1.090- 1.749]; P = 0.007; I 2 = 0.0%) were the independent risk factors for decreased OS. CONCLUSIONS: Clinicians should strengthen the screening of preoperative sarcopenia in patients of EC both receiving NAT and older than 65 years and give active nutritional support to improve the prognosis of patients. SYSTEMATIC REVIEW REGISTRATION: International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202050057.

Application of endoscopic submucosal dissection in duodenal space-occupying lesions.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been advocated by digestive endoscopists because of its comparable therapeutic effect to surgery, reduced trauma, faster recovery, and fewer complications. However, ESD for lesions of the duodenum is more challenging than those occurring at other levels of the gastrointestinal tract due to the thin intestinal wall of the duodenum, narrow intestinal space, rich peripheral blood flow, proximity to vital organs, and high risks of critical adverse events including intraoperative and delayed bleeding and perforation. Because of the low prevalence of the disease and the high risks of severe adverse events, successful ESD for lesions of the duodenum has rarely been reported in recent years. AIM: To investigate the efficacy and safety of ESD in the treatment of duodenal space-occupying lesions. METHODS: Clinical data of 24 cases of duodenal lesions treated by ESD at the Digestive Endoscopy Center of the Affiliated Hospital of Qingdao University from January 2016 to December 2019 were retrospectively analyzed. RESULTS: All of the 24 cases from 23 patients underwent ESD treatment for duodenal space-occupying lesions under general anesthesia, including 15 male and 8 female patients, with a mean age of 58.5 (32.0-74.0) years. There were 12 lesions (50%) in the duodenal bulb, 9 (37.5%) in the descending part, and 3 (12.5%) in the ball-descending junction. The mean diameter of the lesion was 12.75 (range, 11-22) mm. Thirteen lesions originated from the mucosa, of which 4 were low-grade intraepithelial neoplasia, 3 were hyperplastic polyps, 2 were chronic mucositis, 2 were adenomatous hyperplasia, 1 was high-grade intraepithelial neoplasia, and 1 was tubular adenoma. Eleven lesions were in the submucosa, including 5 neuroendocrine neoplasms, 2 cases of ectopic pancreas, 1 stromal tumor, 1 leiomyoma, 1 submucosal duodenal adenoma, and 1 case of submucosal lymph follicular hyperplasia. The intraoperative perforation rate was 20.8% (5/24), including 4 submucosal protuberant lesions and 1 depressed lesion. The mean length of hospital stay was 5.7 (range, 3-10) d, and the average follow-up time was 25.8 (range, 3.0-50.0) mo. No residual disease or recurrence was found in all patients, and no complications, such as infection and stenosis, were found during the follow-up period. CONCLUSION: ESD is safe and effective in the treatment of duodenal lesions; however, the endoscopists should pay more attention to the preoperative preparation, intraoperative skills, and postoperative treatment.

Cucurbitacin B and SCH772984 exhibit synergistic anti-pancreatic cancer activities by suppressing EGFR, PI3K/Akt/mTOR, STAT3 and ERK signaling.

Cucurbitacin B (CuB) is a natural tetracyclic triterpene product and displays antitumor activity across a wide array of cancers. In this study, we explored the anti-pancreatic cancer activity of CuB alone and in combination with SCH772984, an ERK inhibitor, in vitro and in vivo. CuB inhibited proliferation of pancreatic cancer cells by arresting them in the G2/M cell cycle phase. This was associated with inhibition of EGFR expression and activity and downstream signaling, including PI3K/Akt/mTOR and STAT3. Interestingly, ERK activity was markedly enhanced by activating AMPK signaling after 12 h of CuB treatment. SCH772984 potentiates the cytotoxic effect of CuB on pancreatic cancer cells through complementary inhibition of EGFR, PI3K/Akt/mTOR, STAT3 and ERK signaling, followed by an increase in the pro-apoptotic protein Bim and a decrease in the anti-apoptotic proteins Mcl-1, Bcl-2, Bcl-xl and survivin. Furthermore, combined therapy with CuB and SCH772984 resulted in highly significant growth inhibition of pancreatic cancer xenografts. These results may provide a basis for further development of combining CuB and ERK inhibitors to treat pancreatic cancer.

Analysis of mitochondrial haplogroups associated with TTR Val30Ala familial amyloidotic polyneuropathy in Chinese patients.

Extracellular deposition of abnormal transthyretin (TTR) amyloid fibrils leads to familial amyloidotic polyneuropathy (FAP), an inherited autsomal dominant disease. A large number of protein variants, each caused by a different point mutation in the TTR gene have been identified, including TTR Val30Ala. Since the age of onset, organ involvement, and disease progression are highly variable in FAP, even among individuals with the same TTR genetic variation. it is likely that other genetic and environmental factors influence FAP disease phenotype. One study has found a relationship between mitochondrial haplogroups and age of onset of FAP. In this study, we wondered whether certain mitochondrial haplogroups were associated with the cases of TTR Val30Ala FAP in a Chinese population. Mitochondrial haplogroup analysis was performed on a group of patients and their relatives and on a group of healthy controls. All FAP probands were unrelated in their maternal lineages. The chi-squared test for independence found no difference in mitochondrial haplogroup distribution between FAP and control groups. This is the first study reporting frequency and distribution of different haplogroups in FAP in a Chinese population. Although the study group was small, TTR Val30Ala FAP in China seems unrelated to mitochondrial haplogroup.

Clinical and histopathological features of familial amyloidotic polyneuropathy with transthyretin Val30Ala in a Chinese family.

Familial amyloidotic polyneuropathy (FAP) is characterized by extracellular deposition of amyloid fibrils caused by a point mutation in the transthyretin (TTR) gene. TTR amyloidosis is linked to a vast number of mutations with varying phenotype and tissue distribution. Several Chinese kindred with FAP type 1 have been reported in Beijing, Hong Kong, Taiwan, and elsewhere. Here, histopathological features and TTR gene polymorphism were analyzed by using autopsy and blood specimens from a Chinese proband of a family with FAP. This proband is a 34-year old man with FAP type 1 who developed motor, sensory and autonomic impairments with neuropathy, gastrointestinal dysfunction, and orthostatic hypotension. Genetic findings of TTR revealed a T to C transition in codon 30 causing the mutation TTR Ala30. This patient died of respiratory and circulatory failure 7 years after onset. Autopsy showed heavy amyloid deposition in the peripheral nerves, liver, testes, thyroid, pancreas and muscles. There was moderate deposition in the heart, kidneys, bladder, gastrointestinal tract, tongue, lung, blood vessels, and gall bladder. The spleen showed only slight deposition, and none was observed in the central nervous system. TTR amyloidosis was confirmed by immunochemical staining with a specific TTR antibody. These results indicate that the distribution of amyloid deposition, (i.e., heavy in the liver, testes and slight in the spleen), is a characteristic feature and reflects the severity of FAP with TTR Val30Ala.

Induction of cell cycle regulatory proteins by murine B cell proliferating pectic polysaccharide from the roots of Bupleurum falcatum L.

Bupleuran 2IIc, a pectic polysaccharide isolated from the roots of Bupleurum falcatum L., was characterized as a T-cell-independent B cell mitogen, that activates, proliferates and differentiates B cells in vivo and in vitro (Immunology 97 (1999) 540). Studies were focused on elucidating the mechanism by which bupleuran 2IIc causes proliferation of B cells and expression of cell cycle regulatory proteins. B cells showed slower rates of entry into the S and G2/M phases of the cell cycle when stimulated with bupleuran 2IIc versus anti-IgM. However, the Stimulation Index continued up to two times longer with bupleuran 2IIc over anti-IgM. Although both bupleuran 2IIc and anti-IgM induced similar expressions of cell cycle regulatory proteins, cyclins D2, A, and B1, in B cells, those cells stimulated with bupleuran 2IIc appeared to sustain expressions of these protein for longer periods of time. Stimulation of B cells with bupleuran 2IIc induced phosphorylation of retinoblastoma protein, pRB, an important gene product regulating the restriction point, R, which is responsible for the transition from the G0/G1 to the S phases of the cell cycle. The results of this study demonstrate that both bupleuran 2IIc and anti-IgM interact with B cells, thus, leading to expressions of cell cycle regulatory proteins. However, the respective modes of binding and proximity of interactions with the B cell membrane may differ.