Second-look Surgery for Appendiceal High Grade and Colorectal Cancers Following Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND/AIM: Up to a third of patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) of appendiceal or colorectal origin receive a stoma during primary surgery. Stoma reversal provides an opportunity for second-look surgery. PATIENTS AND METHODS: We performed a retrospective analysis of prospectively collected data of patients with colorectal cancer (CRC) or high-grade appendiceal cancer (AC) from 2006 to 2021 from our database. A total of 34 consecutive stoma closure patients with no evidence of preoperative disease recurrence (tumor markers and CT scans) were compared with 141 consecutive re-do CRS/HIPEC patients with known recurrence. RESULTS: Eleven patients (32.4%) were identified to have peritoneal recurrence at stoma closure. Time between first and second CRS was 12 months (4 to 64.2) in the stoma closure group vs. 24.6 months (5.8 to 119.8) in the re-do group, while median peritoneal cancer index (PCI) was 4 (3 to 6) vs. 8 (1 to 39), respectively (p=0.0143). CONCLUSION: Second-look laparotomy during stoma closure identified unexpected PC in 32.4% of our patients with significantly lower PCI than planned re-do operations.

Astragalin, a Flavonoid from Morus alba (Mulberry) Increases Endogenous Estrogen and Progesterone by Inhibiting Ovarian Granulosa Cell Apoptosis in an Aged Rat Model of Menopause.

BACKGROUND: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause. METHODS: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using flow cytometry. In vitro, the effects of AST on cultured GCs were investigated using the MTT proliferation assay and western blot assays. RESULTS: Aged rats had significantly higher GC apoptosis as compared with young female rats. Treatment of aged rats with AST (all three doses; p < 0.01) or Progynova (p < 0.01) significantly reduced GC apoptosis as compared with the aged controls. The proportions of total apoptotic GCs was 25.70%, 86.65%, 47.04%, 27.02%, 42.09% and 56.42% in the normal, aged, 17ß-estradiol (E2), high dose AST, medium dose AST, and low dose AST-treated groups, respectively. Significant increases of serum E2 and P4 levels, as well as altered levels of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. In cultured rat GCs, AST stimulated GC proliferation, E2 and progesterone (P4) secretion, reduced apoptosis, reduced the level of the pro-apoptotic protein Bcl-2 (p < 0.01), but had no effect on BAX. CONCLUSIONS: AST enhanced ovarian function in aged female rats by increasing E2 and P4 levels, and reducing ovarian GC apoptosis via a mechanism involving Bcl-2. These data demonstrate a new pharmacological activity for AST, as well as a novel mechanism of action, and further suggest that AST may be a new therapeutic agent for the management of menopausal symptoms.

The mystery of the thymus gland.

The thymus is the last organ in the human body to have its mechanisms fully understood, having had its function fully delineated more than 50 years ago (Miller , Tissue Antigens 63:509-517). Prior to this, the thymus gland has had an interesting history with theories having included a role in fetal growth and development before becoming more sinisterly, a cause of sudden infant death in the late 19th century known as status lymphaticus (Paltauf , Wien Klin Wochenschr 2:877-881). Until Miller (, Lancet 278:748-749) eventually proved its primarily immunological role, the history of this mysterious gland has closely mirrored the history of medicine itself, troubling the minds of pathologists such as Virchow (, Ueber die Chlorose und die damit zusammenhängenden Anomalien im Gefässapparate, insbesondere über "Endocarditis puerperalis," vorgetragen in der Sitzung der Berliner Geburtshülflichen Gesellschaft vom 12) and Grawitz (, Deut Med Wochenschr 22:429-431), surgeons such as Astley Cooper (, The Anatomy of the Thymus Gland) and Keynes (1953, Ann R Coll Surg 12:88), and eminent medical epidemiologists such as Greenwood and Woods [, J Hyg (Lond) 26:305-326]. This article will hopefully be of interest therefore to both clinician and historian alike. Clin. Anat. 29:679-684, 2016. © 2016 Wiley Periodicals, Inc.

Menoprogen, a TCM Herbal Formula for Menopause, Increases Endogenous E2 in an Aged Rat Model of Menopause by Reducing Ovarian Granulosa Cell Apoptosis.

The effect of Menoprogen (MPG) on ovarian granulosa cell (GC) apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma E2 levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM) analysis of isolated GCs from MPG-treated aged rats showed reductions in the G0/G1 ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases E2 production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms.

Herbal formula menoprogen alters insulin-like growth factor-1 and insulin-like growth factor binding protein-1 levels in the serum and ovaries of an aged female rat model of menopause.

OBJECTIVE: Menoprogen (MPG), a traditional Chinese medicine formula for menopause, improves menopausal symptoms; however, its mechanism remains unknown. Previous studies have shown that MPG is not directly estrogenic; thus, the goal of this study was to investigate the effects of MPG on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) levels in an aged female rat model of menopause. METHODS: In a six-arm study, 14-month-old female Sprague-Dawley rats (n = 8 per arm) were randomly divided into the following groups: untreated aged, 17ß-estradiol-treated aged (estradiol [E2]), and three arms with increasing doses of MPG (162, 324, or 648 mg/kg/d). The sixth arm contained 4-month-old female Sprague-Dawley rats as a normal comparison group. Four weeks after MPG or E2 administration, animals were killed after blood draws, and ovarian tissues were excised. Levels of E2 and progesterone (P4) were determined by radioimmunoassay. Serum and ovarian tissue levels of IGF-1, IGFBP-1, and IGF-1 receptor were determined by enzyme-linked immunosorbent assay. RESULTS: Compared with the normal group, aged rats had significantly reduced serum levels of E2, P4, and IGF-1, and increased serum and ovarian tissue levels of IGFBP-1. MPG restored serum IGF-1 and IGFBP-1 levels and down-regulated ovarian levels of IGFBP-1, which were closely related to increases in E2 and P4 levels in aged rats. No significant differences in either IGF-1 or IGFBP-1 were observed between the three doses of MPG. CONCLUSIONS: MPG exerts a direct in vivo effect on aged female rats by positively regulating serum and ovarian IGF-1 and IGFBP-1 levels.

Ovarian failure-resistant effects of catalpol in aged female rats.

Catalpol, an iridoid glycoside obtained from various natural sources, has many biological functions. However, its ovarian failure-resistant effect has scarcely been studied. The present study used senile 14-month-old Sprague-Dawley female rats to examine the in vivo ovarian failure-resistant activity of catalpol. Daily oral graded doses of catalpol (1, 3, or 5 mg/kg/d) for 4 weeks significantly increased the levels of serum 17ß-estradiol (E2) and progesterone (P4) but reduced follicle-stimulating hormone and luteinizing hormone levels. Electron microscopic analysis and flow cytometry showed that catalpol significantly retarded apoptosis of the ovarian granulocytes of the rats. These findings suggest that catalpol works on the sex organs by nourishing ovarian tissues and improving both the quality and quantity of follicles, thus leading to rebalanced E2 and P4 levels in aged rats so that catalpol has a direct in vivo antiaging effect on the rat ovarian system.

A pilot observational study to assess the safety and efficacy of Menoprogen for the management of menopausal symptoms in Chinese women.

OBJECTIVE: Over the past 5 years, the interest in alternative therapies for menopause has increased dramatically due to the findings of the Women's Health Initiative (U.S. National Institutes of Health). Menoprogen, a traditional Chinese medicine formulation is an herbal remedy that has been used in China for the management of menopause-related symptoms. An observational pilot study was performed to assess the effects of Menoprogen in the management of menopausal symptoms in perimenopausal and postmenopausal women. DESIGN, SUBJECTS, AND SETTING: A multicenter prospective study was conducted at four clinical centers in China. Female subjects were eligible if they had menopausal diagnosis for at least 3 months and wished to use an alternative to hormone replacement therapy (HRT). INTERVENTION: Subjects received two capsules of Menoprogen (a combination product containing 0.2 g extracts of five herbs per capsule) orally, twice daily. MAIN OUTCOME MEASURES: The primary outcome measured was an improvement of Kupperman Menopausal Index (KMI) from baseline. Secondary outcomes measured included hormone levels and the status of the endometrial and vaginal cytology after completion of treatment. RESULTS: After treatment with Menoprogen, a significant reduction in the KMI was observed (mean of paired difference = -14.875; p < 0.01) as compared with baseline. Endogenous estrogen levels were significantly increased with Menoprogen (mean of paired difference = -3.145; p < 0.01). Progesterone levels increased with Menoprogen (mean of paired difference = -10.003; p < 0.01). Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels showed significant before-and-after treatment difference (mean of paired difference = 6.125 mIU/mL for FSH and 4.938 mIU/mL for LH; p < 0.01). No significant endometrial hyperplasia was observed post-treatment with Menoprogen. Most of the postmenopausal women exhibited a vaginal cell proliferation degree of 2-3, suggesting a possible estrogenic effect. CONCLUSIONS: The present pilot study found that Menoprogen reduced symptoms associated with perimenopausal and postmenopausal complaints. Therefore, the rationale for a randomized, placebo-controlled clinical trial is supported.

Pharmacological investigations of the unique herbal formula Menoprogen in rats: estrogenic activity and mechanism.

The present study aimed to evaluate the pharmacological effects of Menoprogen in the management of menopausal symptoms for aged female rats. Menoprogen was supplemented to a group of elderly female rats for 8 weeks. Subsequently, histopathological examinations were conducted in the isolated uterine and ovary tissues and pituitary glands of the rats. Serum levels of estradiol (E(2)), progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined. The ultrastructure of the rat ovarian granulocytes was analyzed. The histopathological examinations revealed no statistical difference in the quantity of follicles in the ovary and of acidophil and basophil cells in the anterior pituitary gland of the Menoprogen-fed rats versus healthy normal rats. Moreover, the cellular morphogenesis was in a healthy state for the Menoprogen-fed rats. Menoprogen significantly increased the levels of serum E(2) and P but reduced FSH and LH levels. The electron microscopic analysis showed that Menoprogen significantly retarded apoptosis of the ovarian granulocytes of the rats. Further investigation of Menoprogen for the alternative treatment of menopausal symptoms is warranted.