Inhibitory effects of estrogen and progesterone on several parameters of pulsatile LH release in the ovariectomized rat

Recent reports on the effects of progesterone on the frequency of pulsatile LH release in several species have compelled a reevaluation of the regulation of pulsatile LH secretion by gonadal steroids in the rat. Long-term ovariectomized (OVX) adult rats were given Silastic implants filled with estradiol-17 beta in oil, and blood samples were taken every 5 min for 3 h, either 1 or 2 days later. Compared with the control group (empty Silastic capsules), estrogen-treated animals had significantly lower mean plasma LH concentrations, because of a significant increase in the time between pulses, pulse amplitude not being significantly affected. In a second experiment, it was determined that progesterone alone had no significant effect on pulse amplitude, frequency or mean plasma LH concentrations. In a third experiment, OVX animals received estrogen-filled (or empty) capsules on 1 day followed by progesterone-filled (or empty) capsules on the next day, and frequent blood samples were taken on the following day. Two-way analysis of variance showed significant inhibitory effects of estrogen on mean LH levels, pulse amplitude and pulse frequency. Progesterone lowered the pulse amplitude significantly, but had no effect on pulse frequency, unlike its reported effects in other species. There were no significant interactions between estrogen and progesterone on any parameter tested, indicating that there is no synergism between the two steroids under these conditions. We conclude that estrogen is the principal ovarian hormone restraining LH secretion in the long-term OVX rat and that progesterone has only a modest effect, even in the presence of estrogen.     

Staging of Adenocarcinoma of the Esophagogastric Junction: Comparison of AJCC 6th and 7th Gastric and 7th Esophageal Staging Systems

Background

Adenocarcinoma of esophagogastric junction (EGJ) is currently staged by the esophageal staging criteria according to the American Joint Committee on Cancer (AJCC) staging system, 7th edition. We compared the performance of 6th gastric (G6), 7th gastric (G7), and 7th esophageal (E7) staging systems.

Methods

A total of 202 curatively resected adenocarcinomas of EGJ were analyzed. Patient outcomes were assessed according to G6, G7, and E7 staging. Tumor invasion to the subserosal or serosa layer was regarded as invasion to the adventitia for E7 staging. Performance was measured based on monotonicity (decreasing survival with increasing stage), distinctiveness (survival difference between different stages), and homogeneity (homogenous survival in the same stage).

Results

Each staging system was monotonous except for T1-2N0 lesions of E7. This was related to the introduction of histologic grade in E7 staging. Distinctiveness in each staging system was variable. As for the homogeneity, patients whose disease was staged as Ib (E7) exhibited different survival when reassessed by G6 and G7; again, this was related to histologic grading. Patients with IIIb (G7) and IIIc (E7) disease had different survival when reassessed by G6 staging, reflecting the poorer survival of patients with more than 15 lymph node metastases.

Conclusions

Staging of EGJ cancer based on the current AJCC, 7th edition, criteria of esophageal cancer staging has several limitations. We recommend considering modifications of the following in future updates of the staging system: accurate anatomical definition of tumor depth, removal of histologic grade from staging parameters, and classification of more than 15 lymph node metastases as a highly advanced stage.     

Inflammatory features of melasma lesions in Asian skin

Melasma is triggered by various factors including ultraviolet radiation and estrogen; however, its pathogenesis is unclear. To investigate the inflammatory features of melasma lesions as triggers for this disorder, 197 women with melasma who attended Asan Medical Center and Kangskin Clinic, Seoul, from June 2011 to October 2011 completed a questionnaire concerning triggering or aggravating factors. These cases were divided into “non‐inflammatory” and “inflammatory” groups. Skin biopsies and immunostaining for CD68, CD117, and leukocyte common antigen (LCA) were performed in the lesional and peri‐lesional skin of ten cases in the non‐inflammatory group and nine cases in the inflammatory group. Among the 197 subjects (mean age, 41.5 years; mean age of melasma onset, 33.8 years), 50 patients (25.4%) were categorized into the inflammatory group. This group comprised cases that had inflammatory symptoms and events that triggered the melasma lesions. The lesional dermis contained more CD68⁺ melanophages, CD117⁺ mast cells, and LCA⁺ leukocytes in the inflammatory group than in the non‐inflammatory group. Inflammatory clinical features and an increased number of inflammatory cells in the lesion may be involved in the development of melasma in Asian skin.     

Clinical Usefulness of AJCC Response Criteria for Neoadjuvant Chemotherapy in Breast Cancer

Purpose

Recently, the American Joint Committee on Cancer (AJCC) 7th edition proposed new response criteria for neoadjuvant chemotherapy (NAC) in breast cancer. The purpose of this study was to evaluate the clinical usefulness of AJCC response criteria.

Methods

A total of 398 consecutive stage II or III breast cancer patients who received NAC were enrolled in this study. AJCC response criteria were as follows: (1) complete response (CR)—absence of invasive carcinoma in the breast and node; (2) partial response (PR)—decrease in either or both T or N stage; (3) no response (NR)—no change or increase in either or both T or N stage.

Results

Complete response, PR, and NR by AJCC criteria were 9.8, 59.3, and 30.7 %, respectively. Among the 398 patients, 337 patients were available for both paired pre- and post- breast MRI and chest CT. AJCC response criteria were significantly associated with RECIST criteria (P < 0.001). AJCC response was significantly associated with relapse-free survival (RFS) and overall survival (OS). The 5-year RFS rates were 89.6 % in CR, 74.1 % in PR, and 62.6 % in NR (P = 0.002). The 5-year OS rates were 97.4 % in CR, 88.6 % in PR, and 78.3 % in NR (P = 0.012). When adjusting potential prognostic factors, AJCC response was independently associated with RFS and OS.

Conclusions

AJCC response criteria for NAC in breast cancer have clinical usefulness in evaluating response of NAC, as well as predicting survival. AJCC response criteria can discriminate among patient subgroups with respect to survival.     

Prognostic Value of Early Postoperative Tumor Marker Response in Gastric Cancer

Background

The clinical usefulness of tumor markers as predictors of treatment outcome in patients with stomach cancer after radical gastrectomy has been poorly defined. The purpose of this study was to evaluate a comprehensive understanding of the impact of early postoperative tumor marker normalization on survival after gastrectomy.

Methods

Between January 2001 and December 2007, we enrolled 206 patients who had received radical gastrectomy as an initial treatment and had elevated carcinoembryonic antigen (CEA) (>5 ng/mL) or carbohydrate antigen (CA) 19-9 (>37 U/mL) levels. Early tumor marker response was defined as a normalization of preoperative CEA or CA19-9 values 1–2 months after gastrectomy.

Results

The mean patient age was 61 years (range 29–84 years), and 139 patients (67.5 %) were male. Early tumor marker response was identified in 150 of 206 (72.8 %) patients. Of the patients, 49 (23.8 %), 41 (19.9 %), and 116 (56.4 %) were stages I, II, and III, respectively, according to the seventh edition of the American Joint Commission on Cancer (AJCC) staging system. Both disease-free survival (DFS) and overall survival (OS) were significantly longer in patients with tumor marker response compared with nonresponse (61.5 vs. 37.6 months; P = 0.010 and 71.3 vs. 50.9 months; P = 0.008, respectively). Multivariate analyses showed that high CA19-9 level, early tumor marker response, and tumor, node, metastasis classification system stage were independent predictors of DFS and OS (P < 0.05).

Conclusions

Early CEA or CA19-9 normalization after radical gastrectomy is a strong prognostic factor for gastric cancer, especially in patients with high preoperative levels of tumor markers.     

Factors associated with complex regional pain syndrome type I in patients with surgically treated distal radius fracture

Purpose

Wrist fracture is considered a typical initiating trauma for complex regional pain syndrome type I (CRPS I). However, few studies have comprehensively evaluated factors associated with the occurrence of CRPS I after the surgical treatment of a distal radius fracture (DRF). This study evaluates the factors influencing the occurrence of CRPS I after the surgical treatment of a DRF.

Methods

A total of 477 patients with a DRF who had been treated surgically were enrolled in this prospective observational study. Patients were followed for 6 months after surgery, and CRPS I was diagnosed using the Budapest diagnostic criteria for research. The factors assessed for the development of CPRS I were age, gender, the body mass index, the type of fracture, the energy of trauma, the number of trial reductions, the type of surgery, and the duration of immobilization. A multivariate logistic regression analysis was conducted to identify independent predictors of the occurrence of CRPS I.

Results

Among the 477 patients, 42 (8.8 %) satisfied the Budapest criteria for CRPS I within 6 months of surgery. Female patients developed CRPS I more frequently, and the patients who developed CRPS I were older and more likely to sustain a high energy injury or have a comminuted fracture. According to the multivariate analysis, female patients and those with a high energy trauma or severe fracture type were significantly more likely to develop CRPS I (p = 0.02, 0.01, and 0.01, respectively).

Conclusions

High energy injuries, severe fractures, and the female gender contribute to the development of CRPS I after the surgical treatment of DRF. The results have important implications for physicians who wish to identify patients at high risk for CRPS I after operative fixation for DRF and instigate treatment accordingly.     

Minimally invasive surgery for remnant gastric cancer: a comparison with open surgery

Background

Completion total gastrectomy for remnant gastric cancer (RGC) is technically challenging, especially using the minimally invasive approach. Only a few small case series have reported the technical feasibility of completion total gastrectomy by minimally invasive surgery (MIS). The aim of this study was to compare the efficacy and safety of MIS and open surgery for RGC.

Methods

We retrospectively analyzed 76 completion total gastrectomies for RGC between 2005 and 2012. Indications for MIS were limited to no evidence of serosa invasion or lymph node metastasis to extraperigastric areas on preoperative evaluation. We compared patient characteristics, intraoperative factors, post-operative outcomes, and survival for the MIS and open surgery groups.

Results

Eighteen patients underwent completion total gastrectomy with MIS (10 laparoscopic, 8 robotic) and 58 patients underwent open surgery. Operation time was longer in the MIS than the open group (266 vs. 203 min, P = 0.004), but the groups had similar estimated blood loss, frequency of unplanned other organ resection, and number of retrieved lymph nodes. The MIS group had a significantly earlier initiation of soft diet, shorter hospital stay, and fewer pain medication injections. Complication rates, recurrence, and overall 5-year survival were similar for the two groups. When we compared laparoscopy with robotic, similar result was shown in all parameters except operation time.

Conclusions

Compared to open surgery, MIS for RGC demonstrated better short-term outcome and comparable oncologic results. MIS for RGC is feasible and safe and maintains advantages of minimal invasiveness. Both laparoscopic and robotic approaches are reasonable to the management of RGC.     

Increased nitric oxide caused by the ketogenic diet reduces the onset time of kainic acid-induced seizures in ICR mice

Although the antiepileptic effects of the ketogenic diet (KD) are well documented, the mechanisms underlying this action remain obscure. Nitric oxide (NO) has long been thought to play a role in regulating seizures. However, the effects of the KD on endogenous NO production have not been characterized. Therefore, the present study was designed to examine the effect of the KD on endogenous NO production, as well as the precise role of NO in kainic acid (KA)-induced seizures, in male ICR mice. We first found that preadministration of the KD for 4 weeks increased endogenous NO generation in the hippocampus. We also demonstrated that the increase in NO induced by the KD resulted from increased neuronal NO synthase (nNOS) activity and exerted an antiepileptic effect on KA-induced seizures, based on the results of experiments using NOS-knockout mice and two NOS inhibitors, N-omega-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). These data suggest that the antiepileptic effects of the KD might be mediated, at least in part, by increased NO levels in the hippocampus.