Clinical significance of immunohistochemically detected lymph node micrometastasis in patients with histologically node-negative esophageal carcinoma: a multi-institutional study

Background  In esophageal carcinoma, the clinical significance of immunohistochemically (IHC)-detected lymph node (LN) micrometastasis is still controversial. We designed this multicenter study to determine the clinical significance of IHC-detected LN micrometastasis in esophageal carcinoma. Methods  The subjects were 164 patients with histopathologically confirmed LN-negative esophageal carcinoma from eight hospitals. A similar IHC technique was used in all institutions, and micrometastasis was diagnosed by a researcher at each hospital as well as independently by pathologists with special interest in esophageal carcinoma. Results  IHC-related micrometastasis in LN was considered positive in 51 (31%) patients by the researchers and in 25 (15%) by the pathologists. The latter micrometastases were further classified into a single (n = 13) and clusters (n = 12) of immunopositive-LN. Kaplan–Meier analysis showed that researcher-based diagnosis of micrometastasis had no significant impact on prognosis whereas the cluster-type micrometastasis diagnosed by pathologists had a significant impact on prognosis. Conclusions  We speculate that the inconsistent results of IHC analyses reported in the literature are caused by the use of different definitions of micrometastasis and the subjective nature of diagnosis of micrometastasis, i.e., dependence on the examiner. Our multiinstitutional study also indicates that the morphological aspects of immunostained cells should be considered when assessing micrometastasis in LN by IHC and that only LN with clusters of IHC-positive cells are prognostically significant in esophageal carcinoma.     

The effect of an elemental diet on oral mucositis of esophageal cancer patients treated with DCF chemotherapy: a multi-center prospective feasibility study (EPOC study)

Purpose

Oral mucositis (OM) is one of the most uncomfortable adverse events experienced by cancer patients undergoing chemotherapy. Previous reports have revealed that the oral administration of an elemental diet (ED) may prevent OM. However, the incidence of OM has not been accurately determined by specialized diagnostic methods and the effects of an ED on OM remain unclear. We investigated the dose that could feasibly be administered and its effects with regard to the suppression of OM in esophageal cancer patients undergoing chemotherapy.

Methods

We performed a prospective multi-center feasibility study of the administration of an ED (160 g/day) with 2 cycles of docetaxel/cisplatin/5-FU (DCF) chemotherapy. We assessed compliance to the ED for 49 days and the incidence of OM according to the amount of the ED that was orally administered. The incidence of OM was graded by a dental specialist who was experienced in dental oncology using a central OM review system.

Results

Fourteen of 20 patients (70%) were able to complete the orally administered ED (160 g/day) during the course of chemotherapy. Three patients (15%) could not take the ED orally for 9, 14, and 21 days, respectively, while 1 patient (5%) took the ED orally at an average dose of 80 g/day for 35 days. The remaining 2 patients (10%) could not take the 80 g/day dose for 11 and 12 days, respectively. The incidence of grade?≥?2 OM in the ED completion group (15.4%, 2 of 13 patients) was significantly lower than that in the non-completion group (66.7%, 4 of 6 patients) (p?=?0.046).

Conclusions

An ED might be a one of the test treatment to reduce the incidence of OM in esophageal cancer patients treated with DCF and should be evaluated in further randomized study.

Clinical trial

The date of submission: Dec 08th, 2017.

     

Contingent electrical lip stimulation for sleep bruxism: a pilot study

STATEMENT OF PROBLEM: No effective method has been found to fully control sleep bruxism, although contingent feedback methods show some promise. PURPOSE: This demonstration-of-concept study evaluated the effect of contingent electrical lip stimulation on sleep bruxism. MATERIAL AND METHODS: Recordings of masseter muscle activity were performed over 5 nights in 7 subjects with acknowledged bruxism and dental attrition (5 men, 2 women). A small electrical switch, activated with light force clenching, was mounted between 2 occlusal orthotics. This switch triggered a stimulator, which delivered slightly noxious electrical pulses to the subject's lip. After a baseline first night recording session, stimulation was delivered in 1-hour blocks for half of each sleep period during nights 2 through 5. Paired t tests (alpha = 0.05) were conducted on 4 recorded bruxism parameters. RESULTS: With stimulation, the number (+/-SD) of events/hour reduced from a baseline level of 3.9 +/- 2.0 to 2.4 +/- 0.8 and the mean amplitude (% maximum voluntary contraction) reduced from 28.7 +/- 20.0 to 17.6 +/- 4.1. There was a mean decrease in the duration (s/event) from 10.6 +/- 1.4 to 9.1 +/- 2.5 and the total event time (s/hour) was reduced from 41.7 +/- 22.4 to 23.2 +/- 11.0. Among these measures, bruxism events with and without stimulation were compared, and only the duration of individual bruxism events (s/event) showed a significant change (P=.038). Finally, no subject reported being awakened from sleep by the stimulation. CONCLUSION: The reductions in bruxism events were noteworthy, especially considering that stimulation was delivered for only half of the sleeping period.     

In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay: ACTH releasing activities by various drugs (author's transl)]

Several procedures have been reported for the assay of corticotrophine-releasing factor (CRF), each having its advantages and disadvantages. This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Rat half pituitary was preincubated in 2 ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25 % BSA (KRBG-BSA) for 1.5 hr (45 min X 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with in the 1st 30 min incubation and expressed as percentage. In ACTH radioimmunoassay, anti-ACTH serum was diluted to 1 : 1,500-3,000. The 125I-alpha 1-24ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH and prolactin. Human 1-39ACTH was used as ACTH standard, and the dilution curve of incubation medium was paralleled with the standard curve. Repeatability of immunoassayable ACTH within-assay was 174 +/- 5.0 pg/tube (CV = 2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME ; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it found that LVP, AVP, norepinephrine (100 ng/ml200 ng/ml) and 5-hydroxytryptophane (1 mug/ml) had ACTH releasing activities but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E1 and indomethacin did not affect the release of ACTH.     

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients: Possible involvement of c-myc suppression by interferon-gamma in situ

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunological point of view, HLA-DR antigen, induced by interferon (IFN)-gamma, is required for tumor-associated antigen recognition by CD4(+) T cells. For instance, as reported previously, the expression of HLA-DR antigen in normal colorectal epithelium immediately adjacent to cancer coincided significantly with the existence of IFN-gamma mRNA in the tissue. From another aspect, IFN-gamma has been revealed to suppress c-myc expression in vivo through a stat1-dependent mechanism, which is important for cell growth, cell cycle and chromosome instability. In the present study, strong HLA-DR-positive expression on cancer cells was significantly related to better prognosis for colorectal cancer patients. High IFN-gamma mRNA expression in situ indicated significantly less activation of c-myc mRNA expression. Further, HLA-DR antigen expression in cancer cells, as well as Dukes stages, was an independent factor for better long-term survival by multivariate analysis. Taken together, IFN-gamma, which induces HLA-DR antigens on the cell surface, also suppresses c-myc expression in situ, and is a possible non-immunological mechanism involved in the better long-term survival of colorectal cancer patients.     

AMINO ACID COMPOSITIONS AND N-TERMINAL AMINO ACID OF ALL THE TRYPTIC PEPTIDES FROM THE α AND β POLYPEPTIDE CHAINS OF ADULT HEMOGLOBIN OF THE JAPANESE MONKEY (Macaca fuscata fuscata)

Globin prepared from adult hemoglobin of the Japanese monkey was separated into α and β polypeptide chains by the countercurrent distribution method. All the tryptic peptides obtained from these polypeptide chains were isolated and purified by column and paper chromatography. The amino acid compositions and the N-terminal amino acid of these tryptic peptides were analyzed. The results thus obtained suggested amino acid exchanges between Japanese monkey and human hemoglobin, that is, at four positions in α polypeptide chain and seven positions in β polypeptide chain. In comparison with the α and β polypeptide chains of adult hemoglobin from the rhesus monkey, the α chain is quite the same, and it is considered that there is one amino acid exchange in the β chains. The outline of this work was presented at Symposium 5 (Biochemical Polymorphisms in Man and Other Primates and their Anthropological Implications) of the 8th International Congress of Anthropological and Ethnological Science (3–10 September 1968, Tokyo