METHODS: Altogether 67 esophageal squamous cell carcinomas histologically diagnosed between 1 January 2004 and 31 December 2014 at the Department of Pathology, University of Malaya Medical Center, Malaysia were considered for HPV analysis using two commercially available methods, polymerase chain reaction with flow-through hybridization (21 HPV GenoArray Diagnostic Kit) and multiplex real-time polymerase chain reaction (Anyplex II HPV28 Detection). The DNA amplifiability of the formalin-fixed, paraffin-embedded tumor was checked by amplification of a 268 bp segment of the human β-globin gene (GH20/PC04) prior to HPV detection.
RESULTS: HPV detection was finally carried out in 51 patients. HPV16 was detected in the moderately differentiated, stage IV lower esophageal tumor of a 32-year-old Malaysian-born Chinese woman by both methods. Except for a predilection for Indians, the clinical characteristics of esophageal squamous cell carcinomas in this Malaysian cohort were generally similar to those of other populations.
CONCLUSION: It appears that HPV is rare and an unlikely oncovirus in esophageal squamous cell carcinomas of Malaysians.
AIM OF STUDY: This study aimed to examine the anti-tumor activities of L. rhinocerus TM02®, using two different sample preparations [cold water extract (CWE) and fraction] via various routes of administration (oral and intraperitoneal) on an MCF7-xenograft nude mouse model. This study also investigated the inhibitory effect of TM02® CWE and its fractions against COX-2 in vitro using LPS-induced RAW264.7 macrophages, on the basis of the relationship between COX-2 and metastasis, apoptosis resistance, as well as the proliferation of cancer cells.
MATERIALS AND METHODS: The first preparation, L. rhinocerus TM02® sclerotium powder (TSP) was dissolved in cold water to obtain the cold water extract (CWE). It was further fractionated based on its molecular weight to obtain the high (HMW), medium (MMW) and low (LMW) molecular weight fractions. The second preparation, known as the TM02® rhinoprolycan fraction (TRF), was obtained by combining the HMW and MMW fractions. TSP was given orally to mimic the daily consumption of a supplement; TRF was administered intraperitoneally to mimic typical tumorous cancer treatment with a rapid and more thorough absorption through the peritoneal cavity. Another experiment was conducted to examine changes in COX-2 activity in LPS-induced RAW264.7 macrophages after a 1-h pre-treatment with CWE, HMW, and MMW.
RESULTS: Our results revealed that intraperitoneal TRF-injection (90 μg/g BW) for 20 days reduced initial tumor volume by ∼64.3% (n = 5). The percentage of apoptotic cells was marginally higher in TRF-treated mice vs. control, suggesting that induction of apoptosis as one of the factors that led to tumor shrinkage. TSP (500 μg/g BW) oral treatment (n = 5) for 63 days (inclusive of pre-treatment prior to tumor inoculation) effectively inhibited tumor growth. Four of the five tumors totally regressed, demonstrating the effectiveness of TSP ingestion in suppressing tumor growth. Although no significant changes were found in mouse serum cytokines (TNF-α, IL-5, IL-6 and CCL2), some increasing and decreasing trends were observed. This may suggest the immunomodulatory potential of these treatments that can directly or indirectly affect tumor growth. Pre-treatment with CWE, HMW and MMW significantly reduced COX-2 activity in RAW264.7 macrophages upon 24 h LPS-stimulation, suggesting the potential of L. rhinocerus TM02® extract and fractions in regulating M1/M2 polarization.
CONCLUSION: Based on the findings of our investigation, both the rhinoprolycan fraction and crude sclerotial powder from L. rhinocerus TM02® demonstrated tumor suppressive effects, indicating that they contain substances with strong anticancer potential. The antitumor effects of L. rhinocerus TM02® in our study highlights the potential for further explorations into its mechanism of action and future development as a prophylactic or adjunct therapeutic against tumorous cancer.
METHODS: Fifty-five patients with achalasia cardia who underwent laparoscopic Heller myotomy between 2010 and 2019 were enrolled. The adverse events and clinical outcomes were analyzed. Overall patient satisfaction was also reviewed.
RESULTS: The mean operative time was 144.1 ± 38.33 min with no conversions to open surgery in this series. Intraoperative adverse events occurred in 7 (12.7%) patients including oesophageal mucosal perforation (n = 4), superficial liver injury (n = 1), minor bleeding from gastro-oesophageal fat pad (n = 1) & aspiration during induction requiring bronchoscopy (n = 1). Mean time to normal diet intake was 3.2 ± 2.20 days. Mean postoperative stay was 4.9 ± 4.30 days and majority of patients (n = 46; 83.6%) returned to normal daily activities within 2 weeks after surgery. The mean follow-up duration was 18.8 ± 13.56 months. Overall, clinical success (Eckardt ≤ 3) was achieved in all 55 (100%) patients, with significant improvements observed in all elements of the Eckardt score. Thirty-seven (67.3%) patients had complete resolution of dysphagia while the remaining 18 (32.7%) patients had some occasional dysphagia that was tolerable and did not require re-intervention. Nevertheless, all patients reported either very satisfied or satisfied and would recommend the procedure to another person.
CONCLUSIONS: Laparoscopic Heller myotomy and anterior Dor is both safe and effective as a definitive treatment for treating achalasia cardia. It does have a low rate of oesophageal perforation but overall has a high degree of patient satisfaction with minimal complications.
Objective: This study aims to determine inter-laboratory variation in HER2 IHC testing through a slide-exchange program between five main reference laboratories.
Method: A total of 20 breast carcinoma cases with different known HER2 expression and gene status were selected by the central laboratory in five testing rounds. Three unstained tissue sections from each case were sent to participating laboratories, which immunostained and interpreted the HER2 immunohistochemistry result. One of the stained slides was sent to one designated participating laboratory for evaluation. Results were analyzed by the central laboratory.
Results: A complete concordance was achieved in six IHC-positive and six IHC-negative cases, its gene status of which was confirmed by in-situ-hybridization (ISH) study. The discordant results were observed in six equivocal cases, one negative case and one positive case with a concordance rate of 50-88.3%. Interestingly, the negative discordant case actually displays tumor heterogeneity. Good inter-observer agreement was achieved for all participating laboratories (k = 0.713-1.0).
Conclusion: Standardization of HER2 testing method is important to achieve optimum inter-laboratory concordance. Discordant results were seen mainly in equivocal cases. Intra-tumoral heterogeneity may impact the final HER2 IHC scoring. The continuous quality evaluation is therefore paramount to achieve reliable HER2 results.