The impact of lymph node ratio on disease recurrence in papillary thyroid microcarcinoma.

INTRODUCTION: Lymph node (LN) metastases in papillary thyroid microcarcinomas (microPTCs) are common. The lymph node ratio (LNR) has been proposed as a risk factor for recurrence in papillary thyroid cancer. However, its relevance in microPTC is undetermined. METHODS: Patients who underwent resection of their microPTC with concomitant LN clearance between 2005 and 2018 were identified. The LNR was calculated as the ratio of positive LNs to the total number of LNs. RESULTS: Data on 50 patients (36 female [72%]; median age 47 years [range: 19-84]) who underwent LN clearance (28 central [56%] vs 22 central + lateral [44%]) were analysed. Positive LNs were found in over two-thirds of the patients (n = 34; 68%). After a median follow-up of 61 months, 14 patients (28%) had developed recurrence. Positive LNs were not found to impact recurrence-free survival; extranodal extension and an LNR ≥ 0.26 were found to significantly increase the risk of recurrence on unadjusted analyses (p < 0.05). CONCLUSIONS: LN metastases are frequent among patients with microPTC. A higher LNR seems to be associated with recurrence. Additional studies are needed to further clarify these findings and to assess the possible role of LNR in treatment and surveillance.

Hashimoto's thyroiditis on outcomes in papillary thyroid cancer revisited: experience from South East Asia.

INTRODUCTION: The association between Hashimoto Thyroiditis (HT) and papillary thyroid cancer (PTC) remains uncertain. HT, the most common inflammatory condition of the thyroid, is postulated to increase the risk of PTC and yet confer cancer-retarding effects. In this study, we aim to evaluate the prevalence of HT in patients surgically treated for PTC and evaluate the long-term prognostic implications. METHODS: This is a retrospective study of 521 patients with PTC who underwent hemi- or total thyroidectomy between January 2000 and December 2018 at a tertiary referral centre. Patients were categorised into two group: group A (n=402) consists of patients with PTC without HT, whereas group B (n=119) consists of patients with PTC and HT. Demographic and clinicopathological details, recurrence rates and overall survival were collected. Univariate and multivariate analyses were performed to evaluate for clinical factors associated with HT. RESULTS: A total of 521 patients with a mean age of 46.7 years were evaluated. HT was detected in 22.8% of patients with PTC. On multivariate analysis, presence of HT was associated with a lower incidence of extrathyroidal extension (hazard ratio: 0.59, 95%confidence interval 0.37-0.95). Also, patients with HT tend to have fewer cycles of radioactive iodine and correspondingly have excellent response to treatment. However, no differences in recurrence rates and overall survival were detected. CONCLUSIONS: One-fifth of patients with PTC have coexisting HT. These patients tend to have less-aggressive tumour features such as extrathyroidal extension. However, the effect of HT on recurrence and overall survival appears to be inconsequential clinically.

Hamatopeduncularia Yamaguti, 1953 (Monogenea: Ancylodiscoididae) from catfish off Peninsular Malaysia: Description of two new species and insights on the genus.

Hamatopeduncularia longiangusticirrata sp. nov. and H. petalumvaginata sp. nov. were collected from Arius maculatus and Nemapteryx caelata, respectively from Tanjung Karang, Peninsular Malaysia. Morphological and molecular investigations were carried out to ascertain the identity of the new species. The two new species differ from previously described Hamatopeduncularia species in the morphology of the male and female reproductive organs. Hamatopeduncularia longiangusticirrata sp. nov. possesses a long penis similar to H. elongata, H. longicopulatrix, H. brisbanensis, H. major and H. petalumvaginata sp. nov., but differs in having a thread-like tapering distal end and can be distinguished from H. brisbanensis and H. major in not having an accessory piece. Hamatopeduncularia longiangusticirrata sp. nov. is also unique in having an ornamented penis initial and a vaginal tube surrounded by fine hair-like structures. Hamatopeduncularia petalumvaginata sp. nov. possesses a simple penis without an accessory piece and a petaloid vaginal opening that resembles the arrangement of petals on a flower. Maximum likelihood trees were constructed from partial 28S and 18S rDNA sequences of the two new species and other ancylodiscoidids to reveal a strongly supported monophyletic branch consisting of the two new species for both markers. According to Lim's classification in 1996 of Hamatopeduncularia species penis type, H. petalumvaginata sp. nov. has been classified within the elegans-type and H. longiangusticirrata sp. nov. is proposed as the longiangusticirrata-type.

Diagnostic significance of serum miR-26b and miR-21 expressions in ovarian cancer and their associations with clinicopathological characteristics and prognosis of patients.

OBJECTIVE: The aim of this study was to detect the expressions of serum micro-ribonucleic acid (miR)-26b and miR-21 in ovarian cancer patients, and to explore their associations with the diagnosis, clinicopathological parameters and prognosis of ovarian cancer. PATIENTS AND METHODS: A total of 86 patients diagnosed with ovarian cancer in our hospital from January 2014 to January 2015 were enrolled in the observation group. Meanwhile, another 86 subjects receiving physical examination in our hospital during the same period were enrolled in the control group. The expressions of serum miR-26b and miR-21 in both groups were detected via Real Time fluorescence-quantitative Polymerase Chain Reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were plotted. Later, the clinical diagnostic value of combined detection of miR-26b and miR-21 in ovarian cancer was analyzed. Moreover, the associations of serum miR-26b and miR-21 expressions with clinicopathological characteristics and prognosis of ovarian cancer patients were explored. RESULTS: The expression of serum miR-26b in ovarian cancer patients was significantly lower than that of healthy subjects, while miR-21 expression was markedly higher in ovarian cancer patients (p<0.05). The area under the ROC curve (AUC), the sensitivity and specificity of miR-26b detection, miR-21 detection and combined detection in the diagnosis of ovarian cancer were 0.753 vs. 0.826 vs. 0.916, 47.2 vs. 76.3 vs. 87.6 and 78.5 vs. 85.6 vs. 90.4, respectively. Therefore, it could be observed that both the sensitivity and specificity of combined detection were remarkably higher than those of single detection (p<0.05). In addition, the expressions of serum miR-26b and miR-21 were associated with clinical stage and lymph node metastasis of ovarian cancer patients, whereas it was not correlated with age and histological type. The 3-year survival rate of patients with high expression of serum miR-26b was significantly higher than that in those with low expression of serum miR-26b. However, the 3-year survival rate of patients with low expression of serum miR-21 was higher than that in those with high expression. CONCLUSIONS: MiR-21 is highly expressed, while miR-26b is lowly expressed in the serum of ovarian cancer patients. Both of them may be involved in the incidence and development of ovarian cancer. Furthermore, combined monitoring of serum miR-26b and miR-21 has a certain value in the clinical diagnosis and treatment of ovarian cancer.

Highly expressed miR-182-5p can promote preeclampsia progression by degrading RND3 and inhibiting HTR-8/SVneo cell invasion.

OBJECTIVE: The role of miR-182-5p in preeclampsia was studied, and its mechanism was also explored. PATIENTS AND METHODS: Fifty patients with preeclampsia were assigned to the study group and 50 normal pregnant women to the control group. The age, weight, blood pressure, urinary protein, and weight of newborns were compared between the two groups. The placental tissues of the above-mentioned subjects were collected, and quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) assay was used to detect the expression of miR-182-5p. MiR-182-5p was overexpressed or knocked down using a cell transfection assay in HTR-8/SVneov cell, which is a kind of human chorionic trophoblast cell. Changes in cell migration and invasiveness before and after transfection were determined by wound healing test and transwell assay, respectively. Western blot was performed to analyze the change of RND3 protein level before and after transfection. The biological prediction of the relationship between miR-182-5p and RND3 was performed and a dual luciferase reporter gene experiment was designed to verify the results. Finally, a rescue experiment was conducted to investigate whether RND3 could affect the role of miRNA-182-5p in the capacity of cell migration and invasion. RESULTS: Preeclampsia patients had higher systolic blood pressure, diastolic blood pressure, and urinary protein than normal pregnant women, while neonatal weight decreased compared with normal pregnant women. MiRNA-182-5p was highly expressed in placental tissues of patients with preeclampsia. After miRNA-182-5p was overexpressed, the migration and invasion of HTR-8/SVneo cells were significantly attenuated, and the mRNA and protein levels of RND3 were markedly downregulated, and vice versa. The dual luciferase reporting assay confirmed that miRNA-182-5p could bind to 3'UTR of RND3. In addition, the results of rescue experiment showed that overexpressing miRNA-182-5p could markedly inhibit the migration and invasion of HTR-8/SVneo cells; however, when RND3 was simultaneously overexpressed, the inhibitory effect of miRNA-182-5p was partially reversed. CONCLUSIONS: The highly expressed miRNA-182-5p in patients with preeclampsia promoted the development of preeclampsia, the possible mechanism of which might be that the increased miRNA-182-5p expression could inhibit the migratory and invasive ability of trophoblast cells through targeted degrading RND3 protein.

Binding of aberrant glycoproteins recognizable by Helix pomatia agglutinin in adrenal cancers.

BACKGROUND: Aberrant glycosylation is a hallmark of cancer cells and plays an important role in oncogenesis and cancer progression including metastasis. This study aimed to assess alteration in cellular glycosylation, detected by lectin Helix pomatia agglutinin (HPA) binding, in adrenal cancers and to determine whether such altered glycosylation has prognostic significance. METHODS: HPA binding lectin histochemistry was performed on archival paraffin wax-embedded specimens of adrenocortical cancers excised from patients attending two tertiary referral centres. Benign tumours were used as controls. Demographic, histological and survival data were collected and compared between patients with HPA-positive and HPA-negative tumours. RESULTS: Thirty-two patients were treated for adrenal cancer between 2000 and 2016; their median age was 49 (range 23-79) years. Fifteen patients had functioning tumours (14 adrenal Cushing's tumours and 1 Conn's tumour). Mean(s.d.) tumour size was 127·71(49·70) mm. None of 10 control tumours expressed HPA-binding glycoproteins. Invasion was associated with HPA-binding glycoproteins (P = 0·018). Local recurrence or metastatic disease did not significantly differ between HPA-positive and HPA-negative adrenocortical cancers. Overall survival was significantly longer in patients with HPA-negative tumours (median survival not reached versus 22 months in patients with HPA-positive tumours; P = 0·002). CONCLUSION: Altered cellular glycosylation detected by lectin HPA is associated with poor survival in patients with adrenocortical cancer.

LINC01116 promotes the progression of epithelial ovarian cancer via regulating cell apoptosis.

OBJECTIVE: To explore the biological function of LINC01116 in epithelial ovarian cancer (EOC) and its underlying mechanism. PATIENTS AND METHODS: The expression level of LINC01116 in 60 EOC tissues, 30 normal ovarian tissues and EOC cells were detected by qRT-PCR (quantitative real-time polymerase chain reaction). Disease-free survival (DFS) and overall survival (OS) of enrolled EOC patients were recorded. The correlation between LINC01116 expression, DFS and OS of EOC patients was analyzed using ROC curve. Influencing factors for DFS and OS were analyzed by univariable and multivariable Cox regression model. For in vitro experiments, the effect of LINC01116 knockdown on proliferation, invasion and apoptosis of EOC cells were detected by CCK-8 (cell counting kit-8), transwell assay and flow cytometry, respectively. Protein expressions of apoptosis-related genes in EOC cells transfected with pc-DNA-LINC01116 or si-LINC01116 were detected by Western blot. RESULTS: LINC01116 was overexpressed in EOC tissues than that of paracancerous tissues. DFS and OS in EOC patients with higher expression of LINC01116 were remarkably shorter than those with lower expression. FIGO (International Federation of Gynecology and Obstetrics) clinical stage and LINC01116 expression were the independent factors that affected DFS and OS of EOC patients. Besides, LINC01116 expression was positively correlated to the diagnostic sensitivity of EOC patients. In vitro experiments found that LINC01116 overexpression promoted proliferation and invasion of EOC cells. Overexpressed LINC01116 resulted in upregulated Bcl-2, and downregulated cleaved Caspase-3 and cleaved Caspase-9 in EOC cells. CONCLUSIONS: Overexpressed LINC01116 promotes EOC progression via increasing proliferation and migration, and inhibiting cell apoptosis.

Rising incidence of thyroid cancer in Singapore not solely due to micropapillary subtype.

Introduction The annual incidence of thyroid cancer is known to vary with geographic area, age and gender. The increasing incidence of thyroid cancer has been attributed to increase in detection of micropapillary subtype, among other factors. The aim of the study was to investigate time trends in the incidence of thyroid cancer in Singapore, an iodine-sufficient area. Materials and methods Data retrieved from the Singapore National Cancer Registry on all thyroid cancers that were diagnosed from 1974 to 2013 were reviewed. We studied the time trends of thyroid cancer based on gender, race, pathology and treatment modalities where available. Results The age-standardised incidence rate of thyroid cancer increased to 5.6/100,000 in 2013 from 2.5/100,000 in 1974. Thyroid cancer appeared to be more common in women, with a higher incidence in Chinese and Malays compared with Indians. Papillary carcinoma is the most common subtype. The percentage of papillary microcarcinoma has remained relatively stable at around 38% of all papillary cancers between 2007 and 2013. Although the incidence of thyroid cancer has increased since 1974, the mortality rate has remained stable. Conclusion This trend of increase in incidence of thyroid cancer in Singapore compares with other published series; however, the rise seen was not solely due to micropapillary type. Thyroid cancer was also more common in Chinese and Malays compared with Indians for reasons that needs to be studied further.

Comparison of prognostic scoring systems in follicular thyroid cancer.

INTRODUCTION Many studies have addressed the accuracy of prognostic scoring systems in the treatment of differentiated thyroid cancers as a whole but few have addressed this issue in patients with follicular thyroid cancer (FTC) alone. The aim of this study was to establish the accuracy of the various scoring systems in determining the overall and disease free survival of FTC patients in Singapore. METHODS Retrospective review was undertaken of 82 patients with FTC treated at a single tertiary institution between January 2000 and December 2014. Demographic, clinical, pathological and treatment outcomes were analysed. Prognostic scoring systems evaluated for the cohort included TNM (Tumour, Nodes, Metastases), AGES (Age, Grade, Extent, Size), MACIS (Metastases, Age, Completeness of resection, Invasion, Size), AMES (Age, Metastases, Extent, Sex) and EORTC (European Organisation for Research and Treatment of Cancer). Statistical analysis was performed by plotting Kaplan-Meier survival curves and using the Cox proportional hazards model. RESULTS There were 29 male and 53 female patients with a mean age of 48 years. The mean follow-up duration was 88 months and there were 7 deaths (9%). The ten-year overall survival rate was 90%. Factors predictive of survival on univariate analysis were age, size of tumour, invasiveness, completeness of resection, metastasis, external beam radiotherapy, and risk scores using the AGES and MACIS scoring systems (p<0.05). On multivariate analysis, AGES and MACIS provided the best prognostic information. CONCLUSIONS MACIS is the best prognostic scoring system currently available for FTC and it is superior to other scoring systems in term of guiding management. The scoring systems require further development to accommodate variations in clinical practice globally and to improve the prognostic accuracy.

Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation.

Introduction Follicular thyroid cancer (FTC) has a good prognosis if treated early. The aim of this study was to look at the difference in outcomes in those who presented with metastasis early or late in their disease. Methods A retrospective cohort study was conducted of patients diagnosed with FTC (n=91) treated between 2000 and 2013. Demographic, laboratory, pathological and survival data were collected and analysed. Results Metastatic FTC was diagnosed in 20 cases (22%). The median age at diagnosis was 65 years (range: 17-86 years) and 65% of the patients were female. Twelve patients (60%) were diagnosed with metastatic disease at presentation, with the bones being the most common site (75%). In the remaining eight cases (40%), metastasis developed at a median of 4.5 years (range: 2-8 years) after initial thyroid surgery, lungs being the most common site (50%). Eighteen patients (90%) underwent surgical intervention for the primary disease. Sixteen patients (80%) received adjuvant radioactive iodine and eight (40%) received external beam radiotherapy. Widely invasive follicular cancer was the predominant histological diagnosis (90%). No prognostic association was observed with any of the parameters studied. The overall disease specific mortality rate was 40%. There was no significant difference in mortality between those who presented with metastatic disease and those who developed metastasis during the follow-up period (33% vs 50%, p=0.61). Conclusions The clinical outcome and prognosis for cases with metastatic disease is generally poor. Despite this, almost half of the patients in our study were still alive at a median follow-up of 5.5 years, regardless of whether they were diagnosed with metastatic disease on initial presentation or whether they developed metastasis after initial thyroid surgery.

Innovative Patient Safety Curriculum Using iPAD Game (PASSED) Improved Patient Safety Concepts in Undergraduate Medical Students.

INTRODUCTION: While healthcare outcomes have improved significantly, the complex management of diseases in the hospitals has also escalated the risks in patient safety. Therefore, in the process of training medical students to be proficient in medical knowledge and skills, the importance of patient safety cannot be neglected. A new innovation using mobile apps gaming system (PAtient Safety in Surgical EDucation-PASSED) to teach medical students on patient safety was created. Students were taught concepts of patient safety followed by a gaming session using iPad games created by us. This study aims to evaluate the outcome of patient safety perception using the PASSED games created. METHODS: An interactive iPad game focusing on patient safety issues was created by the undergraduate education team in the Department of Surgery, Yong Loo Lin School of Medicine at the National University of Singapore. The game employed the unique touched-screen feature with clinical scenarios extracted from the hospital sentinel events. Some of the questions were time sensitive, with extra bonus marks awarded if the student provided the correct answer within 10 s. Students could reattempt the questions if the initial answer was wrong. However, this entailed demerit points. Third-year medical students posted to the Department of Surgery experienced this gaming system in a cohort of 55-60 students. Baseline understanding of the students on patient safety was evaluated using Attitudes to Patient Safety Questionnaire III (APSQ-III) prior to the game. A 20 min talk on concept of patient safety using the WHO Patient Safety Guidelines was conducted. Following this, students downloaded the apps from ITune store and played with the game for 20-30 min. The session ended with the students completing the postintervention questionnaire. RESULTS: A total of 221 3rd year medical students responded to the survey during the PASSED session. Majority of the students felt that the PASSED game had trained them to understand the processes of medical error (p < 0.001), that their understanding on patient safety issues improved (p = 0.007), and the training prepared them to prevent medical errors (p < 0.001). Many students also recognized the importance of error reporting, where they felt comfortable reporting errors committed by themselves (p < 0.001) or by other people (p < 0.001). They also felt comfortable discussing with the supervisor on medical errors (p < 0.001). Students responded that better teamwork will reduce medical errors (p = 0.003), and teaching teamwork skills will reduce medical errors (p = 0.002). After the PASSED session, students felt that patients could play an important role in preventing medical errors (p < 0.001). They felt that patient safety should be emphasized in undergraduate training (p = 0.024). The level of understanding about concepts of patient safety was also found to improve progressively from the 2nd posting to the 5th posting for both the pre-PASSED and post-PASSED intervention. The pre-PASSED scores for Posting 2 (3.59 ± 1.931), Posting 3 (4.11 ± 1.833), Posting 4 (4.84 ± 1.653), and Posting 5 (4.88 ± 1.642) were significantly higher than the post-PASSED scores for Posting 2 (4.46 ± 2.020), Posting 3 (5.17 ± 1.845), Posting 4 (5.88 ± 1.843), and Posting 5 (5.80 ± 1.843), respectively (p < 0.001). CONCLUSION: Using iPad game (PASSED) to enhance the patient safety teaching has successfully improved the awareness and understanding of patient safety in clinical practice. This training model can be used to teach more senior medical students on the complexity of patient safety issues in medicine.

Description of Sinodiplectanotrema malayanum n. sp. (Monogenea: Diplectanidae), with comments on the taxonomic position of the genus.

Monogeneans identified as Sinodiplectanotrema malayanum n. sp. were collected from the fish Pennahia anea (Sciaenidae) off the west coast of Peninsular Malaysia. The new species is recognised on the basis of morphometrical differences in the anchors, marginal hooks and eggs and apparent differences in the 28S rDNA sequence data. The new species possesses features (ovary looping the intestinal caecum, body spines, a vagina and haptoral reservoirs) not noted in the original description of the type and only other species of the genus, S. argyrosomus Zhang, 2001, necessitating the re-assignment of the genus to the Diplectanidae Monticelli, 1903, a move which is supported by 28S rDNA evidence. Sinodiplectanotrema is redefined on the basis of the observation of several features not included in the original diagnosis.

Trianchoratus longianchoratus sp. n. (Monogenea: Ancyrocephalidae: Heteronchocleidinae) from Channa lucius (Osteichthyes: Channidae) in Peninsular Malaysia.

One new and three previously described species of Trianchoratus Price et Berry, 1966 were collected from the gills of Channa lucius (Cuvier) and Channa striata (Bloch) from the Bukit Merah Reservoir, Perak and Endau-Rompin, Pahang, Peninsular Malaysia. They are Trianchoratus longianchoratus sp.n., T. malayensis Lim, 1986 and T. pahangensis Lim, 1986 from C. lucius, and T. ophicephali Lim, 1986 from C. striata. The new species differs from the Trianchoratus species hitherto described from channids and anabantoids in having two ventral anchors with a long curved inner root and one dorsal anchor with a curved inner root and lacking an outer root. A table summarizing the known species of heteronchocleidins (Trianchoratus, Eutrianchoratus and Heteronchocleidus) and Sundanonchus reported from fish hosts of different families (Channidae, Helostomatidae, Anabantidae and Osphronemidae) is provided.

Feasibility and safety of day surgery laparoscopic cholecystectomy in a university hospital using a standard clinical pathway.

INTRODUCTION: Laparoscopic cholecystectomy is currently the treatment of choice for symptomatic gallstone disease. In recent years, there has been a trend towards outpatient cholecystectomy. The aim of our study was to report on our experience with day surgery laparoscopic cholecystectomy and to assess its feasibility and safety. METHODS: Data on all the patients who underwent day surgery laparoscopic cholecystectomy between February 2006 and December 2006 were collected. They all had symptomatic cholelithiasis proven on imaging or had previous history of biliary pancreatitis or cholangitis with normalisation of liver function test and imagery clearance of the common duct. The patients' biographical data (age, gender, American Society of Anaesthesiology [ASA] status, medical comorbidities) and surgical outcomes were then obtained. The success rate of day surgery laparoscopic cholecystectomy, reasons for overnight admission and re-admission rate were evaluated. RESULTS: A total of 50 patients were included in our study. The success rate for day surgery laparoscopic cholecystectomy was 92 percent. The patients who failed day surgery procedure are mostly of an older age group with high ASA grading. Reasons for admission for these patients included persistent abdominal pain and postoperative emesis. Our re-admission rate was four percent. CONCLUSION: Day surgery laparoscopic cholecystectomy is both safe and feasible in local settings. Careful patient selection is essential in ensuring a high success rate.