Clinical Characteristics and Responses to Immune Checkpoint Inhibitors in RET-Aberrant Digestive Tract Tumours.

BACKGROUND: RET plays an oncogenic role, and its aberrations are potentially actionable. However, they have seldom been reported in tumours other than lung or thyroid cancers. The correlation of RET aberrations with clinical characteristics, co-occurring aberrations, and responses to immune checkpoint inhibitors (ICPi) have not been explored in digestive tract tumours. OBJECTIVES: The aim of the study was to elucidate the clinical characteristics, frequently co-altered genes, and treatment responses in RET-aberrant digestive tract tumours. PATIENTS AND METHODS: We retrospectively evaluated patients with digestive tract cancers for RET-aberrant tumours via FoundationOne CDx tumour-based selected genome sequencing from Jan 2016 to Jan 2021. RESULTS: In a median follow-up time of 51 months, a total of 453 patients were analysed. RET-aberrant tumours accounted for 4.4% in the studied population (n = 20), and 1.1% had an oncogenic fusion (n = 5). APC, KRAS, TP53, MSH6 and STK11 were the differentially co-altered genes (all false discovery rates <0.05). The presence of RET aberrations alone was not a significant prognostic factor. Eleven patients with RET-aberrant tumours received ICPi-based treatment and none achieved an objective response. In contrast, 47 patients with non-aberrant tumours received ICPi treatment and had an objective response rate of 27.7% and a significantly longer treatment duration (6.2 vs 2.8 months, p = 0.0008). CONCLUSIONS: Albeit rarely, RET aberrations can be found in digestive tract tumours. Patients with RET-aberrant tumours have a blunted response to ICPi and a comparable prognosis as compared with RET-wild type tumours. Together, these results provide insights into this rare but potentially actionable target in digestive tract tumours.

Lidocaine transdermal patches reduced pain intensity in neuropathic cancer patients already receiving opioid treatment.

BACKGROUND: Limited efficacy has been observed when using opioids to treat neuropathic pain. Lidocaine patches reduce neuropathic pain in postherpetic neuralgia, but their benefits for cancer-related neuropathic pain remain unclear. This study aimed to investigate a treatment for cancer-related neuropathic pain. METHODS: We conducted a prospective, open-label, single-arm study to assess the efficacy and safety of lidocaine transdermal patches in patients experiencing localized, superficial, neuropathic cancer pain. Terminal cancer patients already receiving opioid treatment participated in the 3-day study. The primary endpoint was pain intensity evaluated by the numerical rating scale (NRS). The secondary endpoints were the pain relief score and the quality of analgesic treatment. RESULTS: The results showed a significant difference in the median NRS over 3 days (Kruskal-Wallis test, p < 0.0001). The median NRS pain intensity from Day 1 to Day 3 was 4.0 with 95% C.I. (3.3, 5.0), 3.0 (2.5, 3.5), and 2.6 (2.0, 3.0), respectively. The difference between the median NRS pain intensities of any 2 days was significant (Wilcoxon signed-rank test, p < 0.0001). The generalized estimating equation (GEE) estimation model showed significant differences between the NRS pain intensities on any 2 days. There was no significant difference in the pain relief score or the quality of analgesic treatment. CONCLUSIONS: In this study, the 5% lidocaine transdermal patch reduced the NRS pain intensity in neuropathic cancer patients already receiving opioid treatment. Treatment of localized and superficial neuropathic pain caused by cancer was well tolerated and effective.

Improved survival with induction chemotherapy and conversion surgery in locally advanced unresectable pancreatic cancer: a single institution experience.

Both efficacy and tolerability are critical issues in choosing neoadjuvant chemotherapy in patients with unresectable locally advanced pancreatic cancer (LAPC). The optimal regimen and the impact of conversion surgery on patient survival remains insufficiently reported in Asain population. Therefore, we conducted a retrospective study aiming to evaluate the resection rate after different induction chemotherapy regimen and its impact toward survival. All patients with pancreatic cancer treated in our institute from 2013 to 2020, a total of 730 patients, were reviewed and 131 patients with LAPC were identified. For cohort homogeneity, 14 patients receiving induction concurrent chemoradiotherapy initially were excluded and 117 patients receiving induction chemotherapy were included in the study. Most patients (90 of 117, 77%) received triplet induction chemotherapy, including the combination of S1, leucovorin, oxaliplatin and gemcitabine (SLOG) in 48, modified FOLFIRINOX in 21 and the combination of gemcitabine, oxaliplatin, fluorouracil and leucovorin (GOFL) in 21. The tumor response rate (19%-33%), the surgical exploration rate (38%-52%) and the mOS (15.4-23.0 months) were not significantly different among the three triplets. Both GOFL and SLOG regimen had comparable efficacy and less neutropenia as compared to mFOLFIRINOX. Conversion surgery was performed in 34 of 117 (29%) patients after induction chemotherapy. The median overall survival (mOS) in patients with and without conversion surgery were 29.1 and 14.1 months, respectively (P<0.0001). Radiological response alone was not a reliable indicator of successful conversion surgery. Patients who underwent conversion surgery had significantly better survival and thus highlighted the importance of surgical exploration in all patients who did not have progressive disease after induction chemotherapy.

Hospice delivery models and survival differences in the terminally ill: a large cohort study.

OBJECTIVE: A common difficulty at the end of life (EOL) is to determine an appropriate service model, such as hospice share care (HSC), hospice inpatient care (HIC) and hospice home care (HHC). This study aimed to recommend the appropriate hospice delivery model based on the physical, psychosocial and spiritual needs of patients referred for hospice care. METHODS: This cohort study included patients who received only one kind of hospice delivery model between 2006 and 2020. Data were analysed with descriptive statistics, Fisher's exact test, non-parametric analysis of variance, Kaplan-Meier curves and Cox proportional hazards model that determined the patients' clinical characteristics for a hospice delivery model and overall survival. RESULTS: A total of 8874 hospice patients were recruited, of which 7076 (79.7%) were HSC patients, 918 (10.4%) were HIC patients and 880 (9.9%) were HHC patients. There were significant differences in the physical symptoms and demographic, psychosocial and spiritual factors among the three groups (p<0.001). The patients who received the HHC were less to have dyspnoea (18.5%) and dysphagia (28.7%). The HIC patients showed higher severity of symptoms and experienced greater psychosocial distress (73.2%). The HSC is appropriate for noncancer patients . Patients with cancer were associated with less dyspnoea (32.4%) and dysphagia (46.5%). Patients with lung cancer who received the HHC had better survival than those who received other types of hospice care (HR=0.75, 95% CI: 0.66 to 0.86, p<0.001). CONCLUSIONS: This study provides guidance regarding the appropriate hospice service model, based on individualised palliative needs, targeting improvement in EOL care.

Predict Early Recurrence of Resectable Hepatocellular Carcinoma Using Multi-Dimensional Artificial Intelligence Analysis of Liver Fibrosis.

BACKGROUND: Liver fibrosis is thought to be associated with early recurrence of hepatocellular carcinoma (HCC) after resection. To recognize HCC patients with higher risk of early recurrence, we used a second harmonic generation and two-photon excitation fluorescence (SHG/TPEF) microscopy to create a fully quantitative fibrosis score which is able to predict early recurrence. METHODS: The study included 81 HCC patients receiving curative intent hepatectomy. Detailed fibrotic features of resected hepatic tissues were obtained by SHG/TPEF microscopy, and we used multi-dimensional artificial intelligence analysis to create a recurrence prediction model "combined index" according to the morphological collagen features of each patient's non-tumor hepatic tissues. RESULTS: Our results showed that the "combined index" can better predict early recurrence (area under the curve = 0.917, sensitivity = 81.8%, specificity = 90.5%), compared to alpha fetoprotein level (area under the curve = 0.595, sensitivity = 68.2%, specificity = 47.6%). Using a Cox proportional hazards analysis, a higher "combined index" is also a poor prognostic factor of disease-free survival and overall survival. CONCLUSIONS: By integrating multi-dimensional artificial intelligence and SHG/TPEF microscopy, we may locate patients with a higher risk of recurrence, follow these patients more carefully, and conduct further management if needed.

Surgery alone, adjuvant tegafur/gimeracil/octeracil (S-1), or platinum-based chemotherapies for resectable gastric cancer: real-world experience and a propensity score matching analysis.

BACKGROUND: Adjuvant chemotherapy has changed the paradigm in resectable gastric cancer. S-1 is an oral chemotherapeutic with promising efficacy in Asia. However, comparisons with close observation or platinum-based doublets post D2 gastrectomy have been less reported, notably on real-world experiences. METHODS: We retrospectively evaluated patients with D2-dissected stage IB-III gastric cancer who received S-1 (S-1, n = 67), platinum-based doublets (P, n = 145) and surgery with close observation (OBS, n = 221) from Jan 2008 to Oct 2018. A propensity score matching was used to compare for recurrence-free (RFS) and overall survivals (OS) in patients who had a locally-advanced disease (T3-4 or lymph node-positive). Adverse reactions, dosage, and associated factors for S-1 are also discussed. RESULTS: In a median follow-up time of 51.9 months, adjuvant S-1 monotherapy was associated with an intermediate survival as compared with P and OBS (median RFS/OS: S-1 vs. P, 20.9/35.8 vs. 31.2/50.5 months, HR = 1.76/2.14, p = 0.021/0.008; S-1 vs. OBS, 24.4/40.2 vs. 20.7/27.0 months, HR = 0.62/0.55, p = 0.041/0.024). The survival differences were more prominent in patients with N2-3 diseases. S-1 was well-tolerated with a relative dose intensity of 73.6%, a median duration of 8.3 months and associated with less adverse reactions as compared with P. S-1 monotherapy was selected by physicians based on age, lymph node stage, serum carcinoembryonic antigen and disease stage. CONCLUSIONS: Adjuvant S-1 correlated with intermediate survival outcomes between OBS and P but conferred fewer adverse reactions as compared with P. Patients with a moderate risk of recurrence had comparable survivals when treated with S-1 while platinum-based doublets were favored in advanced cases. The study provides additional information about adjuvant S-1 in patients with selected risk of recurrence.

Health literacy and cancer screening behaviors among community-dwelling female adults in Taiwan.

This study was designed to explore the association among health literacy and cancer screening behaviors in Taiwanese females. A total of 353 community-dwelling females were recruited in this cross-sectional study from February to October 2015. Demographic, socioeconomic and personal behavior variables including physical activity, community activity, smoking, alcohol consumption, and betel nut chewing were recorded. Health literacy was evaluated using the Mandarin version of the European Health Literacy Survey Questionnaire. Data on screening behaviors for cervical, breast and colorectal cancers were confirmed by the Taiwanese National eHealth Database. Most respondents with inadequate or problematic general health literacy had no or irregular screening behaviors for cervical, breast and colorectal cancers. In multivariable regression analysis, women with inadequate health literacy were at a greater risk (Odds ratio = 5.71; 95% CI: 1.40-23.26) of having no previous Pap smear screening or >3 years screening interval regardless of education level. However, this association was not detected for breast or colorectal cancer. Women with inadequate health literacy were more likely to have irregular cervical cancer screening, however no associations among health literacy and breast or colorectal cancer were detected. The impact of health literacy on cancer screening behavior warrants further attention and research.

Comparing the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma with those of other primary liver cancers by use of the updated World Health Organization classification.

AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is an uncommon hepatic malignancy with a poor outcome. The 2019 World Health Organization (WHO) classification modified the definition and discarded the subtypes with stem cell features. However, the differences among cHCC-CCA, hepatocellular carcinoma (HCC), HCC with stem cell/progenitor features (HCCscf) and intrahepatic cholangiocarcinoma (iCCA) remain undetermined. The aim of this study was to investigate the characteristics of cHCC-CCA in comparison with those of other primary liver cancers by utilising the updated WHO classification. METHODS AND RESULTS: We retrospectively analysed 64 cHCC-CCA patients and 55 HCCscf patients from December 2007 to May 2018. Propensity score matching was conducted to compare these with HCC and iCCA patients. Clinicopathological characteristics, event-free survival and overall survival were evaluated with multivariate Cox proportional hazard regression. During a median follow-up of 55.9 months, cHCC-CCA patients had significantly poorer survival than HCCscf patients, and survival intermediate between that of HCC patients and that of iCCA patients. Hepatitis B virus (HBV) infection and high levels of tumour-infiltrating lymphocytes (TILs) were associated with favourable survival in cHCC-CCA patients. In the multivariate analysis, poor hepatic reserve, absence of HBV infection, stage IV disease and low levels of TILs were significant negative prognostic factors in cHCC-CCA patients. After being pooled with other primary liver cancers, cHCC-CCA and iCCA resulted in the worse survival. CONCLUSIONS: cHCC-CCA patients have survival intermediate between that of HCC patients and iCCA patients, and HBV infection and high levels of TILs predict favourable survival. Our study provides clinical correlations for the new 2019 WHO classification.

Factors associated with low health literacy among community-dwelling women in Taiwan.

The present study investigated factors associated with health literacy in community-dwelling Taiwanese women, particularly focusing on those associated with prevalent unhealthy behaviors. This cross-sectional study recruited 353 community-dwelling women aged 39-89 years from February to October 2015 in urban, suburban, and rural areas. Variables investigated included physical activity, community activity, tobacco usage, alcohol consumption, and betel-nut chewing. Degree of health literacy was evaluated using the Chinese-language version of the European Health Literacy Survey Questionnaire. Most respondents had inadequate (17.6%), or problematic (49.3%), general health literacy. Multiple logistic regression analyses showed that low educational attainment was closely associated with inadequate or problematic general health literacy. Women who did not engage in regular physical activity or direct community activity were more likely to have inadequate and problematic general health literacy, respectively. Selected unhealthy behaviors (tobacco usage, alcohol consumption, betel-nut chewing) were not associated with health literacy. Low health literacy was prevalent among participants. Lower educational attainment and a lack of physical or community activity were associated with low health literacy. Health literacy should be considered during the process of delivering health information, and health education programs must enhance health literacy tailored to address individuals' lifestyles.

Distinct clinical characteristics of paroxysmal nocturnal hemoglobinuria in patients in Southern Taiwan: A multicenter investigation.

Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare acquired disorder. The aim of this study was to investigate the demographics, clinical manifestations, and outcomes of PNH patients in southern Taiwan. Data on PNH patients diagnosed over a 30-year period (1985-2015) were retrospectively collected from four tertiary medical centers in southern Taiwan. Blood samples were collected for hematologic panel testing and flow cytometry detection of PNH clones. Radiologic studies were performed to assess the frequency of complications. Twenty-four patients were enrolled in this study. The median duration of disease in the study participants was 10.8 years. The median granulocyte PNH clone size was 92.5% (range, 1.3%-99.8%), and the median lactate dehydrogenase (LDH) level was 2920.2 ± 1462.0 IU/L. The incidence of thromboembolism and impaired renal function was 16.7% and 29.2%, respectively. The primary treatment strategies included steroids (79.2%), androgens (42.0%), eculizumab (33.3%), immunosuppressants (16.7%), and anticoagulants (4.2%). In eight patients treated with eculizumab, there was a marked reduction in the LDH levels of 14.89-fold-1.63-fold that of the upper limit of normal; seven patients exhibited decreased transfusion requirements. Twenty-one patients were alive with regular follow-up at the time of publication. Our study demonstrates that PNH patients in southern Taiwan may exhibit different clinical characteristics and outcomes relative to patients in other countries. There was a trend toward a greater PNH granulocyte clone size, which may lead to more hemolysis. In our study, the percentage of patients with impaired renal function, but not the percentage of patients with thrombotic events, was higher than values reported worldwide and in the observational cross-sectional International PNH Registry. More large-scale studies with comprehensive data on the clinical response to different treatments are needed.

miR-106b promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma.

AIM: To investigate the effect of miR-106b on tumor progression in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). METHODS: A total of 120 patients who underwent liver resection for HCC at National Cheng Kung University Hospital were enrolled in the present study. MicroRNA (miRNA) array was first used to screen the miRNA expression profiles in HCC patients. The clinical records were retrospectively analyzed, and correlations with the miRNA expression profiles were evaluated. The mRNA expression levels of the miR-106b-25 cluster (miR-106b, miR-93 and miR-25), and MCM7 in tumor and non-tumor samples were quantitated using quantitative real-time reverse transcription-polymerase chain reaction (q-RT-PCR) analysis, and correlations in the levels of miR-106b, miR-93 and miR-25 expression were calculated. Kaplan-Meier overall and disease-free survival rates of HBV-associated HCC patients were analyzed using the log-rank test based on miR-106b expression. The comparison of the miR-106b expression levels in patients with different clinical outcomes was analyzed using Mann-Whitney U tests. Furthermore, a hepatitis B virus X protein (HBx) expression plasmid was transfected into Huh7 and Hep 3B cells. The expression levels of the miR-106b-25 cluster and MCM7 in HBx-expressing Huh7 and Hep 3B cells were detected using q-RT-PCR. RESULTS: miRNA array screening showed that miR-106b and its cluster, miR-93 and miR-25 were up-regulated in HCC patients (P < 0.01). The value of miR-106b expression in HBV-associated HCC patients was significantly higher than that in HCV- (P < 0.05) or non-B/non-C- (P < 0.001) associated HCC patients. The expression of the miR-106b-25 cluster was significantly higher in tumor tissue (P < 0.001) and associated with the host gene, MCM7, in clinical specimens from HBV-associated HCC patients. Furthermore, the expression levels of miR-106b, miR-93 and miR-25 were positively correlated in HBV-associated HCC tissues (miR-106 vs miR-93, r = 0.75; miR-93 vs miR-25, r = 0.69; miR-106b vs miR-25, r = 0.33). The overall and disease-free survival curves showed that high-miR-106b expression was correlated with the poor prognosis of HBV-associated HCC. HCC differentiation was significantly correlated with miR-106b expression (P < 0.05). Lower miR-106b expression levels resulted in the well differentiation of HCC. Moreover, the expression of the miR106b-25 cluster and MCM7 was up-regulated in Huh7 and Hep 3B cells after transfection with the HBx expression plasmid. CONCLUSION: The data obtained in the present study suggests that HBx enhances miR-106b transcription to promote tumor progression in HBV-associated HCC.

Benign fibrous histiocytoma associated with a frontoethmoidal mucopyocele and orbital abscess.

A 74-year-old man sought treatment for painful swelling in the right upper eyelid. CT demonstrated a frontoethmoidal mucocele extending in the right orbit with abscess formation. Following functional endoscopic sinus surgery, the inflammatory symptoms in the right eye nearly resolved. However, a firm mass was still noted in the same location. Histopathologic examination proved it to be a benign fibrous histiocytoma. Benign fibrous histiocytoma may occur in association with an orbital abscess secondary to mucocele.