The impact of preoperative waiting time in Stage II-III gastric or gastroesophageal junction cancer: A population-based cohort study.

BACKGROUND: Gastrectomy remains the curative option in gastric cancer. However, the growing concern that preoperative waiting jeopardizes survival has not been fully addressed. The present population-based cohort study aimed to clarify the impact of preoperative waiting time (PreWT). METHODS: We included patients with clinical Stage II-III gastric cancer who received curative surgery from 2008 to 2017 of Taiwan Cancer Registry. PreWT was defined as the time from endoscopic diagnosis to surgery. The prognostic impact on overall survival (OS) was evaluated with Cox and restricted cubic spline regressions. RESULTS: A total of 3059 patients with a median age of 68 years were evaluated. The median PreWT was 16 days (interquartile range, 11-24 days), and patients with a shorter PreWT were younger, had a more advanced disease and received adjuvant therapies. Despite a shorter OS occurring with prolonged PreWT (median OS by PreWT [days]: 7-13, 2.7 years; 14-20, 3.1 years; 21-27, 3.0 years; 28-34, 4.7 years; 35-31, 3.7 years; 42-48, 3.4 years; 49-118, 2.8 years; p = 0.029), the differences were not significant after adjustment. The Cox and restricted cubic spline regressions showed that prolonged PreWT was not a significant prognostic factor for OS (p = 0.719). CONCLUSIONS: The population-based study suggests that a PreWT of 49-118 days does not independently correlate with a poor prognosis in Stage II-III gastric cancer. The study provides rationale for a window period for preoperative therapies and patient optimization.

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.

Safety of ramucirumab treatment in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-induced deaths worldwide, and limited therapeutic options are available for patients with advanced disease. Ramucirumab, a monoclonal antibody that blocks the vascular endothelial growth factor (VEGF) receptor-2, is the first biomarker-selected systemic agent with therapeutic efficacy, tolerability, and favorable patient-reported outcomes in patients with advanced HCC and elevated serum α-fetoprotein levels ≥400 ng/mL, who are resistant or intolerant to sorafenib therapy. However, treatment-induced adverse events (AEs), such as hypertension, proteinuria, bleeding, thromboembolism, and gastrointestinal perforation remain challenging and potentially fatal concerns. AREAS COVERED: This review discusses the published or ongoing studies and subgroup analyses on ramucirumab therapy in patients with advanced HCC. We present information on the risks of ramucirumab-induced common or rare AEs and their management. EXPERT OPINION: Ramucirumab toxicity secondary to VEGF inhibition is similar to the AEs that are known to be associated with other VEGF-blocking antibodies. Common AEs can be safely treated using conventional measures; however, rare and potentially fatal AEs necessitate close monitoring. With regard to the safety profile, more promising ramucirumab-containing combination therapies are likely to pave the future path for effective HCC treatment.

Pure Red Cell Aplasia and Other Haematological Diseases Associated With Thymoma: A Case Series and Systematic Review.

Background: Thymoma-associated haematological diseases (HDs), such as pure red cell aplasia (PRCA) and Good's syndrome, are extremely rare, and due to the paucity of large-scale studies, the characteristics, remission after thymectomy, and long-term evaluation remain undetermined. Methods: We retrospectively assessed patients with thymoma and associated HDs from Jan 2005 to Dec 2020. All patients received thymectomy and/or additional treatments for HDs. A comparison with thymoma-associated myasthenic gravis (MG), and a systematic review from PubMed/MEDLINE and Embase were conducted. Results: In the median follow-up of 56 months, 130 patients were enrolled. Patients with thymoma-associated MG (n = 46) and HDs [n = 8; PRCA (n = 5), PRCA and Good's syndrome (n = 2) and autoimmune haemolytic anaemia (n = 1)] were evaluated. Patients with MG had a significantly higher remission rate after thymectomy (50 vs. 17%; p = 0.0378) as compared to those with other autoimmune diseases. Two of seven patients with PRCA experienced remission with thymectomy alone, and an additional two patients achieved remission with thymectomy plus immunosuppressive therapy (IST). In the systematic review, 60 studies (case reports, n = 46; case series including the present study, n = 14) were evaluated. Forty-four percent of patients were diagnosed with PRCA after thymoma, and 61% achieved remission with thymectomy plus IST; however, Good's syndrome was unaffected. Conclusions: Our study indicates that patients with thymoma-associated autoimmune diseases other than MG have a lower remission rate than those with MG. Remission of thymoma-associated PRCA can be achieved by thymectomy and IST. This study provides insight into extremely rare but puzzling autoimmune manifestations.

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.

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.

The Characteristics and Motivations of Taiwanese People toward Advance Care Planning in Outpatient Clinics at a Community Hospital.

Advance care planning (ACP) provides access to complete advance decisions (ADs). Despite the legalization of ACP in Taiwan, it is underutilized in community settings. The objective of this study is to describe the service at a community hospital in Southern Taiwan. We retrospectively analyzed participants who were engaged in ACP consultations from January 2019 to January 2020. The characteristics, motivations, content, and satisfaction of participants are reported. Factors associated with refusing life-sustaining treatments (LST) or artificial nutrition/hydration (ANH) were analyzed using multivariate logistic regression. Of the 178 participants, 123 completed the ACP. The majority were female (64.2%), aged 61 on average and more than 80% had never signed a do-not-resuscitate order. In the ADs, most participants declined LST (97.2%) and ANH (96.6%). Family-related issues (48.9%) were the most prevalent motivations. Rural residence (OR 8.6, p = 0.005), increased age (OR 7.2, p = 0.025), and reluctance to consent to organ donation (OR 5.2, p = 0.042) correlated with refusing LST or ANH. Participants provided a positive feedback regarding overall satisfaction (good, 83%) compared to service charge (fair/poor, 53%). The study demonstrated high AD completion when refusing LST or ANH. These findings may facilitate the development of ACP as a community-based service.

Maternal survival of patients with pregnancy-associated cancers in Taiwan - A national population-based study.

Pregnancy-associated cancer (PAC), defined as cancers diagnosed during pregnancy or the first year after delivery, affects one to two in every 1000 pregnancies. Although PAC is expected to be a growing issue, information about PAC in the Asian population is still scarce. Women with cancer diagnosed at the age of 16-49 years between 2001 and 2015 were selected from the Taiwan Cancer Registry and linked with the National Birth Reporting Database to identify PAC patients. We compared the overall survival of patients with PAC to patients without pregnancy. Among 126,646 female cancer patients of childbearing age, 512 were diagnosed during pregnancy, and 2151 during the first postpartum year. Breast cancer was the most common PAC (N = 755, 28%). Compared with patients without pregnancy in the control group, patients with cancers diagnosed during pregnancy and the first postpartum year generally had more advanced stages (odds ratio 1.35 and 1.36, 95% confidence interval [CI] 1.02-1.77 and 1.18-1.57, respectively). For all cancer types combined and controlled for the stage, age, and year of diagnosis, patients with PAC had similar overall survival with those in the control group, with a hazard ratio (HR) of 1.07 (95% CI 0.80-1.41) for the pregnancy group and HR 1.02 (95% CI 0.88-1.18) for the postpartum group. The diagnosis of breast cancer during the first postpartum year was linked with shorter survival (HR 1.34, 95% CI 1.05-1.72). In contrast, patients with postpartum lymphoma (HR 0.11, 95% CI 0.02-0.79) and cervical cancer (HR 0.40, 95% CI 0.20-0.82) had better prognosis. In general, the diagnosis of cancer during pregnancy or the first postpartum year does not affect the survival of patients with most cancer types. Exceptions include the worse prognosis of postpartum breast cancer and the better outcome of postpartum lymphoma and cervical cancer.

Organophosphate poisoning presenting as out-of-hospital cardiac arrest: A clinical challenge.

Out-of-hospital cardiac arrest (OHCA) remains a challenge for physicians since effective management and definitive salvage depend upon correct determination of the etiology and the extent of injury. Definitive diagnosis of organophosphate poisoning (OP) requires physicians' clinical awareness of a typical toxidrome, that is, characteristic signs and symptoms of poisoning, and laboratory confirmation. Here we report a case of an OHCA patient with OP, which was initially misdiagnosed as an acute ST segment elevation myocardial infarction based on the patient's medical history and clinical manifestations. .