Patients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses. The benefit ...of adjuvant chemotherapy in these patients remains unclear.
We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival.
The result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval CI, 0.53 to 0.92; P=0.01). Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). Among patients with triple-negative disease, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group (hazard ratio for recurrence, second cancer, or death, 0.58; 95% CI, 0.39 to 0.87), and the overall survival rate was 78.8% versus 70.3% (hazard ratio for death, 0.52; 95% CI, 0.30 to 0.90). The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group.
After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing. (Funded by the Advanced Clinical Research Organization and the Japan Breast Cancer Research Group; CREATE-X UMIN Clinical Trials Registry number, UMIN000000843 .).
The Solitaire FR can be used not only as a tool for mechanical thrombectomy but also as a detachable permanent stent. Our aim was to assess the feasibility and safety of permanent stent placement ...with the Solitaire FR compared with other self-expanding stents for intracranial artery recanalization for acute ischemic stroke.
From January 2011 through January 2016, we retrospectively selected 2979 patients with acute ischemic stroke. Among them, 27 patients who underwent permanent stent placement (13 patients with the Solitaire FR Solitaire group and 14 patients with other self-expanding stents other stent group) were enrolled. The postprocedural modified TICI grade and angiographic and clinical outcomes were assessed. The safety and efficacy of permanent stent placement of the Solitaire FR for acute large-artery occlusion were evaluated.
Stent placement was successful in all cases. Modified TICI 2b-3 reperfusion was noted in 84.6% of the Solitaire group and in 78.6% of the other stent group. Procedural time was significantly shorter in the Solitaire group than in the other stent group (
= .022). Shorter procedural time was correlated with favorable outcome (ρ = 0.46,
= .035). No significant differences were found in the modified TICI grade, NIHSS score, mRS, and hemorrhagic transformation rate between the 2 groups. The acute in-stent thrombosis rate at discharge was significantly lower when a glycoprotein IIb/IIIa inhibitor was injected during the procedure (
= .013).
Permanent stent placement with the Solitaire FR compared with other self-expanding stents appears to be feasible and safe as a rescue tool for refractory intra-arterial therapy.
Background: To determine the clinical and pathologic prognostic factors in surgically treated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB–IIA small cell ...neuroendocrine carcinoma of the uterine cervix (SCNEC). Patients and methods: We retrospectively reviewed a total of 68 patients with FIGO stage IB–IIA SCNEC surgically treated from January 1997 to December 2003 in Korea. Results: Of the 68 patients, 43 had FIGO stage IB1 SCNEC, 15 had stage IB2, and 10 had stage IIA. Seven were treated with radical surgery alone; 11 with neoadjuvant chemotherapy (NACT) followed by radical surgery; 24 with radical surgery followed by adjuvant chemotherapy; and 26 with radical surgery followed by adjuvant radiation or chemoradiation. After a median follow-up of 44 months (range, 6–113 months), the 2-year and 5-year survival rates for all patients were 64.6% and 46.6%, respectively. Univariate and multivariate analysis showed that FIGO stage was predictive of poor prognosis. Patients who received NACT showed poorer prognosis than those who did not receive NACT. Adjuvant chemoradiation did not improve survival compared with adjuvant chemotherapy alone. Conclusions: FIGO stage may act as a surrogate for factors prognostic of survival. Primary radical surgery followed by adjuvant chemotherapy is the preferred treatment modality for patients with early stage SCNEC.
Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic ...topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months). The efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine requires confirmation.
In this two-part, open-label, single-group, multicenter, phase 2 study, we evaluated trastuzumab deruxtecan in adults with pathologically documented HER2-positive metastatic breast cancer who had received previous treatment with trastuzumab emtansine. In the first part of the study, we evaluated three different doses of trastuzumab deruxtecan to establish a recommended dose; in the second part, we evaluated the efficacy and safety of the recommended dose. The primary end point was the objective response, according to independent central review. Key secondary end points were the disease-control rate, clinical-benefit rate, duration of response and progression-free survival, and safety.
Overall, 184 patients who had undergone a median of six previous treatments received the recommended dose of trastuzumab deruxtecan (5.4 mg per kilogram of body weight). In the intention-to-treat analysis, a response to therapy was reported in 112 patients (60.9%; 95% confidence interval CI, 53.4 to 68.0). The median duration of follow-up was 11.1 months (range, 0.7 to 19.9). The median response duration was 14.8 months (95% CI, 13.8 to 16.9), and the median duration of progression-free survival was 16.4 months (95% CI, 12.7 to not reached). During the study, the most common adverse events of grade 3 or higher were a decreased neutrophil count (in 20.7% of the patients), anemia (in 8.7%), and nausea (in 7.6%). On independent adjudication, the trial drug was associated with interstitial lung disease in 13.6% of the patients (grade 1 or 2, 10.9%; grade 3 or 4, 0.5%; and grade 5, 2.2%).
Trastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer. In addition to nausea and myelosuppression, interstitial lung disease was observed in a subgroup of patients and requires attention to pulmonary symptoms and careful monitoring. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast01 ClinicalTrials.gov number, NCT03248492.).
Onychopapilloma: its clinical, dermoscopic and pathologic features Kim, T.‐R.; Bae, K.‐N.; Son, J.‐H. ...
JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology,
November 2022, 2022-11-00, 20221101, Volume:
36, Issue:
11
Journal Article
Peer reviewed
Open access
Background
Onychopapilloma is a benign tumour of the nail bed and distal matrix and commonly presents as longitudinal erythronychia, longitudinal leukonychia or longitudinal melanonychia. Because ...onychopapilloma is rare, its clinical characteristics and dermoscopic findings have not been well investigated in Asia.
Objectives
This study aimed to investigate the clinical characteristics and dermoscopic and pathologic findings of onychopapilloma in Korea.
Methods
We retrospectively reviewed the medical records and clinical/dermoscopic photographs of 39 patients diagnosed with onychopapilloma in the Pusan National University Hospitals (Busan and Yangsan) for 11 years (2010–2021).
Results
Among 39 patients, 23 (59.0%) were men, and 16 (41.0%) were women. The mean age was 46.1 (16–77) years. All lesions were single, and most of them were located on the fingers (92.3%), especially the thumb (66.7%). The most common clinical feature was longitudinal erythronychia (56.4%), and the most common dermoscopic finding was distal subungual hyperkeratosis (100%). We found two new dermoscopic features: macrolunula and trailing lunula along the longitudinal band. Among 18 patients who underwent surgical excision, only 6 (33.3%) showed typical acanthosis and papillomatosis on the nail bed.
Conclusions
We found that Asian onychopapilloma has similar clinicodermoscopic findings to the Caucasian one, that is to say, longitudinal erythronychia and distal subungual hyperkeratosis were the most common nail change and dermoscopic finding, respectively. We propose two new dermoscopic features of onychopapilloma: macrolunula and trailing lunula along the longitudinal band.
Selective blockade of nociceptive neurons can be achieved by the delivery of permanently charged sodium channel blockers through the pores of nociceptive ion channels. To assess the feasibility of ...this application in the dental area, we investigated the electrophysiological and neurochemical characteristics of nociceptive dental primary afferent (DPA) neurons. DPA neurons were identified within trigeminal ganglia labeling with a retrograde fluorescent dye applied to the upper molars of adult rats. Electrophysiological studies revealed that the majority of dental primary afferent neurons showed characteristics of nociceptive neurons, such as sensitivity to capsaicin and the presence of a hump in action potential. Immunohistochemical analysis revealed a large proportion of DPA neurons to be IB4-positive and to express TRPV1 and P2X3. Single-cell RT-PCR revealed mRNA expression of various nociceptive channels, including the temperature-sensitive TRPV1, TRPA1, TRPM8 channels, the extracellular ATP receptor channels P2X2 and P2X3, as well as the nociceptor-specific sodium channel, NaV1.8. In conclusion, DPA neurons have the electrophysiological characteristics of nociceptors and express several nociceptor-specific ion channels. Analysis of these data may assist in the search for a new route of entry for the delivery of membrane-impermeant local anesthetics. Abbreviations: AP, action potential; DiI, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate; DPA, dental primary afferent; FITC, fluorescein 5(6)-isothiocyanate; IB4, isolectin-B4; RT-PCR, reverse-transcription polymerase chain-reaction; TRP, transient receptor potential.
Melanoma cells are relatively resistant to Apo2L/TRAIL (TNF-related apoptosis-inducing ligand). We postulated that resistance might result from higher expression of inhibitors of apoptosis including ...Bcl-2, FLIP (FLICE-like inhibitory protein) or IAPs such as XIAP (X-linked inhibitor of apoptosis) or survivin. Compared to scrambled or mismatch controls, targeting individual inhibitors with siRNA (si-Bcl-2, si-XIAP, si-FLIP or si-Surv), followed by Apo2L/TRAIL resulted in marked increase in apoptosis in melanoma cells. Compared to Bcl-2 or FLIP, siRNAs against XIAP and survivin were most potent in sensitizing melanoma cells. A similar substantial increase in apoptosis was seen in renal carcinoma cells (SKRC-45, Caki-2), following the inhibition of either XIAP or survivin by siRNAs. Apo2L/TRAIL treatment in IAP-targeted cells resulted in cleavage of Bid, activation of caspase-9 and cleavage of PARP (poly ADP-ribose polymerase). Thus, Apo2L/TRAIL resistance can be overcome by interfering with expression of inhibitors of apoptosis regulating both extrinsic (death receptor) or intrinsic (mitochondrial) pathways of apoptosis in melanoma cells.
The treatment paradigm for very large and giant aneurysms has recently changed to flow diversion, in light of the results of the Pipeline for Uncoilable or Failed Aneurysms trial. However, the ...effects of flow diversion were definitely unknown. We explored this topic and identified the predictors of such effects.
We retrospectively reviewed 51 patients with unruptured aneurysms admitted to our institution for flow diversion between February 2014 and August 2019. Patients were categorized into an effect group (no filling or remnant entry) and a no-effect group (subtotal or total filling). We evaluated the aneurysm size and shape, incorporation vessel, parent artery stenosis and curvature, stagnation of contrast medium within the aneurysm, use of balloon angioplasty, and intra-aneurysm thrombus as potential predictors of the effects of flow diversion.
The effect group comprised 34 patients (66.7%, 34/51; no filling, 35.3%, 18/51; and remnant entry, 31.4%, 16/51). The no-effect group comprised 17 patients (33.3%, 17/51; subtotal filling, 29.4%, 15/51; and total filling, 3.9%, 2/51). An incorporation vessel and balloon angioplasty were independent risk factors for the no-effect group in multivariate logistic regression analyses (OR = 0.13 and 0.05; 95% confidence intervals, 0.02-0.62 and 0.00-0.32;
values, .021 and .004, respectively).
Flow diversion is effective for very large and giant aneurysms, but the outcomes require further improvement. The results of this study show that an incorporated vessel and excessive balloon angioplasty might compromise flow diversion. This finding can help improve the outcomes of flow diversion.
To identify the prevalence, clinical characteristics, risk factors of hepatic complications after a Fontan operation.
This was a cross-sectional study of 139 Fontan patients who underwent cardiac CT ...scans out of a total of 204 patients who had undergone the Fontan procedure between 1986 and 2003. Mean age was 19.0 ± 6.3 years and mean elapsed time since the initial Fontan operation was 11.5 ± 4.7 years. Subjects' clinical features, echocardiograms, radiological features and biochemical test results were reviewed. Various non-invasive hepatic fibrosis blood markers were also evaluated.
Fifty-seven patients had hepatic complications, including radiological features of liver cirrhosis (25.9%), thrombocytopenia (7.2%), hyperbilirubinaemia (20.9%) and hepatic masses (2.9%). Hepatic complications were also significantly associated with ventricular dysfunction (p=0.020), absence of fenestration (p=0.004), thrombus in the Fontan tract (p=0.027), sinus node dysfunction (p=0.034) and tachyarrhythmia (p<0.001). In a multivariate analysis, the elapsed time since the initial Fontan operation was the only measure that was correlated with hepatic complications; the odds ratio of the post-Fontan duration of 16-20 years to that of 0-5 years was 9.00 (CI 2.24 to 36.17). The non-invasive hepatic fibrosis blood marker (Forns index) was also correlated with the elapsed time since the initial Fontan operation (r=0.718, p<0.001).
Late hepatic dysfunction and cirrhotic change were often seen in Fontan patients. Moreover, hepatic complications were correlated with the duration of Fontan circulation. Therefore, after a Fontan operation, regular evaluation of the hepatic condition is required--for which some non-invasive hepatic fibrosis markers can be effectively used.
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