Objective: Our goal was to review outcomes of patients with heterotopic pregnancies who under went surgical treatment. Methods: From January 1, 2005 to December 31, 2021, 27 women with heterotopic pregnancies who had undergone surgical treatment were enrolled. We investigated pregnancy outcomes based on clinical records and follow-up telephone interviews. Three of the 27 patients were excluded because we were unable to contact them. Results: Of the 24 patients included in the study, 17 underwent salpingectomies for tubal pregnan cies, 5 underwent wedge resections for cornual pregnancies, and 1 underwent a unilateral salpingooophorectomy for ovarian pregnancy. One patient with a suspected heterotopic cervical pregnancy had undergone extraction with forceps and curettage under abdominal ultrasound guidance. Three patients had spontaneous abortions after treatment for heterotopic pregnancies (2 tubal pregnancies, one cervical pregnancy). Twenty-one of 24 patients had heterotopic pregnancies that occurred after assisted reproductive technology. Three cases were heterotopic pregnancies that occurred without reproductive interventions. Among 24 patients who underwent surgical treatment, 18 patients (75.0%) had full-term deliveries. Conclusion There were no hospitalizations due to preterm labor, and 21 deliveries (87.5%) were either late preterm or full-term. There were no fetal abnormalities or maternal complications. Although the development of assisted reproductive technologies has increased the incidence of heterotopic pregnancy, the outcomes of heterotopic pregnancies are generally good.

Objective: Our goal was to review outcomes of patients with heterotopic pregnancies who under went surgical treatment. Methods: From January 1, 2005 to December 31, 2021, 27 women with heterotopic pregnancies who had undergone surgical treatment were enrolled. We investigated pregnancy outcomes based on clinical records and follow-up telephone interviews. Three of the 27 patients were excluded because we were unable to contact them. Results: Of the 24 patients included in the study, 17 underwent salpingectomies for tubal pregnan cies, 5 underwent wedge resections for cornual pregnancies, and 1 underwent a unilateral salpingooophorectomy for ovarian pregnancy. One patient with a suspected heterotopic cervical pregnancy had undergone extraction with forceps and curettage under abdominal ultrasound guidance. Three patients had spontaneous abortions after treatment for heterotopic pregnancies (2 tubal pregnancies, one cervical pregnancy). Twenty-one of 24 patients had heterotopic pregnancies that occurred after assisted reproductive technology. Three cases were heterotopic pregnancies that occurred without reproductive interventions. Among 24 patients who underwent surgical treatment, 18 patients (75.0%) had full-term deliveries. Conclusion There were no hospitalizations due to preterm labor, and 21 deliveries (87.5%) were either late preterm or full-term. There were no fetal abnormalities or maternal complications. Although the development of assisted reproductive technologies has increased the incidence of heterotopic pregnancy, the outcomes of heterotopic pregnancies are generally good.

Objective: Our goal was to review outcomes of patients with heterotopic pregnancies who under went surgical treatment. Methods: From January 1, 2005 to December 31, 2021, 27 women with heterotopic pregnancies who had undergone surgical treatment were enrolled. We investigated pregnancy outcomes based on clinical records and follow-up telephone interviews. Three of the 27 patients were excluded because we were unable to contact them. Results: Of the 24 patients included in the study, 17 underwent salpingectomies for tubal pregnan cies, 5 underwent wedge resections for cornual pregnancies, and 1 underwent a unilateral salpingooophorectomy for ovarian pregnancy. One patient with a suspected heterotopic cervical pregnancy had undergone extraction with forceps and curettage under abdominal ultrasound guidance. Three patients had spontaneous abortions after treatment for heterotopic pregnancies (2 tubal pregnancies, one cervical pregnancy). Twenty-one of 24 patients had heterotopic pregnancies that occurred after assisted reproductive technology. Three cases were heterotopic pregnancies that occurred without reproductive interventions. Among 24 patients who underwent surgical treatment, 18 patients (75.0%) had full-term deliveries. Conclusion There were no hospitalizations due to preterm labor, and 21 deliveries (87.5%) were either late preterm or full-term. There were no fetal abnormalities or maternal complications. Although the development of assisted reproductive technologies has increased the incidence of heterotopic pregnancy, the outcomes of heterotopic pregnancies are generally good.

Objective: Our goal was to review outcomes of patients with heterotopic pregnancies who under went surgical treatment. Methods: From January 1, 2005 to December 31, 2021, 27 women with heterotopic pregnancies who had undergone surgical treatment were enrolled. We investigated pregnancy outcomes based on clinical records and follow-up telephone interviews. Three of the 27 patients were excluded because we were unable to contact them. Results: Of the 24 patients included in the study, 17 underwent salpingectomies for tubal pregnan cies, 5 underwent wedge resections for cornual pregnancies, and 1 underwent a unilateral salpingooophorectomy for ovarian pregnancy. One patient with a suspected heterotopic cervical pregnancy had undergone extraction with forceps and curettage under abdominal ultrasound guidance. Three patients had spontaneous abortions after treatment for heterotopic pregnancies (2 tubal pregnancies, one cervical pregnancy). Twenty-one of 24 patients had heterotopic pregnancies that occurred after assisted reproductive technology. Three cases were heterotopic pregnancies that occurred without reproductive interventions. Among 24 patients who underwent surgical treatment, 18 patients (75.0%) had full-term deliveries. Conclusion There were no hospitalizations due to preterm labor, and 21 deliveries (87.5%) were either late preterm or full-term. There were no fetal abnormalities or maternal complications. Although the development of assisted reproductive technologies has increased the incidence of heterotopic pregnancy, the outcomes of heterotopic pregnancies are generally good.

Objective: Our goal was to review outcomes of patients with heterotopic pregnancies who under went surgical treatment. Methods: From January 1, 2005 to December 31, 2021, 27 women with heterotopic pregnancies who had undergone surgical treatment were enrolled. We investigated pregnancy outcomes based on clinical records and follow-up telephone interviews. Three of the 27 patients were excluded because we were unable to contact them. Results: Of the 24 patients included in the study, 17 underwent salpingectomies for tubal pregnan cies, 5 underwent wedge resections for cornual pregnancies, and 1 underwent a unilateral salpingooophorectomy for ovarian pregnancy. One patient with a suspected heterotopic cervical pregnancy had undergone extraction with forceps and curettage under abdominal ultrasound guidance. Three patients had spontaneous abortions after treatment for heterotopic pregnancies (2 tubal pregnancies, one cervical pregnancy). Twenty-one of 24 patients had heterotopic pregnancies that occurred after assisted reproductive technology. Three cases were heterotopic pregnancies that occurred without reproductive interventions. Among 24 patients who underwent surgical treatment, 18 patients (75.0%) had full-term deliveries. Conclusion There were no hospitalizations due to preterm labor, and 21 deliveries (87.5%) were either late preterm or full-term. There were no fetal abnormalities or maternal complications. Although the development of assisted reproductive technologies has increased the incidence of heterotopic pregnancy, the outcomes of heterotopic pregnancies are generally good.

Purpose: Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC. Materials and Methods: Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]). Results: Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9). Conclusion Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

Purpose: Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens. Materials and Methods: In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee. Results: The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients. Conclusion The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.

Objective: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). Materials and Methods: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm 2 was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive.The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). Results: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4–79.9), 90.8% (95% CI: 85.6–94.2), and 83.5% (95% CI: 78.6–87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8–97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9–89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1–79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52–0.63) before training and 0.68 (95% CI: 0.62–0.74) after training, with a difference of 0.11 (95% CI: 0.02–0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69–0.74) before training and 0.79 (95% CI: 0.76–0.80) after training (P = 0.002). Conclusion Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

Purpose: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. Results: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. Conclusion This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Purpose: Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. Materials and Methods: We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. Results: Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. Conclusion Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.