Selpercatinib for treating recurrent mixed medullary and follicular cell-derived thyroid carcinoma: a case report.

BACKGROUND: Mixed medullary and follicular cell-derived thyroid carcinoma (MMFCC) is characterized by the coexistence of follicular and C cell-derived tumour cell populations within the same lesion. Due to its rarity, its etiology and clinical course remain unclear, and treatment for advanced or recurrent cases has not been established. CASE PRESENTATION: We report a case of MMFCC treated with selpercatinib. The patient was a 69-year-old male presenting with tumors in the right thyroid lobe and in the upper mediastinum. Fine-needle aspiration (FNA) cytology of the right thyroid lobe tumor revealed a medullary carcinoma; germline RET mutations were not detected. After resection of the right thyroid lobe with central node dissection, rapid intraoperative diagnosis of the mediastinal mass confirmed malignancy, leading to total thyroidectomy with excision of the upper mediastinal tumor. Histologically, the tumor in the right thyroid lobe and the pretracheal lymph node revealed a mixture of medullary and follicular carcinoma components, diagnosed as MMFCC. The mediastinal lymph node exhibited only medullary carcinoma components. At 11 months postoperatively, computed tomography scans showed enlargement of the right supraclavicular and upper mediastinal lymph nodes. FNA cytology of the right supraclavicular lymph node suggested the recurrence of medullary thyroid carcinoma. The gene panel testing (The Oncomine Dx Target Test Multi-CDx system®, Thermo Fisher SCIENTIFIC) of metastatic lymph node revealed RET somatic mutation (M918T). Treatment with selpercatinib was initiated, and both the cervical and mediastinal lymph nodes showed a reduction in size. CONCLUSIONS: We report a rare case of selpercatinib use for MMFCC. Since RET mutations may occur frequently in MMFCC, selpercatinib could be effective in treating MMFCC.

Gel immersion EMR of small-bowel inflammatory fibroid polyp using double-balloon endoscopy.

Video 1A case of an inflammatory fibroid polyp of the ileum that was safely resected using gel immersion EMR with double-balloon endoscopy.

Long-term outcomes of patients with obscure gastrointestinal bleeding after negative capsule endoscopy.

BACKGROUND AND AIM: Although small-bowel capsule endoscopy (CE) is widely used for obscure gastrointestinal bleeding (OGIB), long-term outcomes for OGIB patients after negative CE remain unclear. Herein, we defined negative CE as P0 (no bleeding potential) or P1 (less likely to bleed), based on the P classification using CE. We aimed to clarify long-term outcomes of patients with OGIB after negative CE. METHODS: This single-center observational study enrolled 461 consecutive patients with OGIB who underwent CE from March 2014 to October 2021 and were followed up for >1 year. We examined rebleeding rates and predictive factors. RESULTS: Two hundred and twenty-four (49%) patients had P0, and 237 (51%) had P1 findings. Rebleeding occurred in 9% and 16% of patients in the P0 and P1 groups, respectively. Two patients in the P0 group and 15 in the P1 group showed rebleeding from the small bowel. The rate of small-bowel rebleeding was significantly lower in the P0 group than that in the P1 group (1% vs 6%, P = 0.002), as was the cumulative rebleeding rate (P = 0.004). In the multivariate analysis, history of endoscopic hemostasis (hazard ratio [HR] = 15.958, 95% confidence interval [CI]:4.950-51.447, P < 0.001) and P1 CE findings (HR = 9.989, 95% CI: 2.077-48.030, P = 0.004) were independently predicted small-bowel rebleeding. CONCLUSIONS: OGIB with P0 CE findings rarely showed rebleeding from the small bowel. Rebleeding may occur in patients with OGIB. Patients with history of endoscopic hemostasis for small-bowel lesions or P1 CE findings should be followed up intensively.

Disease surveillance evaluation of primary small-bowel follicular lymphoma using capsule endoscopy images based on a deep convolutional neural network (with video).

BACKGROUND AND AIMS: Capsule endoscopy (CE) is useful in evaluating disease surveillance for primary small-bowel follicular lymphoma (FL), but some cases are difficult to evaluate objectively. This study evaluated the usefulness of a deep convolutional neural network (CNN) system using CE images for disease surveillance of primary small-bowel FL. METHODS: We enrolled 26 consecutive patients with primary small-bowel FL diagnosed between January 2011 and January 2021 who underwent CE before and after a watch-and-wait strategy or chemotherapy. Disease surveillance by the CNN system was evaluated by the percentage of FL-detected images among all CE images of the small-bowel mucosa. RESULTS: Eighteen cases (69%) were managed with a watch-and-wait approach, and 8 cases (31%) were treated with chemotherapy. Among the 18 cases managed with the watch-and-wait approach, the outcome of lesion evaluation by the CNN system was almost the same in 13 cases (72%), aggravation in 4 (22%), and improvement in 1 (6%). Among the 8 cases treated with chemotherapy, the outcome of lesion evaluation by the CNN system was improvement in 5 cases (63%), almost the same in 2 (25%), and aggravation in 1 (12%). The physician and CNN system reported similar results regarding disease surveillance evaluation in 23 of 26 cases (88%), whereas a discrepancy between the 2 was found in the remaining 3 cases (12%), attributed to poor small-bowel cleansing level. CONCLUSIONS: Disease surveillance evaluation of primary small-bowel FL using CE images by the developed CNN system was useful under the condition of excellent small-bowel cleansing level.

Clinical Significance of Cancer Stem Cell Markers in Primary and Metastatic Tissues in Patients With Breast Cancer.

BACKGROUND/AIM: This study aimed to examine the clinical significance of the protein expression of the cancer stem cell (CSC) markers ALDH1A1, CD133, CD44, and MSI-1 in primary and metastatic tissues of patients with breast cancer (BC). PATIENTS AND METHODS: ALDH1A1, CD133, CD44, and MSI-1 protein expression in pairs of primary and metastatic tissues of 55 patients with BC with metastases treated at Kanagawa Cancer Center between January 1970 and December 2016 were evaluated using immunohistochemical assay and their association with clinicopathological factors and survival was examined. RESULTS: There were no significant differences in CSC marker expression rates between primary and metastatic tissues for any CSC markers. Regarding the relationship between CSC marker expression in primary tissues and survival, patients with high CD133 expression had significantly lower recurrence-free survival (DFS) and overall survival. On multivariate analysis, they were also a poor independent predictor of DFS (hazard ratio=4.993, 95%CI=2.189-11.394, p=0.0001). In contrast, there was no significant association between the expression of any CSC marker in metastatic tissues and survival. CONCLUSION: CD133 expression in the primary BC tissue may be a useful risk factor for recurrence in patients with BC.

Efficacy of Clinical Guidelines in Identifying All Japanese Patients with Hereditary Breast and Ovarian Cancer.

Clinical screening using the National Comprehensive Cancer Network (NCCN) testing criteria may fail to identify all patients with hereditary breast and ovarian cancers. Thus, this study aimed to evaluate the strategy of expanding target patients for genetic testing among Japanese patients. We reviewed the medical records of 91 breast cancer patients who underwent genetic testing. Among 91 patients, eight were diagnosed with pathogenic or likely pathogenic variants: BRCA1 (n = 4) and BRCA2 (n = 4). Among 50 patients meeting the testing criteria of the guidelines, 6 (12%) were diagnosed with pathogenic or likely pathogenic variants. The sensitivity and specificity of screening using the testing criteria were 75% and 47%, respectively. Expanding the NCCN criteria to include all women diagnosed with breast cancer aged ≤65 years achieved 88% sensitivity but 8% specificity. The expansion of the NCCN criteria could benefit Japanese patients; however, larger studies are necessary to change clinical practice.

Quality Control of Breast Cancer Surgery Samples: Introducing Time Stamp Checking.

Background: Analytical information obtained from clinical tissue samples has recently become more important due to recent advancements in the clinical practice of medicine, for example, gene panel testing. However, acquiring and managing the sample quality, which greatly influences the analyses, are not sufficient and hence requires immediate attention. We introduced time stamp (TS) recording and documentation using the Standard PREanalytical Code (SPREC) for breast cancer surgery samples to monitor and control their quality. Materials and Methods: The TS recording used SPREC for quality control of each sample by recording seven factors: type of sample, type of collection, warm ischemia time (WIT), cold ischemia time (CIT), fixation type, fixation time (FT), and long-term storage. The responsibilities to record each factor were assigned among group members (breast surgeons, anesthesiologists, pathologists, operating room nurses, and medical technologists in pathology). Results: Records based on SPREC were recorded for 393 surgical cases of first-time breast cancer patients performed at the Kanagawa Cancer Center from May 2018 to April 2019. The vascular clamp time was defined as when skin flap formation was completed, regardless of the surgical procedure. An anesthesiologist recorded the vascular clamp time and sample collection time, and the pathologist recorded the fixation start time and fixation end time. WIT was 23 (3-116) minutes (breast-conserving surgery, 11 [3-38] minutes; mastectomy, 26 [5-116] minutes; and nipple-sparing mastectomy, 39 [31-43] minutes), CIT was 37 (3-1052) minutes, and FT was 43 (17-115) hours. The median CIT and FT were significantly shortened after introducing the TS system, and the variabilities were reduced. Conclusion: A TS system for quality control of breast cancer surgical sample functions well due to the establishment of highly versatile WIT and a working group consisting of multiple members of different occupations who shared roles.

Ion-Transfer Voltammetry at Fluorous Ether | Water Interfaces.

This paper describes that fluorous ethers, 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether and 1H,1H,5H-octafluoropentyl-1,1,2,2-tetrafluoroethyl ether, can be used for a non-aqueous medium in electrochemistry at a liquid | liquid interface. These solvents dissolved a high concentration of tetraalkylammonium salts with highly-fluorinated anions, such as bis(nonafluorobutanesulfonyl)imide and tetrakis[3,5-bis(trifluoromethyl)phenyl]borate ions, and the solution had a high conductivity. The fluorous ether | water interfaces exhibited a substantial polarizable potential window, and various ions, including tetraphenylarsonium and tetraphenylborate ions, gave a reversible voltammetric wave due to their ion transfer across the interfaces. Using the tetraphenylarsonium-tetraphenylborate assumption, the formal potentials for the ion transfer and the formal Gibbs energies of ion transfer from the ethers to water were estimated. The Gibbs energies were close to those from a previously reported fluorous solvent, 1,1,1,2,3,4,4,5,5,5-decafluoropentane; the fluorous ethers also exhibited a higher affinity for fluorinated ions. Because of a lower volatility, the fluorous ethers would be more advantageously used in two-phase electrochemistry, particularly concerning analytical purposes.

EZH2 and MMSET Were Identified as Potentially Useful Therapeutic Targets in Metaplastic Breast Carcinoma.

BACKGROUND/AIM: Metaplastic breast carcinoma (MBC) is a rare malignancy, which is often triple-negative for the hormone receptors and human epidermal growth factor receptor 2, and thus, does not benefit from targeted therapy. In this study, we examined the expression of methylation and demethylation enzymes by immunostaining MBC and the adjacent normal tissues or triple-negative ductal carcinoma (TNDC), and identified alterations that may be used as therapeutic targets. MATERIALS AND METHODS: We retrospectively studied surgical specimens from 15 patients who underwent surgery for MBC at Kanagawa Cancer Center between 2005 and 2016, and similarly from 14 patients with TNDC. The frequencies of high methylation/demethylation enzyme expression were compared among them. RESULTS: The frequencies of high enhancer of zeste homolog 2 (EZH2) and multiple myeloma SET domain (MMSET) expression were significantly higher in both MBC and TNDC than in normal tissue. CONCLUSION: EZH2 and MMSET may be useful therapeutic targets in MBC.

Effects of sleep-disordered breathing and hypertension on cognitive function in elderly adults.

Purpose: The prevalence of sleep-disordered breathing (SDB) increases with aging. SDB is a risk of hypertension, and both might lead to cognitive decline. However, the role of SDB and hypertension on the pathogenesis of age-related cognitive decline remains unclear. We examined the effects of these two diseases on cognitive function in elderly adults.Methods: Fifty-two elderly individuals (mean age, 69.6 ± 4.0 years) free from impairment in daily living activities participated in this study. Apnea/hypopnea index (AHI) and minimum oxygen saturation (SpO2) were assessed using a portable home monitoring device. We evaluated excessive daytime sleepiness with the Epworth sleepiness scale (ESS). Cognitive performance was assessed using the Wisconsin card sorting test (WCST), continuous performance test-Identical pairs (CPT-IP), and N-back task. Hypertension and diabetes mellitus were evaluated via questionnaire and blood pressure value.Results: The WCST category achievement was significantly lower in participants with minimum SpO2 <90% than those with minimum SpO2 ≥90%. The percentage of correct answer on the 0- and 1-back tasks was significantly lower in the hypertensives than normotensives. Minimum SpO2 was correlated with category achievement on the WCST. Multiple regression analysis including age, sex, body mass index, AHI, minimum SpO2, ESS, hypertension, and diabetes mellitus revealed that hypertension was the most significant factor for percentage correct answers on the 0- and 1-back tasks. There were no significant correlations between body mass index, ESS or diabetes mellitus and the parameters of WCST, CPT-IP, or N-back tasks.Conclusion: In elderly adults, nocturnal hypoxia and hypertension had a negative effect on cognitive function.

Clinical and pathological predictors of recurrence in breast cancer patients achieving pathological complete response to neoadjuvant chemotherapy.

INTRODUCTION: Despite the excellent prognosis associated with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), some patients still develop recurrence. Here, we investigated the outcomes of breast cancer patients with pCR, as well as the clinical and pathological predictors of cancer recurrence in these patients. MATERIALS AND METHODS: Of the 1599 breast cancer patients treated with NAC, we evaluated 394 patients who achieved pCR between January 2007 and December 2016. pCR was defined as no evidence of invasive cancer in breast. Residual in situ ductal and axillary lymph node diseases were not considered. We analyzed the outcomes using the Kaplan-Meier method. We assessed the association of clinical and pathological predictors with cancer recurrence using the cox proportional hazards regression model. RESULTS: The median follow-up time was 63 months. The 5-year disease-free survival rate was 92.3%. Cancer recurrence was observed in 28 patients (7.1%): local recurrence 8 patients (2.0%), visceral metastasis 10 patients (2.5%), and brain metastasis 10 patients (2.5%). Brain metastases were found in patients with HER2 type breast cancer. The significant predictors of cancer recurrence were HER2 positivity (p = 0.04), clinical tumor size (p < 0.01), and lymph node metastasis (p < 0.01) before NAC on univariate analysis and only lymph node metastasis on multivariate analysis. CONCLUSION: Patients achieving pCR to NAC showed excellent outcomes. Advanced clinical stage, large tumor size, presence of lymph node metastasis, and HER2 positivity before NAC were identified as significant predictors of cancer recurrence. Residual in situ ductal and lymph node diseases after NAC were not significant predictors.

Nephrectomy for Metastatic Kidney Tumor in Patients with Differentiated Thyroid Cancer: A Report of Two Cases.

The occurrence of renal tumors originating from thyroid cancer is extremely rare with a few effective treatments for renal metastases. Here, we report the cases of two patients with differentiated thyroid cancer who underwent nephrectomy for a metastatic kidney tumor. Case 1 was a 74-year-old man who was diagnosed with right kidney tumor 10 years after initial surgery for papillary thyroid cancer (PTC). Right nephrectomy was performed, and the pathology was metastatic PTC. Case 2 was a 68-year-old woman who was diagnosed with left kidney tumor 24 years after surgery for follicular thyroid carcinoma (FTC). Left nephrectomy was performed, and the pathology was metastatic FTC. Nephrectomy for single renal metastasis could be considered a treatment option if the patients' general condition is positive.

A case of synchronous multiple bilateral breast cancer after breast augmentation.

Breast cancer after breast augmentation is not rare, but cases of bilateral breast cancer after augmentation are not often reported. A 43-year-old woman attended our hospital because of a mass in her left breast. She had undergone breast augmentation by implants 4 years before at a cosmetic surgery clinic. There were operative scars in her bilateral axilla. A detailed examination revealed bilateral breast cancer, and we performed nipple-sparing mastectomy in both breasts. Sentinel lymph node biopsy using dye was performed and it identified stained lymph nodes on both sides. The sentinel lymph node biopsy was negative for metastasis on both sides, so axillary lymph node dissection was not performed.

Surgical intrauterine insemination with cat semen cryopreserved with Orvus ES paste or sodium lauryl sulfate.

The mean post-thaw sperm motilities of feline frozen semen prepared with 1% OEP or 3 g/ml SLS as a cryoprotective agent, in addition to 7% glycerin, were 35.0 ± 2.4 and 37.0 ± 2.5%, respectively, showing no significant difference. On unilateral intrauterine insemination (UIUI) using these semen samples at a sperm number of 40 × 10(6), the conception rate was 70.0% (7/10) in the OEP group and 30% (3/10) in the SLS group, showing that the rate was higher in the OEP group, but the difference was not significant. It was suggested that sperm in frozen semen showing the above qualities were transferred to the contralateral uterine horn on UIUI.

Is the importance of achieving stable disease different between epidermal growth factor receptor tyrosine kinase inhibitors and cytotoxic agents in the second-line setting for advanced non-small cell lung cancer?

BACKGROUND: It is controversial whether achieving stable disease leads to a survival benefit and whether the importance of achieving stable disease differs between cytotoxic agents and molecular targeted agents. To examine these questions, the authors retrospectively reviewed phase II and III studies in the second-line setting for advanced non-small cell lung cancer using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic agents separately. METHODS: The authors chose 45 trials for the chemotherapy group and nine for the EGFR TKI group by searching the PubMed database. All nine trials in the EGFR TKI group concern gefitinib and erlotinib. RESULTS: The median survival time increased 0.0375 month with each 1% increase in stable disease rate (p = 0.039), and each 1% increase in response rate resulted in 0.0744 (p < 0.001) month of median survival time in the analysis combined with both cytotoxic agents and EGFR TKIs. Main and interaction terms for EGFR TKI treatment were not statistically significant. With respect to time to progression, only response rate showed a statistically significant relationship with survival. CONCLUSIONS: To obtain response seems to be more important than to achieve stable disease for both cytotoxic agents and EGFR TKIs, although achieving stable disease is still valuable. The relationship between survival and response or stable disease appears similar for cytotoxic agents and EGFR TKIs.