Nuclear grade and comedo necrosis of ductal carcinoma in situ as histopathological eligible criteria for the Japan Clinical Oncology Group 1505 trial: an interobserver agreement study.

OBJECTIVE: The Japan Clinical Oncology Group 1505 trial is a single-arm multicentre prospective study that examined the possibility of non-surgical follow-up with endocrine therapy for patients with low-grade ductal carcinoma in situ. In that study, the eligible criteria included histopathological findings comprising low to intermediate nuclear grade and absence of comedo necrosis, and cases were entered according to the local histopathological diagnosis. Nuclear grade is largely based on the Consensus Conference criteria (1997), whereas comedo necrosis is judged according to the Rosen's criteria (2017). The purpose of this study was to standardize and examine the interobserver agreement levels of these histopathological criteria amongst the participating pathologists. METHODS: We held slide conferences, where photomicrographs of haematoxylin-eosin-stained slides from 68 patients with ductal carcinoma in situ were presented using PowerPoint. The nuclear grade and comedo necrosis statuses individually judged by the pathologists were analysed using κ statistics. RESULTS: In the first and second sessions, where 22 cases each were presented, the interobserver agreement levels of nuclear grade whether low/intermediate grade or high grade were moderate amongst 29 and 24 participating pathologists, respectively (κ = 0.595 and 0.519, respectively). In the third session where 24 cases were presented, interobserver agreement levels of comedo necrosis or non-comedo necrosis were substantial amongst 25 participating pathologists (κ = 0.753). CONCLUSION: Although the concordance rates in nuclear grade or comedo necrosis were not high in a few of the cases, we believe that these results could provide a rationale for employing the present criteria of nuclear grade and comedo necrosis in the clinical study of ductal carcinoma in situ.

Tubular Carcinoma of the Breast: The Possibility to Omit Sentinel Lymph Node Biopsy.

Background/Aim: Tubular breast carcinoma, classified as a special type of invasive cancer, has a good prognosis. This study aimed to retrospectively investigate the clinical and pathological characteristics of 32 tubular carcinoma cases enrolled at our institution, with a focus on exploring the potential for treatment de-escalation. Patients and Methods: The study included all patients diagnosed with tubular breast carcinoma at our hospital between January 2005 and December 2021. In addition, 549 patients with ductal carcinoma in situ (DCIS) and 1,524 patients with stage I and II invasive cancers [not otherwise specified (NOS)] were selected for comparison. Results: All participants were female, with an average age of 54.4 years. The median follow-up duration was 64 months. The median tumor diameter was 7 mm, and all cases were Luminal A type. Moreover, no lymph vascular invasion was observed in any case, and no local recurrence, distant metastasis, or death occurred. The sentinel lymph node positive rate was 0% in the tubular carcinoma group, significantly lower than that in the NOS group (25.5%, p=0.0019) and not significantly different from that in the DCIS group (0.2%). The tubular carcinoma group tended to have better overall survival (OS) and disease-free survival (DFS) than the NOS group. Furthermore, the tubular carcinoma group was not inferior in OS and DFS compared to the DCIS group. Conclusion: Lymph node metastasis rate, OS, and DFS of the tubular carcinoma group are comparable to those of the DCIS group. Sentinel lymph node biopsy for tubular carcinoma can be omitted with an accurate preoperative diagnosis.

[Leakage from the connecting portion between the anesthesia machine and vaporizer].

We recently encountered three cases of the leakage from the connecting portion of sevoflurane vaporizer in Fabius Tiro produced by Drager company, and in one case of those, oxygen saturation decreased. The connecting portion had leakage merely in the contact with the fixture of the monitor, because of the structure easily displaced by an external force. Further, it was difficult to detect the leakage due to the ability to correct the insufficient supply of fresh gas by taking in air. We hope a reform of the connecting portion and an alarm to inform it if the anesthesia machine detects the leakage.

Comparison of postoperative analgesic effects of thoracic epidural analgesia and rectus sheath block in laparoscopic abdominal surgery: A randomized controlled noninferiority trial.

INTRODUCTION: In the Enhanced Recovery After Surgery program, abdominal wall blocks are strongly recommended as postoperative multimodal analgesia for laparoscopic abdominal surgery. The purpose of this study was to compare the efficacy of single-shot rectus sheath block (RSB) with that of thoracic epidural analgesia (TEA) as a method of multimodal analgesia in patients receiving conventional laparoscopic abdominal surgery. METHODS: A noninferiority comparison was performed. Patients scheduled for laparoscopic gastric or colorectal surgery were enrolled in this study. Patients were divided randomly into two groups: TEA and RSB. The primary endpoint was the numerical rating scale (NRS) score upon coughing as of 24 hours after surgery. RESULTS: In total, 80 patients were randomly assigned to receive TEA (n = 42) or RSB (n = 38). Three patients were excluded from the TEA group after randomization. The NRS score on coughing as of 24 hours after surgery was significantly lower in the TEA group than in the RSB group (least square mean: 3.59 vs 6.39; 95% confidence interval for the difference: 1.87 to 3.74, P < .001). The NRS scores upon coughing and at rest were significantly lower in the TEA group than in the RSB group as of 4, 24 and 48 hours after surgery. Patient satisfaction with postoperative analgesia was significantly higher in the TEA group. Postoperative adverse events were not significantly different between groups. CONCLUSION: This is the first report of comparing RSB with TEA in laparoscopic surgery. TEA may be recommended as a multimodal analgesia protocol for laparoscopic gastric and colorectal surgery.

Reevaluation of serum p53 antibody as a tumor marker in colorectal cancer patients.

PURPOSE: We reevaluated the serum p53 antibody (S-p53Ab) ELISA kit, which was approved as a tumor marker of colon cancer in the Japanese Health Insurance System in 2007. METHODS: S-p53Ab was measured as a tumor marker in 154 colorectal cancer patients, and the results were categorized by clinical and pathological variables. We then compared the positive frequency of S-p53Ab, carcinoembryonic antigen (CEA), and carbohydrate 19-9 (CA19-9). RESULTS: S-p53Ab was positive in 33.1% of the colorectal cancer patients. The positive rate was significantly higher in patients with lymph nodes metastasis (P = 0.025) and lymphatic invasion (P = 0.023). In patients with stage I colorectal cancer, the positive rate of S-p53Ab (23.7%) was significantly higher than that of CEA (5.3%) or CA19-9 (7.9%). CONCLUSION: The approved kit for S-p53Ab testing was found to be an effective tumor marker of colorectal cancer. The positive rate of S-p53Ab was significantly higher in patients with cancer involvement of the lymphoid tissues. The positive rate of S-p53Ab was higher than that of CEA and CA19-9 in patients with stage I colorectal cancer, suggesting that the S-p53Ab is a useful tumor marker for patients with early-stage disease.

An optimal epidural catheter placement site for post-cesarean section analgesia with double-space technique combined spinal-epidural anesthesia: a retrospective study.

BACKGROUND: Epidural anesthesia affects lower extremities, which often prevents early mobilization postoperatively. The incidence of numbness and motor weakness in the lower extremities with respect to epidural catheter placement site in cesarean section (CS) is uncertain. We aimed to investigate the effect of catheter placement site on postoperative lower extremities numbness and motor weakness in patients who received combined spinal-epidural anesthesia (CSEA) for CS including analgesic effects and optimal epidural placement site in CS. METHODS: We retrospectively included 205 patients who underwent CS with CSEA at the University of Tsukuba Hospital between April 2018 and March 2020, and assessed numbness and motor weakness in the lower extremities. We also examined whether differences in the intervertebral space of epidural catheter placement and epidural effect on the lower extremities are related to analgesic effects. ANOVA and Mann-Whitney U test were used for statistical analysis. RESULTS: The incidence of numbness and motor weakness were 67 (33%) and 28 (14%), respectively. All patients with motor weakness had numbness. A more caudal placement was associated with increased incidence of affected lower extremities. There was no significant difference in the analgesic effect depending on the catheter placement site. When the lower extremities were affected, the number of additional analgesics increased (p < 0.001). Patient-controlled epidural analgesia was used for fewer days in patients with motor weakness (p = 0.046). CONCLUSION: In CS, epidural catheter placement at T10-11 or T11-12 interspace is expected to reduce effect on the lower extremities and improve quality of postoperative analgesia.

Patient-controlled epidural analgesia, patient-controlled intravenous analgesia, and conventional intravenous opioids for gynecologic interstitial brachytherapy: A single-center retrospective study.

PURPOSE Interstitial brachytherapy for gynecologic malignancies is stressful physically and mentally; however, optimal analgesic methods remain unclear. We investigated the effect of analgesic methods on pain and adverse events during interstitial brachytherapy for gynecologic malignancies. METHODS The data of 73 patients who underwent interstitial brachytherapy for gynecologic malignancies between April 2015 and March 2020 were retrospectively analyzed. Patient-controlled epidural analgesia (PCEA), patient-controlled intravenous analgesia (PCIA), and conventional intravenous opioid administration were used for analgesia during treatment. We compared the analgesic effects based on a numerical rating scale (NRS), the number of additional analgesics, and the adverse events associated with analgesia. The NRS score was calculated as an average value for every 12 h (NRS1: treatment on the 1st day from 12 to 24 o'clock; NRS2: treatment on the 2nd day from 0 to 12 o'clock; NRS3: treatment on the 2nd day from 12 to 24 o'clock). The mean NRS score differences between the methods were evaluated using mixed models for repeated-measures analyses. RESULTS The NRS score was significantly lower at all times for PCEA (NRS1: p = 0.003; NRS2: p = 0.011; NRS3: p < 0.001). NRS2 and NRS3 were significantly lower for PCIA (NRS2: p = 0.043; NRS3: p < 0.001) than for the conventional method. The NRS scores for PCEA and PCIA were not significantly different. Moreover, additional analgesics and adverse events did not differ between the three treatments. CONCLUSION PCEA and PCIA were superior to conventional intravenous opioids for analgesia in interstitial brachytherapy for gynecologic malignancies. However, adverse events associated with PCEA and PCIA were not reduced.

Sudden cardiac death due to ventricular fibrillation in a case of giant cell myocarditis.

A 70-year-old woman was admitted to our hospital complaining of shortness of breath. She was diagnosed with acute decompensated heart failure due to left ventricular dysfunction. Her symptoms began to improve with standard therapy for heart failure with diuretics, noninvasive pressure ventilation, and inotropes, but paroxysmal atrial fibrillation and premature ventricular contractions (PVCs) occurred. After treatment with amiodarone, the number of PVCs decreased, and the left ventricular wall motion gradually improved. However, on day 28, ventricular fibrillation and cardiopulmonary arrest occurred suddenly, and she could not be resuscitated. She was diagnosed with giant cell myocarditis via an autopsy. The autopsy revealed diffuse inflammatory cells that comprised giant cells and eosinophils as well as cellular degeneration and necrosis. .

Primary Intraosseous Squamous Cell Carcinoma Arising from a Dentigerous Cyst of the Maxillary Wisdom Tooth.

The World Health Organization defines primary intraosseous squamous cell carcinoma (PIOSCC) as a squamous cell carcinoma (SCC) arising primarily within the jaws and having no connection with the oral mucosa. Here, we report a case of PIOSCC in which it was difficult to differentiate the condition from pericoronitis of an impacted maxillary wisdom tooth. The patient was a 27-year-old pregnant woman with a pain in the right maxillary wisdom tooth. The pain was diagnosed as pericoronitis of the right maxillary wisdom tooth, and the tooth was extracted under local anesthesia. During extraction, soft tissue was observed in the coronal part of the tooth, and it was diagnosed as SCC arising in a dentigerous cyst. Because the tumor may still be present, surgical resection was performed under general anesthesia. There has been no recurrence or metastasis at the 1-year follow-up. This case was histopathologically considered from being a benign odontogenic tumor to a malignant tumor. However, it revealed an extensive aberrant type and invasion equivalent to SCC. Thus, the histopathological diagnosis was PIOSCC arising from a dentigerous cyst. Although advanced cases of PIOSCC have been published, diagnosis of PIOSCC in the early stages is rare. In this case, we diagnosed pericoronitis of an impacted maxillary wisdom tooth and extracted the tooth. Therefore, we discovered it accidentally. In the early stages, diagnosis can be difficult both clinically and histopathologically.

Clinical significance of evaluating hormone receptor and HER2 protein using cell block against metastatic breast cancer: a multi-institutional study.

Hormone receptor and human epidermal growth factor receptor 2 (HER2) protein tests in metastatic breast cancer tissue are recommended in the guidelines of the American Society of Clinical Oncology/American Pathology Association. As part of a multi-institutional study by the National Hospital Organization, we conducted an investigation to examine these molecular markers, using cytological specimens as a substitute for tissue specimens from breast cancer metastasis. To confirm the usefulness of receptors tested in metastatic lesions, the treatment course of registered metastatic breast cancer patients was analyzed. During the April 2015 to March 2016 registration period, there were 62 registrations. Types of metastatic lesions include pleural fluid (44 samples), ascites (14 samples), lymph nodes (2 samples), pericardial fluid (1 sample), and dorsal subcutaneous mass (1 sample). A stable test result was obtained by adopting the receptor examination method, using cell block for immunostaining cytological specimens. The discordance rates of estrogen receptor (ER), progesterone receptor (PR), and HER2 protein expression were 18.2% (95% confidence interval (CI): 7.9-28.8%), 36.4% (95% CI: 23.7-49.1%), and 8.2% (95% CI: 0.1-16.3%), respectively, between the primary tumor and metastatic lesion. Patients who changed from primary negative to metastatic positive ER status had taken a significantly longer time for metastatic foci to appear. Patients with positive ER status in metastatic lesions had significantly better prognosis than ER-negative cases (P = 0.030) by the Log-Rank test. The ER status of the metastatic lesion and the metastatic site were independent prognostic factors by Cox multivariate analysis. Receptor examination with cytological specimens in metastatic lesions has been useful as it provides guidance for the treatment of metastatic breast cancer.

A sensitive calorimetric technique to study energy (heat) exchange at the nano-scale.

Every time a chemical reaction occurs, an energy exchange between reactants and the environment takes place, which is defined as the enthalpy of the reaction. During the last few decades, research has resulted in an increasing number of devices at the micro- or nano-scale. Sensors, catalyzers, and energy storage systems are more and more developed as nano-devices which represent the building blocks for commercial "macroscopic" objects. A general method for the direct evaluation of the energy balance of such systems is not available at present. Calorimetry is a powerful tool to investigate energy exchange, but it usually requires macroscopic sample quantities. Here, we report on the development of an original experimental setup able to detect temperature variations as low as 10 mK in a sample of ∼10 ng using a thermometer device having physical dimensions of 5 × 5 mm2. This technique has been utilized to measure the enthalpy release during the adsorption process of H2 on titanium-decorated monolayer graphene. The sensitivity of these thermometers is high enough to detect a hydrogen uptake of ∼10-10 moles, corresponding to ∼0.2 ng, with an enthalpy release of about 23 µJ. The experimental setup allows, in perspective, scalability to even smaller sizes.

Evaluation of the HER2 and Hormone Receptor Status in Metastatic Breast Cancer Using Cell Blocks: A Multi-Institutional Study.

OBJECTIVE: We explore the problems associated with the cell block (CB) method for receptor analysis in breast cancer metastases and propose a method for reporting the results. STUDY DESIGN: Nine institutions used the CB method for the analysis of hormone receptors (HRs) and HER2 (human epidermal growth factor receptor 2) protein in cytological specimens of breast cancer metastases in routine practice. The stained slides were independently evaluated by 8 pathologists. Dual in situ hybridization assay was performed in cases of discordant results for HER2 protein. Based on the results, we propose a method for receptor scoring in the CB method. RESULTS: Of 61 specimens, 57 contained tumor cells. Two or more pathologists disagreed on the results for the estrogen receptor, progesterone receptor, and HER2 protein in 3 (5.3%), 13 (22.8%), and 19 (33.3%) cases, respectively. The discrepant results for the HRs were attributed to the presence of a few positive cells or faintly stained cells. The high interobserver discordance rate for HER2 protein was explained by interobserver differences in the scoring criteria. CONCLUSION: The use of categorical scoring into positive and negative is recommended for evaluating the HR expressions. Use of strict criteria for HER2 protein 2+ and 3+ cases is recommended, as HER2-positive cases should not be missed.

Clinical predictors of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer.

The response of triple-negative breast cancer (TNBC) to chemotherapy is heterogeneous; particular subtype classifications based on mRNA gene expression analysis have been demonstrated to be associated with a pathological complete response (pCR). The aim of the present study was to investigate additional clinical and pathological characteristics associated with pCR status. The pathological and clinical characteristics of 40 TNBC patients who underwent neoadjuvant chemotherapy followed by surgery were retrospectively analyzed by dividing the cases into two groups according to the response to treatment: pCR (n=12) and non-pCR (n=28). Clinically, patients in the pCR group presented tumors with a significantly less advanced Tumor-Node-Metastasis stage (P=0.030) and mammographic calcification was less common (17 vs. 58%; P=0.034). Pathologically, whereas all cases in the pCR group (12/12, 100%) were of the histological type 'invasive ductal carcinoma, not otherwise specified' (IDC-NOS), the non-pCR group consisted of a lower proportion of IDC-NOS cases (20/28, 71%) and more cases of special histological types, including mucinous, metaplastic, medullary and apocrine carcinomas (P=0.079). The positive rates of androgen receptor (AR) and forkhead-box A1 (FOXA1) tended to be lower in the pCR group (AR, 0 vs. 29%, P=0.079; FOXA1, 8 vs. 29%, P=0.233). The Ki-67 score was significantly higher in the pCR group than in the non-pCR group (P=0.041). The results suggest that patients with TNBC who present with clinically less advanced tumors and less frequent mammographic calcification are more likely to respond to chemotherapy. From a pathological standpoint, IDC-NOS type, negative AR status and higher Ki-67 scores may be associated with chemotherapy sensitivity.

Evaluation of Efficacy and Safety of Upfront Weekly Nanoparticle Albumin-bound Paclitaxel for HER2-negative Breast Cancer.

BACKGROUND: Taxanes are among the key drugs for breast cancer treatment. This study aimed to evaluate the efficacy of upfront weekly nanoparticle albumin-bound paclitaxel (Nab-PTX; 100 mg/m2) for human epidermal growth factor 2 (HER2)-negative breast cancer. PATIENTS AND METHODS: Patients with stage II to IV breast cancer received 12 cycles of weekly 100 mg/m2 Nab-PTX as first-line treatment. Preoperative chemotherapy with anthracyclines after Nab-PTX was recommended. RESULTS: From 2012 to 2014, we enrolled 66 patients. The overall response rate after Nab-PTX was 59.1% [95% confidence interval(CI)=47.2% to 71.0%), 63.6% in those with hormone receptor-positive tumors, and 36.4% in those with triple-negative tumors. The pathological complete response rate at surgery was 15% (95% CI=6.1% to 24.4%). Toxicity analysis showed grade 2 peripheral neuropathy in 38 patients (57.6%), grade 2/3 leukocytopenia in 29 (43.9%) and grade 2/3 liver dysfunction in five (7.5%). CONCLUSION: Weekly neoadjuvant Nab-PTX at 100 mg/m2 led to good response rates (59.1%) and was well tolerated.

Intimal Sarcoma of the Pulmonary Artery Treated with Pazopanib.

Intimal sarcoma is a rare disease with a poor prognosis. We herein report the case of a 71-year-old man with intimal sarcoma of the pulmonary artery treated with pazopanib. The tumor showed regression after 1 month of treatment. Hand-foot syndrome led to cessation of pazopanib, which triggered a disease flare. Pazopanib should be considered in patients with intimal sarcoma of the pulmonary artery that is unresectable or recurrent after surgery or cytotoxic chemotherapy. We must be careful about drug cessation, as it can lead to a disease flare.

A subserosal uterus-like mass presenting after a sliding hernia of the ovary and endometriosis: a rare entity with a discussion of the histogenesis.

OBJECTIVE: To report the first case of a subserosal uterus-like mass. DESIGN: Case report. SETTING: A community-based hospital. PATIENT(S): A 44-year-old nulliparous woman who complained of a left inguinal mass had a medical history that was notable for two features. One was left oophorectomy for a sliding hernia at 10 months of age; the other was endometriosis at the oophorectomy site at 26 years of age. INTERVENTION(S): Tumorectomy. MAIN OUTCOME MEASURE(S): Not applicable. RESULT(S): Pathologic examination demonstrated that this subserosal mass mimicked a miniature uterus with a leiomyomatous lesion. CONCLUSION(S): As of September 2010, 23 cases of uterus-like mass had been reported. Three pathologic theories of uterus-like mass have been proposed: [1] congenital anomaly theory, [2] metaplasia theory, and [3] heterotopia. The pathogenesis of this rare entity is currently under debate. Most uterus-like masses have been connected to the genital organs (75.0%) and associated with endometriosis (50.0%). In the present case, the uterus-like mass developed at the surgical scar site of oophorectomy for a sliding hernia and a tumorectomy for endometriosis. We review the literature and discuss the theories regarding the histogenesis of uterus-like mass.

Conjugated carbon monolayer membranes: methods for synthesis and integration.

Monolayer membranes of conjugated carbon represent a class of nanomaterial with demonstrated uses in various areas of electronics, ranging from transparent, flexible, and stretchable thin film conductors, to semiconducting materials in moderate and high-performance field-effect transistors. Although graphene represents the most prominent example, many other more structurally and chemically diverse systems are also of interest. This article provides a review of demonstrated synthetic and integration strategies, and speculates on future directions for the field.

Moiré superstructures of graphene on faceted nickel islands.

Using scanning tunneling microscopy and spectroscopy, in combination with density functional theory calculations, we investigated the morphology and electronic structure of monolayer graphene grown on the (111) and (110) facets of three-dimensional nickel islands on highly oriented pyrolytic graphite substrate. We observed graphene domains exhibiting hexagonal and striped moiré patterns with periodicities of 22 and 12 Å, respectively, on (111) and (110) facets of the Ni islands. Graphene domains are also observed to grow, as single crystals, across adjacent facets and over facet boundaries. Scanning tunneling spectroscopy data indicate that the graphene layers are metallic on both Ni(111) and Ni(110), in agreement with the calculations. We attribute this behavior to a strong hybridization between the d-bands on Ni and the π-bands of carbon. Our findings point to the possibility of preparing large-area epitaxial graphene layers even on polycrystalline Ni substrates.