The Showa University Journal of Medical Sciences

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34 巻 (2022) 3 号 p. 125-132
A comparison of tumor size with ultrasonography and magnetic resonance imaging and histopathology based on ductal carcinoma in situ subtype
Akiko Matsutani, Kanae Taruno, Sadako Akashi-Tanaka, Ayuha Yoshizawa, Aya Nagata, Toshiko Yamochi, Masafumi Takimoto, Eisuke Inoue, Seigo Nakamura

The precise measurement and detection of a tumor is indispensable in establishing the regular use of minimally invasive procedures for breast cancer treatment. We, herein, focused on ultrasonography （US） and magnetic resonance imaging （MRI）, and evaluated their effectiveness in measuring the tumor size of ductal carcinoma in situ （DCIS）. Furthermore, we assessed the DCIS subtype and its relationship with the accuracy of the imaging modalities and some critical histopathological characteristics. A total of 102 DCIS cases （that were diagnosed from 2018 to 2021） were retrospectively analyzed. The tumor sizes measured by US and MRI were compared with those obtained by the postoperative histological examination of the tumors. The DCIS subtypes were classified based on the nuclear grade and immunohistochemical （IHC） pattern; namely, estrogen/progesterone receptor expressing status, human epidermal growth factor receptor 2 （HER2） expressing status, and Ki-67 index. Tumors classified as HER2-enriched DCIS exhibited a high nuclear grade and a high Ki-67 index （Ki-67＞20％） when compared with the luminal DCIS tumors （p＜0.05）. The tumor size measured by US was smaller than the actual tumor size in all DCIS subtypes, while MRI systematically overestimated the tumor size with the exception of the triple-negative DCIS. The median tumor size differences identified between MRI and histopathology were smaller than those identified between US and histopathology, especially in HER2-enriched DCIS cases （p＝0.01）. The HER2-enriched DCIS tumors were more accurately measured by MRI than by US. MRI could measure the DCIS tumor size more accurately than US, especially in HER2-enriched DCIS cases （p＝0.01）. These results might be particularly useful in developing a more tailored DCIS management strategy.
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34 巻 (2022) 2 号 p. 102-110
Methemoglobin concentration for the distinction between antemortem thrombus and postmortem coagulation
Mari Hashimoto, Masaya Fujishiro, Akihiro Nakauchi, Hiromoto Sone, Sawa Minohara, Ng Ming Jui, Yuichiro Tachi, Keizo Sato, Toshiko Onizuka-Yamochi, Taka-aki Matsuyama

Although identifying antemortem pathological thrombi in autopsies is vital in assessing the cause of death, distinguishing them from simple blood clot masses only based on macroscopic appearance is sometimes challenging. This study examined the utility of increased methemoglobin concentrations in identifying antemortem pathological thrombi. From 49 autopsy cases, 98 blood clot samples were collected from the arterial （aorta） or venous （vena cava and proximal pulmonary artery） circulation. The samples were divided into a pathological thrombus group and a simple coagulation group based on macroscopic appearances. Methemoglobin concentrations （MetHb） were determined using a spectrophotometer, while the cutoff value was calculated by plotting the receiver operating characteristic curve. MetHb levels were significantly higher in the pathological thrombus group than in the simple coagulation group in arterial and venous samples （arterial: 15.1％ vs. 6.3％, venous: 15.2％ vs. 5.9％, respectively; p＜0.05）. The cutoff value was 11.1％（area under the curve ［AUC］ 0.85） in arterial samples and 16.7％（AUC 0.75） in venous samples. We also analyzed corrected values by subtracting MetHb values of the reference blood. This corrected value was also significantly higher in the thrombus group than the simple coagulation group in both arterial and venous samples （arterial: 10.1％ vs. 1.5％, venous: 10.1％ vs. 1.3％, respectively; p＜0.05）. The cutoff values were 4.6％（AUC 0.87） in arterial samples and 3.7％（AUC 0.73） in venous samples. The MetHb concentration in blood clot masses of autopsied bodies can help differentiate between antemortem pathological thrombi and simple postmortem coagulation masses.
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34 巻 (2022) 2 号 p. 54-63
Predicting the course of hematopoietic neoplasm through oral bacterial examination
Kyoko Shirakura, Akemi Utsumi, Norimichi Hattori, Tsuyoshi Nakamaki, Ayako Sato, Asako Yamaguchi, Yumi Shibata, Kaori Ono, Luna Osakabe, Mie Myers, Shouji Hironaka, Yasubumi Maruoka

Many medical institutions have recently conducted studies on the relationship between patients with hematopoietic neoplasms and oral cavity. Statistical analysis of the bacterial populations was performed in this study to identify how oral microflora and health conditions （e.g., dental caries and periodontal diseases） affect the prognosis of patients with hematopoietic neoplasms. Patients undergoing inpatient treatment from January to December 2020 at the Department of Hematology at Showa University, Japan, who required perioperative oral management were included in the study. The oral health of the patients was examined at the initial dental visit, and oral bacterial samples were collected from the tongue, buccal mucosa, and palate of 47 patients who consented to participate after receiving an explanation about the study. Statistical analyses performed after dividing the subjects into two groups following the treatment course showed that Stenotrophomonas maltophilia and Gemella sanguinis were significantly more common in the poor-course group. However, no significant difference in bacterial examination results was noted among the four groups （myeloid neoplasm chemotherapy, myeloid neoplasm hematopoietic stem cell transplantation （HSCT）, lymphoid neoplasm chemotherapy, and lymphoid neoplasm HSCT groups） classified based on disease and treatment method. The detection rate of bacteria potentially causing infectious diseases at the initial dental examination tended to be higher in this study in the poor-course group. The findings of the current study suggest that early detection of pathogenic bacteria after commencing hematology treatment could predict the poor-course that may lead to mortality or severe infections.
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34 巻 (2022) 2 号 p. 64-77
The PD-L1/22C3 assay for primary lung cancer is feasible for daily clinical practice irrespective of the diagnostic procedure
Hiromitsu Suganuma, Sojiro Kusumoto, Ryo Manabe, Yasunari Kishino, Tetsuya Endo, Koichi Ando, Hiroo Ishida, Atsushi Horiike, Akihiko Tanaka, Hidefumi Takei, Toshiko Yamochi, Takuya Tsunoda, Hironori Sagara

The programmed death ligand 1 immunohistochemistry 22C3 pharm DX assay （PD-L1/22C3） is commonly used for assessing PD-L1 expression in non-small-cell lung cancer. Although various sample types have been used for the PD-L1 assay, the feasibility of the PD-L1/22C3 assay in clinical practice remains undefined. At Showa University Hospital, 270 patients diagnosed with primary lung cancer and 271 pathological specimens were assessed. The overall failure rate of the PD-L1/22C3 assay, tumor proportion score （TPS） distribution, and clinical characteristics were retrospectively reviewed. Efficacy, including objective response rate, progression-free-survival, and overall survival, following pembrolizumab monotherapy for patients with high PD-L1 expression and anti-PD-1/PD-L1 treatment for previously treated patients were also retrospectively analyzed. The overall failure rate for the PD-L1/22C3 assay was 3.0%. PD-L1 expression classified by TPS＜1%, 1-49%, and≥50% was 31%, 33%, and 33%, respectively. Thirty-one patients with high PD-L1 expression （TPS≥50%） received first-line pembrolizumab monotherapy, which exhibited high efficacy and outcome, irrespective of the diagnostic procedure. In 65 patients, anti-PD-1/PD-L1 monotherapy used as second- or further-line treatment showed moderate efficacy, irrespective of the diagnostic procedure and the period between tumor acquisition and PD-L1 assay. However, PD-L1 positivity did not affect clinical outcome. The PD-L1/22C3 assay is feasible in a clinical setting because of its low failure rate and it is a good predictor of pembrolizumab efficacy. For previously treated patients, prediction of the effectiveness of anti-PD-1/PD-L1 treatment based on PD-L1 expression should be considered.
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34 巻 (2022) 3 号 p. 149-158
The effectiveness of bile cytology during percutaneous transhepatic gallbladder drainage for acute cholecystitis in diagnosing incidental gallbladder cancer
Tomono Usami, Kazuya Inoki, Yu Ishii, Yuta Mitsui, Shu Oikawa, Shigetoshi Nishihara, Kei Nakatani, Akihiro Nakayama, Toshihiro Noguchi, Hitoshi Yoshida

Incidental gallbladder cancers （IGBCs） refer to gallbladder cancers （GCs） that are not preoperatively diagnosed but are diagnosed only after cholecystectomy for benign gallbladder diseases. This exploratory study aimed to investigate the diagnostic performance of bile cytology with percutaneous transhepatic gallbladder drainage （PTGBD） and tumor markers in preoperatively detecting IGBC. Data on consecutive acute cholecystitis cases between January 2018 and March 2020 at the Showa University Hospital in Tokyo, Japan, were retrospectively analyzed. Patient characteristics, bile cytology results, collection date, and blood test results were assessed. Concerning the bile cytology results, classes I–III were categorized as negative, whereas classes IV and V were positive. Bile cytology was performed in 102 patients; of these, 2 cases were diagnosed as GC. The bile cytology results were as follows: class I in 15 cases; class II in 84; class III in 2; class IV in 1; and class V in 0. Therefore, 101 and 1 cases were judged as negative and positive, respectively. Bile cytology had a sensitivity of 50％, specificity of 100％, positive predictive value of 100％, and negative predictive value of 99％. Among 47 patients in whom carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9） levels were measured, 3 and 12 patients exhibited elevated CEA and CA19-9 levels, respectively. Tumor markers were elevated in IGBC cases; however, several false-positive results were present in cases without GC. Bile cytology from PTGBD may be useful for the preoperative diagnosis of IGBC with acute cholecystitis. Measurement of CEA and CA19-9 levels as tumor markers should be performed with caution, as false-positive results due to inflammation would be included.
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