Minimally invasive radical hysterectomy and the importance of avoiding cancer cell spillage for early-stage cervical cancer: a narrative review

Atsushi Fusegi,Hiroyuki Kanao,Shiho Tsumura,Atsushi Murakami,Akiko Abe,Yoichi Aoki,Hidetaka Nomura 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.1

Radical hysterectomy is a standard surgery to treat early-stage uterine cervical cancer. The Laparoscopic Approach to Cervical Cancer (LACC) trial has shown that patients receiving minimally invasive radical hysterectomy have a poorer prognosis than those receiving open radical hysterectomy; however, the reason for this remains unclear. The LACC trial had 2 concerns: the learning curve and the procedural effects. Appropriate management of the learning curve effect, including surgeons’ skills, is required to correctly interpret the result of surgical randomized controlled trials. Whether the LACC trial managed the learning curve effect remains controversial, based on the surgeons’ inclusion criteria and the distribution of institutions with recurrent cases. An appropriate surgical procedure is also needed, and avoiding intraoperative cancer cell spillage plays an important role during cancer surgery. Cancer cell spillage during minimally invasive surgery to treat cervical cancer is caused by several factors, including 1) exposure of tumor, 2) the use of a uterine manipulator, and 3) direct handling of the uterine cervix. Unfortunately, these issues were not addressed by the LACC trial. We evaluated the results of minimally invasive radical hysterectomy while avoiding cancer cell spillage for early-stage cervical cancer. Our findings show that avoiding cancer cell spillage during minimally invasive radical hysterectomy may ensure an equivalent oncologic outcome, comparable to that of open radical hysterectomy. Therefore, evaluating the importance of avoiding cancer cell spillage during minimally invasive surgery with a better control of the learning curve and procedural effects is needed.

Glycomics meets histopathology: Lectin microarray can profile the whole glycoproteins in specific groups of cells isolated by laser microdissection

Atsushi Kuno,Masaharu Nomura,Hideki Matsuzaki,Tomoko Nakagawa,Atsushi Matsuda,Yoshitoshi Hirao,Masao Sasaki,Norihiro Ikeda,Toshitaka Nagao,Yuzuru Ikehara,Hisashi Narimatsu 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1

Cell glycome is defined by the glyco synthesis machinery regulated by harmonized expression of more than 100 glycogenes. The machinery-dependent glycome drastically shifts during cell progression and differentiation in association with tumorigenesis and malformation, and thus it motivates us to discover the disease-related alteration in glycosylation. Glycan-targeted histochemical approaches using lectin and anti-glycogene antibodies have provided some key information to characterize specific histological types of cells in pathology. However, this approach is not suitable for the comprehensive analysis targeting the cell glycome, and thus may fail to provide insight into glycome shift during the disease progression. Several years ago, we developed the methodology for rapid and systematic glycome shift analysis targeting formalin-fixed tissue specimens by means of lectin microarray. The resultant method enabled simultaneous observation of over 40 lectins interacted with glycoproteins in 1 mm2 of the tissue specimens. Recently, we sophisticated this methodology to be suitable for comparative analysis of a series of cells in specific groups isolated from a single tissue specimen by laser microdissection, and now our research has gained interest in the variability and distribution of cell glycome in the tissue, i.e., “tissue glycome mapping”. In this meeting, we will summarize the advantage of this new methodology and its application for glyco-biomarker discovery, as well as the construction of “tissue glycome atlas”.

Clinical implications of the superficial uterine vein pattern for the dissection of the anterior layer of the vesicouterine ligament in radical hysterectomy

Atsushi Fusegi,Hiroyuki Kanao,Mayumi Kamata,Shogo Nishino,Akiko Abe,Makiko Omi,Hidetaka Nomura 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.4

Objective: To describe anatomic patterns of the superficial uterine vein (sUV) and assesstheir association with aspects of the dissection procedure of the anterior layer of thevesicouterine ligament (aVUL) by retrospectively reviewing surgical videos. Methods: We analyzed patients who under went laparoscopic radical hysterectomy forearly-stage cer vical cancer from 2014 to 2019. The primar y endpoint was the time requiredfor aVUL dissection. Multiple linear regression analyses were performed to identif y factorsinfluencing the time required for aVUL dissection. Results: Fifty-three Japanese patients were included. Two sUV configurations were obser ved:type 1 (the vein ran ventral to the ureter along the uterine arter y) and type 2 (the vein did notrun along the usual ventral course; it ran dorsal to the ureter or was absent). Approximately30% of the sUVs were type 2. The total time for dissection of both sides of the aVUL wassignificantly shorter for type 2 sUVs than for type 1 sUVs. The number of hemostaticinter ventions during dissection of each side of the aVUL was significantly lower for type 2sUVs than for type 1 sUVs. In the multivariate analysis, the sUV configuration was the factorsignificantly influencing the duration of aVUL dissection on each side (right side: β=−143.4;left side, β=−160.4). Conclusion: We demonstrated that the sUV had 2 types of courses, ventral and others, and itscourse affected the time required for dissection and the number of hemostatic inter ventions. Our results provide information supportive of improved radical hysterectomy outcomes.

Transvaginal cervical tumor-concealing no-look no-touch technique in minimally invasive radical hysterectomy for early-stage cervical cancer: a novel operation technique

Hiroyuki Kanao,Atsushi Fusegi,Makiko Omi,Ariane C. Youssefzadeh,Hidetaka Nomura,Koji Matsuo 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.3

The Laparoscopic Approach to Cervical Cancer (LACC) trial demonstrated that minimally invasive radical hysterectomy was inferior to the open approach [1]; this unexpected result could be attributed to the spillage of cancer cells [2]. Following the LACC trial, laparoscopic radical hysterectomy without an intrauterine manipulator upon completion of a vaginal cuff closure became the new standard treatment method [3]. However, the lack of intrauterine manipulator results in poor visualization and inadequate paracervical tissue resection. This study describes the no-look no-touch technique to address this difficulty. The core procedures in our no-look, no-touch laparoscopic radical hysterectomy are: (Step 1) Creation and closure of a vaginal cuff; (Step 2) Manipulation of the uterus without an intra-uterine manipulator; and (Step 3) Exposure of the paracervical tissues by the suspension technique. The patient eligibility for our procedure is as follows: 1) previously untreated cervical cancer (those who underwent diagnostic conization could be included); 2) clinical stage IA2, IB1, IB2, and IIA1 based on the 2018 International Federation of Gynecology and Obstetrics staging system; 3) histologically confirmed cervical cancer, including squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. The important indication for this procedure is in cases where the tumor is less than 4 cm in diameter. We previously reported that our no-look no-touch technique enables smooth performance of laparoscopic radical hysterectomy without worsening oncologic outcomes [4]. According to a recent systematic review and meta-analysis [5], minimally invasive radical hysterectomy with vaginal cuff closure is a safe treatment option; however, it involves a steep learning curve, which has impeded its increased application. This video will hopefully make minimally invasive radical hysterectomy with protective maneuvers against cancer cell spillage more accessible. Based on our experiences, we propose that our transvaginal cervical tumor-concealing no-look no-touch technique will mitigate the risk of surgical spill of tumor cells during minimally invasive radical hysterectomy. The informed consent for use of this video was taken from the patient.

Impact of Tumor Location on the Quality of Life of Patients Undergoing Total or Proximal Gastrectomy

Fujisaki Muneharu,Nomura Takashi,Yamashita Hiroharu,Uenosono Yoshikazu,Fukunaga Tetsu,Otsuji Eigo,Takahashi Masahiro,Matsumoto Hideo,Oshio Atsushi,Nakada Koji 대한위암학회 2022 Journal of gastric cancer Vol.22 No.3

Purpose Most studies have investigated the differences in postgastrectomy quality of life (QOL) based on the surgical procedure or reconstruction method adopted; only a few studies have compared QOL based on tumor location. This large-scale study aims to investigate the differences in QOL between patients with esophagogastric junction cancer (EGJC) and those with upper third gastric cancer (UGC) undergoing the same gastrectomy procedure to evaluate the impact of tumor location on postoperative QOL. Methods The Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaire was distributed in 70 institutions to 2,364 patients who underwent gastrectomy for EGJC or UGC. A total of 1,909 patients were eligible for the study, and 1,744 patients who underwent total gastrectomy (TG) or proximal gastrectomy (PG) were selected for the final analysis. These patients were divided into EGJC and UGC groups; thereafter, the PGSAS-45 main outcome measures (MOMs) were compared between the two groups for each type of gastrectomy. Results Among the post-TG patients, only one MOM was significantly better in the UGC group than in the EGJC group. Conversely, among the post-PG patients, postoperative QOL was significantly better in 6 out of 19 MOMs in the UGC group than in the EGJC group. Conclusions Tumor location had a minimal effect on the postoperative QOL of post-TG patients, whereas among post-PG patients, there were definite differences in postoperative QOL between the two groups. It seems reasonable to conservatively estimate the benefits of PG in patients with EGJC compared to those in patients with UGC. Purpose Most studies have investigated the differences in postgastrectomy quality of life (QOL) based on the surgical procedure or reconstruction method adopted; only a few studies have compared QOL based on tumor location. This large-scale study aims to investigate the differences in QOL between patients with esophagogastric junction cancer (EGJC) and those with upper third gastric cancer (UGC) undergoing the same gastrectomy procedure to evaluate the impact of tumor location on postoperative QOL. Methods The Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaire was distributed in 70 institutions to 2,364 patients who underwent gastrectomy for EGJC or UGC. A total of 1,909 patients were eligible for the study, and 1,744 patients who underwent total gastrectomy (TG) or proximal gastrectomy (PG) were selected for the final analysis. These patients were divided into EGJC and UGC groups; thereafter, the PGSAS-45 main outcome measures (MOMs) were compared between the two groups for each type of gastrectomy. Results Among the post-TG patients, only one MOM was significantly better in the UGC group than in the EGJC group. Conversely, among the post-PG patients, postoperative QOL was significantly better in 6 out of 19 MOMs in the UGC group than in the EGJC group. Conclusions Tumor location had a minimal effect on the postoperative QOL of post-TG patients, whereas among post-PG patients, there were definite differences in postoperative QOL between the two groups. It seems reasonable to conservatively estimate the benefits of PG in patients with EGJC compared to those in patients with UGC.

Synthesis of (Imido)vanadium(V) Complexes Containing 8-(2,6-Dimethylanilide)-5,6,7-trihydroquinoline Ligands: Highly Active Catalyst Precursors for Ethylene Dimerization

Tang, Xiao-Yan,Igarashi, Atsushi,Sun, Wen-Hua,Inagaki, Akiko,Liu, Jingyu,Zhang, Wenjuan,Li, Yue-Sheng,Nomura, Kotohiro American Chemical Society 2014 Organometallics Vol.33 No.4

<P>A series of (imido)vanadium(V) dichloride complexes containing 8-(2,6-dimethylanilide)-5,6,7-trihydroquinoline ligands of the type V(NR)Cl<SUB>2</SUB>[8-(2,6-Me<SUB>2</SUB>C<SUB>6</SUB>H<SUB>3</SUB>)N(C<SUB>9</SUB>H<SUB>10</SUB>N)] (R = Ad (<B>3</B>), 2-MeC<SUB>6</SUB>H<SUB>4</SUB> (<B>4</B>), 2,6-Me<SUB>2</SUB>C<SUB>6</SUB>H<SUB>3</SUB> (Ar, <B>5</B>)) have been prepared and identified, and their structures have been determined by X-ray crystallographic analysis. The ethylene dimerization catalyst generated from complex <B>3</B> upon treatment with an excess amount of MAO exhibited remarkable catalytic activities (e.g. TOF = 9600000 h<SUP>–1</SUP> (2670 s<SUP>–1</SUP>), Al/V = 4000 (molar ratio)), affording 1-butene as the major product (95.0–99.4%). The activities of <B>3</B> and <B>4</B> were higher than those exhibited by the corresponding 2-(anilide)methylpyridine analogues; <B>3</B> showed higher 1-butene selectivity than the others and the activity did not decrease remarkably at 50 °C. Complex <B>5</B> afforded a mixture of polymer and oligomers with low activities, suggesting that a fine tuning of both the imido and the anionic donor ligands plays an essential role in this catalysis.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orgnd7/2014/orgnd7.2014.33.issue-4/om401119y/production/images/medium/om-2013-01119y_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/om401119y'>ACS Electronic Supporting Info</A></P>

Cerebral infarction caused by Trousseau syndrome associated with cervical cancer

Motoko Kanno,Mayu Yunokawa,Atsushi Fusegi,Akiko Abe,Hidetaka Nomura,Hiroyuki Kanao 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.4

Objective: The combination of cancer and hypercoagulable states is often called Trousseausyndrome. In particular, cerebral infarction caused by Trousseau syndrome is reported tohave a poor prognosis. In gynecology, there are many reports of ovarian cancer and a fewof uterine cancer. Since there has been no comprehensive report of Trousseau syndrome incer vical cancer, we aimed to summarize Trousseau syndrome in cer vical cancer. Methods: Cerebral infarction caused by cancer-related arterial thrombosis was defined asTrousseau syndrome. Patients with cer vical cancer diagnosed at our hospital between Januar y2014 and December 2021 were retrospectively reviewed using the hospital’s medical records. Results: A total of 1,432 patients were included in the study. Trousseau syndrome occurredin 6 patients (0.4%). The mean age of patients with Trousseau syndrome was 63 years (range:53–78 years). Of the 6 patients who developed Trousseau’s syndrome, 4 patients had it beforeor during initial treatment, and 2 during recurrent/relapsed disease treatment. The 4 patientswho developed the syndrome before or during initial treatment had advanced disease: 1 instage IIIC and 3 in stage IVB. In all cases, the disease was associated with progressive distantmetastasis. The median sur vival time from the onset of Trousseau syndrome was 1 month(range: 0–6 months). Conclusion: Cer vical cancer causes Trousseau syndrome in cases of advanced disease with ashort time between the onset of the syndrome and mortality.

Putative Pathogenic Variants of ABCG5 and ABCG8 of Sitosterolemia in Patients With Hyper-Low-Density Lipoprotein Cholesterolemia

Nobuko Kojima,Tada Hayato,Akihiro Nomura,Soichiro Usui,Kenji Sakata,Kenshi Hayashi,Atsushi Nohara,Akihiro Inazu,Masa-aki Kawashiri,Masayuki Takamura 한국지질동맥경화학회 2024 지질·동맥경화학회지 Vol.13 No.1

ObjectiveSitosterolemia is a rare autosomal recessive disease caused by the deleterious variants of adenosine 5'-triphosphate (ATP)-binding cassette sub-family G member 5 (ABCG5) or ATP-binding cassette sub-family G member 8 (ABCG8). There are only few data on the pathogenicity of ABCG5 and ABCG8. This study aimed to propose a scheme for determining variant pathogenicity and to catalog the putative pathogenic variants in sitosterolemia. MethodsThis study enrolled 377 consecutive Japanese patients with hyper-low-density lipoprotein cholesterolemia (mean age: 46.5±19.8 years, with 192 men) who have targeted-sequenced data on ABCG5 or ABCG8 (among 21 Mendelian lipid genes for any dyslipidemias) and serum sitosterol levels at Kanazawa University Hospital from 2016 to 2021. Serum sitosterol levels were divided by 0.79 in patients treated with ezetimibe, accounting for the average reduction with this drug. ABCG5 or ABCG8 variants were defined as putative pathogenic if associated with serum sitosterol levels ≥5 µg/mL or homozygous if associated with serum sitosterol levels ≥10 µg/mL. ResultsTwenty-three ABCG5 or ABCG8 variants (16 missense, 2 nonsense, 2 frameshift, 2 deletion, and 1 splice mutation) were identified. Based on our definition, 11 putative pathogenic variants (median sitosterol level: 10.1 [6.5–17.1] µg/mL) were found in 36 individuals and 12 benign variants (median sitosterol: 3.5 [2.5–4.1] µg/mL) in 14 individuals. ConclusionThe scheme proposed for assessing the pathogenicity of genetic variations (ABCG5 and ABCG8) is useful. Using this scheme, 11 putative pathogenic, and 12 benign variants in ABCG5 or ABCG were classified.

Image processing by a coupled non-linear oscillator system

Naoko KURATA,Hitoshi MAHARA,Tatsunari SAKURAI,Atsushi NOMURA,Hidetoshi MIIKE 대한전자공학회 2008 ITC-CSCC :International Technical Conference on Ci Vol.2008 No.7

A new algorithm of image processing based on the appropriate solutions of a spatially discrete non-linear oscillator system is presented. This is based on the onset of pattern formation arising in the FitzHugh-Nagumo system with weak-coupled activation and strong-coupled inhibition. The proposed model offers to extract segment or outline of input signals and to be a high performance as noise that is noise reduction and contrast enhancement by noise. Then we discuss the difference between the discrete system of the coupled nonlinear oscillators and continuous reaction-diffusion system.

Identification of glyco-biomarker candidates for lung cancer using novel glyco-technologies

Yoshitoshi Hirao,Hideki Matsuzaki,Jun Iwaki,Minako Abe,Akira Togayachi,Atsushi Kuno,Takashi Ohkura,Hiroyuki Kaji,Masaharu Nomura,Masayuki Noguchi,Yuzuru Ikehara,Hisashi Narimatsu 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1

Lung cancer is the leading cause of cancer death worldwide. Currently, lung cancer is classified into two major types, small-cell lung cancer carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), based on the histological appearance. The histological classification has important implications in the clinical practice guideline and the prediction of the patient prognosis. However, conventional serum markers used in clinical tests are insufficient for clinical demands due to the low sensitivity and the low specificity to distinguish them. We have identified a number of glyco-biomarker candidate molecules from lung cancer cell lines using our developed glycoproteomics technologies such as lectin microarray and LC/MS-based protein analysis. On the validation studies, we found out that the selected molecules showed characteristic lectin biding profiles depending on either SCLC or NSCLC. Therefore, combination of these glyco-biomarkers could be expected to improve the diagnostic accuracy for histological classification in lung cancer compared to protein expression alone.