Evaluation of prognostic prediction ability of the novel Japanese risk factor scoring system in a Japanese cohort of resectable cutaneous squamous cell carcinoma: A retrospective cross-sectional study.

Japanese patients with very high-risk cutaneous squamous cell carcinomas (cSCCs), based on the National Comprehensive Cancer Network guidelines, have been reported to display a higher cumulative incidence of relapse and disease-specific death (DSD) than those with high-risk cSCC. Therefore, prognosis prediction is crucial for Japanese patients with very high-risk cSCCs. Herein, we aimed to evaluate the prognostic prediction ability of our novel Japanese Risk Factor Scoring Systems (JARF scoring) in a Japanese cohort of cSSC patients. Data of 424 Japanese patients with resectable very high-risk cSCCs were analysed. We compared the prognostic ability of the following three staging systems: Brigham and Women's Hospital (BWH) tumour staging, number of NCCN very high-risk factors, and JARF scoring, including recurrent tumour, high-risk histological features, deep tumour invasion and lymphatic or vascular involvement as risk factors. The prognostic ability of these staging systems was evaluated according to the cumulative incidence of local recurrence (LR), regional lymph node metastasis (RLNM), DSD, and overall survival (OS). When BWH staging was used, high T stage led to significantly poor outcomes only in the cumulative incidence of RLNM (p = 0.01). The presence of very high-risk NCCN factors led to significantly poor outcomes in terms of RLNM (p = 0.03) and OS (p = 0.02). Meanwhile, a high number of risk factors in the JARF scoring system clearly led to poor outcomes in terms of LR (p = 0.01), RLNM (p < 0.01), DSD (p = 0.03), and OS (p < 0.01). The JARF scoring system may accurately predict the risk of recurrence and death in very high-risk cSCC patients in Japan.

[Embolization Using a Debranched Left Common Carotid Artery Stump for Gutter Endoleak After Thoracic Endovascular Aortic Repair with the Double-debranching and Chimney Technique].

An 88-year-old male underwent thoracic endovascular aortic repair (TEVAR) with the double-debranching and chimney technique for arch aortic aneurysm. When the aforementioned procedure was performed, the left common carotid artery was closed and transected, and the left subclavian artery was embolized and bypassed, respectively. However, postoperatively, the gutter endoleak persisted, and the aneurysm enlarged;therefore, requiring additional surgery. A skin incision was made on the left side of the neck, and the closed and dissected left common carotid artery stump was detected. A sheath was placed at the stump and an angiographic catheter and guidewire were used to retrograde cannulate the gutter beside the chimney graft, and coil embolization was performed. No endoleak was observed at postoperatively and 6-month follow up computed tomography( CT). We believe that embolization from a deblanched left common carotid artery stump is useful for endoleaks after TEVAR employing the chimney and debranching technique.

Knapperer Resektionsrand bei Plattenepithelkarzinomen mit hohem oder sehr hohem Risiko: eine retrospektive multizentrische Studie mit 1000 Patienten.

HINTERGRUND UND ZIELE: Bei kutanen Plattenepithelkarzinomen (PEK) ist die Einhaltung der in Leitlinien empfohlenen festen Resektionsränder oft schwierig und knappere Ränder sind wünschenswert. Ziel dieser Studie war die Bewertung des Auftretens von Rezidiven und krankheitsspezifischen Todesfällen bei knapperen Resektionsrändern für PEK mit hohem oder sehr hohem Risiko. PATIENTEN/METHODEN: PEK-Patienten mit hohem oder sehr hohem Risiko, bei denen eine Tumorexzision durchgeführt wurde, wurden retrospektiv untersucht. Die Patienten wurden in eine Gruppe mit Standardrand gemäß Leitlinienempfehlung (standard margin group, SMG) und eine Gruppe mit knapperen Rändern (narrower-margin group, NMG) eingeteilt. Gemeinsame primäre Endpunkte waren lokales Rezidiv, PEK-Rezidiv und PEK-bedingter Tod. Die Wahrscheinlichkeit eines PEK-bedingten Tods und konkurrierender Mortalitätsrisiken wurde mittels kumulativer Inzidenzfunktion (CIF) beschrieben. Unterschiede bei der CIF zwischen den Gruppen wurden mit dem Test nach Gray verglichen. ERGEBNISSE: Insgesamt wurden 1.000 Patienten mit PEK (hohes Risiko, 570; sehr hohes Risiko, 430) eingeschlossen. In der Kohorte mit hohem Risiko gab es keine signifikanten Unterschiede bei der unvollständigen Exzisionsrate (IER) zwischen SMG und NMG (2,6 % vs. 3,0 %, P > 0,99). In der Kohorte mit sehr hohem Risiko war die IER in der SMG jedoch signifikant geringer als in der NMG (8.9 % vs. 16.2 %, P = 0,03). Keine signifikanten Unterschiede zwischen SMG und NMG wurden für Lokalrezidiv (hohes Risiko, P = 0.56; sehr hohes Risiko, P = 0,70), PEK-Rezidiv (hohes Risiko, P = 0,30; sehr hohes Risiko, P = 0,47) und PEK-bedingtem Tod (hohes Risiko, P = 0,23; sehr hohes Risiko, P = 0,83) beobachtet. SCHLUSSFOLGERUNGEN: Die Größe des Resektionsrands hat einen begrenzten Einfluss auf Randkontrolle, Rezidive und krankheitsspezifischen Tod bei PEK mit hohem Risiko.

Narrower clinical margin in high or very high-risk squamous cell carcinoma: a retrospective, multicenter study of 1,000 patients.

BACKGROUND AND OBJECTIVES: In cutaneous squamous cell carcinoma (cSCC), adherence to guideline-recommended fixed surgical margins is often difficult, and narrower margins are preferable. This study aimed to evaluate relapse and disease-specific death with narrower margins for high or very high-risk cSCC. PATIENTS/METHODS: We retrospectively investigated high or very high-risk cSCC patients who underwent tumor excision. Patients were divided into guideline-recommended standard margin group (SMG) and narrower-margin group (NMG). Co-primary outcomes were local relapse, SCC relapse, and SCC death. Cumulative incidence function (CIF) was used to describe SCC death probability and competing risk mortality. Gray's test was used to compare differences in CIF between the groups. RESULTS: In total, 1,000 patients with cSCC (high-risk, 570; very high-risk, 430) were included. In the high-risk cohort, there were no significant differences in incomplete excision rate (IER) between SMG and NMG (2.6 % vs. 3.0 %, P > 0.99). However, in the very high-risk cohort, IER in SMG was significantly lower than in NMG (8.9 % vs. 16.2 %, P = 0.03). No significant differences were observed between SMG and NMG for local relapse (high-risk, P = 0.56; very high-risk, P = 0.70), SCC relapse (high-risk, P = 0.30; very high-risk, P = 0.47), and SCC death (high-risk, P = 0.23; very high-risk, P = 0.83). CONCLUSIONS: Surgical margin size has limited impact on margin control, relapse, and disease-specific death in high-risk cSCC.

[Re-operation Using Bovine Pericardium for Infective Endocarditis after Aortic Valve Neocuspidization;Report of a Case].

A 70-year-old man, who had undergone aortic valve neocuspidization using his own pericardium 8 months before, complained of back pain, and was diagnosed with pyrogenic spondylitis. As the result of blood culture, Enterococcus faecalis was found to be the causative bacterium, and antibiotic therapy was started. Six days after admission, hemodynamics collapsed suddenly, and percutaneous cardio-pulmonary support was established. Echocardiography showed severe aortic valve regurgitation, and he was diagnosed with active infective endocarditis. We performed re-do aortic valve neocuspidization using bovine pericardium. There was a tear on the non-coronary cusp and the cusps were thickened because of infection. Aortic annular tissue was not destroyed and we could fix the neo-valve directly to the annulus. After these procedures, severe reduction of antero-septal wall motion was noted, which suggested dissection of the main trunk of the left coronary artery. Coronary artery bypass grafting to the left anterior descending and the circumflex branches was added. The patient came off percutaneous cardio-pulmonary support 5 days after surgery. Although trivial aortic regurgitation remained, he was discharged after 2 months of rehabilitation.

Oocyte-specific gene Oog1 suppresses the expression of spermatogenesis-specific genes in oocytes.

Oog1, an oocyte-specific gene that encodes a protein of 425 amino acids, is present in five copies on mouse chromosomes 4 and 12. In mouse oocytes, Oog1 mRNA expression begins at embryonic day 15.5 and almost disappears by the late two-cell stage. Meanwhile, OOG1 protein is detectable in oocytes in ovarian cysts and disappears by the four-cell stage; the protein is transported to the nucleus in late one-cell to early two-cell stage embryos. In this study, we examined the role of Oog1 during oogenesis in mice. Oog1 RNAi-transgenic mice were generated by expressing double-stranded hairpin Oog1 RNA, which is processed into siRNAs targeting Oog1 mRNA. Quantitative RT-PCR revealed that the amount of Oog1 mRNA was dramatically reduced in oocytes obtained from Oog1-knockdown mice, whereas the abundance of spermatogenesis-associated transcripts (Klhl10, Tekt2, Tdrd6, and Tnp2) was increased in Oog1 knockdown ovaries. Tdrd6 is involved in the formation of the chromatoid body, Tnp2 contributes to the formation of sperm heads, Tekt2 is required for the formation of ciliary and flagellar microtubules, and Klhl10 plays a key role in the elongated sperm differentiation. These results indicate that Oog1 down-regulates the expression of spermatogenesis-associated genes in female germ cells, allowing them to develop normally into oocytes.

[Aortoesophageal Fistula with Infected Thoracic Aortic Aneurysm Rupture;Report of a Case].

A 67-year-old man was referred to our hospital because of fever and discomfort of the throat. Gastrointestinal endoscopy revealed hematoma at the middle thoracic esophagus. Computed tomography revealed posterior mediastinal hematoma extending the descending aorta. Bacillus was detected in the blood culture. Aortoesophageal fistula with an infected thoracic aortic aneurysm rupture was diagnosed. First, thoracic endovascular aortic repair (TEVAR) was performed. Resection of the thoracic esophagus and omentopexy was conducted 15 days after TEVAR. Esophageal reconstruction using a gastric tube was performed 43 days after esophagectomy. He has been doing well since then.

[Papillary Fibroelastoma of the Left Ventricular Outflow Tract;Report of a Case].

Papillary fibroelastoma(PFE) is a rare and benign primary cardiac neoplasm. The incidence of PFE in the left ventricle is lower than that in other parts of the heart. A 67-year-old female was referred to our cardiology department for treatment of severe cardiac failure due to mitral regurgitation. Transthoracic and transesophageal echocardiography coincidently revealed a 1.0 cm highly mobile mass attached by a stalk to the outflow tract wall of the left ventricle. The mass was easily detected using endoscope and successfully removed without any postoperative complications and was pathologically diagnosed as a PFE. In this report, we discuss the echocardiographic character of PFE and the usefulness of endoscope for the identification and resection of a PFE in the left ventricle.

[Mycotic Aneurysm of Distal Aortic Arch, after Total Arch Replacement with Open-stent Graft;Report of a Case].

The patient was a 72-year-old man, who had undergone total arch replacement with an open-stent graft due to saccular aneurysm of distal arch, 2 years before. He was admitted to a local hospital with the complaint of high fever, and was diagnosed as having pyothorax, after computed tomography (CT) scanning. After transferred to our hospital, he was treated by drainage, and antibiotic therapy. But CT scans showed the enlargement of distal arch aneurysm, and migration of the stent graft. Urgent operation was performed. We approached to the site by a full sternotomy, and left anterolateral thoracotomy. Segment 1+2 of the left lung was resected to avoid bleeding and lung injury. Graft replacement of distal arch and descending aorta was performed on cardiopulmonary bypass, with hypothermia, selective brain perfusion and systemic circulatory arrest. To protect from recurrence of infection, the omental flap was transposed to the graft site. Until now, there is no recurrence of infection.

[Successful management of aorto-esophageal fistula, using staged 3 times operation].

A 66-year-old man, presented with hematemesis and hemorrhagic shock, was transported to our institution. Computed tomographic examination suggested a pseudo-aneurysm formed by bleeding from aorto-esophageal fistula( AEF). We planned staged operations. At first, in an emergent operation, graft replacement of descending aorta, was performed under partial cardiopulmonary bypass, by left thoracotomy approach. AEF was 5 mm in diameter, and existed inside of normal-diameter and non-aneurysmal aortic intima. AEF orifice into pseudo-aneurysm was closed with aortic wall and was sutured tightly. Next day, gastrointestinal fiberscopy was performed, and penetrating ulcer was found at lower esophagus.To prevent infective complications, the 2nd operation, subtotal esophagectomy, cervical esophagostomy, gastrostomy and tube ileostomy were performed by right thoracotomy approach. Post- operative course was uneventful. Two months later, 3rd operation, cervical esophago-gastric anastomosis was performed, uneventfully. Two years and four months elapsed, and no evidences of infection and formation of pseudo-aneurysm were observed.

[Discrete type subaortic stenosis disclosed by hemolytic anemia after aortic and mitral valve replacement].

We report a case of discrete type subaortic stenosis disclosed by hemolytic anemia 7 years after aortic and mitral prosthetic valve replacement. A 53-year-old female complained of general fatigue, dyspnea, macrohematuria and hemolysis. She had undergone aortic valve replacement for non-coronary cusp perforation 15 years before, and mitral valve replacement and tricuspid annuloplasty 7 years before. Echocardiography showed mitral prosthetic valve regurgitation (III/IV degree) and symptomatic hemolysis might be caused by accelerated blood flow through the prosthetic valve. A mild aortic stenosis (peak flow verocity:3.73 m/s) was also pointed out. The redo double valve replacement was performed. Intraoperative findings showed discrete type subaortic stenosis due to extensive pannus formation, but that the previously implanted prosthetic valves were intact. The blood flow biased by the interference of the subaortic stenosis might have obstructed closure of the mitral prosthetic valve and caused mitral regurgitation. Postoperatively, hemolysis and mitral regurgitation were diminished, and aortic stenosis was improved.

Favorable efficacy of S-1 treatment for locoregionally advanced cutaneous squamous cell carcinoma in the head and neck region.

Cutaneous squamous cell carcinoma is usually treated with surgery; however, locoregionally advanced cutaneous squamous cell carcinoma can be difficult to resect. Although recent guidelines from Western countries recommend using anti-programmed cell death protein 1 (PD-1) antibodies, including cemiplimab and pembrolizumab, there are no approved anti-PD-1 antibodies for locoregional cutaneous squamous cell carcinoma in Asian countries. S-1 is an oral drug with a low incidence of severe toxicity that can be used for head and neck cancers, including head and neck locoregional cutaneous squamous cell carcinoma, in Japan. We retrospectively evaluated patients with head and neck locoregional cutaneous squamous cell carcinoma treated with S-1 at two Japanese institutions (2008-2022). The initial dosage was determined by the body surface area (<1.25 m2 : 80 mg/day, 1.25-1.5 m2 : 100 mg/day, ≥1.5 m2: 120 mg/day) for 28 consecutive days. The outcome measures were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Fourteen patients were included. The ORR was 78%, and the complete response (CR) rate was 64.3%. The median PFS and OS were not reached (NR) (95% confidence interval [CI], 5.9 months-NR) and NR (95% CI, 13.8 months-NR), respectively. The 12-month PFS and OS rates were 51% and 85%, respectively. Six of the nine patients who achieved CR showed no recurrence during the follow-up period (median follow-up, 24.7 months). After CR, three patients experienced recurrence. Among these, two resumed S-1 treatment and subsequently underwent salvage surgery, resulting in a sustained absence of recurrence. One patient developed lung metastasis and died, although S-1 therapy was resumed. Only one patient (7.1%) developed grade 3 anemia. S-1 showed favorable efficacy and low toxicity in patients with head and neck locoregionally advanced cutaneous squamous cell carcinoma. S-1 may be a good alternative to the anti-PD-1 antibody for treating head and neck locoregionally advanced squamous cell carcinoma.

CD106 in tumor-specific exhausted CD8+ T cells mediates immunosuppression by inhibiting TCR signaling.

T cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T cell exhaustion, such as PD-1, can reinvigorate tumor-specific T cells and activate anti-tumor immunity in various types of cancer. Here, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA-sequencing. High CD106 expression in the TME in clinical samples corresponded to improved response to cancer immunotherapy. CD106 in tumor-specific T cells suppressed anti-tumor immunity both in vitro and in vivo, and loss of CD106 in CD8+ T cells suppressed tumor growth and improved response to PD-1 blockade. Mechanistically, CD106 inhibited T-cell receptor (TCR) signaling by interacting with the TCR/CD3 complex and reducing its surface expression. Together, these findings provide insights into the immunosuppressive role of CD106 expressed in tumor-specific exhausted CD8+ T cells, identifying it as a potential biomarker and therapeutic target for cancer immunotherapy.

[Ventricular septal rupture and right ventricular free wall rupture after acute myocardial infarction].

Cardiac rupture is a catastrophic complication of acute myocardial infarction with highly mortality rate. Three types of rupture are ventricular free wall rupture( VFR), ventricular septal rupture( VSR), and papillary muscle rupture( PMR). A combination of any 2 types of rupture is called ventricular double rupture (VDR), and very rare. We report a case of VDR (VSR and VFR) after acute myocardial infarction. A 76-year-old female with heart failure was admitted to our hospital. Echocardiography showed an apical VSR and pericardial effusion. She was diagnosed with VDR and emergent operation was performed. During operation, the site of VFR was right ventricle, which was the same infarction area of VSR. VSR was closed by infarction exclusion technique, concurrently excluding the site of VFR. VFR was successfully repaired by mattress sutures. Post-operative course was good without heart failure, though residual shunt was remained. The patient survived and was discharged from our hospital.

[Giant pseudoaneurysm of the ascending aorta following the aortic valve replacement;report of a case].

56-year-old male, who had undergone re-aortic valve replacement (AVR) 33 years ago, received preoperative study for pancreatic surgery. Computed tomography (CT) revealed a giant pseudoaneurysm (7 cm diameter) of the ascending aorta. The ascending aorta was not dilated. A midline skin incision was performed, followed by full sternotomy. A tight pericardial adhesion was carefully dissected. Cardiopulmonary bypass was established by femoral arterial and bicaval venous cannulation. The pseudoaneurysm was incised under the retrograde cardioplegic protection. A communication between ascending aorta and aneurysm was found 1 cm distal to the previous aortic suture line. This communication coincided with the cardioplegic root cannulation site. The aortic prosthetic valve was intact. The ascending aorta was replaced with 26 mm prosthetic graft. Postoperative course was uneventful. In this case, CT was useful to select the approach to the complicated postoperative surgical site.

[Successful postoperative percutaneous cardiopulmonary support( PCPS) for the right-heart failure in a patient with recurrent mitral valve stenosis and a calcified left atrium; report of a case].

A 79-year-old female underwent open mitral commissurotomy and thrombectomy for mitral valve stenosis and thrombus in the left atrium 21 years ago. She was admitted for congestive heart failure because of recurrent mitral valve stenosis. Cardiac echocardiography showed severe mitral valve stenosis and the calcification of the left atrium wall. We performed mitral valve replacement and removal of thrombus calcification in the left atrium. Cardiopulmonary bypass was weaned successfully. In the intensive care unit, her blood pressure (BP) dropped, central venous pressure (CVP) increased, and urine volume decreased. Cardiac echocardiography revealed functional deterioration and dilatation of the right ventricle. As medical therapy was not effective, percutaneous cardiopulmonary support(PCPS)was established through the femoral artery and vein. Then her BP increased, CVP decreased, and the right ventricular function and the dilatation improved. PCPS was removed after 3 days, and the respirator on the 13th postoperative day. She moved out of the intensive care unit on the 24th postoperative day.

[Y-graft replacement with left renal artery reconstruction for acute aortic dissection type B].

A 56-year-old male was admitted to our hospital for acute type B aortic dissection. He received conservative therapy but follow-up computed tomography (CT) revealed a low-enhanced left kidney and severe stenosis of the left common iliac artery due to the expansion of the false lumen. Serum blood urea nitrogen (BUN) and creatinine increased and renovascular hypertension worsened with severe intermittent claudication of the left leg. We performed Y-graft replacement with reconstruction of the left renal artery. Postoperative CT showed a well-enhanced left kidney and no stenosis of the left common iliac artery. Intermittent claudication and renal dysfunction improved and his hypertension became controllable. He was discharged on the 17th postoperative day.

[New technique of concomitant replacement of the aortic valve and the ascending aorta with enlargement of the aortic annulus for congenital bicuspid aortic valve].

Congenital bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, with a high incidence of associated valvular lesions and aortic abnormalities including aortic stenosis( AS), aortic regurgitation, aortic dilatation, and aortic dissection. Patients with BAV and AS often have a small aortic annulus. We encountered a case of BAV in which a 51-year-old woman with severe AS having a small aortic annulus and a dilated ascending aorta required surgical intervention. We performed the surgery using new technique that involved concomitant replacement of the aortic valve and the ascending aorta with enlargement of the aortic annulus using a single uniquely-shaped graft to avoid prosthesis patient mismatch. We trimmed the proximal end of the straight graft in shape of 2 teardrops hanging on it to fit the cut annulus. It requires only a single suture line to replace the ascending aorta and enlarge the aortic annulus, which entails a decreased risk of bleeding during surgery. We believe that it could be applicable to many cases requiring concomitant surgery.

Comparison of surgical morbidities between LigaSure™ and conventional techniques in inguinal or ilioinguinal lymph node dissection for skin cancer: A single center retrospective study.

Skin cancer patients with clinical nodal disease or whose positive sentinel nodes had great tumor burden remain candidates for regional lymph node dissections. Among these patients, inguinal or ilioinguinal lymph node dissection is frequently required in clinical practice, which is associated with significant postoperative morbidity-including lymphatic leakage. The aim of this retrospective study was to evaluate the efficacy of LigaSure™, an electrothermal bipolar vessel sealing system, in reducing lymphatic leakage in inguinal or ilioinguinal lymph node dissection. In total, 58 patients who received inguinal or ilioinguinal lymph node dissection (conventional group, 48; LigaSure™ group, 10) and shared similar characteristics were included in this study. Lymphatic leakage after drain removal was significantly lower in the LigaSure™ group than that in the conventional group (present ratio, 0% vs. 37%; p = 0.02). The daily lymphatic drainage volume also tended to be lower in the LigaSure™ than that in the conventional group, with significant differences on postoperative day 1 (p = 0.02). Other perioperative outcomes including the operating time, intraoperative blood loss, time to drain removal, duration of hospital stay, flap necrosis, and wound infection showed no significant differences between the two groups. The use of the LigaSure™ in inguinal or ilioinguinal lymph node dissection for the treatment of skin cancer could reduce the incidence of postoperative lymphatic leakage after drain removal.

Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration.

Some patients experience mixed response to immunotherapy, whose biological mechanisms and clinical impact have been obscure. We obtained two tumor samples from lymph node (LN) metastatic lesions in a same patient. Whole exome sequencing for the both tumors and single-cell sequencing for the both tumor-infiltrating lymphocytes (TIL) demonstrated a significant difference in tumor clonality and TILs' characteristics, especially exhausted T-cell clonotypes, although a close relationship between the tumor cell and T-cell clones were observed as a response of an overlapped exhausted T-cell clone to an overlapped neoantigen. To mimic the clinical setting, we generated a mouse model of several clones from a same tumor cell line. Similarly, differential tumor clones harbored distinct TILs, and one responded to programmed cell death protein 1 (PD-1) blockade but the other did not in this model. We further conducted cohort study (n = 503) treated with PD-1 blockade monotherapies to investigate the outcome of mixed response. Patients with mixed responses to PD-1 blockade had a poor prognosis in our cohort. Particularly, there were significant differences in both tumor and T-cell clones between the primary and LN lesions in a patient who experienced tumor response to anti-PD-1 mAb followed by disease progression in only LN metastasis. Our results underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome. Significance: Several patients experience mixed responses to immunotherapies, but the biological mechanisms and clinical significance remain unclear. Our results from clinical and mouse studies underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.