Impact of distribution of carotid intraplaque neovessels on plaque vulnerability.

BACKGROUND AND PURPOSE: Intraplaque neovessels (INVs) are considered important contributors to carotid plaque vulnerability. The purpose of this study was to examine whether differences in INV distribution affect plaque vulnerability. METHODS: The study cohort comprised 110 patients with significant stenosis of the carotid artery who had undergone carotid endarterectomy. The distribution of INVs within carotid plaques was assessed by immunohistochemical studies using anti-CD-34 antibody as a marker for endothelial cells. First, we divided the patients into M group and S group depending on the numbers of INVs in middle and shoulder region. Next, we categorized carotid plaques into four categories according to the distributions of INVs: Shoulder, Middle, Mixed, and Scarce. We then compared total area of intraplaque hemorrhage, cholesterol, and calcification, width of thinnest fibrous cap, and number of INVs between the four categories of plaque. RESULTS: The area of intraplaque hemorrhage was significantly larger in the M group than in the S group (P = 0.011). Meanwhile, symptomatic carotid stenosis was significantly more frequently associated with the Middle and Mixed than the Shoulder and Scarce categories (P < 0.01). The area of intraplaque hemorrhage was significantly different between the four groups (P = 0.022). Rupture of the fibrous cap was more frequently detected in the Middle and Mixed than the other categories (P = 0.002). CONCLUSIONS: INVs in the middle region of carotid plaques are strongly associated with symptomatic carotid stenosis, intraplaque hemorrhage, and rupture of the fibrous cap. Our findings indicate that the distribution of INVs may affect plaque vulnerability.

Efficacy and Safety of a New Delivery Assist Catheter with a Flexible, Spindle-Shaped Shaft in Mechanical Thrombectomy.

OBJECTIVE: Large-bore aspiration catheters (ACs) are used successfully in mechanical thrombectomy (MT). However, tortuous access routes prevent device navigation because of the ledge effect. The AXS Offset Delivery Assist Catheter is designed to reduce the ledge effect. The purpose of this study was to evaluate whether the Offset affects AC navigation compared with standard inner microcatheters in MT. METHODS: We retrospectively investigated 75 MTs for anterior circulation occlusion between January 2018 and May 2022 at our hospital. All MTs were performed using an AC, and 2 types of inner microcatheter (Offset or 0.021-0.027-inch standard microcatheter) were chosen randomly during AC navigation. The patients' characteristics, MT techniques, angiographic findings, and clinical outcomes were compared between the Offset and standard group (Non-Offset). The puncture to first pass of the lesion time was investigated to compare the characteristics of the inner catheters. RESULTS: The Offset group comprised 12 patients versus 63 in the Non-Offset group. Although most baseline clinical characteristics and outcomes were similar between the groups, the puncture to first pass of the lesion time was significantly shorter in the Offset versus Non-Offset group (31 ± 10 vs. 46 ± 24 minutes, respectively; P = 0.032). In the Offset group, all stent retrievers were deployed via the Offset. One artery dissection and 8 symptomatic intracranial hemorrhages occurred in the Non-Offset group; no complications occurred in the Offset group. CONCLUSIONS: The AXS Offset delivery assist catheter permitted faster and safer navigation of various ACs to the occlusions compared with standard delivery microcatheters in MT.

Analysis of Cerebrovascular Events after Coil Embolization of Unruptured Cerebral Aneurysms in Patients Taking Anticoagulants.

Objective: Antiplatelet therapy is advised to prevent thrombotic complications during endovascular coil embolization of unruptured cerebral aneurysms. Due to multiple antithrombotic treatments, bleeding risk is a concern in patients using oral anticoagulants for existing comorbidities. We investigated the hemorrhagic and ischemic events following endovascular treatment (EVT) of unruptured cerebral aneurysms in patients taking anticoagulation and antiplatelet therapy. Methods: Between March 2013 and February 2019, 262 patients undergoing EVT for unruptured cerebral aneurysms and having at least 6 months of postoperative follow-up data were included in this retrospective study. Patients taking oral anticoagulants and antiplatelet drugs for cerebral vascular events following EVT were compared with those taking only antiplatelet agents. Results: Of the 262 patients, 12 (4.6%) used anticoagulants before EVT for a preexisting condition. Cerebrovascular events after coil embolization were observed in 3 patients taking both anticoagulant and antiplatelet drugs and in 14 patients taking only antiplatelet drugs (25% vs. 5.6%, respectively, p = 0.035). Vitamin K antagonist (VKA) was administered in five patients and direct oral anticoagulants (DOACs) in seven patients. Patients taking VKA experienced cerebrovascular events, whereas those taking DOACs did not (p = 0.045). Conclusion: Our study showed that patients using oral anticoagulants and antiplatelet drugs experienced more cerebrovascular events after EVT for unruptured cerebral aneurysms. These results suggest that in patients requiring oral anticoagulants, DOACs may be more beneficial than VKA for preventing stroke occurrences after EVT.

Pooled blood volume measured by final flat-panel detector computed tomography predicts outcome after endovascular thrombectomy for acute ischemic stroke.

Background: Pooled blood volume (PBV), measured in real-time in the angiography room using an angiography system, correlates with cerebral blood volume (CBV). We examined the usefulness of PBV in endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Methods: EVT for AIS in the anterior circulation (internal carotid artery (ICA) and middle cerebral artery (MCA)) was performed in 31 cases (13 males, 18 females, average age 75.7 years). PBV was acquired using a biplane flat-panel detector (FD) angiographic system. Then, we measured the average PBV value in the M1-6 regions similar to the Alberta Stroke Program Early CT score (ASPECTS) before and after EVT. We investigated factors associated with favorable outcome at 90 days after EVT. Results: There were 13 patients (41.9%) in the good outcome group (mRS (modified Rankin Scale) ≦2) and 18 patients (58.1%) in the poor outcome group (mRS>2). In univariate analysis, NIHSS (National Institutes of Health Stroke Scale) (odds ratio [OR] 0.74, 95% CI 0.57-0.87, p < 0.0001) and post PBV value (odds ratio [OR] 1.13, 95% CI 1.03-1.29, p = 0.0086) were significantly associated with good outcome. The good outcome group had significantly higher post-thrombectomy PBV value (3.69 ± 0.32 ml/100 g versus 2.78 ± 0.93 ml/100 g, P = 0.002) compared to that of the poor outcome group. The relationship between pre-thrombectomy PBV value and outcome at 90 days was not significant. Conclusions: Post-operative PBV value measured by FD-CT (computed tomography) correlated with 90-day outcome after EVT for AIS. FD-CT-PBV would be one of the good predictors of clinical outcome.

Early Enhancement with Contrast-Enhanced Ultrasonography Relates to the Number of Small-Diameter Neovessels in the Carotid Plaque.

BACKGROUND AND PURPOSE: Intraplaque neovessels (INVs) have been recognized as a major cause of intraplaque hemorrhage and subsequent vulnerability of the carotid plaque. However, the exact mechanisms by which INVs cause intraplaque hemorrhage remain unclear. Various sizes of INVs coexist in carotid plaques pathologically, and we hypothesized that the size of INVs would be associated with carotid plaque histology, particularly in terms of intraplaque hemorrhage. Detection method of INV is important when determining whether carotid plaques are vulnerable, and contrast-enhanced ultrasonography (CEUS) is one of the most useful methods to detect them. The purpose of this study was to examine the relationship between findings from CEUS and vascular pathology obtained by carotid endarterectomy (CEA). We focused on associations between small and large INVs evaluated by CEUS and histologically defined intraplaque hemorrhage. METHODS: Participants comprised 115 patients (mean age, 73.0 ± 7.2 years; 96 men) who underwent preoperative CEUS and underwent CEA. CEUS findings were evaluated as vascular grade at 0 min (Vas-G0) and 10 min (Vas-G10) after contrast injection. Plaques were histologically evaluated quantitatively for the total area of intraplaque hemorrhage, cholesterol, and calcification and the thinnest fibrous cap. Immunohistochemical studies were conducted using anti-CD-34 antibody as a marker for endothelial cells. INVs were divided into two groups depending on diameter: small INVs, <50 µm; and large INVs, ≥50 µm. The numbers of small and large blood vessels in the plaque were quantified histologically. Associations of small and large INVs with CEUS, plaque histology, and clinical findings were assessed by uni- and multivariable analyses. RESULTS: Multivariable analyses indicated that CEUS Vas-G0 was associated with the 4th quartile of the number of small INVs compared with other quartiles, and Vas-G10 was associated with the 4th quartile of the number of large INVs. Histologically, the presence and area of intraplaque hemorrhage were associated with the number of small INVs, while the increased number of large INVs was associated with infrequent plaque disruption and thicker fibrous cap. CONCLUSIONS: Our study showed that early phase enhancement in the CEUS can help identify plaque vulnerability by predicting a larger number of small INVs. This information can also help determine treatment strategies for carotid plaque.

A refractory human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis patient with lymphoma-type adult T-cell leukemia/lymphoma: A case report and review of the literature.

RATIONALE: Adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are caused by HTLV-1, but the coexistence of both disorders is rare. The estimated incidence is approximately 3%. PATIENT CONCERNS: A 54-year-old man was unable to stand up because of spastic paraparesis 1 month after the onset. He developed lymphadenopathy in the left supraclavicular fossa 5 months after the onset. The spastic paraplegia and sensory symptoms below the thoracic spinal cord level worsened. DIAGNOSES: Both blood and cerebrospinal fluid (CSF) tests were positive for anti-HTLV-1 antibodies. The patient was diagnosed with rapidly progressive HAM/TSP. He was also diagnosed with lymphoma-type ATL by the biopsy specimen of the lymph node. CSF examination at the time of symptom exacerbation showed abnormal lymphocytes, suggesting central infiltration of the ATL in the central nervous system. INTERVENTIONS: Methylprednisolone pulse therapy and oral prednisolone maintenance therapy were administered for rapidly progressive HAM/TSP. Intrathecal injection of methotrexate was administered for the suggested central infiltration of the ATL. OUTCOMES: Methylprednisolone pulse therapy and intrathecal injection of methotrexate did not improve the patient's exacerbated symptoms. Five months later, clumsiness and mild muscle weakness of the fingers appeared, and magnetic resonance imaging showed swelling of the cervical spinal cord. Clonality analysis showed monoclonal proliferation only in the DNA of a lymph node lesion, but not in the CSF and peripheral blood cells. LESSONS: This was a case of rapidly progressive HAM/TSP associated with lymphoma-type ATL that was refractory to steroids and chemotherapy. The pathogenesis was presumed to involve ATL cells in the brain and spinal cord because of the presence of abnormal lymphocytes in the CSF, but DNA analysis could not prove direct invasion. This case suggests that when we encounter cases with refractory HAM/TSP, it should be needed to suspect the presence of ATL in the background.

Proposed definition for young-onset ischemic stroke according to its cause.

OBJECTIVE: Young-onset stroke has a greater social impact than does stroke in older persons, indicating the importance of its prevention. Although there have been studies comparing stroke risk factors in young versus older individuals, no definition of young-onset ischemic stroke has been established. Large extracranial and intracranial atheroma, small vessel disease and atrial fibrillation have a major role in cases of stroke in the elderly, while these disorders are much less frequent in young adults. The purpose of this study was to determine the optimal cut-off point for defining young-onset ischemic stroke according to its cause. METHODS: We identified 203 patients aged 65 years or less who had been admitted to our hospital between 2010 and 2017 with ischemic stroke, and we divided them into two groups according to the causes of the stroke. We allocated patients with strokes caused by small vessel occlusion, large artery atherosclerosis, atrial fibrillation, or aortic atheroma to Group A and those with strokes of other causes to Group B which included dissection, Trousseau syndrome and cerebral sinus thrombosis. We then used receiver operating characteristics curve analysis by the above groups and by sex to determine the cut-off age for defining young-onset. RESULTS: Group A comprised 131 patients (58 ± 7 years, 92 men, 39 women) and Group B 72 (45 ± 15 years, 47 men, 25 women). Receiver operating characteristics curve analysis to differentiate Group B from Group A in all participants indicated a cut-off value of 53 years of age (area under curve: 0.78 [0.71-0.85], P < 0.001), which we therefore considered should define young-onset ischemic stroke. After dividing all patients by their sex, ROC analyses identified a cut-off for age of between 53 and 54 years for men (AUC: 0.75, 95% CI: 0.65-0.85, P < 0.001). In comparison, ≤ 48 years was the cut-off for young ischemic stroke in women (AUC: 0.83, 95% CI: 0.71-0.94, P < 0.001). CONCLUSIONS: The age of 53 years may be the optimal cut-off point for young-onset ischemic stroke. Of note, the cut-off point between young- and non-young-onset stroke was 48 years for women, whereas it was 53 years for men. It is therefore important to carefully examine and treat female patients with this sex difference in mind.

Quantification of Carotid Plaque Histology Using iPlaque Software.

The iPlaque software package can use integrated backscatter (IB) values of carotid plaque to extract information on tissue composition. The aim of this study was to evaluate the association between the plaque histologic classification and IB values evaluated by iPlaque. In 49 patients undergoing carotid endarterectomy, IB values of whole carotid plaque were measured using iPlaque from the long-axis ultrasonographic image. Histologic findings of resected plaques were defined using the classification of the American Heart Association. The average IB values were statistically compared with the classification. Plaque samples from 49 patients were categorized into V, VI and VII, (13, 32 and 4 cases, respectively). Both the average and standard deviation of the IB values in each plaque sample significantly differed among the three classifications (p = 0.001). The IB of carotid plaque obtained by iPlaque analysis was associated with its histologic characteristics.

Isolated Cerebral Vasculitis in the Unilateral Middle Cerebral Artery in a Case with SLE.

A 47-year-old woman, who was diagnosed to have systemic lupus erythematosus (SLE), was admitted because she suffered a severe ischemic stroke three weeks after experiencing a transient attack of aphasia. Diffusion-weighted MRI revealed high intensity at the borderzone of the middle cerebral artery (MCA), while the proximal portion of the left MCA was occluded with its vascular wall enhanced by gadolinium. Intravenous methylprednisolone and heparin were administrated without any symptomatic benefit. She developed severe right hemiparesis with aphasia. Isolated cerebral vasculitis in the large vessel has been rarely reported in SLE patients. The presence of an enhanced vascular wall in the MRI with gadolinium could support the diagnosis.

Serum B-type natriuretic peptide level and timing of its measurement as a predictor of acute ischemic stroke outcome.

An increased B-type natriuretic peptide (BNP) level is associated with cardioembolic stroke because of atrial fibrillation. However, data associating the measurement time of BNP and clinical influence of BNP are limited. Herein, we examined the utility of BNP level for prediction of stroke severity when accounting for measurement time. We retrospectively registered 327 patients admitted within 7 days from onset of ischemic stroke. We collected information on patients' background, stroke risk factors, subtype and severity, and outcome at discharge. Measurement of BNP was performed by chemiluminescent enzyme immunoassay. Patients were divided into 3 groups according to the time of BNP measurement from disease onset. Multivariate analyses were performed to evaluate the association of BNP value with outcome after patients were grouped according to BNP measurement time. Of the 327 patients, the numbers of patients whose BNP was measured within 24 h of symptom onset, between 24 and 48 h of symptom onset, and after 48 h of symptom onset were 102, 92, and 133, respectively. Favourable outcome at discharge was negatively correlated with BNP value in patients with a BNP level measured within 24 h of stroke onset. BNP value may be useful for prediction of stroke outcome if measured within 24 h after stroke onset.

Imaging-based definition of lower uterine segment carcinoma to improve the detection sensitivity of probable Lynch syndrome.

OBJECTIVE: The aim of this study was to investigate a magnetic resonance imaging-based definition of lower uterine segment carcinoma. METHODS: We retrospectively reviewed 587 consecutive patients with endometrial cancer who underwent hysterectomy. Lower uterine segment carcinoma was determined through pathological examination and magnetic resonance imaging assessment. For imaging assessment, the location of the inner lining of the uterus was classified into four equal parts on a sagittal section image. A tumor was defined as lower uterine segment carcinoma when its thickest part was located in the second or the third part from the uterine fundus. Lower uterine segment carcinoma was further divided into lower uterine segment in a narrow sense, upon which diagnosis was exclusively based on pathological findings, and lower uterine segment in a broad sense that were the remaining lower uterine segment carcinomas except lower uterine segment carcinomas in a narrow sense. The relationship between lower uterine segment carcinoma and probable Lynch syndrome was investigated. Patients with loss of MSH2, MSH6, and PMS2 expression or those with tumors with loss of MLH1 and absence of MLH1 promoter methylation were diagnosed as probable Lynch syndrome. RESULTS: Lower uterine segment carcinoma was identified in 59 (10.2%) patients. Twenty-eight (47.5%) patients were categorized as lower uterine segment in a narrow sense and 31 (52.5%) as lower uterine segment in a broad sense. Among them, probable Lynch syndrome was identified in 12 (20.3%) cases. There was no difference in clinical profiles, including the prevalence of probable Lynch syndrome between the two categories. CONCLUSIONS: A magnetic resonance imaging-based expanded definition of lower uterine segment carcinoma is likely to secure characteristics equivalent to a conventional pathology-based definition of lower uterine segment carcinoma. The novel definition of lower uterine segment carcinoma might improve the detection of probable Lynch syndrome.

A feasibility study of sentinel lymph node mapping by cervical injection of a tracer in Japanese women with early stage endometrial cancer.

OBJECTIVE: The aim of this study was to investigate the feasibility of sentinel lymph node mapping characterized by a cervical tracer injection in endometrial cancer. MATERIALS AND METHODS: This retrospective study was carried out using data for 57 patients with endometrial carcinoma who had undergone intraoperative sentinel lymph node mapping and subsequent surgical staging. Technetium colloid and/or indocyanine green was injected into the uterine cervix and a gamma-detecting probe and/or photodynamic eye camera system was used intraoperatively to locate hot spots. RESULTS: Of the 57 patients, 52 (91.2%) had FIGO Stage I disease. Successful unilateral or bilateral mapping occurred in 54 patients (94.7%) and 46 (80.7%), respectively. The median number of sentinel lymph nodes detected was two (range, 0-5). Following sentinel lymph node mapping, 41 patients (71.9%) underwent pelvic lymphadenectomy alone and 16 (28.1%) full lymphadenectomy. The median number of lymph nodes resected was 17 (range, 8-110). Sentinel lymph nodes were involved in four patients (7.0%), two with macrometastases and two with low-volume metastases. The sensitivity and negative predictive value for detecting lymph node metastasis were both 100%. CONCLUSION: Sentinel lymph node mapping with the use of cervical tracer injection is highly feasible in Japanese women with early stage endometrial cancer.

Expression of P-REX2a is associated with poor prognosis in endometrial malignancies.

P-REX2a is a PTEN inhibitor that also activates Rac 1. No associations with P-REX2a and human endometrial cancers have been reported to date. In this study, we immunohistochemically analyzed 155 uterine endometrial malignancies for P-REX2a expression. The P-REX2a-positive tumors displayed worse prognosis independent of PTEN expression. Then, we transduced either P-REX2a expression vector or short hairpin RNAs targeting P-REX2a into 2 uterine endometrioid carcinoma cell lines, OMC-2 and JHUEM-14. Ectopic expression of P-REX2a led to increased cell proliferation only in the PTEN-expressing OMC-2 cells but did not show any change in the PTEN-negative JHUEM-14 cells or the P-REX2a-knockdown cells. Induction of P-REX2a increased and knockdown of P-REX2a decreased cell migration in both cell lines. Then, we performed expression microarray analysis using these cells, and pathway analysis revealed that the expression of members of the GPCR downstream pathway displayed the most significant changes induced by the knockdown of P-REX2a. Immunohistochemical analysis revealed that Vav1, a member of the GPCR downstream pathway, was expressed in 139 of the 155 endometrial tumors, and the expression levels of Vav1 and P-REX2a showed a positive correlation (r = 0.44, p < 0.001). In conclusion, P-REX2a enhanced cell motility via the GPCR downstream pathway independently of PTEN leading to progression of uterine endometrioid malignancies and poor prognosis of the patients.

Role of Extensive Lymphadenectomy in Early-Stage Cervical Cancer Patients With Radical Hysterectomy Followed by Adjuvant Radiotherapy.

OBJECTIVES: The objective of this study was to assess the effect of extensive lymphadenectomy on survival of early-stage cervical cancer patients with radical hysterectomy followed by adjuvant radiotherapy (RT). MATERIALS AND METHODS: A retrospective analysis was performed on early-stage patients with high-risk factors who received radical hysterectomy with lymphadenectomy followed by adjuvant RT. All patients were divided into the less than or equal to 40 dissected pelvic lymph nodes (DPLN ≤40) and greater than 40 dissected pelvic lymph nodes (DPLN >40) groups to assess the effect of extensive lymphadenectomy. Distributions of disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Significance of survival was assessed by the log-rank test. Cox proportional hazards models were applied to assess the effects of the factors on survival by univariate and multivariate analyses. RESULTS: After a median follow-up of 76 months for a total of 178 patients, 5-year DFS of the DPLN >40 group was significantly higher than that of the DPLN ≤40 group (86% vs 74%, P = 0.045). Five-year OS was comparable between the 2 groups (85% vs 78%, P = 0.49). The multivariate analysis showed that the DPLN ≤40 group was at a significantly higher risk of recurrence (hazard ratio, 2.3; 95% confidence interval (CI), 1.1-4.8; P = 0.020), whereas OS was not affected by the DPLN group (P = 0.26). Positive pelvic lymph node, parametrial invasion, histological type, and the absence of RT-combined chemotherapy remained significant prognostic factors for lower DFS and OS by the multivariate analysis. Adjusted hazard ratio of DPLN ≤40 for DFS was 1.2 (95% CI, 0.11-12; P = 0.91) in patients with negative pelvic lymph node (PLN) whereas it was 2.6 (95% CI, 1.1-5.8; P = 0.024) in patients with positive PLN. CONCLUSIONS: These results suggest that more extensive lymphadenectomy significantly improve the outcomes of patients with positive PLN even followed by adjuvant RT.

Multiple Thrombi in the Heart in Trousseau Syndrome Caused by Pancreatic Carcinoma.

A 65-year-old woman presented to our emergency room because of sudden onset of right hemiparesis with severe fatigue. Neurological examination revealed right hemiparesis with right facial numbness and an extensor planter response on the right side.Magnetic resonance imaging with diffusion-weighted imaging revealed multiple highintensity areas in both cerebral hemispheres and the right cerebellum. A diagnosis of acute stage of multiple brain infarctions caused by emboli was made. An abdominal computed tomography showed a pancreatic tumor with multiple liver metastases. High D-dimer and serum carbohydrate antigen 19-9 concentration strongly suggested Trousseau syndrome associated with pancreatic cancer. The patient had another large embolic stroke and died on day 47. Autopsy was performed. There were large thrombi in the left ventricular apex and in the left atrial appendage There was also a papillary-shaped vegetation on the aortic valve that consisted mainly of fibrin without any inflammatory cells or destruction of the valve, these findings being characteristic of NBTE. This case is remarkable in that the patient had 3 different types of cardiac thrombi in her heart associated with Trousseau syndrome.

Therapeutic significance of full lymphadenectomy in early-stage ovarian clear cell carcinoma.

OBJECTIVES: This study evaluated the therapeutic significance of full lymphadenectomy in early-stage ovarian clear cell carcinoma (OCCC). METHODS: We retrospectively reviewed records of 127 consecutive patients with pT1/pT2 and M0 OCCC who were treated between January 1995 and December 2015. We compared survival outcomes between those who did and did not undergo para-aortic lymph node dissection (PAND), and analyzed independent prognostic factors (Cox proportional hazards model with backward stepwise elimination). RESULTS: Of the 127 patients, 36 (28%) did not undergo lymphadenectomy; 12 (10%) patients underwent pelvic lymph node dissection (PLND) only; and 79 (62%) patients underwent both PLND and PAND. Of the 91 patients with lymphadenectomy, 11 (12%) had lymph node metastasis (LNM). The PAND⁻ and PAND⁺ groups did not significantly differ in age, distribution of pT status, radiologically enlarged lymph nodes, positive peritoneal cytology, capsule rupture, peritoneal involvement, and combined chemotherapy. Cox regression multivariate analysis confirmed that older age (hazard ratio [HR]=2.1; 95% confidence interval [CI]=1.0-4.3), LNM (HR=4.4; 95% CI=1.7-11.6), and positive peritoneal cytology (HR=4.2; 95% CI=2.1-8.4) were significantly and independently related to poor disease-specific survival (DSS), but implementation of both PLND and PAND (HR=0.4; 95% CI=0.2-0.8) were significantly and independently related to longer DSS. CONCLUSION: Although few in number, there are some patients with early-stage OCCC who can benefit from full lymphadenectomy. Its therapeutic role should be continuously investigated in OCCC patients at potential risk of LNM.

Radiation therapy versus surgery for patients with cervical squamous cell carcinoma who have undergone neoadjuvant chemotherapy revisited.

BACKGROUND: The therapeutic significance of neoadjuvant chemotherapy (NAC) followed by radiation therapy (RT) was negated during the early 1990s. Here, we compared post-NAC RT to surgery for chemo-sensitive cervical squamous cell carcinoma (SCC). METHODS: This study included 79 consecutive patients with cervical SCC who were treated by NAC followed by surgery (n = 49) or by definitive RT (n = 30). We compared characteristics and survival outcomes between the surgery and RT groups by their responses to NAC. RESULTS: Of the 79 patients, 70 (89%) had stage II-IV disease and 41 (52%) had radiological pelvic lymph node enlargement. The 5-year disease-specific survival (DSS) rate of the entire cohort was 66.4% (median follow-up 54 months). Fifty-five patients (70%) achieved sufficient (complete or partial) responses to NAC. Among patients with insufficient NAC responses, the 5-year DSS rate of the surgery group (55.6%) was significantly higher than the RT group (20.0%; P = 0.044). However, among patients with sufficient responses to NAC, 5-year DSS rates did not significantly differ between the surgery and RT groups (82.3 vs 78.6%; P = 0.79) even though the RT group had many more unfavorable prognostic factors and received fewer subsequent treatments than the surgery group. CONCLUSIONS: Post-NAC survival outcomes among patients with chemo-sensitive cervical SCC who then underwent RT were not inferior to those treated with surgery, and NAC did not detract from the efficacy of subsequent RT. Among selected patients who respond favorably to NAC, RT could be a less invasive substitute for surgery without compromising treatment outcomes.

Implications of para-aortic lymph node metastasis in patients with endometrial cancer without pelvic lymph node metastasis.

OBJECTIVE: The aim of this study was to confirm the incidence and implications of a lymphatic spread pattern involving para-aortic lymph node (PAN) metastasis in the absence of pelvic lymph node (PLN) metastasis in patients with endometrial cancer. METHODS: We carried out a retrospective chart review of 380 patients with endometrial cancer treated by surgery including PLN dissection and PAN dissection at Hokkaido Cancer Center between 2003 and 2016. We determined the probability of PAN metastasis in patients without PLN metastasis and investigated survival outcomes of PLN-PAN+ patients. RESULTS: The median numbers of PLN and PAN removed at surgery were 41 (range: 11-107) and 16 (range: 1-65), respectively. Sixty-four patients (16.8%) had lymph node metastasis, including 39 (10.3%) with PAN metastasis. The most frequent lymphatic spread pattern was PLN+PAN+ (7.9%), followed by PLN+PAN- (6.6%), and PLN-PAN+ (2.4%). The probability of PAN metastasis in patients without PLN metastasis was 2.8% (9/325). The 5-year overall survival rates were 96.5% in PLN-PAN-, 77.6% in PLN+PAN-, 63.4% in PLN+PAN+, and 53.6% in PLN-PAN+ patients. CONCLUSION: The likelihood of PAN metastasis in endometrial cancer patients without PLN metastasis is not negligible, and the prognosis of PLN-PAN+ is likely to be poor. The implications of a PLN-PAN+ lymphatic spread pattern should thus be taken into consideration when determining patient management strategies.

Prognostic factors for patients with brain metastasis from gynecological cancer: a significance of treatment-free interval of more than 6 months.

OBJECTIVE: Treatment-free interval has been confirmed as a significant prognostic factor in recurrent gynecological cancers. However, treatment-free interval has not been evaluated in previous studies investigating brain metastasis from gynecological malignancies. The aim of the study was to establish a predictive model of survival period after brain metastasis from gynecological cancer. METHODS: Of a total of 2848 patients with gynecological cancer, patients with brain metastasis were included in the study. Data at the time of brain metastasis diagnosis, which included primary origin, presence of extracranial metastasis, the Eastern Cooperative Oncology Group (ECOG) performance status, the number of brain metastases, brain-metastasis free-interval, treatment-free interval and treatment for brain metastasis were collected. Survival data were analyzed using Kaplan-Meier methods and Cox proportional hazards models. RESULTS: Incidences of brain metastasis were 1.7% (47/2848). Median survival period after diagnosis of brain metastasis was 20 weeks (4-5 months). The 6-, 12- and 24-month survival rates after brain metastasis were 44.0%, 22.0% and 16.5%, respectively. Cox regression analysis showed that extracranial metastasis (hazard ratio [HR], 5.2; 95% confidence interval [CI]: 1.04-26.3), ECOG performance status of 3-4 (HR, 3.1; 95% CI: 1.20-7.91), treatment-free interval of <6 months (HR, 3.8; 95% CI: 1.09-13.1), and no anti-cancer treatment for brain metastasis (HR, 3.6; 95% CI: 1.34-9.41) were significantly and independently related to poor survival. CONCLUSION: Treatment-free interval should be assessed in a future study to verify prognostic predictors of brain metastasis from gynecological cancer.

A prediction model of survival for patients with bone metastasis from uterine corpus cancer.

OBJECTIVE: The aim of the study was to establish a predictive model of survival period after bone metastasis from endometrial cancer. METHODS: A total of 28 patients with bone metastasis from uterine corpus cancer were included in the study. Data at the time of bone metastasis diagnosis, which included presence of extraskeletal metastasis, performance status, history of any previous radiation/chemotherapy and the number of bone metastases, were collected. Survival data were analyzed using Kaplan-Meier methods and Cox proportional hazard models. RESULTS: The most common site of bone metastasis was the pelvis (50.0%), followed by lumbar spine (32.1%), thoracic spine (25.0%) and rib bone (17.9%). The median survival period after bone metastasis was 25 weeks. The overall rate of survival after bone metastasis of the entire cohort was 75.0% at 13 weeks, 46.4% at 26 weeks and 42.9% at 52 weeks. Performance status of 3-4 was confirmed as an independent prognostic factor (Hazard ratio, 3.5; 95% confidence interval, 1.41-8.70) and multiple bone metastases tended to be associated with poor prognosis (Hazard ratio, 2.4; 95% confidence interval, 0.95-5.97). A prognostic score was calculated by adding up the number of these two factors. The 26-week survival rates after bone metastasis were 88.9% for those with a score of 0, 45.5% for those with a score of 1 and 0% for those with a score of 2 (P = 0.0006). CONCLUSIONS: This scoring system can be used to determine the optimal treatment for patients with bone metastasis from endometrial cancer.