Clinical Outcomes of Proton Beam Therapy for Ground-Glass Opacity-Type Lung Cancer.

PURPOSE: Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC), including ground-glass opacity (GGO)-type lung cancer. However, some patients are inoperable or refuse to undergo surgery. To explore whether proton beam therapy (PBT) can be an alternative to surgical resection in these patients, this study aimed to examine the retrospective treatment outcomes of patients with GGO-type lung cancer who underwent PBT. PATIENTS AND METHODS: Patients with stage I NSCLC and GGOs who underwent PBT at the Medipolis Proton Therapy and Research Center (Kagoshima, Japan) between April 2011 and September 2015 were included. Patients were treated with a total dose of 66 GyE delivered in 10 fractions. Survival curves were calculated using the Kaplan-Meier method, and treatment-related adverse events (AEs) were assessed. RESULTS: A total of 48 patients (median age: 70.9 ± 9.2 years; men: 54.2%) were analyzed, among whom 53 tumors were observed. The 3-year overall survival rate after PBT was 91.7% (95% confidence interval [CI], 79.3-96.8%), the 3-year disease-free survival rate was 85.4% (95% CI: 71.8-92.8%), and the 3-year local control rate among 53 tumors was 92.5% (95% CI: 81.1-97.1%). During the 3-year follow-up period, 4 patients died, and 3 survived despite recurrence or metastasis. Common AEs were radiation pneumonitis (89.6%), rib fracture (27.1%), and cough (27.1%). None of the patients developed grade ≥3 treatment-related AEs. CONCLUSION: The results of this study suggest that PBT may be a promising alternative for patients with GGO-type lung cancer when surgical resection is not feasible, with excellent survival outcomes and tolerable treatment-related AEs.

Lung adenocarcinoma expressing receptor for advanced glycation end-products with primary systemic AL amyloidosis: a case report and literature review.

BACKGROUND: Receptor for advanced glycation end-products (RAGE), a receptor for amyloids, is constitutively expressed in lungs and generally observed to be downregulated in lung cancer tissues. However, increasing levels of RAGE or serum amyloids is associated with poor outcome in lung cancer patients. We report a rare case of primary systemic amyloid light-chain (AL) amyloidosis in biopsy-proven multiple organs with early-stage non-small cell lung cancer (NSCLC) that displayed strong staining for RAGE in the tumour tissue. Interestingly, compared with randomly selected lung cancer biopsy samples, including all representative histological subtypes of NSCLC and small-cell lung cancer, only the NSCLC in the present case showed strong expression for RAGE that can bind amyloids. CASE PRESENTATION: A 71-year-old woman was admitted to our hospital for comprehensive investigation of nephrotic syndrome. Computed tomography showed a small nodule in the right upper lung lobe with hilar mediastinal lymph node enlargement. Pathological examination of transbronchial biopsy samples of the nodule yielded a diagnosis of lung adenocarcinoma. Furthermore, the pathological detection of amyloid deposition in biopsy samples of a subcarinal lymph node, gastric and duodenal mucosa, cardiac muscle, and bone marrow led to a diagnosis of primary systemic AL amyloidosis with nephrotic syndrome and cardiomyopathy. In addition, RAGE was detected in lung tumour tissues surrounded by normal lung tissues with amyloid deposition. CONCLUSION: The RAGE positivity of the lung cancer cells in this case suggests an interaction between amyloid-containing tissues and RAGE-expressing cancer cells. Lung adenocarcinoma with RAGE expression may be a complication of underlying amyloidosis.

Bladder neck evaluation by perineal ultrasound before and after reconstructive surgery for pelvic organ prolapse.

PURPOSE: To study the correlation between stress urinary incontinence (SUI) and the mobility and funneling of the bladder neck (BN) by observation of pre- and postoperative course by perineal ultrasound (PUS). METHODS: We investigated 123 cases that underwent reconstructive surgery for pelvic organ prolapse (POP). We prospectively checked bladder neck mobility (BNM) during the Valsalva maneuver and funneling of the BN at rest by PUS. We defined the width multiplied by the depth of the funnel-like profile of the BN as the funneling index (FI). We checked BNM, FI, and the presence of SUI just before the operation, and we checked the postoperative course of BNM and SUI. RESULTS: When BNM was ≥10 mm before surgery, the odds ratio for accompanying SUI was 2.68 relative to BNM <10 mm (p = 0.031). When FI was ≥150 before surgery, the odds ratio for accompanying SUI was 4.12 relative to FI <150 (p = 0.004). Although postoperative BNM values were significantly improved immediately after surgery, they gradually increased within 2 years. Among the cases with preoperative SUI, the recurrence rate was significantly higher in the patients whose FI was <150 (p = 0.019). CONCLUSIONS: Our results yielded by PUS suggested that larger BNM and FI values were the causative factors of SUI. PUS may be beneficial for selecting a suitable surgical procedure for POP, and it may also be helpful for assessing surgical efficacy.

Nerve preservation in tension-free vaginal mesh procedures for pelvic organ prolapse: a cadaveric study using fresh and fixed cadavers.

The aims of this study were, using fixed and fresh cadavers, to clarify how closely the pelvic splanchnic nerve, levator ani nerve (LAN), and sacrospinous ligament (SSL) are located and to examine how to avoid nerve injury during the posterior tension-free vaginal mesh procedure (TVMP), in which mesh is applied through the SSL. Macroscopic dissection of fixed cadavers demonstrated that the LAN crossed the inside of the SSL at a point 0-18 mm medial to the ischial spine and entered the muscle at a point 12-26 mm inferior to the ischial spine and 40-55 mm anterolateral to the coccyx. Dissection after TVMP of fresh cadavers revealed that the point of penetration of mesh through the SSL was close to the LAN. To preserve the LAN, penetration of the SSL should be within 5 mm of the lower margin at a point 20-25 mm medial to the ischial spine.

A histotopographic study of the perineal body in elderly women: the surgical applicability of novel histological findings.

Female perineal structures located around the perineal body were histologically examined using semiserial sections obtained from 15 elderly female cadavers. The smooth muscle content of the perineal body was greater in multiparous women. The connective tissue of the perineal body extended inferolaterally and provided a fibromuscular mass that was 10-30 mm long mediolaterally and 3-15 mm long superoinferiorly. The lateral extension (LEX) of the perineal body occupies a space that is surrounded by the vestibular bulb, internal anal sphincter, and levator ani slings. The LEX did not directly connect to the ischiopubic bony rami but did connect indirectly via the vestibular bulb and ischiocavernosus. Thus, the LEX appears to play a critical role for maintaining the topographical relationship between the vagina and the rectum. The surgical approximation of bilateral LEX instead of levator ani may be of key importance when doing a perineorrhaphy. As pudendal nerve branches run along the inferior margin of the LEX, a mediolateral episiotomy may not be the best option.

Histological features of the rectovaginal septum in elderly women and a proposal for posterior vaginal defect repair.

To get support from morphological findings to develop a novel surgical procedure for posterior vaginal defect repair, we histologically examined the rectum-vagina interface tissues obtained from 20 elderly female cadavers. The rectovaginal septum (RVS) was defined here as an elastic fiber-rich plate (EFRP) along the posterior vaginal wall. It lined the posterior surface of the vein-rich zone of the vaginal wall and extended between the bilateral paracolpiums. The septum was more evident in the lower half of the interface than in the upper half. The RVS was often thin and interrupted. Since the RVS was not so clearly demonstrated in the upper vagina histologically, augmentation using some implant is considered to be necessary for the enterocele and high rectocele. Since the thickness and tightness of the RVS vary with the case in the lower vagina, surgical procedures for low rectocele repair should be individualized, including implant-augmentation.

Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan.

OBJECTIVE: To investigate whether somatic mutations in cell cycle checkpoint genes, TP53 and p21, are involved in the development of ovarian cancer with or without BRCA1 germline mutation. METHODS: We analyzed somatic genetic alterations of TP53 and p21 in 46 ovarian cancer patients with BRCA1 germline mutations and 93 sporadic patients, using direct sequencing for the entire coding sequences in TP53 and p21. RESULTS: TP53 somatic mutations were detected in 25 of the 46 BRCA1 cases and 40 of the 93 sporadic cases (54.3% vs. 43.0%). In contrast, p21 somatic mutations were detected in 1 of the 46 BRCA1 cases and 2 of the 93 sporadic cases (2.2% vs. 2.2%). TP53 mutations in sporadic cases more frequently occurred in exons 6-11 than those in cases with germline BRCA1 mutations (84.4% vs. 56.3%: P = 0.013). The proportion of sporadic cases with TP53 mutations in non-serous tumors (e.g. endometrioid, clear cell, or mucinous) was significantly lower than that in serous tumors (18.5% vs. 53.0%: P = 0.0038). However, there was no significant difference between the proportion of BRCA1 cases with TP53 mutation in non-serous and in serous tumors (37.5% vs. 57.9%). CONCLUSIONS: Our results suggest that somatic mutation of TP53 plays less of a role in the carcinogenesis of sporadic non-serous tumors than in that of sporadic serous tumors or BRCA1-related tumors. Furthermore, p21 somatic mutation appears to be less involved in the development of ovarian cancer than TP53 somatic mutation.

Surgical reinforcement of support for the vagina in pelvic organ prolapse: concurrent iliococcygeus fascia colpopexy (Inmon technique).

To reinforce the support of the vagina, concurrent use of iliococcygeus fascia colpopexy with the McCall culdeplasty was scheduled for primary uterine prolapse. Forty-five women with primary uterine prolapse without stress urinary incontinence were treated by McCall culdeplasty alone or McCall culdeplasty plus iliococcygeus fascia colpopexy for suspension of the upper portion of the vagina. Recurrence of vaginal support defects were carefully followed for 15-50 months. Additional iliococcygeus fascia colpopexy did not change with the axis of the vagina obtained by McCall culdeplasty, although it prolonged total operation time by 32 min and increased blood loss by 94 ml. Two cases (8.3%) had postoperative vaginal defects in the group undergoing combined procedures and seven recurrent cases (33.3%) were observed in the group undergoing McCall culdeplasty alone. The durability of the combined procedures was superior to that of the modified McCall culdeplasty alone by Kaplan-Meier analysis. These results suggest that iliococcygeus fascia colpopexy is reasonably safe and strengthens not only the attachment of the upper part of the vagina but also that of the anterolateral vaginal wall.

Immunological and endocrinological studies on lymphocyte subpopulation and medical treatment for infertility in patients with endometriosis.

We investigated the relationship between interleukin-6 (IL-6) levels and subset profiles of T lymphocyte (T-cell) and macrophage in peritoneal fluid (PF) with or without endometriosis (EM). IL-6 levels in PF with EM were significantly higher than those without EM. IL-6 producing cells with EM were analyzed in each activated mature T-cell (CD3+CD69+) and macrophage (CD14+) were 0.5 and 3.5%, respectively, whereas it was mostly negative in those without EM. Cytotoxic T-cell (CD8+CD11b-) profiles in PF with EM were also quiet different from those without EM. Cellular immunity in the peripheral blood did not change during the course of IVF-ET cycles, although plasma levels of ovarian steroid hormones significantly increased comparing with that in normal ovarian cycles. Cytotoxic T-cell type 1 (Tc1) profiles might be useful predictive values in the pregnancy outcome for infertile patients with EM.

Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer.

To define the involvement of p16/CDKN2 and p15/MTS2 tumor-suppressor genes for response to chemotherapy in primary epithelial ovarian cancer, we analyzed alterations of the gene in 45 patients who were treated with primary cytoreductive surgery followed by 6 courses of cis-diamminedichloroplatinum (II) (cisplatin)-based combination chemotherapy. Homozygous deletion of p16/CDKN2 and p15/MTS2 genes was found in 8 (18%) and 15 (33%) cases, respectively. Response to the chemotherapy was confirmed by finding at second surgery after the chemotherapy in 26 patients, resulting in 17 responders and 9 nonresponders. The abundance of gene deletion in nonresponders (56%) was significantly higher (p = 0.0463) when compared to that in responders (18%). Moreover, the deletion of genes was a significant poor prognostic factor (p = 0.0441) in advanced ovarian cancer. These results suggest that deletion of p16/CDKN2 and/or p15/MTS2 is a potential indicator for poor chemotherapy response and adverse prognosis in ovarian cancer patients.