A modified transabdominal cervicoisthmic cerclage with the monofilament thread: Its efficacy and safety for women with extremely short cervix due to cervical conization.

AIM: The study aimed to examine the usefulness of modified transabdominal cervicoisthmic cerclage (TAC) using monofilament thread for the prevention of preterm delivery in women with an extremely short cervix after deep conization. METHODS: We devised a monofilament thread for picking up the seromuscular layer of the site that is slightly cephalad to the internal ostium to prevent injury of the vessels around the uterine cervix. From 2017 to 2020, we performed this modified operation in eight women (nine pregnancies) at 12-16 weeks of gestation with a history of deep cervical conization. RESULTS: A modified TAC was successfully performed in all patients. There was no measurable bleeding, and all patients were discharged without postoperative complications. Their pregnancy courses after the operation were uneventful. Of nine, one patient had premature uterine contractions and underwent cesarean section at 36 weeks (preterm delivery). In the other eight pregnancies, planned cesarean section was performed after 37 weeks of gestation. The median birth weight of the babies was 2996 g (range 2604-3374 g). All patients were discharged on the sixth postoperative day without complications. CONCLUSION: A modified TAC can be safely performed and may prolong pregnancy without adverse events in patients with an extremely short cervix.

Predictive value of the sFlt-1/PlGF ratio for preeclampsia in twin pregnancies: a retrospective study.

Objective: This study aimed to investigate the efficiency of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in predicting preeclampsia (PE) within 4 weeks in twin pregnancies.Methods: Seventy-eight women with serum angiogenic markers measured at 28 + 0 to 30 + 6 weeks of gestation were enrolled. A receiver-operating characteristic curve was used to determine the sFlt-1/PlGF ratio threshold to predict PE.Results: A cutoff value for the sFlt-1/PlGF ratio of 22.2 predicted PE presence within 4 weeks.Conclusion: An sFlt-1/PlGF ratio of ≤22.2 is potentially indicative of PE absence within 4 weeks in twin pregnancies.

Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction.

OBJECTIVE: To assess whether the high soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is associated with adverse outcomes (e.g., HELLP syndrome [hemolysis, elevated liver enzymes, and low platelets], severe hypertension uncontrolled by medication, non-reassuring fetal status, placental abruption, pulmonary edema, growth arrest, maternal death, or fetal death) and a shorter duration to delivery in early-onset fetal growth restriction (FGR). METHODS: Thirty-four women with FGR diagnosed at <34.0 weeks were recruited. Serum angiogenic marker levels were estimated within 6 hours of a diagnosis of FGR. A receiver operating characteristic curve was used to determine the threshold of the sFlt-1/PlGF ratio to predict adverse outcomes. We used multivariable logistic regression analysis to examine the association between the sFlt-1/PlGF ratio and adverse outcomes. Finally, we used Kaplan-Meier analysis and the log-rank test to assess the probability of delay in delivery. RESULTS: Women who developed adverse outcomes within a week had a significantly higher sFlt-1/PlGF ratio than did those who did not develop complications. A cutoff value of 86.2 for the sFlt-1/PlGF ratio predicted adverse outcomes, with a sensitivity and specificity of 77.8% and 80.0%, respectively. Moreover, 58.4% of women with an sFlt-1/PlGF ratio ≥86.2 versus 9.1% of those with an sFlt-1/PlGF ratio <86.2 delivered within a week of presentation (p < 0.001). In multivariate analyses, an sFlt-1/PlGF ratio ≥86.2 (adjusted odds ratio 9.52; 95% confidence interval, 1.25-72.8) was associated with adverse maternal and neonatal outcomes. CONCLUSION: A high sFlt-1/PlGF ratio was associated with adverse outcomes and a shorter duration to delivery in early-onset FGR.

Association between total dose of ritodrine hydrochloride and pulmonary oedema in twin pregnancy: a retrospective cohort study in Japan.

OBJECTIVE: Pulmonary oedema is recognised as a severe side effect of ritodrine hydrochloride. Recently, the number of twin pregnancies has been increasing. Few studies have reported the association between total dose of ritodrine hydrochloride prior to delivery and pulmonary oedema in twin pregnancy. We aimed to examine this association and determine the optimal cut-off threshold of total ritodrine hydrochloride dose to predict the incidence of pulmonary oedema in twin pregnancy based on obstetric records. DESIGN: Retrospective cohort study. SETTING: Yamanashi Prefectural Central Hospital, Japan. PARTICIPANTS: Two hundred and twenty-six women with twin pregnancy who delivered at Yamanashi Prefectural Central Hospital between September 2009 and November 2016. METHODS: The obstetric records of the participants were analysed. We defined 1 unit of ritodrine hydrochloride as 72 mg per 24 hours continuous transfusion at 50 µg/min to calculate the dose of ritodrine used for tocolysis. OUTCOME MEASURES: Multivariable logistic regression analysis was performed to examine the association between total dose of ritodrine hydrochloride used for threatened preterm labour and pulmonary oedema, while controlling for potential confounding factors. Then, a receiver-operating characteristic curve was used to determine the optimal cut-off of total ritodrine dose to predict pulmonary oedema incidence. RESULTS: Mean maternal age was 32 (range, 18-46) years; 143 participants were nulliparous (63.3%), 109 had (48.2%) term deliveries and 194 (85.8%) had caesarean deliveries. The overall incidence of pulmonary oedema was 13.7% (31/226). Multivariable analysis showed that the total dose of ritodrine was significantly associated with pulmonary oedema (adjusted OR 1.02; 95% CI 1.004 to 1.03). The best cut-off point to predict the incidence of pulmonary oedema was 26 units (1872 mg) (sensitivity, 61.3%; specificity, 87.8%). CONCLUSION: Our results suggest that consideration of the total dose of ritodrine hydrochloride is helpful in the management of patients with threatened preterm labour in twin pregnancy.

Relationship between maternal hypoglycaemia and small-for-gestational-age infants according to maternal weight status: a retrospective cohort study in two hospitals.

OBJECTIVE: The relationship between pre-pregnancy body mass index (BMI) and low glucose challenge test (GCT) results by maternal weight status has not been examined. This study aimed to clarify the relationship between a low GCT result and small for gestational age (SGA) by maternal weight status. DESIGN: A retrospective cohort study in 2 hospitals. SETTING: This study evaluated the obstetric records of women who delivered in a general community hospital and a tertiary perinatal care centre. PARTICIPANTS: The number of women who delivered in both hospitals between January 2012 and December 2013 and underwent GCT between 24 and 28 weeks of gestation was 2140. Participants with gestational diabetes mellitus or diabetes during pregnancy, and GCT results of ≥140 mg/dL were excluded. Finally, 1860 women were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: The participants were divided into low-GCT (≤90 mg/dL) and non-low-GCT groups (91-139 mg/dL). The χ2 tests and multivariate logistic regression analyses were conducted to investigate the association between low GCT results and SGA by maternal weight status. RESULTS: The incidence of SGA was 11.4% (212/1860), and 17.7% (330/1860) of the women showed low GCT results. The patients were divided into 3 groups according to their BMI (underweight, normal weight and obese). When the patients were analysed separately by their weight status after controlling for maternal age, pre-pregnancy maternal weight, maternal weight gain during pregnancy, pregnancy-induced hypertension, thyroid disease and difference in hospital, low GCT results were significantly associated with SGA (OR 2.10; 95% CI 1.14 to 3.89; p=0.02) in the underweight group. CONCLUSIONS: Low GCT result was associated with SGA at birth among underweight women. Examination of maternal glucose tolerance and fetal growth is necessary in future investigations.

Modified mother-child technique using a buddy wire.

For percutaneous coronary intervention, 6 Fr guiding catheters are the current standard. However, when treating complex coronary lesions, stent delivery is sometimes difficult with a 6 Fr system because of limited back-up support. Several strategies have been proposed in order to overcome this disadvantage, including active/passive guiding- catheter support, wire support, and the anchor-balloon technique. The 4-in-6 mother-child technique is one of the most effective techniques to deliver stents into complex lesions. In the present study, we introduced a new technique in which a second guidewire was used as a buddy wire in combination with the 4 Fr mother-child technique in a case in which stent delivery via the standard 4-in-6 technique failed.

Successful treatment of a patient with penetrating injury of the esophagus and brachiocephalic artery due to migration of Kirschner wires.

Pins and wires offer the simplest and most effective tools for managing bone fractures and dislocations. Migration of these devices within the chest is rare, but can cause serious problems. The spontaneous migration of Kirschner wires from the right clavicle to the mediastinum resulted in penetrating injury of the esophagus and pseudo-aneurysm of the brachiocephalic artery in an 84-year-old patient. Two Kirschner wires were removed via a vertical incision on the right shoulder without thoracotomy and the brachiocephalic artery was replaced with a Dacron graft.

Electron spin resonance spectroscopy studies on the free radical scavenging activity of wine anthocyanins and pyranoanthocyanins.

Anthocyanins are a group of natural occurring pigments responsible for the red-blue color of grapes and many fruits and vegetables. Anthocyanins and derived pigments are of double interest, one technological, as they can be used as natural colorants, and another one due to their implication on human health through their antioxidant activity. Although there are numerous studies regarding the antioxidant activity of grape extracts as well as red wine, the free radical scavenging activity of purified anthocyanins and pyranoanthocyanins is largely unknown. In the present study, the hydroxyl and superoxide anion scavenging activities of anthocyanins and their pyruvic acid adducts were systematically investigated by electron spin resonance spectroscopy and spin trapping. The 3-glucosides of delphinidin, cyanidin, petunidin, pelargonidin and malvidin, and the pyruvic adduct of the 3-glucoside of delphinidin exhibited a potent superoxide anion radical scavenging and, to a lesser extent hydroxyl anion radical scavenging activity. The pyranoanthocyanins of cyanidin, petunidin, malvidin and pelargonidin showed a high capacity to scavenge superoxide anion radicals but did not scavenge hydroxyl radicals. Current data indicate that formation of anthocyanin adducts with pyruvic acid, which may occur during wine ageing or fruit juice processing, decreases the hydroxyl and superoxide anion scavenging and thus could decrease the antioxidant potential of these compounds.

Is a metallic stent useful for non resectable esophageal cancer?

A flexible nitinol stent was inserted to treat malignant stricture of the esophagus in 28 patients. Stenting was successful in all 28 patients, leading to an improved oral intake that was maintained for >80% of the survival period in 26 patients. Patients with tumors arising in the esophagus (n=24) were divided into two groups to compare complications and prognosis: patients who underwent stenting only (n=10); and patients who underwent stenting after radiochemotherapy (n=14). Fatal complications associated with stenting were seen in four patients (28.6%) who underwent stenting after radiochemotherapy and in one patient (10.0%) who underwent stenting only. Although survival was significantly longer for patients who underwent prior radiochemotherapy than for patients who did not, the incidence of fatal complications tended to be higher. No significant differences in background factors other than radiochemotherapy before stenting were observed between patients with fatal and non-fatal complications. Stenting was shown to represent a useful treatment for malignant stricture of the esophagus, as oral intake improved and was maintained for a long period of time in most patients. However, incidence of fatal complications was high among patients who underwent radiochemotherapy, and caution must be exercised due to the difficulty in predicting fatal complications.

Sulfation of genistein alters its antioxidant properties and its effect on platelet aggregation and monocyte and endothelial function.

Soy isoflavones have been extensively studied because of their possible benefits to human health. Genistein, the major isoflavone aglycone, has received most attention; however, it undergoes extensive metabolism (e.g. conjugation with sulfuric acid) in the gut and liver, which may affect its biological properties. This study investigated the antioxidant activity and free radical-scavenging properties of genistein, genistein-4'-sulfate and genistein-4'-7-disulfate as well as their effect on platelet aggregation and monocyte and endothelial function. Electron spin resonance spectroscopy (ESR) and spin trapping data and other standard antioxidant assays indicated that genistein is a relatively weak antioxidant compared to quercetin and that its sulfated metabolites are even less effective. Furthermore, genistein-4'-sulfate was less potent than genistein, and genistein-4'-7-disulfate even less potent, at inhibiting collagen-induced platelet aggregation, nitric oxide (NO) production by macrophages, and secretion by primary human endothelial cells of monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). The current data suggest that sulfation of genistein, with the associated loss of hydroxyl groups, decreases its antioxidant activity and its effect on platelet aggregation, inflammation, cell adhesion and chemotaxis.

Arteriovenous fistula of internal thoracic vessels.

Arteriovenous fistula of internal thoracic vessels is rare. We report a case of a 77-year-old woman with a fistula between the left internal thoracic artery and vein after a mediastinal needle biopsy through the anterior chest wall. The incidence of internal thoracic arteriovenous fistulas seems to be increasing because the number of cardiac and thoracic surgical procedures is increasing. It is important to consider an internal thoracic arteriovenous fistula as part of the differential diagnosis in patients with continuous murmur in the parasternal area.

The organization of the lamina muscularis mucosae in the human esophagus.

The structural organization of the lamina muscularis mucosae of the human esophagus was studied by light microscopy and scanning electron microscopy (SEM). The organization of the lamina muscularis mucosae varied considerably among the cervical, the thoracic, and the abdominal part of the esophagus. In the cervical part, the lamina muscularis mucosae was not well developed and only islets of the smooth muscle bundles were scattered within the connective tissue. In the thoracic part, the lamina muscularis mucosae consisted of several layers of smooth muscle bundles, individual muscle cells of which ran in a longitudinal direction. In the abdominal esophagus near the cardia, the muscular bundles in the lamina muscularis mucosae ran in various directions forming a reticular configuration. The differences in density and arrangement of the lamina muscularis mucosae are discussed in relation to the swallowing of food and submucosal invasion of esophageal cancer.

[A case of multiple lung metastases of colon cancer with long-term survival following 5'-DFUR and cimetidine therapy].

A 77-year-old woman treated for diabetes mellitus was admitted to our hospital for further examination of abnormal findings on chest plain radiograph. Many nodular shadows in both lung fields were seen on chest X ray and chest CT scan. Colonoscopic examination revealed a type 2 tumor in the ascending colon. We diagnosed this case as ascending colon carcinoma with multiple lung metastases, and performed right hemicolectomy and D1 lymph node dissection. After surgery, the patient was administered 5'-DFUR 600 mg/body/day, cimetidine 800 mg/body/day orally. Though no remarkable reduction of tumors was recognized, the increase of tumor size was relatively slow. The patient remains alive 3 years after surgery.

Coexistent multiple adenocarcinomas arising in Barrett's esophagus 23 years after total gastrectomy and esophageal small cell carcinoma.

A 69-year-old Japanese man undergoing total gastrectomy for multiple gastric ulcers at age 46 was found endoacopically to have multiple esophageal cancers in the upper, mid, and lower esophagus. Esophageal mucosa associated with tumors was replaced with columnar epithelium. He underwent total esophagectomy combined with laryngectomy, pharyngectomy, and lymph node dissection using the large bowel for reconstruction. The resected esophagus had multiple cancers, including well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and small-cell carcinoma. Barrett's mucosa consisted mainly of specialized columnar epithelium while both junctional and fundic Barrett's epithelium was observed partially but not clearly. This case is indicative of the high and totipotential carcinogenetic risk of Barrett's epithelium and the relationship between duodenal content reflux and esophageal carcinogenesis after total gastrectomy.

Lymph node metastasis could be predicted by evaluation of macrophage infiltration and hsp70 expression in superficial carcinoma of the esophagus.

Macrophages have been reported to play an important role in suppressing tumor growth, and heat shock protein 70 (HSP70) in presenting tumor specific antigens. The objective of the present study was to investigate the relationship between lymph node metastasis and these two molecular biological markers in superficial esophageal carcinoma. Subjects were 37 patients with untreated submucosal esophageal carcinoma who underwent curative surgery. Among these patients, expression of CD68-positive macrophages in the tumor stroma and expression of HSP70 in tumor cells were analyzed. The results demonstrated that expression of CD68-positive macrophages was significantly greater among patients without lymph node metastasis (p<0.0001), and a significant correlation existed between HSP70 expression and CD68 expression (p=0.0125). In superficial esophageal carcinoma, lymph node metastasis is correlated with expression of CD68-positive macrophages in tumor stroma and expression of HSP70 in tumor cells. These two markers may therefore prove useful for therapy planning.

Clinical implication of cyclin B1 in non-small cell lung cancer.

Cyclin B1 plays an important role in the mitotic cycle, in which it regulates the G2-M transition, and has been suggested to play a role in development and progression of various cancers. The present study was undertaken in order to clarify the role of the cell cycle regulator cyclin B1 in non-small cell carcinoma (NSCLC). We retrospectively investigated 174 patients with NSCLC who previously underwent complete resection. There were two study groups: the squamous cell carcinoma (SCC) group (n=62); and the non-SCC group (n=112). Expression of cyclin B1 in cancer cells was analyzed immunohistochemically. The rate of cyclin B1 positivity in cancer cells ranged from 0% to 56.5% (average 10.9%). Seventy-four cases (42.5%) were designated as cyclin B1 positive in the present study. Cyclin B1 expression was observed more frequently in SCC cases than in non-SCC cases. In SCC, cyclin B1 expression demonstrated significant correlation with gender (p<0.01) and histological type (p<0.01). In non-SCC, only gender was correlated with cyclin B1 expression. Five-year survival rates for cyclin B1-positive and cyclin B1-negative cases were 45.8 and 57.9%, and 10-year survival rates were 39.3 and 51.4%, respectively. Patients with positive cyclin B1 staining showed a lower survival rate than those with negative staining (p=0.11). The prognostic value in SCC cases was p=0.48. In non-SCC cases, the survival rate of non-SCC patients who were positive for cyclin B1 was significantly lower than that of patients who were negative (p<0.01). Using multivariate analysis, tumor size (p=0.037) and N factor (p=0.026) were found to be independent prognostic parameters. Cyclin B1 expression was not an independent prognostic factor in the present series. These data suggest that elevated levels of cyclin B1 expression may be an indicator of poor prognosis in NSCLC, particularly in non-SCC.

Chromosomal imbalance in esophageal squamous cell carcinoma: 3q gain correlates with tumor progression but not prognostic significance.

DNA copy number changes were analyzed by comparative genomic hybridization (CGH) in 53 esophageal squamous cell carcinomas (ESCC) to clarify the relationship between DNA sequence copy number aberrations and clinicopathological factors. Changes in DNA copy number were observed in all 53 ESCC patients. The average number of DNA copy number gains was 9.32 (range 1-23), most frequently located on chromosomes 3q, 5p, 8q, 11q and Xq in over 40% of tumors. Loss of DNA copy number was detected on 3p, 5q, 4p, 1p and Xp in over 20% of tumors. No statistically significant differences in the frequency of DNA copy number changes were observed. However, some loci showed correlation with clinicopathologic factors: 8q gain correlated with the pattern of tumor infiltration, 3q gain correlated with pT, 2p gain, 1p loss and 16p loss correlated with lymphatic invasion, and 3q gain correlated with clinical stage. Thus, in ESCC, gain of 3q is the only specific recurrent pattern of DNA aberration that correlates with clinicopathologic parameters, although no particular loci correlated with patient prognosis. Further CGH analysis may reveal new, recurrent genetic changes in ESCC affecting chromosomes sites that harbor genes known to participate in tumorigenesis and progression of several human malignant neoplasms.

[A case of colon cancer with liver metastases and lymph node metastases successfully treated with surgery followed by CPT-11 and 5-FU chemotherapy].

A sixty-year-old woman underwent right hemicolectomy and D2 lymph node dissection. However, a solitary liver metastasis and para-aortic lymph node metastasis were detected three months after surgery. Chemotherapy using CPT-11 and 5-FU (civ) was immediately performed. After one course of this regimen, the chemotherapeutic effect was evaluated as a partial response (PR) in the liver metastasis, and as a complete response (CR) in the para-aortic lymph node. There was a massive therapeutic effect without side effects. Two further courses of chemotherapy were performed after changing from 5-FU to 5'-DFUR. Both regions of metastasis (liver and lymph nodes) continue to exhibit CR and the patient is free from any symptoms almost one year after surgery. The authors believe that this regimen is very effective and will contribute quality of life in advanced colon cancer patients.

Prognostic significance of p27/kip1 and apoptosis in patients with colorectal carcinoma.

The protein p27/kip1 is a cyclin-dependent kinase inhibitor that regulates cell-cycle progression. In the present study, p27/kip1 expression as well as tumor cell proliferation and apoptosis were investigated in 80 colorectal carcinomas, using anti-p27/kip1 antibodies, in situ apoptosis detection kits and anti-PCNA antibodies. Immunohistochemical staining indicated that p27/kip1 was localized heterogeneously in the nuclei of cancer cells. The frequency of samples positive for p27/kip1 was 53.8% (43/80). There was no significant correlation between p27/kip1 status and clinicopathologic factors. Mean apoptotic index (AI) in p27/kip1-positive patients (3.22+/-1.65) was significantly higher than in p27/kip1-negative patients (2.46+/-1.44; p=0.033). No correlation was observed between p27/kip1 expression and the PCNA labeling index (PCNA-LI) (p=0.47). Overall survival was significantly longer for patients who were p27/kip1-positive (80.7%) compared to those who were negative (49.3%; p=0.0003). Univariate analysis revealed no significant differences between prognosis and AI or PCNA-LI. In multivariate analysis, p27/kip1 expression was found to be an independent prognostic marker (p=0.015). In conclusion, the present study shows that p27/kip1 is a potentially important prognostic and predictive marker for outcome in colorectal carcinoma. These results might be explained by the role of p27/kip1 in promoting apoptosis.

Clinical impact of thymidine phosphorylase expression in gastric cancer.

Thymidine phosphorylase (dThdPase) is an enzyme that is involved in pyrimidine nucleoside metabolism and DNA synthesis and converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU). The aim of this study was to elucidate the relationship between dThdPase expression and biological malignancy, prognosis, and sensitivity to postoperative chemotherapy, using immunohistochemical staining. We studied 148 patients with gastric cancer who underwent surgery at Department of Surgery II in Oita Medical University between 1990 and 1999. Immunohistochemical expression of dThdPase was correlated to clinicopathological factors and postoperative survival. Tumor tissue was dThdPase-positive in 112 patients. The results suggested a relationship between the degree of histological differentiation and dThdPase expression (p=0.0697). Examination of dThdPase expression based on the site of the tumor revealed that the groups with upper or lower gastric cancer included a significantly greater number of dThdPase-positive patients (p=0.0011). Analysis of the patients as a whole showed no significant difference between the survival. In the chemotherapy group, the dThdPase-positive patients tended to have a more favorable prognosis than the dThdPase-negative patients (p=0.0578). The results suggest that postoperative adjuvant chemotherapy that makes use of FU metabolic pathways may improve prognosis in patients with dThdPase-positive gastric cancer.