Minimally invasive oesophagectomy with extended lymph node dissection and thoracic duct resection for early-stage oesophageal squamous cell carcinoma.

BACKGROUND: Oesophageal squamous cell carcinoma is an aggressive disease owing to early and widespread lymph node metastases. Multimodal therapy and radical surgery may improve prognosis. Few studies have investigated the efficacy of radical lymph node and thoracic duct resection. METHODS: Patients with oesophageal squamous cell carcinoma who underwent transthoracic minimally invasive oesophagectomy (TMIE) for cancer at Keio University Hospital between January 2004 and December 2016 were selected. Between 2004 and 2008, TMIE was performed in the lateral decubitus position without thoracic duct resection (standard TMIE). From 2009 onwards, TMIE with extended lymph node and thoracic duct resection was introduced (extended TMIE). Demographics, co-morbidity, number of retrieved lymph nodes, pathology, postoperative complications and recurrence-free survival (RFS) were compared between groups. RESULTS: Forty-four patients underwent standard TMIE and 191 extended TMIE. There were no significant differences in clinical and pathological tumour stage or postoperative complications. The extended-TMIE group had more lymph nodes removed at nodal stations 106recL and 112. Among patients with cT1 N0 disease, RFS was better in the extended-TMIE group (P < 0·001), whereas there was no difference in RFS between groups in patients with advanced disease. CONCLUSION: Extended TMIE including thoracic duct resection increased the number of lymph nodes retrieved and was associated with improved survival in patients with cT1 N0 oesophageal squamous cell carcinoma.

Outcomes following the main treatment options in patients with a leaking esophagus: a systematic literature review.

Leakage from the esophagus and gastroesophageal junction can be lethal due to uncontrolled contamination of the mediastinum. The most predominant risk factors for the subsequent clinical outcome are the patients' delay as well as the delay of diagnosis. Two major therapeutic concepts have been advocated: either prompt closure of the leakage by insertion of a self-expandable metal stent (SEMS) or more traditionally, surgical exploration. The objective of this review is to carefully scrutinize the recent literature and assess the outcomes of these two therapeutic alternatives in the management of iatrogenic perforation-spontaneous esophageal rupture as separated from those with anastomotic leak. A systematic web-based search using PubMed and the Cochrane Library was performed, reviewing literature published between January 2005 and December 2015. Eligible studies included all studies that presented data on the outcome of SEMS or surgical exploration in case of esophageal leak (including >3 patients). Only patients older than 15 years of age by the time of admission were included. Articles in other languages but English were excluded. Treatment failure was defined as a need for change in therapeutic strategy due to uncontrolled sepsis and mediastinitis, which usually meant rescue esophagectomy with end esophagostomy, death occurring as a consequence of the leakage or development of an esophagorespiratory fistula and/or other serious life threatening complications. Accordingly, the corresponding success rate is composed of cases where none of the failures above occurred. Regarding SEMS treatment, 201 articles were found, of which 48 were deemed relevant and of these, 17 articles were further analyzed. As for surgical management, 785 articles were retrieved, of which 82 were considered relevant, and 17 were included in the final analysis. It was not possible to specifically extract detailed clinical outcomes in sufficient numbers, when we tried to separately analyze the data in relation to the cause of the leakage: i.e. iatrogenic perforation-spontaneous esophageal rupture and anastomotic leak. As for SEMS treatment, originally 154 reports focused on iatrogenic perforation, 116 focused on spontaneous ruptures, and only four described the outcome following trauma and foreign body management. Only five studies used a prospective protocol to assess treatment efficacy. Regarding a leaking anastomosis, 80 reports contained information about the outcome after treatment of esophagogastrostomies and 35 reported the clinical course after an esophagojejunostomy. An overall success rate of 88% was reported among the 371 SEMS-treated patients, where adequate data were available, with a reported in hospital mortality amounting to 7.5%. Regarding the surgical exploration strategy, the vast majority of patients had an attempt to repair the defect by direct or enforced suturing. This surgical approach also included procedures such as patching with pleura or with a diaphragmatic flap. The overall reported success rate was 83% (305/368) and the in-hospital mortality was 17% (61/368). The current literature suggests that a SEMS-based therapy can be successfully applied as an alternative therapeutic strategy in esophageal perforation rupture.

Long-term functional outcomes after replacement of the esophagus with gastric, colonic, or jejunal conduits: a systematic literature review.

It is generally recognized that in patients with an intact stomach diagnosed with esophageal cancer, gastric tubulization and pull-up shall always be the preferred technique for reconstruction after an esophageal resection. However, in cases with extensive gastroesophageal junction (GEJ) cancer with aboral spread and after previous gastric surgery, alternative methods for reconstruction have to be pursued. Moreover, in benign cases as well as in those with early neoplastic lesions of the esophagus and the GEJ that are associated with long survival, it is basically unclear which conduit should be recommended. The aim of this study is to determine the long-term functional outcomes of different conduits used for esophageal replacement, based on a comprehensive literature review. Eligible were all clinical studies reporting outcomes after esophagectomy, which contained information on at least three years of follow-up after the operation in patients who were older than 18 years of age at the time of the operation. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic web-based search using MEDLINE, the Cochrane Library, and EMBASE databases was performed, reviewing medical literature published between January 2006 and December 2015. The scientific quality of the data was generally low, which allowed us to incorporate only 16 full text articles for the final analyses. After a gastric pull-up, the proportion of patients who suffered from dysphagia varied substantially but seemed to decrease over time with a mild dysphagia remaining during long-term follow-up. When reflux-related symptoms and complications were addressed, roughly two third of patients experienced mild to moderate reflux symptoms a long time after the resection. Following an isoperistaltic colonic graft, the functional long-term outcomes regarding swallowing difficulties were sparsely reported, while three studies reported reflux/regurgitation symptoms in the range of 5% to 16%, one of which reported the symptom severity as being mild. Only one report was available after the use of a long jejunal segment, which contained only six patients, who scored the severity of dysphagia and reflux as mild. Very few if any data were available on a structured assessment of dumping and disturbed bowel functions. Few high-quality data are available on the long-term functional outcomes after esophageal replacement irrespective of the use of a gastric tube, the right or left colon or a long jejunal segment. No firm conclusions regarding the advantages of one graft over the other can presently be drawn.

Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5 alpha-reductase, in healthy volunteers.

The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor of steroid 5 alpha-reductase, were investigated in healthy volunteers, with use of plasma FK143 concentrations and serum dihydrotestosterone levels as an index for pharmacologic effects. The area under the plasma concentration-time curve from zero to infinity [AUC(0-infinity)] and maximum plasma concentration [Cmax] were increased dose proportionally after oral administration (100 to 500 mg) while subjects were in the fed state. The AUC(0-infinity) and Cmax after 500 mg oral administration during fed conditions were significantly larger than those during the fasted state, suggesting an increase of the absorption of FK143. Dihydrotestosterone concentrations after a single administration of FK143 (100 to 500 mg) during fed conditions decreased to about 65% of predose values and thereafter slowly recovered to the same levels as predose values at 168 hours. A combined pharmacokinetic-pharmacodynamic model was constructed with use of changes in dihydrotestosterone concentrations. The pharmacokinetic-pharmacodynamic profiles of FK143 after repeated administration were predictable with use of the pharmacokinetic-pharmacodynamic parameters obtained after a single administration of FK143.

Angiographic manifestations in postrecanalized cerebral infarction.

In 14 stroke patients showing angiographic recanalization of the occluded internal carotid artery or middle cerebral arterial axis, the postrecanalized angiograms demonstrated several findings that have been considered to be generally rare in cerebral infarction. These findings principally consisted of narrowing of arterial caliber in six cases (43 percent), mass effect in eight cases (57 percent) and capillary blush in five cases (36 percent).

Reduction of reaction differences between human mercaptalbumin and human nonmercaptalbumin measured by the bromcresol purple method.

Although the bromcresol purple (BCP) method provides high specificity in measurements of serum albumin concentrations, we discovered a reaction difference between the values for human mercaptalbumin (HMA) and human nonmercaptalbumin (HNA) measured by the BCP. We found that the color intensity of HMA with BCP present in the reduced form in the albumin of fresh serum, was lower than for HNA. While maintaining specificity for albumin, we reduced the reaction difference between HMA and HNA, with the addition of sodium dodecylsulfate and 5,5'-dithiobis(2-nitrobenzoic acid) to the BCP reagent. The mean albumin concentration by the BCP procedure for 63 fresh sera and the 63 sera stored for 2 days at room temperature were 35.6 g/L and 38.1 g/L, respectively. Those by the modified BCP procedure were 39.8 g/L and 39.9 g/L, respectively. The difference in measured values between the fresh and stored sera which is believed to be caused by the conversion of HMA to HNA during the storage of sera was not observed in the case of the modified BCP procedure. Our modified BCP method is effective in eliminating uncertainty of the albumin concentration assigned to assay calibrators for the conventional BCP method.

Determination of proteins by a reverse biuret method combined with the copper-bathocuproine chelate reaction.

A method of protein determination has been developed which combines the biuret reaction and the copper(I)-bathocuproine chelate reaction. Protein in the specimen forms a Cu(2+)-protein chelate complex (biuret reaction) during the first step. Excess Cu2+ is reduced to Cu+ by ascrobic acid, allowing the Cu+ to form a Cu(+)-bathocuproine chelate complex during the second step. The amount of Cu(+)-bathocuproine chelate complex formed is inversely proportional to the protein concentration. The sensitivity (epsilon = 1.4 x 10(6) 1.mol-1.cm-1 against human albumin) of this method was higher than that of the original Lowry (9.8 x 10(5)), pyrogallol red (1.0 x 10(6)) and commercially available Coomassie Brilliant Blue G.250 methods (6.7 x 10(5)). The color intensities of human gamma-globulin, human globulin (fractions IV-1 and IV-4), bovine albumin, egg albumin and horse gamma-globulin against human albumin (100%) ranged from 92 to 101%. The results obtained with the present method (y) correlated well with those determined by the biuret method (r = 0.998, y = 0.98 chi - 0.002, x = 1.31, y = 1.29 g/l) in 30 diluted sera. These results confirm that this assay is similar in sensitivity to the original Lowry method, is rapid and has similar reactivity to each of the various proteins in biological fluids.

Changes in intestinal alkaline phosphatase isoforms in healthy subjects bearing the blood group secretor and non-secretor.

We found the high molecular mass intestinal alkaline phosphatase (HIAP) and normal molecular mass intestinal alkaline phosphatase (NIAP) in serum at fasting and after fatty meal by use of 6.0% polyacrylamide gel electrophoresis (PAGE) in the presence of 1% Triton X-100. HIAP only appeared in serum of Lewis blood group secretors ¿Le(a-b+)¿, and HIAP levels were dependent on ABO blood groups. Among the secretors, the highest activities of HIAP in fasting serum were observed in subjects with blood groups O and B (8.6+/-1.4 U/1; mean+/-SD) and the lowest activities were associated with blood group A (0.7+/-0.2 U/1; mean+/-SD), and the HIAP activities did not change after fatty meal. In contrast, NIAP was present in the serum of both secretors and non-secretors regardless of ABO blood group. Trace amounts of NIAP remained in fasting serum; however serum NIAP activities rose sharply after fatty meal. The remaining ratios of NIAP activity at fasting and 9 h after fatty meal of secretors were approximately the same as those of non-secretors. The electrophoretic mobility on PAGE or the apparent molecular mass estimated by gel filtration of serum NIAP in secretors was slightly different from that in non-secretors. In addition, HIAP can be normalized to NIAP on PAGE in the absence of Triton X-100, and the electrophoretic mobility of normalized-NIAP was identical to that of original NIAP in secretors. Accordingly, it can be concluded that the structure of serum NIAP in the secretor was different from that in the non-secretor, because HIAP is only formed by serum NIAP in the secretor. These results suggest that differences in serum NIAP in the secretor and the non-secretor may be closely related to the appearance of IAP in the circulation.

Cerebellar infarction with obstructive hydrocephalus.

The authors review 15 patients with acute cerebellar infarction accompanied by obstructive hydrocephalus. These patients were among 1700 consecutive patients with acute cerebrovascular disease who were examined by angiography and also, except for the initial 320 cases. by computerized tomography (CT) scan. The CT scans were helpful in diagnosis and management of the patients. It demonstrated cerebellar mass lesions as being low density, isodense, or high density, according to the amount of hemorrhage into the infarcted area. Such cerebellar mass lesions caused acute compression of the posterior fossa. The clinical picture was determined mainly by the extent of the initially infarcted area in the vertebrobasilar territory and the speed of enlargement of the subsequently developing cerebellar mass lesion. Suboccipital decompressive surgery was performed in 10 patients and was generally beneficial. The postoperative prognosis depended mainly on the presence or absence of coexisting brain-stem infarction. Five patients who were managed conservatively died during the acute stage. Prompt and correct diagnosis of this illness is required to ensure adequate therapy.

Properties of high-molecular-mass placental alkaline phosphatases in normal pregnancy sera.

We examined the appearance of high-molecular-mass placental alkaline phosphatases (HPLAPs) in the serum of normal pregnant women by means of polyacrylamide gel electrophoresis (PAGE) in the presence of Triton X-100. The HPLAPs were undetectable or only slightly detectable by PAGE in the absence of Triton X-100. The HPLAPs were detected in all sera sampled during the last trimester of pregnancy. The catalytic activities of total placental alkaline phosphatase (TPLAP) and HPLAPs were correlated (r = 0.96) and the ratio of HPLAPs/TPLAP catalytic activity was 0.20 (0.06) (mean and SD) in 40 serum samples from pregnant women. The HPLAPs appear to be formed from a common dimeric placental alkaline phosphatase (PLAP) (common-PLAP), as judged by the fact that they were formed again after removal of HPLAPs from serum by gel filtration. The formation of HPLAPs was more prominently observed with the faster fractions of gel filtration. The apparent molecular mass of the HPLAPs in pregnancy serum was 720 KDa by gel filtration. HPLAPs were not converted to common-PLAP by phosphatidylinositol-specific phospholipase (PIPL) C and PIPL-D treatments. The HPLAPs were selectively incorporated into liposomes consisting of phosphatidylcholine/cholesterol, and most of the PIPL-D-treated PLAP could from HPLAPs, while a small amount of PLAP could not form HPLAPs. On the other hand, HPLAPs in pregnant women's sera and HPLAPs prepared from partially purified PLAP in vitro could be converted to common-PLAP by brief treatment with subtilisin. However, the highly purified PLAP could not form HPLAPs in the presence of Triton X-100. These results suggest that PIPL-D-resistant and PLAP-associated serum protein may regulate the conversion of PLAP to HPLAP in the presence of Triton X-100.

Optimized Stoneley wave device by proper choice of glass overcoat.

The characteristics of a Stoneley wave propagated along an interface between a piezoelectric material and an isotropic material were investigated both theoretically and experimentally. First, the condition for the existence of Stoneley waves was shown for various piezoelectric materials. A rule of thumb for selecting the combination of the two materials was obtained. Then, LiTaO(3) was selected as the piezoelectric material and SiO(2) was selected the isotropic material. After the calculation of the Stoneley wave characteristics, actual devices were fabricated and measured. The experimental results were found to be in good agreement with the theory; zero slope temperature and high electromechanical coupling coefficient ( K(2)=1.5%) were obtained for Stoneley wave propagation between SiO(2)/X-148 degrees LiTaO(3). As a result, future surface-acoustic-wave (SAW) devices can be made without any package.

Propagation of boundary acoustic waves along a ZnO layer between two materials.

Theoretical and experimental results on boundary acoustic waves propagated along a ZnO layer sandwiched between two materials are presented. It is shown that boundary acoustic waves can exist only when the material constants of the three materials satisfy the particular conditions obtained here. Experiments on SiO(2)/ZnO/SiO(2 ) were performed to verify the theoretical prediction of the existence of boundary waves. Boundary waves were excited and received by interdigital transducers and propagated along the ZnO layer. Propagation loss was practically the same as for Rayleigh waves, indicating a proper mode of the system. The results suggest that future SAW (surface acoustic wave) devices can be made without any package.

[Non-specific neurological complaints and silent cerebral infarction].

To clarify the relationship between non-specific neurological complaints and silent cerebral infarction (SCI), we studied 82 patients (56 +/- 8 years old; mean +/- SD) who presented with at least one complaint (headache, dizziness, forgetfulness) and 76 normal volunteers with no complaints (55 +/- 7 years old). All subjects were evaluated with a questionnaire for complaints and with 0.5 T magnetic resonance imaging of the brain for the presence of SCI. Several risk factors for stroke were also studied. SCI was significantly more common in the patients (18%) than in the normal subjects (7%, p < 0.05). SCI was more common in subjects with dizziness (40%) and in those with headache (18%) than in those with no complaints (p < 0.01, p < 0.05, respectively). Dizziness and forgetfulness were closely associated with SCI (p < 0.05). Two risk factors for stroke, age and hypertension, correlated with SCI. These results clearly show that non-specific neurological complaints are closely related to SCI.