Perioperative outcomes of single-port mediastinoscope-assisted transhiatal esophagectomy for thoracic esophageal cancer.

We developed an en bloc lymphadenectomy method in the upper mediastinum with a single-port mediastinoscopic cervical approach. This study was designed to evaluate the safety and efficacy of single-port mediastinoscope-assisted transhiatal esophagectomy for thoracic esophageal cancer. The perioperative outcomes of 60 patients with thoracic esophageal cancer who underwent this operation between March 2014 and June 2016 were retrospectively analyzed. The upper mediastinal dissection including lymphadenectomy along the left recurrent laryngeal nerve, using a left cervical approach, was performed with a single-port mediastinoscopic technique, which was used to improve the visibility and handling in the deep mediastinum around the aortic arch. The lymphadenectomy along the right recurrent laryngeal nerve was performed under direct vision using a right cervical approach. Bilateral cervical approaches were followed by hand-assisted laparoscopic transhiatal esophagectomy with en bloc lymphadenectomy in the middle and lower mediastinum. Tumors were mainly located in the middle thoracic esophagus (n = 33), and most tumors were squamous cell carcinoma (n = 58). Pretreatment diagnoses were stage I, 19; II, 13; III, 24; IV, 4. Preoperative chemotherapy was performed for 40 patients. The median operation time and blood loss were 363 minutes and 235 mL, respectively. There were two patients who underwent conversion to thoracotomy. Perioperative complications were evaluated and graded according to the Clavien-Dindo (CD) and the Esophagectomy Complications Consensus Group (ECCG) classifications. Postoperatively, pneumonia was observed in four patients (CD, Grade II, 2; Grade IIIb, 2), although vocal cord palsy was more frequent (ECCG, Type I, 12; Type III, 8). The median number of thoracic lymph nodes resected was 21, and the R0 resection rate was 95%. Single-port mediastinoscope-assisted transhiatal esophagectomy is feasible, in terms of perioperative outcomes, for a radical surgery for thoracic esophageal cancer, although its safety needs to be further demonstrated.

Proximal margin length with transhiatal gastrectomy for Siewert type II and III adenocarcinomas of the oesophagogastric junction.

BACKGROUND: A gross proximal oesophageal margin greater than 5 cm is considered to be necessary for curative surgery of adenocarcinoma of the oesophagogastric junction. This study investigated whether a shorter proximal margin might suffice in the context of total gastrectomy for Siewert type II and III tumours. METHODS: The gross proximal margin was measured on stretched specimens just after resection. Relationships between gross proximal margin lengths and clinicopathological features were investigated in patients with Siewert type II and III adenocarcinoma of the oesophagogastric junction treated by R0-1 surgical resection. For survival analyses, only patients who had undergone R0 resection for pathological (p) T2-4N0-3M0 tumour via a transhiatal approach were evaluated. RESULTS: Of the 140 patients, 120 had a total gastrectomy. Two patients (1·4 per cent) had histologically positive proximal margins and another two (1·4 per cent) developed anastomotic recurrence. Of 100 patients with pT2-4N0-3M0 tumours who underwent gastrectomy via a transhiatal approach, those with gross proximal margins larger than 20 mm appeared to have better survival than those with shorter margins (P = 0·027). Multivariable analysis demonstrated that a gross proximal margin of 20 mm or less was an independent prognostic factor (hazard ratio (HR) 3·56, 95 per cent confidence interval 1·39 to 9·14; P = 0·008), as was pathological node status (HR 1·76, 1·08 to 2·86; P = 0·024). CONCLUSION: Gross proximal margin lengths of more than 20 mm in resected specimens seem satisfactory for patients with type II and III adenocarcinoma of the oesophagogastric junction treated by transhiatal gastrectomy.

Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma.

BACKGROUND: Several recent studies demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We hypothesised that plasma miRNAs concentrations contributed to potential biomarkers in patients with oesophageal squamous cell carcinoma (ESCC). METHODS: We selected three oncogenic miRNAs (miR-21, miR-184, miR-221) and one tumour suppressive miRNA (miR-375), which are frequently reported in squamous cell carcinoma, as candidate targets for this plasma miRNA assay. This study was divided into three steps: (1) Determination of appropriate plasma miRNAs in preliminary tests. (2) Evaluation of whether the plasma miRNA assays could monitor tumour dynamics. (3) Validation study on the clinical application of plasma miRNA assays in 50 ESCC patients and 20 healthy volunteers. RESULTS: (1) In preliminary tests, the plasma level of miR-21 was significantly higher (P=0.0218) and that of miR-375 (P=0.0052) was significantly lower in ESCC patients than controls. (2) The high plasma miR-21 levels reflected tumour levels in all cases (100%). The plasma level of miR-21 was significantly reduced in postoperative samples (P=0.0058). (3) On validation analysis, the plasma level of miR-21 tended to be higher in ESCC patients (P=0.0649), while that of miR-375 was significantly lower (P<0.0001) and the miR-21/miR-375 ratio was significantly higher (P<0.0001) in ESCC patients than in controls. The value of the area under the receiver-operating characteristic curve (AUC) was 0.816 for the miR-21/miR-375 ratio assay. Patients with a high plasma level of miR-21 tended to have greater vascular invasion (P=0.1554) and to show a high correlation with recurrence (P=0.0164). CONCLUSION: Detection of circulating miRNAs might provide new complementary tumour markers for ESCC.

Prediction of CCND1 amplification using plasma DNA as a prognostic marker in oesophageal squamous cell carcinoma.

BACKGROUND: We aimed to develop a new biomarker to predict cyclin D1 (CCND1) status using plasma DNA in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: We evaluated the ratio of the CCND1 (11q13) dosage to the dopamine receptor D2 (DRD2; 11q22-23) dosage (C/D ratio) as CCND1 copy number. This study was divided into three steps: (1) Determination of a cutoff value for the C/D ratio in test scale; (2) Comparison of the C/D ratio in between plasma samples and cancer tissues in ESCC patients showing high plasma C/D ratio; (3) Validation study of the clinical application of the plasma C/D ratio as a diagnostic and prognostic marker, by comparing with clinicopathologic factors in 96 ESCC patients. RESULTS: The plasma C/D ratio was significantly higher in the ESCC group than the controls (P=0.0134). A high plasma C/D ratio reflected the tumour C/D ratio, and significantly correlated with a poorer prognosis (P=0.0186). Moreover, the high C/D ratio was found to be an independent prognostic factor on multivariate analysis (P=0.0266; hazard ratio 5.988). CONCLUSION: Prediction of CCND1 amplification using plasma DNA is thought to be a promising prognostic biomarker in ESCC patients.

Circulating microRNAs in plasma of patients with gastric cancers.

BACKGROUND: We examined plasma microRNA (miRNA) concentrations from patients with gastric cancers (GCs) to assess their clinical application for diagnosing and monitoring diseases. METHODS: We initially investigated the appropriateness of plasma miRNA assay, and then compared plasma miRNA results with the expressions in cancer tissues from eight GC patients, and also compared plasma miRNAs between pre- and post-operative paired samples from 10 GC patients. Then, plasma miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b and let-7a) were analysed in 69 GC patients and 30 healthy volunteers in total. RESULTS: The initial analysis showed that miRNAs were stable and detectable in all plasma samples, and the plasma miRNA levels reflected the tumour miRNAs in most cases. The levels of these miRNAs were significantly reduced in post-operative samples. In large-scale analysis, the plasma concentrations of miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b) were significantly higher in GC patients than controls (P=0.05, 0.006, 0.008 and <0.001 respectively), whereas let-7a was lower in GC patients (P=0.002). The values of the area under the receiver-operating characteristic curve were 0.721 for the miR-106b assay and 0.879 for the miR-106a/let-7a ratio assay. CONCLUSION: Detection of circulating miRNAs might provide new complementary tumour markers for GC.

Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies.

PURPOSE: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. METHODS: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. RESULTS: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. CONCLUSION: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.

Evaluation of prognostic value and stage migration effect using positive lymph node ratio in gastric cancer.

AIMS: To detect the best cut-off value of the positive lymph node ratio (PLNR) for stratifying the prognosis and analyzing its value with regard to stage migration effect using PLNR in gastric cancer. METHODS: We retrospectively analyzed 1069 consecutive gastric cancer patients, who underwent curative gastrectomy with radical lymphadenectomy from 1997 through 2009. RESULTS: 1) The mean number of dissected lymph nodes was 42.6 in pStage I, 32.4 in pStage II and 37.1 in pStage III. The PLNR of 0.2 was proved to be the best cut-off value to stratify the prognosis of patients into two groups (P < 0.0001; PLNR <0.2 vs. PLNR ≥0.2), and patients were correctly classified into four groups: PLNR 0, PLNR 0-<0.2, PLNR 0.2-<0.4 and PLNR ≥0.4 by the Kaplan-Meier method. 2) Compared patients with the PLNR <0.2, those with the PLNR ≥0.2 had a significantly higher incidence of pT3 or greater, pN2 or greater, lymphatic invasion, vascular invasion and undifferentiated cancer. Multivariate analysis showed that the PLNR ≥0.2 was an independent prognostic factor [P < 0.0001, HR 2.77 (95% CI: 1.87-4.09)]. 2) The PLNR cut-off value of 0.2 could discriminate a stage migration effect in pN2-N3 and pStage II-III, which patients with PLNR ≥0.2 might be potentially diagnosed as a lower stage after gastrectomy. CONCLUSION: The PLNR contributes to evaluating prognosis and stage migration effect even in a single institute and enable to identify those who need meticulous treatments and follow-up in patients with gastric cancer.

Surgery for primary cardiac tumors. Clinical experience and surgical results in 60 patients.

BACKGROUND: We reviewed our clinical experience with primary cardiac tumors, attempting to clarify the surgical management of these rare entities. METHODS: Between October 1978 and November 1999, we experienced 60 surgical cases of primary cardiac tumors. There were 23 male and 37 female patients (age range, 7 months to 84 years). Tumors included the following 3 groups: myxomas (n=49), nonmyxoma benign tumors (n=3), and malignant tumors (n=8). We reviewed the presenting symptoms, diagnostic data, anatomical findings, and surgical techniques, and evaluated the surgical RESULTS. Late follow-up was 95% complete (mean follow-up, 7.7+/-7.1 years). RESULTS: Tumors produced obstructive, embolic, and/or constitutional symptoms in most cases. Generally, echocardiography alone gave sufficient information for operation. Full-thickness excision was performed in 42 patients with myxoma. Complete excision was achieved in all of the nonmyxoma benign tumors and in none of the malignancies. Early mortalities in the 3 groups were 8.2% (4/49), 0% (0/3), and 12.5% (1/8), respectively. Late mortalities were 9.5% (4/42), 0% (0/3), and 100% (7/7), respectively. One patient with myxoma had recurrence, the cause of which was likely to be inadequate resection. The late deaths in patients with malignancies were due to metastasis or local recurrence. CONCLUSIONS: Benign tumors are generally curable if surgically excised. Preoperative refractory cardiac dysfunction or embolism should be avoided by the accurate evaluation on echocardiography. The prognosis of malignant tumors is poor if they are only debulked. However, aggressive surgery that can palliate obstruction and allow time for adjuvant therapy should be carried out.

A case report of surgical treatment of quadricuspid aortic valve associated with regurgitation.

A case of a 65-year-old woman who had a quadricuspid aortic valve associated with aortic regurgitation is reported. The patient had severe aortic regurgitation and four equally divided aortic cusps. The valve abnormality was detected by a transesophageal echo and an aortography. The incomplete aortic valve was excised and replaced by a St. Jude Medical prosthesis. Although this case had no coronary abnormality, a coronary displacement is often reported in quadricuspid aortic valve cases. In order to perform an operation safely, accurate information which is obtained by a non-invasive examination of the transesoph-ageal echo is quite valuable as it can indicate the need for further preoperative examinations of the coronary arteries.

Effects of supplemental L-arginine during warm blood cardioplegia.

OBJECTIVES: Effects of supplemental L-arginine, nitric oxide precursor, during warm blood cardioplegia were assessed in the blood perfused isolated rat heart. METHODS: The isolated hearts were perfused with blood at 37 degrees C from a support rat. After 20 minutes of aerobic perfusion, the hearts were arrested for 60 minutes with warm blood cardioplegia given at 20-minute intervals. This was followed by 60 minutes of reperfusion. The hearts were divided into the following three groups according to the supplemental drugs added to the cardioplegic solution. The control group (n = 10) received standard warm blood cardioplegia. The L-ARG group (n = 10) received warm blood cardioplegia supplemented with L-arginine (3 mmol/l). The L-NAME group (n = 10) received warm blood cardioplegia supplemented with L-arginine (3 mmol/l) and L-nitro-arginine methyl ester, a competitive inhibitor of nitric oxide synthase (1 mmol/l). After 60 minutes of cardioplegic arrest, cardiac function, myocardial metabolism and myocardial release of circulating adhesion molecules were measured during reperfusion. RESULTS: Left ventricular end-diastolic pressure was significantly lower (p<0.05) in the L-ARG group than in the control group and the L-NAME group during reperfusion. Isovolumic left ventricular developed pressure, dp/dt and coronary blood flow were significantly greater (p< 0.05) in the L-ARG group during reperfusion. The L-ARG group resulted in early recovery of lactate metabolism during reperfusion. Myocardial release of circulating intercellular adhesion molecule-1 (ICAM-1) and E-selectin were significantly less (p<0.05) in the L-ARG group at 15 minutes of reperfusion. CONCLUSIONS: The results suggest that augmented nitric oxide by adding L-arginine to warm blood cardioplegia can preserve left ventricular function and ameliorate endothelial inflammation. The technique can be a novel cardioprotective strategy in patients undergoing cardiac surgery.

The effect of allogeneic or xenogeneic immune responses and preservation techniques on transplanted aortic valve grafts.

We examined the effect of allogeneic and xenogeneic immune responses on the histopathological changes in aortic valve grafts and the influence of preservation techniques on these changes. Brown Norway rats and Syrian hamsters were used as allogeneic and concordant xenogeneic donors of aortic valve grafts, respectively. The allografts and xenografts were implanted heterotopically in the abdominal aorta of Lewis rat recipients immediately after harvest (homovital), after cryopreservation, or after preservation with antibiotics at 4 degrees C (fresh preservation). Allografts and xenografts were explanted at days 7, 28 or 56 and at days 3, 7 or 14, respectively, for the histopathological examination. The allografts underwent histological changes characteristic of graft arteriosclerosis. No significant effect of cryopreservation on these changes was observed. The fresh-preserved graft was, however, predisposed to focal destruction of the elastic fibers and to early disappearance of the leaflet. The lesions in xenografts were characterized by severe destruction of the elastic fibers. Compared to homovital xenografts, both cryopreserved and fresh-preserved xenografts showed more prominent disruption of the elastic fibers, well-developed valvular and vascular thrombi and earlier disappearance of the leaflet. In conclusion, it could be assumed that failure in retention of cellular and extracellular components during fresh preservation accelerates structural deterioration of allografts. As for xenografts, even the extracellular matrix may have potential xenogeneic immunogenicity. There is a possibility of these preservation techniques reducing xenogeneic immunogenicity of the endothelial cells, probably because of loss of these cells. However, it appears that, even in this setting, other cellular and extracellular components could trigger immune responses causing structural deterioration of xenografts.

Ventricular septal defect of the atrioventricular canal type--report of a surgically treated case.

A 19-month-old male infant with Down syndrome was referred for investigation of heart murmur. An electrocardiogram showed normal axis (+100 degrees) of the QRS complex, incomplete right bundle branch block, and biventricular hypertrophy. Echocardiography revealed a ventricular septal defect (VSD) and a cleft of the anterior mitral leaflet with mild value regurgitation. The anterior mitral leaflet and the septal tricuspid leaflet attached to the same level of the ventricular septum were also delineated, however, no atrial septal defects were detected. Cardiac catheterization demonstrated pulmonary hypertension and a left to right shunt at the right ventricle. During operation, no defects in the atrial septum and no cleft of the septal tricuspid leaflet were found. Cleft of the anterior mitral leaflet, continuity between the mitral anterior leaflet and the tricuspid septal leaflet, and a VSD of the atrioventricular canal type were confirmed. The cleft of the anterior mitral leaflet and the VSD were repaired with the aid of cardiopulmonary bypass. The patient recovered uneventfully.

Coronary artery bypass surgery in a patient with myasthenia gravis.

A 73-year-old man with myasthenia gravis required quadruple coronary artery bypass grafting due to triple-vessel disease. Anesthetic management was performed with general anesthesia using a reduced dose of muscle relaxant with the aid of a neuromuscular transmission monitor. He was extubated 14 hrs after surgery without difficulty under this monitor. His postoperative course was uneventful. A patient with myasthenia gravis who required coronary artery bypass surgery was successfully performed by the deliberate preoperative evaluation of patient's myasthenic and cardiac status, and by the careful perioperative management.

[Influence of milrinone on internal mammary artery grafts].

To evaluate the effects of milrinone on blood flow in the left internal mammary artery (LIMA) grafts and hemodynamic variables, we conducted a prospective randomized study. Twenty-four patients undergoing coronary artery bypass grafting were randomized to receive milrinone treatment (Milrinone; n = 12) or no milrinone treatment (Control; n = 12). Milrinone was given after induction of anesthesia at a speed of 0.5 microgram/kg/min for 24 hours. After start of cardiopulmonary bypass (CPB), CPB perfusion flow was adjusted to 2.4 l/m2 and LIMA blood flow was measured. Blood samples for determination of plasma cAMP levels were collected and hemodynamic measurements were also assessed perioperatively. LIMA blood flow was significantly greater in Milrinone than that in Control (40 +/- 4 vs 29 +/- 4 ml/min/m2, p < 0.05). Plasma levels of cAMP were significantly (p < 0.05) greater in Milrinone than those in Control at tha start of CPB (18 +/- 1 vs 13 +/- 1 pmol/ml) and at the end of CPB (24 +/- 2 vs 17 +/- 2 pmol/ml). Systemic vascular resistance was significantly (p < 0.05) lower and cardiac index was significantly (p < 0.05) greater in Milrinone than those in Control postoperatively. With its positive inotropic and systemic vasodilator activities, milrinone may have direct vasodilator effect on LIMA.

Oxidative phosphorylation in mitochondria isolated from stressed rat heart.

Oxidative phosphorylation was measured polarographically in mitochondria isolated from rat heart. With regard to ADP/O ratio and respiratory control index, no differences were found among mitochondria isolated from normal, acutely (increased pneumatic resistance of the heart-lung preparation) and chronicly (renal hypertension) stressed heart. However, the acute stressed heart induced by strangulating the outflow tract of the heart-lung preparation showed clear depression and tendency to depression, respectively, in the level of ADP/O ratio and respiratory control index in mitochondria. The results indicate that there is no change in the oxidative phosphorylating mechanism of the myocardial mitochondria of nonfailed heart despite acute or chronic pressure loadings; however, there is an uncoupling of oxidative phosphorylation in mitochondria of the failed heart after acute strangulation of the outflow tract.

Biocompatibility of heparin-coated extracorporeal bypass circuits: new heparin bonded bioline system.

Biocompatibility of a new type of heparin-coated cardiopulmonary bypass equipment, the Bioline, was evaluated in coronary artery bypass surgery cases. The heparin-coated (H) group (n = 15; Quadrox Bioline oxygenator/reservior and Carmeda BioMedicus BP-80 centrifugal pump) was compared with the nonheparin-coated (N) group (n = 12; uncoated, otherwise similar oxygenator, centrifugal pump, tubing, and filter set). Both groups used full systemic heparinization. The peak values of neutrophil elastase, C3a, IL-6, and IL-8 at 2 h after cardiopulmonary bypass (CPB), and C3a levels at the end of CPB and at 2 h after CPB were significantly reduced in the H group compared with those of the N group. However, no statistically significant intergroup differences were observed in thrombin-antithrombin complex, D-dimer, beta-thromboglobulin, or platelet factor-4. No significant differences were observed in hemostasis time, postoperative 12 h blood loss, required amount of blood transfusion, or intubation time. In conclusion, the Bioline demonstrated partially improved biocompatibility, in terms of leukocyte and complement activation, and proinflammatory cytokine production. However, it did not improve platelet activation, coagulation, or fibrinolysis cascade under full systemic heparinization. As a result, the clinical beneficial impact seemed to be the minimum.

Plasma exchange for hyperbilirubinemia following implantation of a left ventricle assist system: a case report.

A 49-year-old patient with end-stage dilated cardiomyopathy underwent implantation of a left ventricular assist system (LVAS). Although the systemic circulation seemed to be improved, the serum total bilirubin (Tbili) level increased sharply in the early postoperative period (preoperative Tbili, 5.7 mg/dl; postoperative day 3, 33.6 mg/dl). Plasma exchange (PE) was performed 7 times from postoperative day 4, and the Tbili level decreased to 16.3 mg/dl by postoperative day 11. Thereafter, serum Tbili normalized concomitant with improved circulatory condition. The cause of the hyperbilirubinemia was considered to be temporary right ventricular dysfunction or hepatic sinusoid endothelial dysfunction. The liver function was recoverable, so PE had been effective in this case. Unfortunately, the patient suffered a midbrain infarction and ultimately died. From this experience, PE is recommended if it is judged that liver function can be preserved and circulation is adequate, but its implementation should not be delayed. It is essential that LVAS is implanted before damage occurs to end-organ function and thus prevent hyperbilirubinemia.

Surgical treatment for graft stenosis after repair of an interrupted aortic arch: report of two cases.

We report herein two cases of patients who underwent successful reoperation for graft stenosis after repair of an interrupted aortic arch (IAA). The first patient was a 10-year-old girl who suffered from upper limb hypertension 9 years after her initial operation. Cardiac catheterization revealed a pressure gradient of 55 mmHg across the repaired arch. At reoperation, a left subclavian turndown anastomosis was performed, following which the hypertension resolved and a cardiac catheterization done 5 years later demonstrated sufficient growth of the restored arch with no significant gradient. The second patient was a 17-year-old boy who suffered from general fatigue and intermittent hypertension 12 years after his initial operation. Cardiac catheterization revealed a gradient of 60 mmHg across the repaired arch. He underwent an extraanatomic ascending to descending aortic bypass employing an additional 18-mm graft, and a postoperative cardiac catheterization showed no gradient between the ascending and descending aorta. Our experience has shown that IAA should be repaired without prosthetic grafts if possible. Although extraanatomic bypass is useful for reducing the operative risks at reoperation, a large graft should be used to avoid the need for a third operation. For young children expected to outgrow a second graft, performing an endogenous anastomosis, such as a left subclavian turndown anastomosis, should be considered as an alternative.