Combination treatment of transjugular retrograde obliteration and endoscopic embolization for portosystemic encephalopathy with esophageal varices

The treatment of chronic portosystemic encephalopathy with esophageal varices has not yet been established. We were able to control a case of chronic portosystemic encephalopathy with esophageal varices using a combination treatment of transjugular retrograde obliteration and endoscopic embolization. A 57-year-old man came to our hospital in a confused, apathetic and tremulous state. The grade of encephalopathy was II. The plasma ammonia level was abnormally elevated to 119 microg/dL, and the ICGR15 was 59%. Endoscopic examination revealed nodular esophageal varices with cherry-red spots. There were no gastric varices. Ultrasonography and CT revealed liver cirrhosis with a splenorenal shunt. We first applied endoscopic embolization for the esophageal varices before transjugular retrograde obliteration. We injected 5% ethanolamine oleate with iopamidol retrogradely into the esophageal varices and their associated blood routes under fluoroscopy and obliterated the palisade vein, the cardiac venous plexus and left gastric vein. Transjugular retrograde obliteration was performed 14 days after endoscopic embolization. Retrograde shunt venography visualized the splenorenal shunt and communicating route to the retroperitoneal vein. There was no communicating route to the azygos vein. After obliteration of the communicating route to the retroperitoneal vein with absolute ethanol, 5% ethanolamine oleate with iopamidol was injected into the splenorenal shunt as far as the root of the posterior gastric vein. After transjugular retrograde obliteration, the encephalopathy improved to grade 0 even without the administration of lactulose and branched-chain amino acid. The plasma ammonia level and ICGR15 were reduced to 62 microg/dL and 26%. We conclude that combination treatment of transjugular retrograde obliteration and endoscopic embolization is a rational, effective and safe treatment for chronic portosystemic encephalopathy complicated with esophageal varices.     

Future perspectives on the standardization of surgical treatment for esophageal cancer

The Japanese Society for Esophageal Diseases published guidelines for the treatment of esophageal cancer in December 2002. Radical surgery is indicated for T1N1 and T2,3 disease without M1 metastasis to other organs, which consists of transthoracic esophagectomy through the right chest with mediastinal and abdominal (two-field), and cervical if necessary (three-field) resection, lymphadenectomy, and esophageal reconstruction by pulling up the stomach. The survival benefit of cervical lymphadenectomy remains controversial. A randomized, controlled trial (RCT) comparing two-field and three-field resection is needed to evaluate the efficacy of cervical lymphadenectomy. In the West, especially in the USA, surgeons prefer transhiatal esophagectomy, which is illogical in cancer surgery, rather than transthoracic esophagectomy. A recent Dutch RCT comparing transhiatal and transthoracic esophagectomy reported lower morbidity and a trend toward improved long-term survival in the transhiatal group. Minimally invasive surgery for esophageal cancer is common in clinical practice today. However, there is little evidence showing that less-invasive procedures are superior to radical surgery. Further investigation is needed to determine the efficacy of thoracoscopic esophagectomy and laparoscopic mobilization of the stomach for esophageal replacement. The efficacy of neoadjuvant chemotherapy and chemoradiotherapy also remains controversial. However, the effectiveness of adjuvant chemotherapy after surgery on disease-free survival was confirmed by the Japanese Clinical Oncology Group RCT.     

Objective evaluation of shoulder pain by measuring skin impedance

The subjective nature of pain has made its objective evaluation rather difficult. Recently, skin impedance was reported to reflect pain. The purpose of this study was to determine the usefulness of measuring skin impedance in evaluating shoulder pain. Fifty-three patients with shoulder pain were examined. Skin impedance was measured by a skin impedance meter in three different conditions and was compared with the visual analog scale recorded at the same time.     

Visualizing recycling synaptic vesicles in hippocampal neurons by FM 1-43 photoconversion

Exo-endocytotic turnover of synaptic vesicles (SVs) at synapses between hippocampal neurons in culture was examined by electron microscopy (EM). We carried out photoconversion (PC) of the fluorescent endocytotic marker FM 1-43 by using 3,3'-diaminobenzidine to convert the dye signal into an electron-dense product. Electron-dense products were located almost exclusively in SVs, whose densities were bimodally distributed in two sharply demarcated populations, PC-positive (PC+) and PC-negative (PC-). The median densities of these populations did not vary with the proportion of vesicles stained within a presynaptic terminal (bouton). The proportion of PC+ SVs remained constant across consecutive thin sections of single boutons, but varied greatly from one bouton to another, indicating marked heterogeneity in exo-endocytotic activity. Our experiments indicated that only a minority of SVs were stained in most boutons after stimuli known to cause complete turnover of the functional vesicular pool. A direct spatial correlation was found between FM 1-43 fluorescent spots seen with light microscopy and PC+ boutons by EM. The correlation was clearer in isolated boutons than in clusters of boutons. Photoconversion in combination with FM dyes allows clarification of important aspects of vesicular traffic in central nervous system nerve terminals.     

Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population

The MUTYH gene encodes a DNA glycosylase that can initiate the base excision repair pathway and prevent G:C > T:A transversion by excising adenine mispaired with 8-hydroxyguanine. Biallelic germline mutations of MUTYH have been shown to predict familial and sporadic multiple colorectal adenomas and carcinomas, however, whether there is an association between single nucleotide polymorphisms (SNPs) of MUTYH and sporadic colorectal cancer (CRC) risk has remained unclear. In this study we investigated four MUTYH SNPs, IVS1+11C > T, IVS6+35G > A, IVS10–2A > G, and 972G > C (Gln324His), for an association with increased CRC risk in a population-based series of 685 CRC patients and 778 control subjects from Kyushu, Japan. A statistically significant association was demonstrated between IVS1+11T and increased CRC risk (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.012–2.030; P  = 0.042) and one of the five haplotypes based on the four SNPs, the IVS1+11T – IVS6+35G – IVS10–2A – 972C (TGAC) haplotype containing IVS1+11T, was demonstrated to be associated with increased CRC risk (OR, 1.43; 95% CI, 1.005–2.029; P  = 0.046). Subsite-specific analysis showed that the TGAC haplotype was statistically significantly ( P  = 0.013) associated with an increased risk of distal colon, but not proximal colon or rectal cancer. Furthermore, IVS1+11C > T was found to be in complete linkage disequilibrium with –280G > A and 1389G > C (Thr463Thr). The results indicated that Japanese individuals with – 280A/IVS1+11T/1389C genotypes or the TGAC haplotype are susceptible to CRC. ( Cancer Sci 2008; 99: 355–360)     

Incidence and Risk Factors of Postoperative Delirium in Patients with Esophageal Cancer

Background

Postoperative delirium is a common complication after major surgery and is characterized by acute confusion with fluctuating consciousness. The aim of this study was to investigate the incidence and risk factors of postoperative delirium in patients with esophageal cancer.

Methods

We conducted a retrospective cohort analysis of 306 consecutive patients who had undergone an esophagectomy at Keio University Hospital from January 1998 to December 2009. All data were assessed by psychiatrists, and delirium was diagnosed according to criteria of the Diagnostic and Statistical Manual Disorder, fourth edition. Univariate and multivariate analyses were performed.

Results

Postoperative delirium developed in 153 (50.0?%) of 306 patients. One hundred fourteen (37.3?%) of the 306 patients required psychoactive medication for symptoms associated with delirium. Univariate analyses showed that older age, male gender, additional flunitrazepam for sedation in intensive care unit (ICU) after surgery, longer periods of time under mechanical ventilation after surgery, longer ICU stays, occurrence of postoperative complications, and longer hospital stays were significantly associated with postoperative delirium. Multivariate analysis revealed that development of delirium was linked to older age, additional flunitrazepam in ICU, and occurrence of postoperative complication.

Conclusions

The development of postoperative delirium in patients with esophageal cancer is a problem that cannot be ignored. Our results suggest that the risk of developing delirium is associated with older age, use of flunitrazepam in ICU, and postoperative complications.     

A Randomized Trial Comparing Postoperative Adjuvant Chemotherapy with Cisplatin and 5-Fluorouracil Versus Preoperative Chemotherapy for Localized Advanced Squamous Cell Carcinoma of the Thoracic Esophagus (JCOG9907)

Background

Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing??that is, before or after surgery??for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Methods

Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival.

Results

We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P?=?0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54?C0.99, P?=?0.04), where the median follow-up of censored patients was 61.6?months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1.

Conclusions

Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.     

Randomized study of low‐dose versus standard‐dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303)

Low‐dose cisplatin and 5‐fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard‐dose cisplatin and 5‐fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78–1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3‐year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.