Katsuhiko Tsukada

Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma.

The role and potential value of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. The authors retrospectively assessed the performance of 18‐F‐fluorodeoxyglucose (FDG)‐PET in the assessment of esophageal squamous cell carcinoma (SCC).

The incremental effect of positron emission tomography on diagnostic accuracy in the initial staging of esophageal carcinoma

The purpose of the current study was to assess whether [18F]fluorodeoxyglucose positron emission tomography (FDG‐PET) provides incremental value (e.g., additional information on lymph node involvement or the presence of distant metastases) compared with computed tomography (CT) in patients with esophageal carcinoma.

Usefulness of positron emission tomography for assessing the response of neoadjuvant chemoradiotherapy in patients with esophageal cancer.

BACKGROUND In this study, we retrospectively assessed the performance of 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) compared with computed tomography (CT) and esophagography for assessing the response of advanced esophageal squamous cell carcinoma (SCC) to neoadjuvant chemoradiotherapy. METHODS We studied 10 patients with thoracic esophageal SCC who received neoadjuvant chemoradiotherapy followed by surgery. Tumor response was assessed by CT, endoscopy, esophagography and FDG-PET before and after neoadjuvant treatment. RESULTS Assessment of the rate of decrease in standardized uptake value (SUV) revealed a partial response (more than 50% decrease) in 5 (50%) of the patients, and assessment of length decrease of FDG uptake showed a partial response in 9 (90%) of the patients. Comparison of the histological response and the rate of decrease of various parameters revealed significant associations between histological response and tumor length (P <0.05), SUV after neoadjuvant therapy (P <0.05), and reduction in the extent of FDG uptake (P <0.01). However histological response was not significantly correlated with the rate of reduction of SUV, for both CT and esophagography. CONCLUSIONS FDG-PET may be of considerable value for predicting the pathologic response of esophageal SCC to neoadjuvant therapy. Despite assessment of SUV before neoadjuvant therapy, low FDG uptake after therapy and reduction in the extent of FDG uptake may provide a reliable assessment of the response to therapy.

Increased expression of c-Ski as a co-repressor in transforming growth factor-β signaling correlates with progression of esophageal squamous cell carcinoma

Transforming growth factor‐β (TGF‐β) regulates cell growth inhibition, and inactivation of the TGF‐β signaling pathway contributes to tumor development. In our previous study, altered expression of TGF‐β, TGF‐β‐specific receptors and Smad4 was shown to correlate with tumor progression in esophageal squamous cell carcinoma (SCC). These components, however, were maintained normally in some patients with esophageal SCC. In our study, the mechanism by which aggressive esophageal SCC maintains these components was investigated, with particular emphasis on the participation of c‐Ski and SnoN as transcriptional co‐repressors in TGF‐β signaling. Immunohistochemistry for c‐Ski and SnoN was carried out on surgical specimens obtained from 80 patients with esophageal SCC. The expression of c‐Ski and SnoN was also studied in 6 established cell lines derived from esophageal SCC and compared to an immortalized human esophageal cell line by Western blotting. High levels of expression of c‐Ski, detected immunohistologically, were found to correlate with depth of invasion (p = 0.0080) and pathologic stage (p = 0.0447). There was, however, no significant correlation between expression of SnoN and clinicopathologic characteristics. A significant correlation between c‐Ski and TGF‐β expression was observed. Moreover, in patients with TGF‐β negative expression, the survival rates of patients with c‐Ski positive expression were significantly lower than those of patients with c‐Ski negative expression (p = 0.0486). c‐Ski was expressed at a high level in 5 of 6 cell lines derived from esophageal SCC compared to immortalized esophageal keratinocytes. Furthermore, the cyclin‐dependent kinase (CDK) inhibitor, p21 that was up‐regulated by TGF‐β signaling was expressed at a low level in the 5 cell lines. The expression of c‐Ski protein as a transcriptional co‐repressor in TGF‐β signaling seems to be correlated with tumor progression of esophageal SCC.

Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma

KAI1/CD82, a tumor metastasis suppressor gene, is correlated inversely with the progression and invasion of several tumors. It also has been reported that the KAI1 gene is related to the tumor suppressor gene p53. This study was performed to clarify the correlation between KAI1/CD82 expression and clinicopathologic characteristics and p53 expression in patients with esophageal squamous cell carcinoma (ESCC). The authors also investigated mutation of the KAI1 gene coding region to determine whether this may reduce KAI1 expression in ESCC.

Sentinel lymph nodes with technetium‐99m colloidal rhenium sulfide in patients with esophageal carcinoma

The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium‐99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging.

Predictive value of blood flow in the gastric tube in anastomotic insufficiency after thoracic esophagectomy.

Anastomotic insufficiency is considered to be one of the most serious complications associated with esophageal reconstruction. The purposes of this study were to identify (1) the relationship between anastomotic insufficiency and tissue blood flow (TBF) in the gastric tube in the perioperative period, and (2) the effects of intravenous prostaglandin E1 (PGE1) on TBF in the gastric tube. The study group consisted of 44 patients who were to undergo esophagectomy for esophageal cancer. Intraoperative and postoperative TBF on the serosal side of the gastric tube were measured by laser-Doppler tissue blood flowmetry. The TBF of the Leakage(+) group (n=5) was poorer than that of the Leakage(−) group (n=39) during the intraoperative and postoperative periods. There was a significant difference in TBF between the two groups at postoperative day (POD) 3. There was a tendency in the PGE1(+) group (n=18) to exhibit richer blood flow through the anastomosis than the PGE1(−) group (n=26), intraoperatively, but the difference was not significant. Two of five Leakage(+) cases were also in the PGE11(+) group. There was no relationship between intraoperative medication with PGE1 and incidence of leakage. The TBF of three-field lymph node dissection and reconstruction of the retrosternal route group (n=21) was poorer than that of the two-field lymph-node dissection and reconstruction of the posterior mediastinal route group (n=23). The TBF in the gastric tube after esophagectomy may be a predictor of anastomotic insufficiency. However, PGE1 treatment in the intraoperative period alone is not effective in preventing anastomotic insufficiency.RésuméLa fistule anastomotique après anastomose oesophagienne est une des complications les plus sévères. Les buts de cette étude ont été d’identifier: (1) dans la période postopératoire, les rapports entre la fistule anastomotique et le débit sanguin des tissus (DST) du tube gastrique, (2) les effets de la prostaglandine E1 (PGE1) administrée en intraveineux sur le DST du tube gastrique. Le groupe d’étude a comporté 44 patients ayant eu une œsophagectomie pour cancer de l’œsophage. Le DST a été mesuré au niveau de la séreuse du tube gastrique par une débitométrie sanguine au laser-Doppler en peropératoire et en postopératoire. Le DST mesuré en peropératoire et en postopératoire a été plus faible dans le groupe avec fistule (+) (n=5) que dans le groupe sans fistule (−) (n=39). Au jour postopératoire 3, la différence observée du DST des deux groupes a été significative. On a noté une tendance dans le groupe PGE1(+) (n=18) à un débit plus élevé à travers l’anastomose que dans le groupe PGE1(−) (n=26), en peropératoire, mais cette difference n’était pas significative. Deux des cinq cas de fistule (+) étaient dans le groupe PGE1(+). Il n’y avait aucun rapport entre la prise de PGE1 peropératoire et l’incidence de fistule. Le DST après oesophagectomie par trois champs et reconstruction par voie rétrosternale (n=21) était moins bon que celui de l’oesophagectomie par deux champs et reconstruction par voie médiastinale postérieure (n=23). Le DST du tube gastrique après oesophagectomie pourrait être un facteur prédictif de fistule anastomotique. Cependant, le traitement par PGE, pendant la période peropératoire seul n’est pas efficace dans la prévention de fistule anastomotique.ResumenLa complicación más grave de las reconstrucciones esofágicas es la insuficiencia o fuga anastomótica. Los objetivos de este trabajo fueron: (1) establecer las relaciones existentes, durante el periodo perioperatorio, entre la insuficiencia o fuga anastomótica y el flujo sanguíneo tisular (TBF) del tubo gástrico, (2) averiguar los efectos de la administración intravenosa de prostaglandina E1 (PGE1) en el TBF del tubo gástrico. Estudiamos 44 pacientes esofagectomizados por cáncer. Utilizando un flujómetro sanguíneo textura! tipo Laser-Doppler se midió, en el periodo tanto intra como postoperatorio, el TBF en la serosa del tubo gástrico. Durante estos periodos el TBF, en el grupo insuficiencia o fuga anastomótica (+) n=5 fue menor que en el grupo sin insuficiencia (−) n=39. Se constató al tercer día del postoperatorio (POD) una diferencia muy significativa del TBF entre ambos grupos. Se registró en el grupo PGE1 (+) (n=18) en relación con el grupo PGE1 (−) (n=26) una tendencia no significativa por lo que a un mayor flujo sanguíneo textural, a través de la anastomosis, se refiere. Dos de las 5 insuficiencias anastomóticas se registraron en el grupo PGE1 (+). No hubo relación alguna entre la administración intraoperatoria de PGE1 y la frecuencia de la dehiscencia. El TBF en tres áreas ganglionares tras disección y reconstrucción retroesternal (n=21) fue menor, que en dos áreas anglionares tras disección y reconstrucción mediastínica posterior (n=23). El TBF del tubo gástrico es un factor pronóstico válido de la dehiscencia o fuga anastomótica. El tratamiento intraoperatorio con PGE, no es eficaz en la prevención de la misma.

Predictive value of interleukin-8 and granulocyte elastase in pulmonary complication after esophagectomy

BACKGROUND We investigated whether or not interleukin-8 (IL-8) and granulocyte elastase (GE) can be associated with pulmonary complication after esophagectomy (the most common cause of postoperative death). METHODS We measured serial changes in the IL-8 concentration and GE activity in the plasma and bronchoalveolar lavage fluid (BALF) of 17 patients who had undergone esophagectomy, and examined the relationship between these mediators and postoperative pulmonary complication. RESULTS Pulmonary complication occurred in 6 patients (35%, Pneum+ group). Plasma IL-8 increased at the end of the surgery then decreased, but there was no significant difference between the Pneum+ group and the group without pulmonary complication (11[65%], Pneum- group). IL-8 and GE in BALF were significantly higher in the Pneum+ group than in the Pneum- group on days 1 and 3 after the operation. There was a significant and positive correlation between IL-8 and GE in BALF. CONCLUSIONS Our results indicate that IL-8 and GE in BALF may be useful for the prediction of postoperative pulmonary complication.

Expression of p53 protein related to smoking and alcoholic beverage drinking habits in patients with esophageal cancers

In esophageal squamous cell carcinoma (SCC), we used immunohistochemical analysis to further elucidate the correlation of p53 protein expression with clinicopathological factors, as well as with risk factors, such as tobacco smoking, alcohol consumption and a family history of cancer, using odds ratios (ORs). The expression of p53 protein was demonstrated in 55.1% of 89 esophageal SCC cases examined by immunohistochemistry. The expression of p53 protein did not correlate with gender, age, histological grading, lymph node metastasis, or TNM stage. The prevalence of p53 expression was significantly higher in patients with multiple primary esophageal cancers (P<0.05). p53 expression did not correlate with prognosis in univariate survival analysis. The esophageal SCC in either smokers or alcohol users was 4.67-5.83 times more likely to express p53 protein, while the likelihood of p53 expression in patients who use both tobacco and alcohol was more than 14.0 times. However, a significant association was not found between p53 expression and a family history of cancer, this having an OR as low as 1.85. The expression of p53 protein did not correlate with clinicopathological factors and prognosis in univariate and multivariate survival analyses. In contrast, tobacco smoking and alcohol consumption were shown to be strongly associated with p53 mutations in esophageal carcinogenesis.

Peritoneal interleukin‐6, interleukin‐8 and granulocyte elastase activity after elective abdominal surgery

In this study we investigated the interleukin‐8 concentration (IL‐8) and granulocyte elastase activity (GE) after elective abdominal surgery. Postoperative interleukin‐6 (IL‐6), IL‐8 concentrations and GE in the peritoneal fluid were examined in 27 patients who underwent various types of elective abdominal surgery. We compared these results with clinical parameters of surgical stress, operating time (OT) and blood loss during the operation (BL). P‐IL‐6 and P‐IL‐8 were significantly correlated with OT (P‐IL‐6; r=0.67, P<0.001: P‐IL‐8; r=0.59, P<0.001) and BL (P‐IL‐6; r=0.61, P<0.001: P‐IL‐8: r= 0.48, P<0.01). P‐IL‐8 was significantly correlated with P‐IL‐6 (r=0.68, P<0.001) and there was a positive correlation between GE and P‐IL‐8 (r=0.37, P<0.05). These findings indicate that IL‐8 might activate granulocytes in the peritoneal cavity after elective abdominal surgery and that assaying P‐IL‐6 and P‐IL‐8 is useful in assessing the hosts response to surgical stress.