Comparison of synchronous versus staged surgeries for patients with synchronous double cancers of the esophagus and head-and-neck.

Esophageal and head and neck (H&N) cancers often occur synchronously, this study aimed to clarify the benefits and disadvantages of synchronous and staged operations for double H&N/esophagus cancers. We retrospectively reviewed 43 patients with synchronous double cancer of H&N and esophagus treated between July 2005 and July 2014, of whom 33 patients underwent synchronous operation (SYN) and 10 underwent staged operations (STG). We compared the short-term outcomes between the groups. Operation time was longer, amount of blood loss was larger, and hospital stay was longer in the SYN group than in each single surgery of the STG group. Incidence of postoperative complications did not differ between the groups. Tracheal necrosis was observed only in the SYN group. One patient died because of postoperative bleeding in the SYN group, whereas no mortality was seen in the STG group. Both the peripheral white blood cell counts and serum CRP levels during postoperative period were significantly higher in the SYN group than each single surgery of STG group. The staged surgery strategy for patients with synchronous esophagus/H&N cancers can attenuate surgical stress and thus may increase safety.

Reconstruction after esophagectomy for esophageal cancer patients with a history of gastrectomy.

Pedicled jejunal flap and colon graft interposition are choices for esophageal reconstruction in patients with a history of gastrectomy or those who have undergone synchronous esophagogastrectomy. However, the optimal conduit in this situation is still being debated. We reviewed the literature concerning esophageal reconstruction using a conduit other than the stomach. Approximately 10 % of esophagectomized patients undergo esophageal reconstruction using pedicled jejunum or colon interposition in Japan. The jejunal graft and colon graft are selected evenly, although the percentage of jejunal graft use is gradually increasing. Microvascular supercharge was performed in most of the reports of pedicled jejunal graft reconstruction, whereas vascular enhancement was not popularly used in the reports of colon graft interposition. Although the incidences of graft loss and anastomotic leakage were comparable between grafts, mortality rates seem to be higher in patients who undergo colon graft reconstruction than in those who undergo reconstruction with a jejunal graft. Prospective comparisons of short-term outcomes as well as long-term quality of life are needed to identify the best method of reconstruction.

Mediastinal Adiposity Influences the Technical Difficulty of Thoracic Procedure in Minimally Invasive Esophagectomy.

BACKGROUND: Obesity is considered to influence the difficulty of surgery. However, whether mediastinal adiposity influences the difficulty of the thoracic procedure in minimally invasive esophagectomy (MIE) remains unclear. METHODS: Computed tomography volumetry was performed in 142 patients who underwent MIE between 2012 and 2014. We measured abdominal visceral fat area (AVFA) at the umbilicus level and mediastinal fat area (MFA) at the tracheal carina level. The influence of MFA on the difficulty of the thoracic procedure was assessed using the thoracic procedure duration as a parameter, and the effect of MFA on morbidity after MIE was assessed. RESULTS: MFA was significantly smaller than AVFA (p < 0.01). There was a positive correlation between them (p < 0.01). A significant positive correlation was observed between MFA and thoracic procedure duration (p < 0.01). Multivariate analysis revealed that MFA was independently correlated with prolonged thoracic procedure duration (p < 0.01). Regarding postoperative complications associated with the thoracic procedure, there were no significant differences in MFA between patients with or without pneumonia and those with or without chylothorax. Patients who experienced recurrent laryngeal nerve palsy (RLNP) had greater MFA than those who did not (p = 0.04). Multivariate analysis revealed that MFA was a significant predictor of the occurrence of RLNP (p = 0.04). CONCLUSIONS: Although the extent of mediastinal adiposity was much lesser than that of abdominal visceral adiposity, it could be a predictor of the difficulty of the thoracic procedure as well as the risk of RLNP in MIE.

Spirometric Lung Age Predicts Postoperative Pneumonia After Esophagectomy.

BACKGROUND: Despite advances in treatment, postoperative pneumonia remains a major problem after esophagectomy. Lung age has been proposed as a comprehensive indicator for respiratory function. The aim of this study is to reveal the efficacy of lung age in predicting occurrence of pneumonia after esophagectomy. METHODS: We assessed 342 consecutive patients who underwent subtotal esophagectomy for primary esophageal cancer from 2011 to 2014. Lung age was calculated from the preoperative spirometric test using the methods advocated by the Japanese Respiratory Society. We investigated factors predicting the occurrence of postoperative pneumonia after esophagectomy. RESULTS: The incidence of postoperative pneumonia was 28.9 %. According to the Clavien-Dindo classification, grade II and grade III-V pneumonia were observed in 21.3 and 7.6 % patients, respectively. In multivariate logistic regression analysis for the factors predicting the occurrence of postoperative pneumonia, higher lung age (p = 0.010) and lower body mass index (p = 0.006) were independent factors. Patients with grade III-V pneumonia tended to have higher lung age than those with grade II pneumonia (p = 0.084). In addition, lung age was significantly higher in patients who experienced pneumonia within postoperative days 7 than those who experienced pneumonia after postoperative days 7 (p = 0.028). CONCLUSION: Spirometric lung age was associated with occurrence, severity, and time of onset of postoperative pneumonia after esophagectomy. This simple parameter deserves a greater consideration as a predictor of postoperative pneumonia after esophagectomy and can support both surgeons and patients in understanding the status of respiratory function.

Factors influencing difficulty of the thoracic procedure in minimally invasive esophagectomy.

BACKGROUND: Minimally invasive esophagectomy (MIE) is being increasingly performed worldwide. When performing MIE, we sometimes experienced difficulties due to a narrow upper mediastinum or a middle to lower thoracic esophagus hidden by the projection of the vertebral body. However, there were no reports regarding the influence of anatomical factors on the difficulty of performing MIE. The aim of this study was to evaluate whether anatomical factors could be related to the difficulty of the thoracic procedure in MIE. METHODS: We investigated 87 consecutive patients undergoing MIE for primary esophageal cancer between 2013 and 2015 and created novel indices to assess the upper mediastinal narrowness and vertebral body projection at middle thoracic part on preoperative computed tomography images. We assessed clinicopathological and anatomical factors and determined the factors influencing the thoracic procedural difficulty in MIE. The thoracic procedure duration was selected as the variable representing technical difficulty. RESULTS: The mean thoracic procedure duration was 280.2 ± 52.5 min. There were no significant correlations between the indices and patient factors such as age, sex, and body mass index. Meanwhile, there was a significant correlation between the upper mediastinal narrowness and the vertebral body projection (p < 0.01). Of the clinicopathological and anatomical factors, blood loss during the thoracic procedure, thoracic duct resection, and vertebral body projection independently were related to the prolonged thoracic procedure duration in multiple linear regression analysis (p = 0.01, 0.03, and <0.01, respectively). The other factors including upper mediastinal narrowness were not statistically significant. CONCLUSIONS: This is the first study to reveal the influence of anatomical factors on the difficulty of the thoracic procedure in MIE. The vertebral body projection at middle thoracic part appears to be a useful tool for predicting the thoracic procedural difficulty in MIE preoperatively.

Clinical Impact of Abdominal Fat Distribution on Prognosis After Esophagectomy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Excessive visceral fat may promote cancer development and progression because of metabolic derangements. The purpose of this study was to clarify the impact of abdominal fat distribution on patient prognosis after esophagectomy for esophageal squamous cell carcinoma (ESCC). METHODS: Computed tomography volumetry was performed in 150 patients who underwent curative esophagectomy for ESCC between 2012 and 2013. Visceral fat area (VFA) and subcutaneous fat area (SFA) at umbilicus level were measured, and the VFA/SFA ratio was calculated in each patient. Prognoses of the patients were compared between groups classified according to VFA/SFA ratio. RESULTS: Both relapse-free survival and overall survival of the low VFA/SFA group were significantly better than those of the high VFA/SFA group (log-rank test p = 0.005, p = 0.01). Univariate analysis also found that low VFA/SFA ratio significantly predicted an increase in relapse-free and overall survival. In multivariate analysis, low VFA/SFA ratio was an independent factor for relapse-free survival [p = 0.042, hazard ratio (HR) 0.12, 95 % confidence interval (CI) 0.01-0.93]. In addition, low VFA/SFA ratio tended to be a significant variable that predicted better overall survival (p = 0.057, HR 0.14, 95 % CI 0.01-1.05). CONCLUSIONS: Low VFA/SFA ratio was significantly associated with better prognosis in patients who undergo curative esophagectomy for ESCC. Abdominal fat distribution may influence the biological features of ESCC.

Efficacy of Staged Treatment Strategy for Patients with Synchronous Double Cancers of the Esophagus and Head and Neck: A Retrospective Study.

BACKGROUND: Synchronous occurrence of esophageal and head and neck (H&N) cancers is frequently observed. METHODS: We retrospectively reviewed the records of 109 patients with synchronous double cancers of the esophagus and H&N treated between 2005 and 2011. Fifty-one patients underwent synchronous treatment and 58 underwent staged treatment. We measured the delay in treatment for the second cancer in the staged treatment group and evaluated how many patients experienced progression of the second cancer during the first cancer treatment. Overall survival (OS) was analyzed in 100 patients who underwent potentially curative treatment. RESULTS: Synchronous treatment strategy was frequently selected for patients with both advanced cancers (77 %) compared with those who had early cancers in either or both organs (43 %) (P = 0.02). The median delay in the treatment for the second cancer was 80 days; 77.5 days in the H&N-first group and 96 days in the esophagus-first group. Only one patient experienced stage progression during the waiting period. There was no significant difference in OS between the synchronous treatment group and the staged treatment group (P = 0.73), and no significant difference in OS among patients who had advanced cancer in the H&N, esophagus, or both. CONCLUSIONS: Prognosis of patients with synchronous cancers depends on that of the more advanced cancer, and waiting for treatment of early cancers may not influence survival. The staged treatment strategy is acceptable when either of the double cancers is at an early stage.

Salvage Esophagectomy After Definitive Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: Who Really Benefits from this High-Risk Surgery?

PURPOSE: The aim of this study was to identify good candidates for salvage esophagectomy after definitive chemoradiotherapy (dCRT), based on safety and survival. METHODS: Sixty-three patients who underwent salvage esophagectomy, after dCRT, at the Cancer Institute Hospital, Tokyo, Japan, between 1988 and 2013, were retrospectively analyzed. Short-term outcomes were evaluated by reviewing postoperative complications, length of postoperative hospital stay, and mortality. Survival rates were calculated using the Kaplan-Meier method, and statistical significance was determined using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses of overall survival. Univariate logistic regression analysis was used to identify factors related to R0 resection. RESULTS: Postoperative complications occurred in 41 patients (65.1 %), and the mortality rate was 7.9 %. In-hospital deaths did not occur among patients with less advanced tumors prior to dCRT (cT1-2 and cN0), or among those who had previously achieved a complete response (CR); the 3- and 5-year overall survival rates were 29.8 % and 15.0 %, respectively. Univariate analysis revealed that residual disease, tumor depth, dCRT response, lymph node metastasis, and time to relapse were significant factors affecting overall survival. Multivariate analysis demonstrated that R0 resection and ypT0-2 tumors were significant, favorable prognostic factors in patients undergoing salvage esophagectomy. In addition, cT1-2 tumors, initially resectable tumors, ycT1-2 tumors, and relapse after CR were factors predicting R0 resection. CONCLUSIONS: Based on both short- and long-term outcomes, patients with pretreatment or preoperative T1-2 tumors and those with relapse after CR are good candidates for salvage esophagectomy.

Intussusception causing postoperative intestinal obstruction following free jejunum transfer in adults: two case reports and review of the literature.

Intussusception is a rare cause of postoperative intestinal obstruction in adults. We experienced two cases of bowel obstruction due to the jejuno-jejunal intussusception after harvest of a free jejunum graft for reconstruction after cervical esophagectomy. Bowel obstruction occurred early in the postoperative course, and reoperations were needed in both cases. In both case, the anastomotic site was resected and re-anastomosed in a side-to-side fashion. Recurrence of intussusception has not been observed. In the literature, such a complication has been documented in two case series and a case report. The reported incidence of postoperative intussusception of the case series was 2.8% and 7.4%, respectively. The jejuno-jejunal anastomoses were performed with end-to-end fashion by two layered hand-sewn suture (Albert-Lembert method) in all cases reported. In order to prevent the occurrence of postoperative intussusception, we recommend to harvest a free jejunal graft as far from the Treitz ligament as possible and to avoid reconstruction by an Albert-Lembert end-to-end anastomosis.

Usefulness and clinical significance of quantitative real-time RT-PCR to detect isolated tumor cells in the peripheral blood and tumor drainage blood of patients with colorectal cancer.

The clinical significance of isolated tumor cells (ITC) circulating in the blood of patients with colorectal cancer is unclear. In this study, we investigated the relationship between the presence of ITC that express carcinoembryonic antigen (CEA) and/or cytokeratin 20 (CK20) transcripts in the blood and the clinicopathological findings and prognosis using the quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. We studied peripheral blood and tumor drainage blood from 167 patients with colorectal cancer. Quantitative real-time RT-PCR assay was able to detect one tumor cell in 3x10(6) peripheral blood mononuclear cells. Applying a cut-off value, CEA and/or CK20 (CEA/CK20) were detected in 10.2% (17/167) of the patients' preoperative peripheral blood samples and 34.1% (57/167) of the patients' tumor drainage blood samples. In the relationship between the CEA/CK20 of the blood and the clinicopathological factors, a significant correlation was demonstrated between the positivity of marker genes and the depth of invasion, venous invasion, lymph node metastasis, liver metastasis or stage. The disease-free and overall survival of patients with CEA/CK20-positive peripheral or tumor drainage blood was significantly shorter than that of marker gene-negative patients. CEA/CK20 transcripts in tumor drainage blood were independent factors for prognosis in disease-free survival and overall survival. These results suggest that detecting CEA/CK20 mRNA in tumor drainage blood by real-time RT-PCR has prognostic value in patients with colorectal cancer. Large scale and long-term clinical studies are needed to confirm the prognostic value of genetically detecting ITC in the peripheral blood.

Global analysis of altered gene expressions during the process of esophageal squamous cell carcinogenesis in the rat: a study combined with a laser microdissection and a cDNA microarray.

The genetic alterations that occur during esophageal tumorigenesis have yet to be determined. We previously established a Wister rat carcinogenesis model of esophageal squamous cell carcinoma. To understand more about the molecular mechanisms during carcinogenesis, we produced esophageal neoplastic lesions by administering N-amyl-N-methylnitrosamine and 12-O-tetradecanoylphorbol-13-acetate to rats. We used laser microdissection to specifically isolate the cells from the normal epithelium, papilloma, dysplasia, and invasive carcinoma. Using a cDNA microarray representing 14,815 clones, we then analyzed the gene expression profiles for each esophageal lesion. The number of differentially expressed genes compared with the normal control dramatically increased in a step-by-step fashion from normal epithelium (1,151 +/- 119 genes) to papilloma (1,899 +/- 543 genes), dysplasia (1,991 +/- 193 genes), and invasive carcinoma (2,756 +/- 87 genes). A hierarchical clustering analysis showed that the three stages of normal epithelium, dysplasia (papilloma), and invasive carcinoma could be clearly classified, whereas the gene expression patterns of papilloma and dysplasia were indistinguishable. Using the Fisher criterion, we also identified 50 genes whose expression level had either significantly increased or decreased in a step-by-step manner from the normal epithelium to dysplasia and then finally to invasive carcinoma. Many of these genes were not previously known to be associated with esophageal carcinogenesis. The present findings in our rat model thus seem to provide us with a better understanding of the molecular alterations that occur during esophageal carcinogenesis and hopefully will also help lead to the development of novel diagnostic and therapeutic targets.

Cyclin-dependent kinase 1 gene expression is associated with poor prognosis in gastric carcinoma.

PURPOSE: A low expression level of cyclin-dependent kinase (Cdk) inhibitor p27 is associated with high aggressiveness and poor prognosis of various carcinomas. Human Cdk subunit 1 (Cks1), as well as S-phase kinase-associated protein 2 (Skp2), is an essential and specific factor in the p27 proteolysis by SCF(Skp2) ubiquitin ligase. The purpose of this study is to clarify the clinical significance of Cks1 expression and the relationship between Cks1 and p27 expression in gastric carcinomas. EXPERIMENTAL DESIGN: We measured Cks1 expression using quantitative reverse transcription-PCR in 76 human gastric carcinomas and p27 expression using immunohistochemistry in 28 cases. Moreover, we established Cks1- and/or Skp2-transfected gastric carcinoma cell lines and assessed the relationship between Cks1, Skp2, and p27 expression using quantitative reverse transcription-PCR and Western blot analysis. RESULTS: Cks1 high expression was correlated with poor prognosis (P < 0.05) and Cks1 expression was inversely correlated with the expression level of p27 protein in gastric carcinomas (P < 0.05). Using combined Skp2 data [T-a. Masuda, Cancer Res., 62: 3819-3825, 2002], 88.9% of the Cks1/Skp2 double-high cases expressed a low level of p27 protein and showed the poorest prognosis (P < 0.05). Western blot analysis showed that Cks1/Skp2-cotransfected cells expressed a much lower level of p27 protein than the controls. CONCLUSIONS: These findings indicate that Cks1, as well as Skp2, regulates the expression level of p27 protein in gastric carcinomas. Cks1 could play an important role in gastric carcinoma progression and would be a novel target for the treatment of gastric carcinomas as well as a strong prognostic marker.