Chikara Kunisaki

High Expression of Atypical Protein Kinase C λ/ι in Gastric Cancer as a Prognostic Factor for Recurrence

BackgroundThe atypical protein kinase C lambda/iota (aPKCλ/ι) is involved in several signal transduction pathways that influence cell growth, apoptosis, and the establishment and maintenance of epithelial cell polarity. Overexpression of aPKCλ/ι has been reported in several cancers and been shown to be associated with oncogenesis. However, the expression and role of aPKCλ/ι in gastric cancer, one of the commonest cancers in Asia, have not so far been investigated. This study aimed to clarify the relationship between aPKCλ/ι expression and the clinicopathological features of gastric cancer.Patients and MethodsGastric adenocarcinoma samples were obtained from 177 patients who underwent gastrectomy at the Yokohama City University Hospital between 1999 and 2004. Expression of aPKCλ/ι and E-cadherin was examined immunohistochemically and compared with clinicopathological features of the tumors. Univariate and multivariate analyses were performed for both disease-specific and relapse-free survival.ResultsOverexpression of aPKCλ/ι protein was detected in 126 of the 177 (71.2%) gastric cancers. Immunohistological staining for aPKCλ/ι was stronger in gastric adenocarcinoma of intestinal type than diffuse type (pxa0=xa00.036), but was not correlated with E-cadherin expression. A multivariate analysis suggested that nodal metastasis and aPKCλ/ι overexpression were prognostic factors for disease recurrence.ConclusionsOur results suggested that aPKCλ/ι overexpression was a strong prognostic factor for gastric adenocarcinoma recurrence. As well as being a new prognostic indicator, aPKCλ/ι is also likely to be a novel therapeutic target for gastric cancer.

The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease

BackgroundThe guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies.Methods144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed.ResultsPatients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology.ConclusionsOur study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis

Predictive Factors of Microvascular Invasion in Patients with Hepatocellular Carcinoma Larger Than 5 cm

BackgroundPatients with hepatocellular carcinoma (HCC) who undergo liver resection and transplantation are predicted to have a poor outcome if the disease is associated with vascular invasion. This study aimed to identify preoperative predictors of microvascular invasion in patients with HCCs larger than 5xa0cm.MethodsFrom May 1992 to October 2005, 231 patients underwent curative hepatic resection for HCC. Of these, 96 patients had HCCs larger than 5xa0cm. Analysis was limited to patients without macroscopic vascular invasion (nxa0=xa065).ResultsMultivariate analysis showed that patients with tumors larger than 7xa0cm and type 2 (single nodular type with extranodular growth) and type 3 (contiguous multinodular type formed by a cluster of small and contiguous nodules) tumors had an increased risk of microscopic vascular invasion. The overall incidence of microscopic vascular invasion was 46.2% (nxa0=xa030), but only 12.5% (2/16) in patients with type 1 tumors (single nodular type that is approximately round with a clear demarcation) measuring less than 7xa0cm.ConclusionLarger tumors (>7xa0cm) and type 2 and type 3 tumors are strong predictors of microvascular invasion in patients with HCCs larger than 5xa0cm.

Impact of body mass index and visceral adiposity on outcomes in colorectal cancer

Aim:u2003 Obesity and visceral obesity are closely related to the development of colorectal cancer, as well as other metabolic complications. We investigated the prognostic significance of body mass index (BMI) and visceral obesity in 273 patients with resectable colorectal cancer.

Practical usefulness of ultrasonic surgical aspirator with argon beam coagulation for hepatic parenchymal transection.

The objective of this study was to evaluate the effectiveness and feasibility of using the Cavitron ultrasonic surgical aspirator (CUSA) with argon beam coagulation (ABC) during hepatic resection, in comparison with a conventional method using CUSA with bipolar cautery. Between April 2003 and March 2004, a series of 14 consecutive patients underwent hepatic resection of normal liver. Hepatectomies were performed using CUSA and bipolar irrigation electrocautery (BP) in eight patients between April 2003 and December 2003. CUSA and an ABC were used in six patients between January 2004 and March 2004. There were no differences in patient characteristics between the two groups. Blood loss per area of transected liver surface was significantly lower for CUSA with ABC than for CUSA with BP (2.9 ± l.44 vs. 6.33 ± 3.14 ml/cm2). Furthermore, the speed of resection, defined as resection time per area of transected liver surface, was significantly greater for CUSA with ABC than for CUSA with BP (0.53 ± 0.14 vs.2.18 ± 1.73 min/cm2). This new technique of combining CUSA with ABC can decrease blood loss during hepatic parenchymal transection and shorten the resection time.

Priority of lymph node dissection for Siewert type II/III adenocarcinoma of the esophagogastric junction

ObjectiveThe purpose of this study was to clarify the priority of nodal dissection in Siewert types II and III adenocarcinoma of the esophagogastric junction (AEG).MethodsThe priority of nodal dissection was evaluated based on the therapeutic value index calculated by multiplying of the frequency of metastasis to each station and the 5-year survival rate of patients with metastasis to that station.ResultsA total of 176 patients (95 type II and 81 type III) were examined. Among the lymph nodes that had a metastatic incidence exceeding 10xa0%, the stations showing the first to fourth highest index were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the node at the root of the left gastric artery (No. 7) in the total cohort, as well as in each type. The next station was the lower thoracic paraesophageal lymph node (No. 110), followed by the nodes along the proximal splenic artery (No. 11p) in type II, whereas it was the nodes along the proximal splenic artery (No. 11p) followed by the para-aortic nodes (No. 16a2), the nodes at the celiac artery (No. 9), and the nodes around the splenic hilum (No. 10) in type III.ConclusionsThese results suggest that the highest priority nodal stations to be dissected were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the nodes at the root of the left gastric artery (No. 7), regardless of the Siewert subtype, but the subsequent priority was different depending on the subtype.

Assessment of postoperative quality of life following pylorus-preserving gastrectomy and Billroth-I distal gastrectomy in gastric cancer patients: results of the nationwide postgastrectomy syndrome assessment study

BackgroundPylorus-preserving gastrectomy (PPG) is increasingly being used to treat early gastric cancer in the middle third of the stomach, with the hope of ameliorating postoperative dysfunction and improving quality of life (QOL). We evaluated symptoms of postgastrectomy syndrome (PGS) and QOL by means of a newly developed integrated questionnaire, the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45), and compared PPG with Billroth-I distal gastrectomy (DGBI).MethodsThe PGSAS-45 consists of 45 items, including items from the SF-8 and GSRS instruments, as well as 22 newly selected items. It was designed to assess the severity of PGS and the living status and QOL of gastrectomized patients. The nationwide PGSAS surveillance study enrolled 2,368 gastric cancer patients who underwent various types of gastrectomy. In this study we analyzed 313 PPG patients and 909 DGBI patients.ResultsBody weight loss was −6.9xa0% in the PPG group and −7.9xa0% in the DGBI group (Pxa0=xa00.052). The PPG group scored better on the diarrhea subscale (PPG; 1.8 vs. DGBI; 2.1, Pxa0<xa00.0001), dumping subscale (1.8 vs. 2.0, Pxa0=xa00.003), and frequency of additional meals (1.8 vs. 1.9, Pxa0=xa00.034). Multiple regression analysis revealed that age and the preservation of the celiac branch of the vagus nerve were independent factors predicting diarrhea and dumping.ConclusionsIt has been suggested that PPG is superior to DGBI for ameliorating PGS. Preservation of the celiac branch of the vagus nerve is recommended to reduce postoperative disorders regardless of the reconstruction method used.

Clinical significance of SPARC gene expression in patients with gastric cancer.

Secreted protein acidic and rich in cysteine (SPARC) is one of the first known matricellular proteins that modulates interactions between cells and extracellular matrix. Recent studies investigated the clinical significance of SPARC gene expression in the development, progression, and metastasis of cancer. The present study examined the relations of the relative expression of the SPARC gene to clinicopathological factors and overall survival in patients with gastric cancer.

Omentum-preserving gastrectomy for advanced gastric cancer: a propensity-matched retrospective cohort study

Background and objectivesWe clarified the impact of omentectomy for advanced gastric cancer on patient survival from the surgical results of a high-volume center in Japan.MethodsPatients who received curative gastrectomy were divided into two groups based on whether they underwent omentectomy. The propensity score-matching method was used to assemble a well-balanced cohort, and relapse-free survival and the pattern of recurrence were compared.ResultsFor this study, 330 patients who fulfilled the inclusion criteria participated and were divided into two groups: group R, patients who received omentectomy, and group P, patients who received omentum-preserving gastrectomy. After performing score-matching, 196 patients were selected. The 3- and 5-year relapse-free survival rates were 72.9xa0% (95xa0% confidence interval, 64.1–81.7) and 66.2xa0% (56.6–75.8xa0%) in group R, and 76.7xa0% (67.9–81.2) and 67.3xa0% (55.1–79.5) in group P, which were not significantly different (Pxa0=xa00.750). Regarding sites of relapses, no differences were observed between the groups (Pxa0=xa00.863).ConclusionsIn this series, omentum-preserving gastrectomy for advanced gastric cancer did not increase the peritoneal relapse rate or affect patient survival compared to conventional gastrectomy. The non-inferiority of the omission of omentectomy should be evaluated by a randomized controlled trial.

Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer.

PurposeTo evaluate clinical and dosimetric factors retrospectively affecting the risk of symptomatic cardiac disease (SCD) in esophageal cancer patients treated with radiotherapy.Patients and methodsA total of 343xa0patients with newly diagnosed esophageal cancer were managed with concurrent chemoradiotherapy or radiotherapy alone. Of these, 58xa0patients were followed at our hospital for at least 4xa0years. Median clinical follow-up was 79xa0months. Cardiac toxicity was determined by Common Terminology Criteria for Adverse Events (CTCAE) v.xa04.0. The maximum and mean doses to the heart and percentage of the volume were calculated from the dose–volume histograms.ResultsSCD manifested in 11xa0patients. The heart diseases included three pericardial effusions, one pericardial effusion with valvular disease and paroxysmal atrial tachycardia, three atrial fibrillations, one sinus tachycardia, one coronary artery disease, one chest pain with strongly suspected coronary artery disease, and one congestive heart failure. The actual incidence of SCD was 13.8u2009% at 5xa0years. Univariate and multivariate analyses of continuous variables revealed that the risk of developing an SCD depended on the volume of the heart receiving a dose greater than 45xa0Gy (V45), 50xa0Gy (V50), and 55xa0Gy (V55). No other clinical factors were found to influence the risk of SCD. For V45, V50, and V55, the lowest significant cutoff values were 15, 10, and 5u2009%, respectively.ConclusionHigh-dose and large-volume irradiation of the heart increased the risk of SCD in long-term survivors. Using modern radiotherapy techniques, it is important to minimize the heart dose–volume parameters without reducing the tumor dose.ZusammenfassungZielBeurteilung von klinischen und dosimetrischen Faktoren, die mit Risiken eines retrospektiven Auftretens von symptomatischen Herzerkrankungen (SCD) bei Patienten zusammenhängen, die aufgrund eines Ösophaguskarzinoms strahlentherapeutisch behandelt wurden.Patienten und MethodenInsgesamt 343xa0Patienten mit neu diagnostiziertem Ösophaguskarzinom wurden mit kombinierter Chemo- und Strahlentherapie oder nur strahlentherapeutisch behandelt. In dieser Gruppe wurden 58xa0Patienten über mindestens 4xa0Jahre beobachtet. Die mediane klinische Beobachtungsdauer betrug 79xa0Monate. Die kardiale Toxizität wurde mit CTCAExa0v.4.0 ermittelt. Anhand der Dosis-Volumen-Histogramme wurden maximale und mittlere Strahlendosis im Herzen und der Prozentsatz des Volumens berechnet.ErgebnisseBei 11xa0Patienten trat eine SCD auf: 3 perikardiale Effusionen, 1 perikardiale Effusion mit Klappenfehler und paroxysmaler atrialer Tachykardie, 3 atriale Fibrillationen, 1 Sinustachykardie, 1 Koronararterienerkrankung, 1 Brustschmerz mit starkem Verdacht auf Koronararterienerkrankung, 1 kongestive Herzinsuffizienz. Die tatsächliche SCD-Inzidenz betrug nach 5xa0Jahren 13,8%. Uni- und multivariate Analysen mit den stetigen Variablen ergaben, dass das Risiko für eine SCD vom Volumen des Herzens abhängt, das Dosen von mehr als 45xa0Gy (V45), V50 und V55 erhielt. Keine anderen klinischen Faktoren zeigten Auswirkungen auf das Risiko für symptomatische Herzerkrankungen. Bei V45, V50 und V55 betrug der niedrigste signifikante Toleranzwert jeweils 15, 10 und 5%.SchlussfolgerungHochdosierte, großvolumige Bestrahlungen des Herzens wirkten sich auf das SCD-Risiko bei Langzeitüberlebenden aus. Dosis-Volumen-Parameter für das Herz müssen mit modernen Strahlentherapiemethoden verringert werden, ohne die Tumordosis zu reduzieren.