Optimal treatment for Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction: A retrospective cohort study with long-term follow-up

AIM To determine the optimal treatment strategy for Siewert type Ⅱ and?Ⅲ?adenocarcinoma of the esophagogastric junction.METHODS We retrospectively reviewed the medical records of 83 patients with Siewert type?Ⅱ?and?Ⅲ?adenocarcinoma of the esophagogastric junction and calculated both an index of estimated benefit from lymph node dissection for each lymph node(LN) station and a lymph node ratio(LNR: ratio of number of positive lymph nodes to the total number of dissected lymph nodes). We used Cox proportional hazard models to clarify independent poor prognostic factors. The median duration of observation was 73 mo.RESULTS Indices of estimated benefit from LN dissection were as follows, in descending order: lymph nodes(LN) along the lesser curvature, 26.5; right paracardial LN, 22.8; left paracardial LN, 11.6; LN along the left gastric artery, 10.6. The 5-year overall survival(OS) rate was 58%. Cox regression analysis revealed that vigorous venous invasion(v2, v3)(HR = 5.99; 95%CI: 1.71-24.90) and LNR of > 0.16(HR = 4.29, 95%CI: 1.79-10.89) were independent poor prognostic factors for OS.CONCLUSION LN along the lesser curvature, right and left paracardial LN, and LN along the left gastric artery should be dissected in patients with Siewert type?Ⅱ?or?Ⅲ?adenoca rcinoma of the esophagogastric junction. Patients with vigorous venous invasion and LNR of > 0.16 should be treated with aggressive adjuvant chemotherapy to improve survival outcomes.

Trend in gastric cancer:35 years of surgical experience in Japan

AIM:To investigate the trend in gastric cancer surgery in the context of rapid therapeutic advancement in Japan and East Asia.METHODS:A retrospective analysis was performed on 4163 patients who underwent gastric resection for gastric cancer with histological confirmation between 1971 and 2007 at the surgical unit in Kitasato University Hospital,to determine the trend in gastric cancer requiring surgery.RESULTS:Gastric cancer requiring surgical resection increased in our hospital,but the incidence adjusted for population was constant during the observed pe-riod.Interestingly,the ratio of diffuse type/intestinal type gastric cancer was unexpectedly unchanged,and that of advanced/early gastric cancer(EGC)was,however,markedly reduced,while the actual incidence of potentially curative advanced gastric cancer tended to decrease.The incidence of EGC requiring surgery tended to increase as a whole,which is consistent with increased prevalence of endoscopic surveillance.As a result,overall survival and mortality of gastric cancer requiring gastric resection has recently markedly improved.CONCLUSION:In Japan,planned interventions may improve surgical gastric cancer mortality,but an unexpected trend of persistent existence of intestinal type cancer suggests the need for more robust medical intervention.

Early gastric cancer frequently has high expression of KKLC-1, a cancer-testis antigen

AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.

Present laparoscopic surgery for colorectal cancer in Japan

In many clinical studies,laparoscopic surgery(LS) for colon cancer has been shown to be less invasive than open surgery(OS) while maintaining similar safety.Furthermore,there are no significant differences between LS and OS in long-term outcomes.Thus,LS has been accepted as one of the standard treatments for colon cancer.In the treatments of rectal cancer as well,LS has achieved favorable outcomes,with many reports showing long-term outcomes comparable to those of OS.Furthermore,the magnification in laparoscopy improves visualization in the pelvic cavity and facilitates precise manipulation,as well as providing excellent educational effects.For these reasons,rectal cancer has seemed to be well indicated for LS,as has been colon cancer.The indication for LS in the treatment of locally advanced rectal cancer,which is relatively unresectable(e.g.,cancer invading other organs),remains an open issue.In recent years,new techniques such as singleport and robotic surgery have begun to be introduced for LS.Presently,various clinical studies in our country as well as in most Western countries have demonstrated that LS,with these new techniques,are gradually showing long-term outcomes.

Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers

BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.

Simplifying Laparoscopic Surgery for Left Side Colon and Rectal Cancer Using Linear Stapler for Vascular Ligation: A Prospective Cohort Study

Introduction: Systematic lymphadenectomy and ligation of the feeding artery is extremely important when performing radical resection in colorectal cancer. However, vascular surgery via laparoscopy requires advanced skills and techniques;thus, this procedure needs to be simplified while maintaining quality of the surgery to make it a preferred technique for the surgeons. Methods: There were 49 patients who underwent laparoscopic sigmoidectomy or anterior resection till T2 level for sigmoid colon cancer and recto-sigmoid colon cancer. We analyzed short-term and long-term outcomes between stapling ligation and clipping ligation techniques used in these surgeries. Results: The mean volume of blood loss in the stapling ligation group was 12.8 ± 12.3 ml, which was significantly lower than 41.9 ± 71.2 ml of mean volume of blood loss in the clipping ligation group. There was no significant difference in the mean duration of surgery, the mean number of harvested lymph nodes, morbidity, recurrence, and 5-year relapse free survival rates between the 2 groups. Conclusions: This study demonstrates a surgical technique using staplers for vascular treatment of tumor-feeding arteries as a new technical improvement in laparoscopic colectomy for the treatment of early-stage colon cancer. We found that the described procedure was technically safe, simple, convenient, and oncologically valid.

Macroscopic appearance of TypeⅣand giant Type Ⅲ is a high risk for a poor prognosis in pathological stage Ⅱ/Ⅲ advanced gastric cancer with postoperative adjuvant chemotherapy

AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.

Newly emerging standard chemotherapies for gastric cancer and clinical potential in elderly patients

With the increase in average life expectancy,the rate of occurrence of gastric cancer in elderly patients is also rising.While many clinical trials have been conducted to examine the effect of chemotherapy treatment on gastric cancer,age limits for eligible subjects have prevented the establishment of standards for chemotherapy in elderly patients with gastric cancer.As of March 2009,evidence-based standard chemotherapy regimens were established.In the Western world,debates centered on the ECF(Epirubicin/cisplatin/5FU) or DCF(Docetaxel/cisplatin/5-FU) regimens based on the phase □ randomized controlled trial at the Royal Marsden Hospital(RMH) or the V325 study,respectively.The JCOG9912 and SPIRITS trials emerged from Japan indicating attractive regimens that include S-1 for advanced gastric cancer patients.Using these active anticancer drugs,the trials that studied the eff icacy of adjuvant therapies or surgical approaches,such as the Int-116/MAGIC/ACTS-GC trials,have actually succeeded in demonstrating the benefits of adjuvant therapies in gastric cancer patients.For cases of gastric cancer in elderly patients,treatment policies should consider these studies while analyzing not only the therapeutic effects but also drug toxicity,individual general health conditions,and social factors to select treatments that emphasize quality of life.

Efficacy of Modified Expansive Open-Door Laminoplasty for Cervical Myelopathy

Objectives: Expansive open-door laminoplasty is used widely for the treatment of cervical spondylosis and Ossification of the Posterior Longitudinal Ligament (OPLL). We have developed a unique modification of the surgical procedure to keep the lamina expanded, with the aim of preventing reclosure of the vertebral arch. To examine the effectiveness of and problems associated with the modified expansive open-door laminoplasty technique developed at our institution by evaluating the surgical outcomes. Methods and Materials: Fifty-six patients (46 men and 10 women) underwent the modified expansive open-door laminoplasty and were followed up for at least 1 year. Thirty-eight had Cervical Spondylotic Myelopathy (CSM) and 18 had OPLL. The patients were 34 to 89 years of age (mean: 60.9 years). The severity of myelopathy was evaluated according to the Japanese Orthopaedic Association’s scoring system. Surgical outcomes were evaluated using Hirabayashi’s system for determining recovery rate. In the radiographic analysis, the following angles were measured before and after surgery: lordosis angle and Range of Motion (ROM) at C2 - C7 on lateral radiographs, and opening angle on computerized tomography (CT). The presence and absence of axial pain and postoperative C5 palsy were also evaluated. Results: The rate of JOA score improvement was about 60%, the lordosis angle observed on lateral radiographs was maintained. ROM decreased after surgery in both the CSM and OPLL groups, and the extent of the decrease was similar to that in previous reports. The opening angle of the lamina was 62°- 65° on post-operative CT. Axial pain was reported by 34% of patients. Conclusions: Our modified procedure produced satisfactory postoperative outcomes based on the clinical data and imaging findings for both CSM and OPLL. The advantage of this procedure is that it avoids potential complications associated with bone grafts or implants.

Mobile Schwannoma of the Cauda Equina for Which Intraoperative Myelography Was Useful in Locating

We report on a case of a mobile schwannoma of the cauda equina. The patient was a 24-year-old woman who visited our hospital with the chief complaints of low back pain and numbness of the right leg. A tumor was noted from the L2 midbody level to the L3 upper endplate on preoperative MRI and myelogram. During the surgery, a right L2 hemilaminectomy was performed, and the dura was incised, but no tumor was founded in the surgical field, and this was noted as a missing tumor. Intraoperative myelography showed that the tumor had moved to the adjacent vertebra on the caudal side. Myelography applied again to the caudal side of the mobile tumor. Then, the tumor had moved upward, and could be excised without an additional laminectomy.

Clinicopathological Evaluation and Prognostic Analysis in Breast Cancer Patients with Brain Metastasis

Background: Brain metastases are diagnosed in 5% - 15% of patients with breast cancer. Clinical management of brain metastases appears to be crucial in improving the prognosis of patients with breast cancer that has metastasized to the brain. However, few studies have investigated whether treatment of metastatic brain tumors would lead to improved prognosis. Methods: A total of 41 breast cancer patients whose tumors metastasized to the brain and who were diagnosed and treated at our hospital were enrolled. This study was conducted to determine the characteristics of brain metastases and to identify the factors that may affect the treatment and prognosis of patients with brain metastases. Results: There were more patients with HER2 and triple negative subtypes than of the luminal subtype. The median time from the initiation of breast cancer treatment to the onset of brain metastasis was 31 months (range, 7 - 134 months). Significantly greater disease-specific survival (DSS) was observed in patients who had a performance status of 0 - 2 at the time of diagnosis of metastatic brain tumors than those with a performance status of 3 - 4 (p = 0.04). DSS was also significantly greater in patients who underwent surgery to remove brain metastases and in patients treated with systemic therapy (p = 0.0007 and 0.0001, respectively). Conclusions: It may be possible to improve the prognosis of patients with brain metastases if lesions are detected early enough when the patients’ performance status is still good. In order for these findings to be definitive, however, results of future prospective studies are eagerly awaited.

CB_1 Cannabinoid Receptor-Dependent and-Independent Inhibition of Depolarization-Induced Calcium Influx in Oligodendrocytes

Ca2+稳态平衡的调节在少突胶质细胞功能和存活中起重要作用。大麻素CB1和CB2受体在许多细胞中调节Ca2+水平和/或K+电流。本文利用培养的少突胶质细胞中,通过增高细胞外K+浓度(50 mM诱导膜去极化,研究大麻素复合物在此过程引发钙内流中的作用。CB2受体激动剂ACEA导致去极化诱导的少突胶质细胞胞浆的Ca2+瞬变表达浓度依赖性抑制,最大效应为(94±3)%,半效应浓度(EC50)为(1.3±0.03)μM。这种作用可被CB2/CB2激动剂CP55、940、内源性大麻素类AEA和2-AG所模拟,但是CB2受体选择性激动剂J WH133没有作用。CB2受体拮抗剂AM251(1μM)也可减少细胞外高K+诱导的Ca2+反应,但不能防止ACEA(3μM)诱发的抑制效应。然而,ACEA和AEA减少去极化诱导的Ca2+瞬变的能力在CB2受体敲除小鼠和经百日咳毒素预处理的少突胶质细胞中明显降低。内流性K+通道阻断剂BaCl2(300μM)和CsCl2(1 mM)降低电压诱导的Ca2+内流并部分阻断ACEA的抑制效应。本文表明,大麻素抑制少突胶质细胞中去极化诱导的Ca2+瞬变是通过包括PTX-敏感的Gi/o蛋白和阻断K+内流通道的CB2受体依赖性和非依赖性机制。