Panel of autoantibodies against multiple tumor-associated antigens for detecting gastric cancer.

Gastric cancer is the second leading cause of cancer death in the world, and effective diagnosis is extremely important for good outcome. We assessed the diagnostic potential of an autoantibody panel that may provide a novel tool for the early detection of gastric cancer. We analyzed data from patients with gastric cancer and normal controls in test and validation cohorts. Autoantibody levels were measured against a panel of six tumor-associated antigens (TAAs) by ELISA: p53, heat shock protein 70, HCC-22-5, peroxiredoxin VI, KM-HN-1, and p90 TAA. We assessed serum autoantibodies in 100 participants in the test cohort. The validation cohort comprised 248 participants. Autoantibodies to at least one of the six antigens showed a sensitivity/specificity of 49.0% (95% confidence interval [CI], 39.2-58.8%)/92.4% (95% CI, 87.2-97.6%), and 52.0% (95% CI, 42.2-61.8%)/90.5% (95% CI, 84.8-96.3%) in the test and validation cohorts, respectively. In the validation cohort, no significant differences were seen when patients were subdivided based on age, sex, depth of tumor invasion, lymph node metastasis, distant metastasis, peritoneal dissemination, or TNM stage. Patients who were positive for more than two antibodies in the panel tended to have a worse prognosis than those who were positive for one or no antibody. Measurement of autoantibody response to multiple TAAs in an optimized panel assay to discriminate patients with early stage gastric cancer from normal controls may aid in the early detection of gastric cancer.

[A Case of Locally Advanced Rectal Cancer Invading Posteriorly Adjacent to Sacrum Resected by Laparoscopic Low Anterior Resection].

We report a case of locally advanced rectal cancer invading toward sacrum treated by laparoscopic low anterior resection. A man in his 60's was diagnosed with rectal cancer expanding near to sacrum. The circumferential resection margin was assessed to be scarce. After preoperative chemotherapy, we performed laparoscopic low anterior resection. In order to obtain surgical margin, we had to cut into presacral venous plexus. With prepared sufficient devices, hemostasis was safely acquired. Pathological findings revealed clear surgical margin. It is important to prepare appropriate hemostasis devices in managing cases with high risks of intraoperative hemorrhage. Laparoscopic approach may contribute to these cases, making hemostasis easier than laparotomy with the magnified view, pneumoperitoneum and Trendelenburg position.

[The Present Status of Surgical and Endoscopic Treatment for Gastric Cancer Patients Aged 85 Years or Older].

This study aimed to survey treatment ofgastric cancer via gastrectomy or endoscopic submucosal dissection(ESD)in patients aged 85 years or older and to clarify the risks and benefits of gastrectomy in terms of postoperative complications and prognosis. The analysis included 40 patients who were treated via gastrectomy and 41 who were treated via ESD. All patients were aged 85 years or older. Although most ofthe patients who had gastrectomy had good performance status(PS), comorbidities were found in 72.5%, and limited operation was often performed. In the gastrectomy group, R0 tumor-free resection margins were achieved in 75%, and postoperative complications occurred in 45%. Despite R0 surgery, the 2-year overall survival rate was 61.7% and the 3-year overall survival was 42.9%. Seven patients(17.1%)in the ESD group were diagnosed with T1b tumors, and no patients were shifted to surgery. Treatment decisions for super-elderly gastric cancer patients are made with regard to age, PS, and comorbidities. There is a limit to survival time after radical gastrectomy. It is necessary to examine the negative effect of gastrectomy on survival time. Selected patients aged 85 years or older with T1b gastric cancer should be given the option of ESD.

[A Case of Mucinous Adenocarcinoma of the Appendix with Peritoneal Dissemination Diagnosed by Laparoscopic Abdominal Exploration and Appendectomy].

We report a case of mucinous adenocarcinoma of the appendix with peritoneal dissemination diagnosed by laparoscopic abdominal exploration and appendectomy. A man in his 60's was diagnosed with peritoneal dissemination of mucinous adenocarcinoma incidentally during an operation for an inguinal hernia. Carcinoma of the appendix was suspected as the primary lesion after further examination. We performed laparoscopic abdominal exploration and appendectomy. The purpose of the operation was to detect the primary lesion, make a pathological diagnosis, and to evaluate the extent of peritoneal dissemination. Laparoscopic findings revealed wide spread peritoneal dissemination and the pathological findings confirmed mucinous adenocarcinoma of the appendix. These laparoscopic procedures lead to a precise diagnosis and allowed for adequate treatment selection.

NY-ESO-1 autoantibody as a tumor-specific biomarker for esophageal cancer: screening in 1969 patients with various cancers.

BACKGROUND: Although serum NY-ESO-1 antibodies (s-NY-ESO-1-Abs) have been reported in patients with esophageal carcinoma, this assay system has not been used to study a large series of patients with various other cancers. PATIENTS AND METHODS: Serum samples of 1969 cancer patients [esophageal cancer (n = 172), lung cancer (n = 269), hepatocellular carcinoma (n = 91), prostate cancer (n = 358), gastric cancer (n = 313), colorectal cancer (n = 262), breast cancer (n = 365)] and 74 healthy individuals were analyzed using an originally developed enzyme-linked immunosorbent assay system for s-NY-ESO-1-Abs. The optical density cut-off value, determined as the mean plus three standard deviations for serum samples from the healthy controls, was fixed at 0.165. Conventional tumor markers were also evaluated in patients with esophageal carcinoma. RESULTS: The positive rate of s-NY-ESO-1-Abs in patients with esophageal cancer (31 %) was significantly higher than that in the other groups: patients with lung cancer (13 %), patients with hepatocellular carcinoma (11 %), patients with prostate cancer (10 %), patients with gastric cancer (10 %), patients with colorectal cancer (8 %), patients with breast cancer (7 %), and healthy controls (0 %). The positive rate of s-NY-ESO-1-Abs was comparable to that of serum p53 antibodies (33 %), squamous cell carcinoma antigen (36 %), carcinoembryonic antigen (26 %), and CYFRA 21-1 (18 %) and gradually increased with the tumor stage. CONCLUSIONS: The positive rate of s-NY-ESO-1-Abs was significantly higher in patients with esophageal cancer than in patients with the other types of cancers. On the basis of its high specificity and sensitivity, even in patients with stage I tumors, s-NY-ESO-1-Abs may be one of the first choices for esophageal cancer.

[A Case of Early Recurrence after Esophagectomy for Cancer Following Neoadjuvant Chemotherapy Resulting in a Complete Response of the Primary Lesion].

A 78-year-old man presented with a chief complaint of dysphagia. He was diagnosed with an esophageal squamous cell carcinoma and referred to our hospital. A type 3 tumor was identified in the lower thoracic esophagus on endoscopy. A CT scan revealed lymph node metastases at the No. 3 station. The clinical stage of the tumor was T3N1M0, Stage III. The patient was treated with neoadjuvant chemotherapy consisting of2 courses of5 -FU and nedaplatin. He had a partial response and underwent a radical esophagectomy. Histopathological examination revealed a complete response of the primary lesion and viable cancer cells in only one lymph node at the No. 3 station. No adjuvant chemotherapy was administered. Three months after the operation, recurrences in the upper abdominal multiple para-aortic lymph nodes were detected. Although he was treated with chemotherapy, he died 7 months after the operation. Even after a complete response of the primary lesion was achieved using neoadjuvant chemotherapy, esophageal cancer with lymph node metastasis has the potential for an early recurrence. Therefore, we should consider adjuvant therapy in such cases.

[The Different Indications and Treatment Effect between Preoperative Chemotherapy and Preoperative Radiotherapy for Advanced Rectal Cancer].

We evaluated the difference in effectiveness between preoperative radiotherapy (RT) and chemotherapy (C) as part of multimodal therapy for locally advanced rectal cancer. In the RT group, 43 patients were enrolled and preoperative radiotherapy was performed with 42.6 Gy for 4 weeks. In the C group, 16 patients were treated with preoperative chemotherapy consisting of mFOLFOX6/XELOX plus bevacizumab for 3 months. All 43 tumors in the RT group were located in the lower rectum. The C group was composed of 9 in the lower rectum and 7 in the middle or upper rectum. The C group was more advanced than the RT group in terms of depth of invasion, lymph node metastasis, and tumor diameter. The histological treatment response was better after RT (7 with little, 10 with a minor, 24 with a major, and 2 with a complete response) than after C (10 with little, 4 with a minor, 1 with a major, and 1 with a complete response). The tumor reduction ratio by colonography showed 36.5% after RT and 28.7% after C. CEA was reduced by 47.2% after RT and 45.2% after C. Though RT is more effective for local lesions than C, C is expected to be preferred as the local and systemic therapy for locally advanced rectal cancer with pelvic organ involvement or lateral lymph node metastases.

[A Case of Sigmoid Colon Cancer with Metastasis to the Uterus].

A 65-year-old woman complaining of fetor ex vagina was diagnosed with endometrial adenocarcinoma of the uterus based on the pathological findings of an endometrial biopsy. Sigmoid colon cancer was found on a pre-operative CT scan. Diagnosis of double cancer was made and we performed sigmoidectomy and panhysterectomy with associated resection of both adnexa. Histopathological examination found that the tumor accounted for almost all of the uterine mucosa and over half of the muscular layer. Immunostaining showed CK7 (-), CK20 (+), CDX2 (+), ER (-), and PgR (-), and we diagnosed it as a metastasis to the uterus of the sigmoid colon cancer. The pathological diagnosis was a moderately differentiated adenocarcinoma, pT4b (SI: urinary bladder), pN0 (0/12), H0, P1,M1a (uterus), pStage Ⅳ. As adjuvant chemotherapy, she was administered XELOX for 6 months. Although colorectal cancer rarely metastasizes to the uterus, due to the increase in the prevalence of colorectal cancer, it may be also increase. To choose the best treatment course, it is necessary to diagnose whether it is a primary uterine cancer or a metastatic uterine cancer.

[A Case of Anal Canal Carcinoma with Inguinal Lymph Node Metastasis Treated with Laparoscopic Abdominoperineal Resection].

We report a case of anal canal cancer with inguinal lymph node metastasis treated with laparoscopic abdominoperineal resection combined with inguinal lymph node dissection. A 52-year-old woman was diagnosed with anal squamous carcinoma after excision of an anal canal tumor. Further examination revealed right inguinal lymph node metastasis. Chemoradiotherapy was administered but was discontinued because of serious adverse events. We therefore performed laparoscopic abdominoperineal resection combined with inguinal lymph node dissection. The pathological findings revealed residual squamous cell carcinoma at the lymphatic vessels in the rectal wall and lymph nodes, including the right inguinal region. Therapeutic effect of Grade 1a was achieved in spite of interruption of the chemoradiotherapy. She was discharged 17 days after the operation, and no recurrence was observed for 11 months. Radical resection was performed for the anal canal squamous cell carcinoma with the metastasis to the right inguinal lymph node, even after interruption of the chemoradiotherapy.

Long-term monitoring of serum p53 antibody after neoadjuvant chemotherapy and surgery for esophageal adenocarcinoma: report of a case.

We monitored serum p53 antibody (s-p53-Ab) titers in a 76-year-old man with esophageal adenocarcinoma, clinical stage III (T2N2M0), for over 4 years, including during the perioperative period and throughout follow-up after surgery. Screening tests for CA19-9 (205 IU/ml) and s-p53-Abs (381 U/ml) were positive before treatment. After neoadjuvant chemotherapy with 5-FU and cisplatin, CA19-9 decreased to the normal range, but the s-p53-Ab titer remained positive (224 U/ml). Pathological findings of surgically resected specimens showed stage T1b disease and no lymph node metastases. After surgery, s-p53-Ab titers consistently decreased, with no disease recurrence. Although the s-p53-Ab titer remained positive even after 4 years, it decreased to 8.66, 3.59, 2.38, and 1.92 U/ml, 1, 2, 3, and 4 years after surgery, respectively. Thus, monitoring perioperative changes in s-p53-Ab titers proved useful for detecting the presence of residual cancer cells in a patient with superficial esophageal adenocarcinoma.

Performing simple and safe dunking pancreaticojejunostomy using mattress sutures in pure laparoscopic pancreaticoduodenectomy.

BACKGROUND: Although recent technological developments and improved endoscopic procedures have further spread the application of laparoscopic pancreatic resection, laparoscopic pancreaticoduodenectomy still presents major technical difficulties, such as when performing pancreatic-enteric anastomosis. METHODS: Laparoscopic dunking pancreaticojejunostomy using mattress sutures was performed in 15 consecutive patients with a soft pancreas and a nondilated pancreatic duct between October 2011 and December 2012. RESULTS: According to the International Study Group on Pancreatic Fistula criteria, 3 patients developed PF (grade A), whereas the remaining 12 patients did not. CONCLUSIONS: Dunking pancreaticojejunostomy using mattress sutures is considered to be a feasible and safe method for performing pure laparoscopic pancreaticoduodenectomy.

[Intraperitoneal chemotherapy with CDDP for patients with peritoneal recurrent gastric cancer following surgical intervention].

We evaluated the efficacy of intraperitoneal chemotherapy with cisplatin (CDDP) for peritoneal recurrent gastric cancer following surgical intervention. Twelve patients were enrolled. The combination systemic chemotherapy was S-1 or S-1 plus paclitaxel (S-1+PTX). PTX was administered intravenously at 80 mg/m² on day S-1 and 15. S-1 was administered at 80 mg/ m²/ day for 7 consecutive days, followed by 7 days of rest, and the cycle was repeated. CDDP was administered intraperitoneally at 40 mg/body on day 8. This treatment was repeated every 4 weeks until disease progression was diagnosed. The survival time(ST)and time to treatment failure(TTF)were estimated. The surgical interventions were gastrectomy in 3 patients, colostomy in 8 patients, and enterostomy in 1 patient. Overall, the median TTF and ST were 294 days and 455 days, respectively. When stratified by surgical method and combination chemotherapy, the median TTF and ST were not statistically significant. However, when stratified by performance status (PS), the median TTF was 352 days for patients with PS 0 and 218 days for those with PS 1, 2 (p=0.0029), whereas the median ST was 553 days for patients with PS 0 and 331 days for those with PS 1, 2 (p=0.0198). In conclusion, the data suggest that intraperitoneal CDDP chemotherapy with systemic chemotherapy is effective for the treatment of extensive peritoneal recurrent gastric cancer, especially in patients with good PS.

[A case of rectal gastrointestinal stromal tumor (GIST) locally resected after long-term chemotherapy with imatinib mesylate].

We report a case of gastrointestinal stromal tumor (GIST) locally resected after long-term chemotherapy with imatinib mesylate. A 78-year-old woman was diagnosed with GIST in the lower rectum on screening colonoscopy for anemia. The tumor was 7 cm in diameter, and the anal sphincter was considered to be difficult to preserve due to the extent of the tumor. The patient refused surgery, so she was administered imatinib mesylate chemotherapy. The medication was continued for 5 years without any major adverse events, and the status of the tumor was stable. Five years later, she underwent transanal local resection for anal prolapse and incarceration of the tumor. Pathological findings revealed a 7 cm sized high-risk GIST. The long-term stable status of the tumor was maintained, and the anal function was preserved by the local resection.

Extrahepatic Glissonean approach for laparoscopic major liver resection (with video).

Although recent technological developments and improved endoscopic procedures have further spread the application of laparoscopic liver resection, laparoscopic major liver resection remains a highly specialized field because there are major technical difficulties, such as hilar dissection and pedicle control. The entire length of the primary branches of the Glissonean pedicle and the origin of the secondary branches are located outside the liver. In contrast, the trunks of the secondary branches and more peripheral branches run inside the liver. The right, left, anterior, or posterior Glissonean pedicle can thus be tied and divided en bloc extrahepatically during open anatomical liver resection. Each Glissonean pedicle can be easily and safely encircled and divided en bloc extrahepatically during laparoscopic anatomical liver resection using an Endo Retract Maxi or Endo Mini-Retract. This report describes a novel technique by which the extrahepatic Glissonean approach appears to be both feasible and safe for the performance of laparoscopic major liver resection.

Arantius' ligament approach for the left extrahepatic Glissonean pedicle in pure laparoscopic left hemihepatectomy.

INTRODUCTION: Laparoscopic hemihepatectomy has not yet become widely accepted because of the technical difficulties in controlling each Glissonean pedicle laparoscopically. MATERIALS AND SURGICAL TECHNIQUE: The subjects in the present study included 12 patients who underwent laparoscopic left hemihepatectomy between August 2007 and June 2011. Arantius' ligament was divided. Retracting the caudal stump of the ligament revealed a space between the left Glissonean pedicle and the liver parenchyma. The left Glissonean pedicle could be easily encircled by using an Endo Retract Maxi. No Glissonean injuries, including bleeding or biliary leakage, occurred in any of the 12 patients. DISCUSSION: Therefore, the Arantius' ligament approach for the left extrahepatic Glissonean pedicle appears to be feasible and safe for successfully performing pure laparoscopic left hemihepatectomy.

Totally laparoscopic pancreas-sparing duodenectomy.

Pancreas-sparing duodenectomy (PSD) is a practical surgical procedure for patients with duodenal adenoma, which is difficult to resect endoscopically. We describe how we performed a totally laparoscopic PSD to resect a duodenal adenoma in a 64-year-old woman, who had been referred for treatment of a 50-mm villous polypoid mass in the second portion of the duodenum. We performed end-to-side anastomosis between the common duct of the bile and pancreatic ducts and the jejunal limb intracorporeally following the duodenal resection. A biliary leak developed, but resolved spontaneously and the patient was discharged on postoperative day (POD) 32. The surgical margin was free of neoplastic change. Although there is limited experience and appropriate indications must await future studies, this case demonstrates that laparoscopic PSD is feasible, safe, and effective for selected patients.

A phase I/II clinical trial of preoperative short-course carbon-ion radiotherapy for patients with squamous cell carcinoma of the esophagus.

BACKGROUND: Carbon-ion radiotherapy (CIR) has been under development. We report the results of a phase I/II clinical trial of preoperative CIR for esophageal squamous cell carcinoma (ESCC). METHODS: Thirty-one thoracic ESCC patients were enrolled. They were first treated with CIR. The radiation dose was escalated from the initial dose of 28.8 GyE up to 36.8. Four to 8 weeks after CIR followed by clinical evaluation of the therapy, surgery was performed. Thereafter, a pathological evaluation was made. RESULTS: Acute toxicity was not seen except in one case (3.2%), and there were no late toxicities. Throughout the study period, there were no cases of withdrawal due to the effects of preoperative CIR. Twelve out of 31 (38.7%) patients achieved a clinical complete response (CR) and 13 patients (41.9%) achieved a partial response. Twelve out of 31 patients (38.7%) achieved a pathological CR. The overall 1-, 3-, and 5-year survival rates in the stage I cases were 91%, 81%, and 61%, and was 100%, 85%, and 77% for the stage II, and 71%, 43%, and 29% for the stage III cases, respectively. CONCLUSIONS: CIR showed strong local tumor control and is highly effective as a neoadjuvant therapy without severe adverse events.

Pure laparoscopic distal pancreatectomy with en bloc celiac axis resection.

BACKGROUND: Recent technological developments and improved endoscopic procedures have greatly enlarged the applications of laparoscopic pancreatic resection. PATIENT AND METHODS: A 77-year-old female with invasive ductal cancer of the pancreatic body touching the common hepatic and splenic arteries underwent a pure laparoscopic distal pancreatectomy with en bloc celiac axis resection (DP-CAR). The celiac axis, the celiac plexus and ganglions, the left gastric artery, the Gerota fascia, the left adrenal gland, and the retroperitoneal fat tissues above the left renal vein were removed en bloc. RESULTS: The procedure took 245 minutes and there was minimal blood loss. The postoperative course was uneventful and the patient was discharged on the seventh postoperative day. The surgical margins were histologically clear (R0 resection). CONCLUSION: Pure laparoscopic DP-CAR is minimally invasive, safe and feasible, and can achieve R0 resection in selected patients with pancreatic invasive ductal adenocarcinoma.