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.

[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.

[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.

[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.

[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.

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.

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.

[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.

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.

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.

Safe and feasible extrahepatic Glissonean access in laparoscopic anatomical liver resection.

BACKGROUND: Although recent technological developments and improved endoscopic procedures have further spread the application of laparoscopic liver resection, laparoscopic anatomical liver resection still presents major technical difficulties, such as pedicle control. METHODS: Subjects comprised 27 patients who underwent laparoscopic anatomical liver resection using an extrahepatic Glissonean pedicle transaction between August 2005 and February 2010. RESULTS: A total of 61 Glissonean pedicles could be encircled en bloc extrahepatically, as planned. No serious complications, including major bleeding or injury of the portal triad, were encountered during procedures. CONCLUSIONS: Extrahepatic Glissonean access seems to be feasible and safe for laparoscopic anatomical resection of the liver.

[Laparoscopic pancreatic resection of pancreatic cancer].

Laparoscopic pancreatic resection of pancreatic cancer is still not universally accepted as an alternative approach to open surgery because of technical difficulties and a lack of consensus regarding the adequacy of this approach for malignancy. Ten patients with pancreatic cancer underwent laparoscopic pancreatic resection, including pancreaticoduodenectomy and distal pancreatectomy in our institution. Eight of the 10 patients recovered without any complications and were discharged on the 10-29th postoperative day. The remaining 2 patients developed pancreatic fistula and were discharged on the 46 and 60th postoperative day, respectively. All lesions were well clear of surgical margins in 6 patients (R0). In the remaining 4 patients, microscopic neoplastic change was found at the surgical margin (R1). Those 4 patients developed tumor recurrence, including liver metastases or peritoneal dissemination, and 3 of the 4 died of the primary disease. Although experience is limited, laparoscopic pancreatic resection of pancreatic cancer can be feasible, safe, and effective in carefully selected patients. However, the benefit of this procedure has yet to be confirmed. Not only adequate experience in pancreatic surgery but also expertise in laparoscopy is mandatory, and careful selection of patients is essential for successful application of this procedure.

Therapy-related leukemia following chemoradiotherapy for esophageal cancer.

Chemoradiotherapy has improved the outcome of patients with esophageal cancer. Although a sufficiently long-time survival has resulted in the increase of several treatment-related late toxicities, little is still known about the incidence of secondary malignancies. In our hospital, 348 patients with esophageal cancer received chemotherapy consisting of nedaplatin and 5-fluorouracil and concurrent irradiation. Median and average follow-up durations were 8 and 21 months (1-92), respectively. Four patients developed leukemia after 19-48 months of follow-up. Two patients were diagnosed with overt leukemia from myelodysplastic syndrome presenting a complex karyotype, including the deletion of chromosome 5 or 7. Notably, one patient showed an additional chromosomal abnormality with t(9;22)(q34;q11). Other patients developed acute myeloid leukemia with t(9;22)(q34;q11) and Burkitt leukemia with t(8;14)(q24;q32). All patients eventually succumbed to leukemia. Platinum and fluorouracil have shown relatively lower risks for secondary malignancies in comparison with alkylating agents and topoisomerase II inhibitors. Especially, nedaplatin has never been described to introduce secondary neoplasms. Our report supports the idea that the concurrent administration of radiotherapy with these agents affects the risk of leukemia. Interestingly, rare balanced chromosomal abnormalities were observed in the present cases, thus providing new insights into the leukemogenesis of therapy-related leukemia.

High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) reflects inflammatory status. An elevated NLR has been reported to be a prognostic indicator in some malignant tumors. The aim of this study was to evaluate the clinical significance of the preoperative NLR in patients with primary gastric cancer. METHODS: A total of 709 men and 319 women, with a mean age of 64.4 years, who underwent gastrectomy were included. The numbers of patients in each pathological stage were as follows: stage I, 584; stage II, 132; stage III, 153; and stage IV, 159. The mean NLR was 2.62 +/- 1.68. A total of 127 patients (12.4%) with an NLR of 4.0 or more were classified as high NLR individuals in this study. The prognostic significance of a high NLR, together with various clinicopathological factors, was evaluated by multivariate analysis. RESULTS: The 5-year survival of patients with a high NLR was significantly worse than that of patients with a low NLR (57% vs 82%, P < 0.001). Univariate and multivariate analyses of clinicopathological factors affecting survival revealed that high NLR, depth of tumor, positive lymph nodes, distant metastasis, peritoneal metastasis, poorly differentiated type, and high platelet count were significant risk factors for reduced survival. On multivariate analysis, after adjusting for tumor stage, a high NLR was an independent risk factor for reduced survival (P = 0.003; adjusted hazard ratio, 1.845; 95% confidence interval, 1.236-2.747). CONCLUSION: A high preoperative NLR may be a convenient biomarker to identify patients with a poor prognosis after resection for primary gastric cancer.

Multicenter randomized comparison of LigaSure versus conventional surgery for gastrointestinal carcinoma.

PURPOSE: We conducted this randomized trial to compare the LigaSure Vessel Sealing System with conventional methods in gastrointestinal carcinoma surgery at five specialty cancer hospitals. METHODS: Patients with resectable stomach or colorectal cancers were randomized to the LigaSure (n = 100) or conventional surgery (n = 74) groups according to sealed envelopes. The operative data were compared. RESULTS: There were no significant differences in operating times, blood loss, postoperative complications, or hospital stay. However, at the hospital where most of the procedures took place, the LigaSure was associated with a shorter operating time (173 ± 43 min for gastric carcinoma and 157 ± 43 min for colorectal carcinoma vs 211 ± 55 min and 202 ± 55 min for conventional surgery; P = 0.0046 and P = 0.0200, respectively) and less blood loss (300 ± 196 ml and 150 ± 133 ml, respectively, vs 453 ± 387 ml and 382 ± 444 ml; P = 0.0482 and P = 0.0465, respectively). CONCLUSIONS: The LigaSure is safe for both gastric and colorectal cancer surgery with extended lymph node dissection. Used effectively, the device appears to reduce operating times and blood loss, although this requires confirmation in a larger series.

Mandibular bone metastasis of rectal cancer: Report of a case.

A 56-year-old man was referred with lower rectal cancer showing anal canal invasion and liver metastasis. He underwent an abdominoperineal resection and a partial hepatectomy. Adjuvant therapy with tegafur-uracil and leucovorin was administered postoperatively. Lung metastasis was detected 2 years later and was resected. Right mandibular metastasis was diagnosed 2 months after the resection of the lung metastasis. A partial mandibular resection was performed after chemoradiotherapy, followed by reconstruction with a titanium frame and oral cavity reconstruction with a greater pectoral musculocutaneous flap. The pathological diagnosis was metastatic rectal cancer, and the therapeutic effect chemoradiotherapy was Grade 2. He is presently alive without any evidence of cancer, and has maintained a good quality of life 3 years after the mandibular resection and more than 5 years after his first operation. Mandibular metastasis from rectal cancer is very rare and the prognosis is poor according to the literature, so this case is considered to be very unusual.