A phase II study of S-1 and oxaliplatin (SOx) combination chemotherapy as a first-line therapy for patients with advanced gastric cancer.

BACKGROUND: Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer. 5-fluorouracil (5-FU) and cisplatin have been widely used in a variety of combinations. We conducted a phase II study of combination chemotherapy with new agents, S-1 and oxaliplatin (SOx), in advanced gastric cancer patients in an effort to evaluate the efficacy and toxicity of this regimen. METHOD: Histologically confirmed recurrent or metastatic gastric cancer were treated by the oral administration of S-1 80 mg/m(2)/day on days 1-28, and oxaliplatin 85 mg/m(2) administered as a 90-min intravenous infusion on days 1, 15, and 29. Treatment courses were repeated every 6 weeks. Patients received a maximum of four cycles. RESULTS: From Feb 2006 to May 2008, 41 patients were enrolled in this study. The ratio of males to females was 28 to 13. The median patient age was 61 years (range, 36-74 years), and 85.4% (35/41) of the patients had a performance status (ECOG) of 1. The median number of chemotherapy cycles administered was 3 (range, 1-4). According to the results of our Intent-to-Treat analysis, 22 patients (53.7%) achieved a partial response (95% CI, 38-70%). 15 patients (36.6%) evidenced a stable disease, and 1 patient (2.4%) progressed during the course of the treatment. 3 patients were lost to follow-up prior to evaluation. The median time to progression and overall survival time were 4.6 months (95% CI, 3.4-5.8 months) and 7.8 months (95% CI, 6.9-8.7 months) from the start of the chemotherapy, respectively. A total of 114 cycles were assessed for toxicity. The major hematologic toxicities included grade 2 anemia (41.2%), grade 1-2 neutropenia (28.1%), and grade 1 thrombocytopenia (23.7%). Only 1 cycle of neutropenic fever occurred. The non-hematological toxicities observed were grade 3 vomiting (12.2%) and grade 3 diarrhea (4.9%). No treatment-related deaths occurred in our patient population during the study period. CONCLUSION: The SOx regimen evidenced a relatively high response rate and was well tolerated as a first-line therapy for advanced gastric cancer.

Trans-vaginal specimen extraction following totally laparoscopic subtotal gastrectomy in early gastric cancer.

BACKGROUND: Although natural orifice extraction is now widely performed, there have been no reports of this procedure following subtotal gastrectomy for gastric cancer. This report describes trans-vaginal specimen extraction in four patients with early gastric cancer. METHODS: The clinical data of four patients with early gastric cancer were reviewed. Totally laparoscopic subtotal gastrectomy and D1 + ß lymph node dissection was performed using five trocars and a conventional procedure. Posterior colpotomy was performed by an experienced gynecologist, who retrieved the specimens in a retrieval bag via the trans-vaginal route. The colpotomy site was repaired immediately following specimen removal. Reconstruction was performed using the intracorporeal Billroth II method and an endo-GIA 60. RESULTS: Totally laparoscopic subtotal gastrectomy and trans-vaginal specimen extraction was successfully accomplished in all patients without intraoperative complications. CONCLUSIONS: The present technique may be a safe and feasible operative procedure for some limited groups of elderly female patients with early gastric cancer.

Risk of recurrence after laparoscopy-assisted radical gastrectomy for gastric cancer performed by a single surgeon.

BACKGROUND: The risk of recurrence after laparoscopy-assisted radical gastrectomy (LAG) was investigated. MATERIALS AND METHODS: Clinical data of 398 consecutive patients who underwent radical gastrectomy with R0 resection for gastric cancer at Gyeongsang National University Hospital between January 2005 and December 2007 were reviewed retrospectively. RESULTS: Of the patients, 65.4% (n = 261) and 34.6% (n = 138) underwent LAG and open radical gastrectomy (OG), respectively. Of the LAG cases, 73.2% (n = 192), 10.7% (n = 28), 12.6% (n = 33), and 3.1% (n = 8) had stage I, II, III, and IV gastric cancer, respectively. All patients were followed up for a mean of 36.8 ± 13.7 months, and 14.6% (n = 58) had recurrence during the follow-up period. Univariate analysis revealed that tumor size, tumor-node-metastasis (TNM) stage, method of approach (LAG versus OG), and operation type were associated significantly with recurrence. Multivariate analysis revealed that only high TNM stage was significantly associated with recurrence (P = 0.00). While patients who underwent OG had higher incidence of recurrence than patients who underwent LAG, OG was not significantly associated with recurrence on multivariate analysis (P = 0.06). CONCLUSIONS: LAG and OG did not differ significantly in terms of recurrence, even when used in advanced gastric cancer cases. Multivariate analysis revealed that high TNM stage was significantly associated with recurrence. Thus, LAG appears to be a safe and feasible procedure that has the potential to be an alternative to open surgery, even for advanced gastric cancer.

Gastric lymphatic basin dissection for sentinel node biopsy using hybrid natural orifice transluminal endoscopic surgery (NOTES).

The aim of the present study was to describe a method of gastric lymphatic basin dissection for sentinel node biopsy using natural orifice transluminal endoscopic surgery with laparoscopic assistance (hybrid NOTES) in a porcine model. Lymph node dissection was performed in three healthy female domestic farm pigs (each around 40 kg) between October, 2007, and December, 2007. The pigs were administered a general anesthetic and laparoscopy-guided transvaginal colpotomy was performed. A two-channel endoscope was then inserted through the incision into the peritoneal cavity via the transvaginal route. An endoscope was inserted simultaneously into the mouth and indocyanine green solution was injected into the submucosal layer of the gastric wall at four sites. Dyed omentum and lymphatics were dissected using a laparoscopic dissector and the grasping forceps of a transvaginal endoscope. Lymphatics and omentum (mean 13.3 cm, range 8-20 cm) were removed transvaginally. The mean number of detected and resected sentinel nodes was 2.6 (range 1-4, diameter 2~12 mm). Sentinel lymphatic basin dissection was performed successfully and without intraoperative complications in all three cases. Hybrid NOTES is technically feasible, and this procedure may represent an alternative to laparoscopic sentinel lymph node dissection of the stomach.

Clinical factors affecting the length of minilaparotomy incision in laparoscopy-assisted distal gastrectomy.

This study investigated the factors affecting the length of the minilaparotomy incision (LOMI) in laparoscopy-assisted distal gastrectomy with Billroth I reconstruction. By using abdominal computed tomography scans, we measured the thickness of the rectus muscle (TRM), the thickness of the abdominal wall (TAW), and the distance from the gastroduodenal artery to the skin (GDAS) in 80 patients with early gastric cancer who had undergone surgery. There were positive correlations between the LOMI and body mass index (BMI), TRM, and TAW, and the LOMI increased significantly in patients with BMI > or =25 kg/m2, TAW > or =2.1 cm, and TRM > or =1.0 cm. These observations suggest that patients with two or more of the following clinical factors, BMI > or =25 kg/m2, TAW > or =2.1 cm, and TRM > or =1.0 cm, may require surgical procedures other than laparoscopy-assisted Billroth I, such as total laparoscopic intracorporeal Billroth I, Billroth II, or uncut Roux-en-Y reconstruction.

Endoscopic thyroidectomy using a gasless axillary approach.

PURPOSE: We have recently developed an endoscopic thyroidectomy using a gasless axillary approach and report the surgical outcome of the procedure. MATERIALS AND METHODS: The gasless axillary approach was performed through a 3-cm axillary incision using a retractor instead of carbon dioxide insufflation. We performed a total of 35 thyroidectomies using this technique in patients with benign thyroid nodules. RESULTS: Thirty-four cases were successfully completed with the gasless axillary approach; one case had to be converted to a conventional technique after intraoperative frozen section revealed papillary carcinoma. The mean operative time and mean hospital stay were 180.6 +/- 54.5 minutes and 7.1 +/- 0.9 days, respectively. The mean tumor size was 2.9 +/- 1.4 cm. There were three minor postoperative complications: one case each of wound seroma, transient voice change, and persistent wound pain. All patients were satisfied with the cosmetic result. The axillary scars were not visible when the ipsilateral arms were in their natural position. CONCLUSION: Endoscopic thyroidectomy using a gasless axillary approach is a safe procedure that offers a good cosmetic result and has the merits of minimal invasiveness even in patients with a large thyroid mass. It is a safe and feasible alternative to traditional thyroid surgery, especially in young female patients with a large thyroid mass.

Intra-abdominal angiosarcoma developing in a capsule of a foreign body: report of a case with associated hemorrhagic diathesis.

BACKGROUND: Angiosarcoma occurs very rarely in the gastrointestinal tract and can present great diagnostic difficulty, especially when it is associated with intraabdominal abscess or granulation tissue. CASE PRESENTATION: We report a case where the angiosarcoma was diagnosed after the occurrence of disseminated angiosarcoma and concurrent hemoperitoneum. The tumor developed in the fibrous capsule of a foreign body, which was possibly related to the previous appendectomy twenty years ago, and became a widely disseminated malignant neoplasm in the abdomen. After the operation, the patient's course was dominated by a fatal consumptive coagulapathy. Pathologic examination of the multiple intra-abdominal lesions showed the histological and immunohistological characteristics of the angiosarcoma. CONCLUSION: Even though angiosarcoma in the gastrointestinal tract is extremely rare, when dealing with intraabdominal abscess or the gastrointestinal bleeding in patients who have undergone surgery or radiation therapy in the past, the possibility of angiosarcoma should be considered. To make the definite diagnosis of angiosarcoma and to avoid the misdiagnosis of foreign body granuloma, thorough histological examination and immunohistochemical staining may be prerequisite.

Fatty acid-binding protein 5 promotes cell proliferation and invasion in human intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a rare primary malignant liver tumor with an extremely poor prognosis. Recently its incidence has increased, however, little attention has been directed to factors related to its molecular carcinogenesis, including oncogenes, tumor suppressor genes and cell cycle-related proteins. ICC is generally characterized by strong proliferation, invasion and early metastasis. These biological behaviors of ICC, with respect to the genetic and molecular aspects, remain to be clarified. In this study, we performed a proteomic analysis to identify the proteomic alterations associated with carcinogenesis of ICC. Protein expression profiles of sixteen cases of ICC were compared with those of adjacent non-involved bile duct tissue. Among the 151 protein spots that showed a statistically significant expression difference (P<0.05), there were 50 spots with significantly increased intensity (3-fold increase) and 17 spots with decreased intensity (3-fold decrease) in cancerous tissues. Of these, increased expression of fatty acid-binding protein 5 (FABP5) was further confirmed by western blot analysis and immunohistochemical analysis. Immunohistochemical analysis of FABP5 expression in tumor specimens obtained from 43 patients with mass-forming (MF) type ICC showed a positive correlation of FABP5 immunoreactivity with tumor size (P=0.047), lymph node metastasis (P=0.013), angioinvasion (P=0.032) and staging (P=0.007). In addition, silencing FABP5 with short hairpin RNA (shRNA) suppressed cell proliferation and invasiveness in HuCCT1 cells, and conversely, overexpression of FABP5 in FABP5-negative Hep3B cells increased cell proliferation and invasiveness. Our study shows that FABP5 is significantly overexpressed in ICC combined lymph node metastasis and is involved in cell proliferation and invasion in vitro. Our data suggest that FABP5 may be associated with tumor progression in ICC.

Role of ultrasonography in predicting malignancy in patients with thyroid nodules.

The use of ultrasonography (USG) has become an essential part of endocrine surgical practice. We evaluated the value of USG in predicting malignancy of thyroid nodules. The accuracy of USG in 857 patients who underwent fine-needle aspiration (FNA) with or without surgery was analyzed in a prospective setting. The diagnostic accuracy of USG was compared to that of FNA and of combined models in 153 operated patients. The malignancy-predicting value of USG in follicular neoplasms and its relation to nodule size were also investigated. Sensitivity, specificity, and overall accuracy (OA) of USG were 84.9%, 95.5%, and 93.7%, respectively. In operated patients, USG had accuracy comparable to that of FNA and combined models (sensitivity 93.3%, specificity 90.6%, OA 92.0%) regardless of nodule size but showed a significant rate of indeterminate results (29.4%). For follicular neoplasms, the sensitivity, specificity, and OA of USG were 100%, 95.4%, and 96.1%, respectively, with indeterminate results for three malignant nodules (42.8%). This acceptable malignancy-predicting value of USG in thyroid nodules supports the potential role of USG for predicting malignancy in selected patients with thyroid nodules. However, the high rate of indeterminate results precludes it from being a standard independent diagnostic method for the present time.

Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer.

Understanding the molecular background of breast cancer biology is critical in developing new biomarkers for earlier diagnosis and more optimized treatment. We performed a proteomic analysis of human breast carcinoma tissues to investigate the tumor-specific protein expression in breast carcinoma. Using 2-dimensional electorphoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), we were able to identify a list of proteins which are upregulated in cancerous tissue. There was significant increase of galectin-1 expression in all cancerous tissues compared to noncancerous tissues, and its increased expression was further confirmed by western blot immunostaining. Subsequent immunohistochemical staining against galectin-1 in 105 breast cancer specimens showed significant correlation between galectin-1 expression in cancer-associated stromal cells and tumor invasiveness, T stage, TNM stage, and axillary lymph node metastasis. Galectin-1 expressionin cancer cells showed no correlation to above-mentioned pathologic variables. Hormonal receptor status and galectin-1 expression showed no correlation. This study demonstrates the upregulation of galectin-1 in breast carcinoma tissues and the clinical significance of galectin-1 in breast cancer patients. Our data supports the recently highlighted roles of galectin-1 in cancer-associated stroma and in tumor immune privilege.

Malignant peripheral nerve sheath tumor arising from the colon in a newborn: report of a case and review of the literatures.

A malignant peripheral nerve sheath tumor (MPNST) is a rare neoplasm arising from peripheral nerve sheath. Here, we report the first case of MPNST arising in the colon and also the youngest case of MPNST in the gastrointestinal tract. The patient was a 2-day-old neonate with symptoms and signs of intestinal obstruction. The patient had no family history or stigmata of neurofibromatosis type 1. A computed tomographic scan revealed a 5-cm-sized mass in ascending colon causing intestinal obstruction, and emergent right hemicolectomy was performed. The microscopic examination showed atypical spindle cells with hyperchromatic nuclei and high mitotic activity. The results of immunohistochemical staining, which showed positivity for S-100 and vimentin as well as negativity for smooth muscle actin, CD34, and c-Kit, supported the final diagnosis of MPNST. Genetic analysis of the patient revealed no abnormalities. After surgery, the patient recovered uneventfully and has been free of the disease for 17 months.

Myositis ossificans of the abdominal rectus muscle: report of a case.

We herein report a rare case of myositis ossificans originating from the abdominal rectus muscle, found in a 38-year-old woman who presented with a left upper abdominal mass. The mass was initially suspected to be a malignant neoplasm because no history of either operation or trauma existed for this patient. Moreover, the location of the mass was unusual and the enhancement patterns of the dynamic magnetic resonance images were similar to that of a malignant tumor. Based on the radiologic findings, a surgical exploration was performed. A well-circumscribed mass, which measured 3.2 x 2 cm, was found in the rectus muscle. Microscopic findings showed a typical zonal pattern with a fibroblastic central zone and a zone of ossification at the periphery. Although abdominal myositis ossificans is extremely rare, it is one of the causes of abdominal mass lesions and can be mistaken for a malignant tumor. Therefore, a thorough knowledge of the evolution of myositis ossificans is necessary and in cases with malignant suggestion on magnetic resonance imaging, like that seen in our case, we suggest that a surgical excision may be necessary for both the diagnosis and treatment.

The value of intraoperative imprint cytology in the assessment of lymph node status in gastric cancer surgery.

BACKGROUND: The intraoperative assessment of lymph node status is important when performing limited surgery in gastric cancer patients. Currently available techniques for this assessment are frozen section, imprint cytology, and other molecular methods; most current studies use the frozen-section method. In the present study, we focused on the accuracy and feasibility of imprint cytology as a tool to assess lymph node status intraoperatively in gastric cancer surgery. METHODS: Between April 2001 and March 2003, we performed imprint cytology of the sentinel nodes in 260 consecutive patients. After review by an experienced cytopathologist, the sensitivity, specificity, and overall accuracy of the method were determined. RESULTS: The time required for the intraoperative imprint cytology was 8 min, and the sensitivity, specificity, and overall accuracy were 52.2%, 88.8%, and 73.8%, respectively. CONCLUSION: Imprint cytology could be a useful technique for the assessment of lymph node status intraoperatively if the sensitivity and specificity can be improved to an acceptable level.