Phase II study of neo-adjuvant chemotherapy for locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy improves survival of locally advanced gastric cancer patients. However, benefit is limited and the best regimen remains controversial. OBJECTIVES: Our primary objective of this prospective, multicenter phase 2 study was to evaluate the pathological complete response rate (PCR) with 2 cycles of docetaxel and capecitabine. METHODS: To be eligible, patients had to have histologically documented gastric cancer, a ECOG performance status 0 or 1, T3or4 Nany M0 staging after oesophagogastroduodenoscopy (OGD), endoscopic ultrasound (EUS), CT scan of thorax and abdomen, and negative laparoscopic examination and peritoneal washing. Eligible patients received two cycles of intravenous docetaxel 60 mg/m(2) on day 1 and oral capecitabine 900 mg/m(2) two times per day from day 1 to day 14 every 3 weeks. We evaluated the response by CT scan and EUS. The patients underwent curative resection with D2 lymphadenectomy subsequently. RESULTS: 18 patients were enrolled in the study: 66% were male and the median age was 60 years. 17 patients had T3 disease at diagnosis. There was no pCR noted. 4 patients had a partial response of 22% (95% CI: 7-42%), 8 patients had stable disease and 3 patients had disease progression. The median survival was 17.1 months with 3 long-term survivors after at least 3 years of follow-up. The treatment was well tolerated with neutropenia being the most common toxicity. We observed 22% grade III and 33% grade IV neutropenia, but no neutropenic fever or death was observed from chemotherapy. CONCLUSION: Neo-adjuvant chemotherapy with docetaxel and capecitabine has limited activity against GC. More effective treatment regimens are needed urgently. TRIAL REGISTRATION NUMBER: NCT00414271.

Early outcome following emergency gastrectomy.

INTRODUCTION: Emergency gastrectomy has been shown to be associated with poor morbidity and mortality rates. The aims of this study were to review the outcomes of emergency gastrectomy in our institution and to determine any factors that were associated with worse perioperative outcomes. MATERIALS AND METHODS: A retrospective review of all patients who underwent emergency gastrectomy for various indications from October 2003 to April 2009 was performed. All the complications were graded according to the classification proposed by Clavien and group. RESULTS: Eighty-fi ve patients, median age 70 (range, 27 to 90 years), underwent emergency gastrectomy. The indications for the surgery included perforation, bleeding and obstruction in 45 (52.9%), 32 (37.6%) and 8 (9.4%) patients, respectively. The majority of the patients (n = 46, 54.1%) had an American Society of Anesthesiologists (ASA) score of 3. Partial or subtotal, and total gastrectomy were performed in 75 (88.2%) and 10 (11.8%) patients, respectively. Malignancy was the underlying pathology in 33 (38.8%) patients. The perioperative mortality rate was 21.2% (n = 18) with another 27 (31.8%) patients having severe complications. Twelve (14.1%) patients had a duodenal stump leak. The independent factors predicting worse perioperative complications included high ASA score and in perforation cases. Other factors such as malignancy, age and extent of surgery were not signifi cantly related. The presence of a duodenal stump leak was the only independent factor predicting mortality. CONCLUSION: Emergency gastrectomy is associated with dismal morbidity and mortality rates. Patients with high ASA scores and perforations fared worse, and duodenal stump leak increases the risk of mortality.

Role of staging laparoscopy in gastric malignancies - our institutional experience.

AIM: To investigate the value of staging laparoscopy with laparoscopic ultrasound (LUS) and peritoneal lavage cytology in patients with newly-diagnosed gastric tumours in our department. METHODS: Retrospective review of prospectively-collected data was conducted in all patients with newly-diagnosed gastric tumours on oesophagogastroduodenoscopy between December 2003 and July 2008. All the patients had a pre-treatment histological diagnosis and were discussed at the hospital multidisciplinary tumour board meeting for their definitive management. Computed tomography scan was performed in all patients as a part of standard preoperative staging work up. Staging laparoscopy was subsequently performed in selected patients and staging by both modalities was compared. RESULTS: Twenty seven patients were included. Majority of patients had cardio-oesophageal junction adenocarcinoma. Thirteen patients (48%) were upstaged following staging laparoscopy and one patient was downstaged (3.7%). None of the patients had procedure-related complications. None of the patients with metastasis detected at laparoscopy underwent laparotomy. Gastrectomy after staging laparoscopy was performed in 13 patients (9 R0 resections, 3 R1 resections and 1 R2 resection). Only one patient did not have gastrectomy at laparotomy because of extensive local invasion. Three patients were subjected to neoadjuvant therapy following laparoscopy but only one patient subsequently underwent gastrectomy. CONCLUSION: In this small series reflecting our institutional experience, staging laparoscopy appears to be safe and more accurate in detecting peritoneal and omental metastases as compared to conventional imaging. Peritoneal cytology provided additional prognostic information although there appeared to be a high false negative rate.

Emergency surgery for perforated gastric malignancy: An institution's experience and review of the literature.

OBJECTIVES: The aim was to evaluate the outcome of patients who underwent surgery for perforated gastric malignancies. METHODS: A review of all patients who underwent surgery for perforated gastric malignancy was performed. RESULTS: Twelve patients (nine gastric adenocarcinoma and three B-cell lymphoma) formed the study group. Ten (83.3%) had subtotal gastrectomy performed, while two (16.7%) underwent total gastrectomy. All eight patients with adenocarcinoma who survived the initial operation fared poorly. The two patients with lymphoma who survived the surgery underwent subsequent chemotherapy has no disease recurrence currently. CONCLUSION: Surgery in perforated gastric malignancy is fraught with numerous challenges.

Upregulation of plasma C9 protein in gastric cancer patients.

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Current biomarkers used in the clinic do not have sufficient sensitivity for gastric cancer detection. To discover new and better biomarkers, protein profiling on plasma samples from 25 normal, 15 early-stage and 21 late-stage cancer was performed using an iTRAQ-LC-MS/MS approach. The level of C9 protein was found to be significantly higher in gastric cancer compared with normal subjects. Immunoblotting data revealed a congruent trend with iTRAQ results. The discriminatory power of C9 between normal and cancer states was not due to inter-patient variations and was independent from gastritis and Helicobacter pylori status of the patients. C9 overexpression could also be detected in a panel of gastric cancer cell lines and their conditioned media compared with normal cells, implying that higher C9 levels in plasma of cancer patients could be attributed to the presence of gastric tumor. A subsequent blind test study on a total of 119 plasma samples showed that the sensitivity of C9 could be as high as 90% at a specificity of 74%. Hence, C9 is a potentially useful biomarker for gastric cancer detection.

ITIH3 is a potential biomarker for early detection of gastric cancer.

Gastric cancer has one of the highest morbidities and mortalities worldwide. Early detection is key measure to improve the outcome of gastric cancer patients. In our efforts to identify potential markers for gastric cancer detection, we coupled xenotransplantation mouse model with a plasma proteomic approach. MKN45 gastric cancer cells were subcutaneously injected into nude mice and plasma samples from mice bearing different sizes of tumors were collected and subjected to iTRAQ and mass spectrometry analysis. ITIH3 protein was found to be more highly expressed in plasma of tumor bearing mice compared to control. Subsequent screening of ITIH3 expression in 167 clinical plasma samples, including 83 cancer-free subjects and 84 gastric cancer patients, revealed higher ITIH3 level in the plasma of gastric cancer patients. A receiver operating characteristics (ROC) curve estimated a maximal sensitivity of 96% at 66% specificity for ITIH3 in gastric cancer detection. In addition, plasma from early stage gastric cancer patient has significantly (p < 0.001) higher level of ITIH3 compared to that from noncancer subject. Our data suggest that ITIH3 may be a useful biomarker for early detection of gastric cancer.

Reduced plasma APOA1 level is associated with gastric tumor growth in MKN45 mouse xenograft model.

There is no suitable diagnostic and prognostic biomarker for gastric cancer. The biggest hurdles in biomarker discovery are (i) the low abundance of cancer cell-specific proteins that limits their detection and (ii) complex inter-patient variations that complicate the discovery process. To circumvent these issues, we conducted proteomics on the plasma of gastric cancer mouse xenograft and attempted to identify proteins released by cancer cells. MKN45 gastric cancer cells were subcutaneously implanted into immune-incompetent nude mice. Plasma samples collected from mice with different tumor sizes (low, mid and high tumor loads) were subjected to iTRAQ and mass spectrometric analyses. Detection of human APOA1 in mouse plasma was verified and its expression level was shown to be lower in mice with large tumors compared to those with small tumors. Studies on a panel of about 14 gastric cancer cell lines supported the notion that APOA1 in mouse plasma was of human gastric cancer cell origin. While the clinical utility of APOA1 remains to be ascertained with a larger scale study, the current work supported the feasibility of using mouse xenograft model for gastric cancer biomarker discovery.

Novel approach to laparoscopic resection of tumours of the distal pancreas.

BACKGROUND: Laparoscopic resection for small lesions of the pancreas has recently gained popularity. We report our initial experience with a new approach to laparoscopic spleen-preserving distal pancreatectomy so that the maximum amount of normal pancreas can be preserved while ensuring adequate resection margins and preservation of the spleen and splenic vessels. METHODS: Three patients underwent laparoscopic distal pancreatectomy with spleen and splenic vessel preservation over a 2-month period. Surgical techniques and patient outcomes were examined. RESULTS: All three patients were females, with ages ranging from 31 to 47 years. Two patients underwent resection using the conventional medial-to-lateral dissection as the lesion was close to the body or proximal tail of the pancreas. The third patient had a lesion in the distal tail of the pancreas and surgery was carried out in a lateral-to-medial manner. This new approach minimized excessive sacrifice of normal pancreatic tissue for such distally located lesions. The splenic artery and vein were preserved in all cases and there was no significant difference in clinical outcome, operative time or intraoperative blood loss. CONCLUSION: Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels is a feasible surgical technique with acceptable outcome. We have shown that a tailored approach to dissection and pancreatic transection based on the location of the lesion allows the maximum amount of normal pancreatic tissue to be preserved without additional morbidity. Although the conventional 'medial-to-lateral' approach is recommended for more proximal tumours of the pancreas, distal lesions can be safely addressed using the 'lateral-to-medial' approach.

Lap-band causing left gastric artery erosion presenting with torrential hemorrhage.

A 61-year-old lady presented 2 years after lap-band surgery with hemetemesis. She was stable on admission and band erosion was diagnosed on gastroscopy. Laparotomy was performed to remove the lap band. Upon division of the lap band, torrential hemorrhage from the eroded left gastric artery was encountered. An anterior gastrostomy was done to expose the artery. Intraoperative gastroscopy was also performed to define the cardioesophageal junction. The artery was ligated and the perforation and gastrostomy were repaired. The patient was discharged after 9 days in hospital. This case highlighted the potential injury to the left gastric artery in patients with band erosion presenting with hemetemesis. Torrential bleeding may be encountered upon division of the lap band, and this should be anticipated during laparotomy.