A novel protein isoform of the RON tyrosine kinase receptor transforms human pancreatic duct epithelial cells.

The MST1R gene is overexpressed in pancreatic cancer producing elevated levels of the RON tyrosine kinase receptor protein. While mutations in MST1R are rare, alternative splice variants have been previously reported in epithelial cancers. We report the discovery of a novel RON isoform discovered in human pancreatic cancer. Partial splicing of exons 5 and 6 (P5P6) produces a RON isoform that lacks the first extracellular immunoglobulin-plexin-transcription domain. The splice variant is detected in 73% of xenografts derived from pancreatic adenocarcinoma patients and 71% of pancreatic cancer cell lines. Peptides specific to RON P5P6 detected in human pancreatic cancer specimens by mass spectrometry confirm translation of the protein isoform. The P5P6 isoform is found to be constitutively phosphorylated, present in the cytoplasm, and it traffics to the plasma membrane. Expression of P5P6 in immortalized human pancreatic duct epithelial (HPDE) cells activates downstream AKT, and in human pancreatic epithelial nestin-expressing cells, activates both the AKT and MAPK pathways. Inhibiting RON P5P6 in HPDE cells using a small molecule inhibitor BMS-777607 blocked constitutive activation and decreased AKT signaling. P5P6 transforms NIH3T3 cells and induces tumorigenicity in HPDE cells. Resultant HPDE-P5P6 tumors develop a dense stromal compartment similar to that seen in pancreatic cancer. In summary, we have identified a novel and constitutively active isoform of the RON tyrosine kinase receptor that has transforming activity and is expressed in human pancreatic cancer. These findings provide additional insight into the biology of the RON receptor in pancreatic cancer and are clinically relevant to the study of RON as a potential therapeutic target.

Oncogenic Ras/Src cooperativity in pancreatic neoplasia.

Pancreas cancer is one of the most lethal malignancies and is characterized by activating mutations of Kras, present in 95% of patients. More than 60% of pancreatic cancers also display increased c-Src activity, which is associated with poor prognosis. Although loss of tumor suppressor function (for example, p16, p53, Smad4) combined with oncogenic Kras signaling has been shown to accelerate pancreatic duct carcinogenesis, it is unclear whether elevated Src activity contributes to Kras-dependent tumorigenesis or is simply a biomarker of disease progression. Here, we demonstrate that in the context of oncogenic Kras, activation of c-Src through deletion of C-terminal Src kinase (CSK) results in the development of invasive pancreatic ductal adenocarcinoma (PDA) by 5-8 weeks. In contrast, deletion of CSK alone fails to induce neoplasia, while oncogenic Kras expression yields PDA at low frequency after a latency of 12 months. Analysis of cell lines derived from Ras/Src-induced PDA's indicates that oncogenic Ras/Src cooperativity may lead to genomic instability, yet Ras/Src-driven tumor cells remain dependent on Src signaling and as such, Src inhibition suppresses growth of Ras/Src-driven tumors. These findings demonstrate that oncogenic Ras/Src cooperate to accelerate PDA onset and support further studies of Src-directed therapies in pancreatic cancer.

The chemokine receptor CXCR4 is expressed in pancreatic intraepithelial neoplasia.

OBJECTIVE: The chemokine CXCL12, together with its specific receptor, CXCR4, have been shown to mediate invasiveness and metastatic behaviour in pancreatic cancer cells. The expression of CXC12/CXCR4 has not been previously examined in pancreatic intraepithelial neoplasias (PanIN), the accepted precursor lesions to pancreatic duct cancer. DESIGN: In this study we sought to characterise the expression of CXCL12 and CXCR4 during the progression of PanIN using both a murine model and human tissues. RESULTS: These studies reveal that both CXCL12 and CXCR4 are expressed in PanIN and that the frequency increases during PanIN progression (0% CXCR4 expression in normal mouse and human ducts vs 100% in mouse PanIN 3 and 77% in human PanIN 3). Next we demonstrate a dose-dependent increase in the proliferation of murine PanIN cells when exposed to CXCL12. Finally, we show that expression of CXCR4 in murine PanIN cells is partially dependent on mitogen-activated protein kinase (MAPK) signalling and that the effect of CXCL12 on PanIN proliferation can be abrogated by an MAPK inhibitor. CONCLUSIONS: Together these results demonstrate that CXCL12/CXCR4 expression begins in the pre-invasive stages of pancreatic neoplasia, and suggest that the presence of an autocrine loop that is at least partially regulated by MAPK signalling. Further studies that define the role of CXCR4 signalling in PanIN progression will determine if CXCR4 could serve as a novel target for chemoprevention and early stage therapy in pancreatic cancer.

The significance and clinical factors associated with a subcentimeter resection of colorectal liver metastases.

BACKGROUND: Prognosis after resection of colorectal liver metastases is influenced by various factors. A positive margin of resection (MOR) has been shown to adversely influence prognosis. Although a 1-cm MOR has been accepted as adequate, the data to support this guideline are sparse. METHODS: Our hepatobiliary database was queried for patients who underwent liver resection for colorectal metastases between January 1992 and July 2003. All patients were divided into three groups: MOR <.5 cm (group A), .5 to 1 cm (group B), and >1 cm (group C). Operative reports from each hepatic resection were analyzed to determine local factors that may have contributed to a subcentimeter MOR. RESULTS: A total of 112 patients (67 men and 45 women) underwent liver resection for colorectal metastases with negative margins. Fifty-three patients were in group A, 26 patients were in group B, and 33 patients were in group C. Group C demonstrated decreased local recurrence (LR; P = .003), distant recurrence (DR; P = .008), and disease-free recurrence (P = .002). A significant difference in the overall time to LR (P = .003), time to DR (P = .003), and disease-free survival (P = .002) was also demonstrated. Factors associated with a subcentimeter MOR included nonanatomical resection (P = .043), proximity to a major vessel (P = .003), and central location (P = .002). CONCLUSIONS: A <1-cm resection for colorectal liver metastases is associated with increased LR and DR, as well as decreased disease-free survival. When a nonanatomical resection is performed, a MOR >1 cm should be attempted, because an adequate margin is often underestimated. Considerations should be made for extended resections when tumors are centrally located or near major vessels.

Numerous colonic adenomas in an individual with Bloom's syndrome.

Bloom's syndrome (BS) is a rare recessive disorder caused by germline mutation of the BLM gene. Individuals with BS manifest growth retardation, immunodeficiency, and a predisposition to cancer. In this report, we describe an individual with BS and multiple colonic adenomas reminiscent of familial adenomatous polyposis coli (FAP). Molecular studies revealed APC mutations in 4 of 6 adenomas, including 2 adenomas with the identical APC mutation and microsatellite instability in 1 of 6 adenomas. These results demonstrate similar pathways to colorectal neoplasia in BS as in the normal population and suggest that individuals with BS may be particularly susceptible to colorectal neoplasia.

A pilot study of preoperative chemoradiotherapy for resectable gastric cancer.

BACKGROUND: The goals of this study were to assess the feasibility and toxicity of a regimen of preoperative chemoradiotherapy, surgery, and intraoperative radiotherapy in the treatment of patients with potentially resectable gastric cancer. A secondary objective was to assess pathologic response to chemoradiotherapy in the treated tumors. METHODS: Twenty-four patients were entered in the protocol. Treatment regimen consisted of 45 Gy of external beam radiotherapy with concurrent 5-FU given as a continuous infusion at a dose of 300 mg/m2. Patients were restaged 4-6 weeks after chemoradiotherapy and then underwent surgical resection and intraoperative radiotherapy to a dose of 10 Gy. RESULTS: Twenty-three patients (96%) completed chemoradiotherapy in accordance with the study protocol. Nineteen (83%) of 23 patients who completed chemoradiotherapy underwent surgical resection with D2 lymphadenectomy. Four patients (17%) had progressive disease and were not resected. The morbidity and mortality rates were 32% and 5%, respectively. Of the resected patients, two (11%) had complete pathologic responses while 12 (63%) had pathologic evidence of significant treatment effect. CONCLUSIONS: Preoperative chemoradiotherapy for gastric cancer can be delivered safely and is well tolerated. The rate of surgical complications is consistent with that of other recently reported prospective trials of gastrectomy alone. Preoperative chemoradiotherapy resulted in significant pathologic responses in the majority of treated tumors, and complete pathologic responses were achieved in some patients.

Surgical management of hereditary pancreatic cancer.

Pancreatic cancer continues to be a leading cause of cancer death in the United States. Seven genetic syndromes are now known to be associated with an increased incidence of pancreatic cancer. Other familial forms of pancreatic cancer exist although the genetic basis for this predisposition remains elusive. The similarities in the genetic and clinical manifestations of the sporadic and familial forms of pancreatic cancer suggest that pretreatment staging and management of patients with established pancreatic cancer should be similar. For carcinomas of the pancreatic head, pancreaticoduodenectomy should be performed according to current surgical practice, whereas the use of total pancreatectomy should be limited to cases in which margins are found to be positive or if the anatomy precludes a safe pancreaticojejunostomy. Total pancreatectomy may be considered in high-risk kindreds who strongly desire prophylactic surgery and in those with premalignant lesions. Identification of the precise genetic basis for inherited pancreatic cancer will someday make it possible to examine scientifically the effectiveness of specific management strategies.

Adjuvant/neoadjuvant chemoradiation for gastric and pancreatic cancer.

Both gastric and pancreatic cancer remain leading causes of cancer death in the United States and worldwide. While surgical resection continues to be required for long-term cure of both these neoplasms, 5-year survival rates remain poor following surgery alone. For both gastric and pancreatic cancers, studies examining patterns of recurrence following apparently curative resection repeatedly demonstrate high rates of locoregional relapse. In this setting, the addition of chemoradiation delivered either before or following surgery represents a logical strategy to improve local tumor control and possibly improve survival. Data suggest that 5-fluorouracil-based chemoradiation, when given at sufficient doses, can effectively palliate patients with unresectable gastric cancer. Whether this approach improves response and survival in patients with resectable gastric cancer remains investigational. Results of ongoing and recently completed trials will provide further information on the utility of 5-fluorouracil-based regimens, as well as the use of other radiation sensitizers, in the adjuvant setting. In patients with resectable pancreatic cancer, the primary goal should be to perform a margin-negative pancreaticoduodenectomy. The use of neoadjuvant chemoradiation may increase the likelihood of achieving this goal, and this approach is being investigated.

Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer.

OBJECTIVE: In Western populations, long-term survival rates after curative resection of gastric cancer remain extremely poor. The lack of effective adjuvant therapy has prompted the evaluation of neoadjuvant approaches. Since 1988, we have conducted three separate phase II trials using neoadjuvant chemotherapy to treat patients with potentially resectable gastric cancer. The present study was conducted to evaluate whether response to neoadjuvant chemotherapy is predictive of survival in patients with resectable gastric cancer. METHODS: Eighty-three patients with pathologically confirmed gastric adenocarcinoma were treated with neoadjuvant chemotherapy before planned surgical resection. Response was assessed by upper gastrointestinal series, endoscopy, computed tomography scan, and pathologic examination. RESULTS: For the three phase II trials, clinical response rates ranged from 24% to 38%. Three patients (4%) had a complete pathologic response. Sixty-one patients (73%) underwent a curative resection. Median follow-up was 26 months. Univariate analysis revealed T stage, number of positive nodes, and response to chemotherapy to be significant predictors of overall survival. However, on multivariate analysis, response to chemotherapy was found to be the only independent prognostic factor. CONCLUSIONS: Response to neoadjuvant chemotherapy is the single most important predictor of overall survival after neoadjuvant chemotherapy for gastric cancer. These findings support further evaluation of neoadjuvant approaches in the treatment of this disease.

Pancreatic cancer: can we screen? How should we stage?

Pancreatic cancer remains a deadly disease, with few patients surviving 5 years following diagnosis. Surgical resection remains the only treatment associated with the potential for cure; however, most patients have locally advanced or metastatic disease at presentation and thus are not surgical candidates. Advances in imaging technologies, biochemistry, and molecular genetics have raised hopes of improving the outcome for patients with pancreatic cancer through earlier and more accurate diagnosis. As our knowledge of the genetics of pancreatic cancer has increased, the possibility of screening to identify patients at risk to develop the disease also holds promise. This review focuses on the utility of current modalities to screen for pancreatic cancer as well as the most accurate and expedient methods to stage the disease.

Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head.

BACKGROUND: The survival of patients who underwent pancreaticoduodenectomy with or without en bloc resection of the superior mesenteric-portal vein (SMPV) confluence for adenocarcinoma of the pancreatic head was compared. METHODS: To be considered for surgery, patients were required to fulfil the following computed tomography criteria for resectability: (1) absence of extrapancreatic disease, (2) no evidence of tumour extension to the superior mesenteric artery (SMA) or coeliac axis, and (3) a patent SMPV confluence. Tumour adherence to the superior mesenteric vein (SMV) or SMPV confluence was assessed at operation and en bloc venous resection was performed when necessary to achieve complete tumour extirpation. RESULTS: Seventy-five consecutive patients underwent pancreaticoduodenectomy, 44 without venous resection and 31 with en bloc resection of the SMPV confluence. There were no perioperative deaths in either group; late (more than 6 months) occlusion of the reconstructed SMPV confluence contributed to the death of two patients. Median survival in the 31 patients who required venous resection at the time of pancreaticoduodenectomy was 22 months, and that for the 44 control patients was 20 months (P = 0.25). CONCLUSION: Patients with adenocarcinoma of the pancreatic head who require venous resection during pancreaticoduodenectomy for isolated tumour extension to the SMV or SMPV confluence (in the absence of tumour extension to the SMA or coeliac axis) have a duration of survival no different from that of patients who undergo standard pancreaticoduodenectomy. These data suggest that venous involvement is a function of tumour location rather than an indicator of aggressive tumour biology.

Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease.

OBJECTIVE: This study was conducted to determine whether the perioperative administration of octreotide decreases the incidence of pancreatic anastomotic leak after pancreaticoduodenectomy for malignancy. SUMMARY BACKGROUND DATA: Three multicenter, prospective, randomized trials concluded that patients who receive octreotide during and after pancreatic resection have a reduction in the total number of complications or a decreased incidence of pancreatic fistula. However, in the subset of patients who underwent pancreaticoduodenectomy for malignancy, either no analysis was performed or no benefit from octreotide could be demonstrated. METHODS: A single-institution, prospective, randomized trial was conducted between June 1991 and December 1995 involving 120 patients who were randomized to receive octreotide (150 microg subcutaneously every 8 hours through postoperative day 5) or no further treatment after pancreaticoduodenectomy for malignancy. The surgical technique was standardized, and the pancreaticojejunal anastomosis was created using the duct-to-mucosa or invagination technique. RESULTS: The two patient groups were similar with respect to patient demographics, treatment variables, and histologic diagnoses. The rate of clinically significant pancreatic leak was 12% in the octreotide group and 6% in the control group (p = 0.23). Perioperative morbidity was 30% and 25%, respectively. Patients who underwent reoperative pancreaticoduodenectomy had an increased incidence of pancreatic anastomotic leak, whereas those who received preoperative chemoradiation had a decreased incidence of pancreatic anastomotic leak. CONCLUSIONS: The routine use of octreotide after pancreaticoduodenectomy for malignancy cannot be recommended.

Phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) by the cyclin-dependent kinase p34.

Mutations in the tumor suppressor gene APC invariably lead to the development of colorectal cancer. The vast majority of these mutations are nonsense or frameshifts resulting in nonfunctional, truncated APC protein products. Eleven cyclin-dependent kinase (CDK) consensus phosphorylation sites have been identified in the frequently deleted carboxyl-terminal region of APC; loss of these phosphorylation sites by mutation could therefore compromise the ability of APC to inhibit cell growth. This report demonstrates that immunoprecipitates of full-length, but not truncated, APC protein include a mitosis-specific kinase activity in vivo. Biochemical and Western analysis of these immunoprecipitates confirms the presence of the CDK p34(cdc2). We also show that APC is a substrate for recombinant human p34(cdc2)-cyclin B1. Modification of APC by p34(cdc2) implicates phosphorylation as a mechanism for regulating APC function via a link to the cell cycle.

Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas.

PURPOSE: The effects of preoperative versus postoperative fluorouracil (5-FU)-based chemotherapy and irradiation on treatment toxicity, duration of treatment, tumor recurrence, and survival were compared in patients who underwent potentially curative therapy for adenocarcinoma of the pancreatic head during a 5-year period. METHODS: From July 1990 to July 1995, 142 patients with localized adenocarcinoma of the pancreatic head deemed resectable on the basis of radiographic images were treated with curative intent using a multimodality approach involving either preoperative or postoperative chemoradiation. Patients with biopsy confirmation of adenocarcinoma and a low-density mass in the pancreatic head identified by computed tomography (CT) received preoperative chemoradiation. Patients without a mass on CT or in whom the preoperative biopsy was negative underwent pancreaticoduodenectomy with planned postoperative chemoradiation. Protocol-based preoperative chemoradiation consisted of external-beam irradiation at a dose of 50.4 Gy (standard fractionation; 1.8 Gy/d, 5 d/wk) or 30 Gy (rapid fractionation; 3 Gy/d, 5 d/wk) combined with continuous infusion 5-FU (300 mg/m2/d, 5 d/wk). Postoperative chemoradiation combined 50.4 Gy of external-beam irradiation (standard fractionation) with continuous-infusion 5-FU. RESULTS: No patient who received preoperative chemoradiation experienced a delay in surgery because of chemoradiation toxicity, but six of 25 eligible patients (24%) did not receive postoperative chemoradiation because of delayed recovery after pancreaticoduodenectomy. No significant differences in toxicities from chemoradiation were observed between groups. Patients treated with rapid-fractionation preoperative chemoradiation had a significantly (P < .01) shorter duration of treatment (median, 62.5 days) compared with patients who received postoperative chemoradiation (median, 98.5 days) or standard-fractionation preoperative chemoradiation (median, 91.0 days). At a median followup of 19 months, no significant differences in survival were observed between treatment groups. No patient who received preoperative chemoradiation and pancreaticoduodenectomy experienced a local recurrence; peritoneal (regional) recurrence occurred in 10% of these patients. Local or regional recurrence occurred in 21% of patients who received pancreaticoduodenectomy and postoperative chemoradiation. CONCLUSION: Delivery of preoperative and postoperative chemoradiation in patients who underwent potentially curative pancreaticoduodenectomy for adenocarcinoma of the pancreatic head resulted in similar treatment toxicity, patterns of tumor recurrence, and survival. Rapid-fractionation preoperative chemoradiation ensured the delivery of all components of therapy to all eligible patients with a significantly shorter duration of treatment than with standard-fractionation chemoradiation given either before or after pancreaticoduodenectomy. Prolonged recovery after pancreaticoduodenectomy prevents the delivery of postoperative adjuvant chemoradiation in up to one fourth of eligible patients.

Mutation of phosphoserine 389 affects p53 function in vivo.

To study the importance of phosphorylation for p53 transactivation function, we generated mutations at each of its known phosphorylated serine amino acids. Mutations of murine p53 serine residues individually to either alanine or glutamic acid at positions 7, 9, 12, 18, 37, 312, and 389 resulted in equivalent levels of transcriptional activation in standard transient transfection experiments. However, when p53 transcriptional activity was measured in cells that attain G1 arrest upon contact inhibition, wild-type p53 was inactive, and only alteration at serine 389 to glutamic acid resulted in a functional p53 protein. This Ser --> Glu mutant also has an increased ability to bind DNA. Elimination of the phosphorylation site by substitution of an alanine amino acid resulted in loss of transcriptional activity. We also demonstrated that specific phosphorylation of p53 at serine 389 is induced by cyclin E overexpression in high-density cells. Our data establish for the first time that phosphorylation of p53 at serine 389 is important in activating its function in vivo.

Reoperative pancreaticoduodenectomy for periampullary carcinoma.

BACKGROUND: We have noted a continued increase in the number of patients referred to our institution for presumed or biopsy-proven periampullary carcinoma following an "exploratory" laparotomy during which tumor resection was not performed. Although previous work has demonstrated the safety of reoperative pancreaticoduodenectomy (PD), the need to avoid nontherapeutic laparotomy in these patients is obvious. In the current study, we sought to determine why PD was not performed at the initial operation. METHODS: Using the prospective pancreatic cancer database, we identified all patients who underwent reoperative PD at our institution between June 1990 and October 1995. Radiologic imaging prior to reoperation was standardized and based on thin-section, contrast-enhanced computed tomography (CT); helical CT was used in more recent cases. Pathologic data were obtained, and initial outside operative reports were reviewed to determine why a PD was not performed at the initial procedure. RESULTS: Twenty-nine patients underwent reoperative PD. Resection was not performed at the initial laparotomy because of the surgeon's assessment of local unresectability (17 patients), lack of a tissue diagnosis of malignancy (9), misdiagnoses (2), and error in intraoperative management (1). In the 17 patients deemed to have unresectable disease, successful reoperative PD required vascular resection in 10. All 10 of these patients had resection with negative microscopic margins of excision. Of the 9 patients who did not have resection owing to diagnostic uncertainty, all 9 had undergone multiple intraoperative biopsies interpreted as negative for malignancy; 6 of 9 had carcinoma confirmed on permanent-section analysis of the biopsy specimens. Four patients suffered major complications from intraoperative large-needle biopsy. CONCLUSIONS: Detailed preoperative imaging and a clearly defined operative plan would have allowed successful resection at the initial operation in 27 of 29 patients who underwent reoperative PD. Avoidable patient morbidity and the cost of unnecessary surgery argue strongly against "exploratory" surgery in patients with presumed periampullary neoplasms.

Association of gastric adenocarcinoma with the HLA class II gene DQB10301.

BACKGROUND & AIMS: The HLA class II gene DQB1*0301 has been linked to several cancers. This study was designed to determine if HLA-DQB1*0301 is present at altered frequency in patients with gastric, colorectal, or pancreatic adenocarcinoma. METHODS: Oligotyping for HLA-DQB1*0301 was performed for 159 Caucasian patients with 160 gastrointestinal adenocarcinomas (52 gastric, 62 colorectal, and 46 pancreatic adenocarcinomas) and compared with 260 Caucasian noncancer controls. Patients with gastric adenocarcinoma underwent extended HLA class II region oligotyping. Immunoglobulin G to Helicobacter pylori was detected by enzyme-linked immunosorbent assay. RESULTS: HLA-DQB1*0301 was more common in patients with gastric adenocarcinoma than controls (54% vs. 27%; bonferroni-corrected chi 2 P = 0.003; odds ratio, 3.2). HLA-DQB1*0301 was not associated with colorectal or pancreatic adenocarcinoma. No other HLA-DQB1 allele and no HLA-DQA1 or transporter associated with antigen processing 2 (TAP2) allele were present at altered frequency in patients with gastric adenocarcinoma. Serological evidence for H. pylori infection was less frequent in HLA-DQB1*0301-positive patients with gastric adenocarcinoma compared with HLA-DQB1*0301-negative patients (52% vs. 88%; Fisher's Exact Test; P = 0.007). CONCLUSIONS: HLA-DQB1*0301 is more common in caucasian patients with gastric adenocarcinoma than noncancer controls. The mechanism linking HLA-DQB1*0301 with gastric adenocarcinoma is not likely through increased susceptibility to H. pylori infection.

Laparoscopic staging for gastric cancer.

BACKGROUND: Laparoscopy has become an increasingly important diagnostic tool for the staging of intraabdominal malignancies. Some investigators have suggested laparoscopy to be of questionable value in the preoperative staging of gastric cancer because many patients may require palliative surgery despite laparoscopic findings. However, in other studies laparoscopy was found to be a more accurate staging technique and useful in avoiding unnecessary laparotomy when compared with abdominal sonography, liver scintigraphy, or early generation computed tomography (CT). In recent years marked improvements have been made in CT technology, and laparoscopy has not been compared with current generation CT. Therefore we sought to determine the usefulness of laparoscopy for staging gastric adenocarcinoma in the era of current generation CT scanning. METHODS: Staging laparoscopy was performed in 71 patients with potentially resectable gastric cancer as determined by physical examination and current generation CT. The results of laparoscopy were evaluated in the context of negative or equivocal CT findings. RESULTS: Laparoscopic staging was successful in 69 patients (97%). Laparoscopy identified distant metastatic disease in 16 (23%) patients judged to be eligible for potentially curative resection by current generation CT scanning. Only one of these patients required laparotomy for palliation. Combined CT and laparoscopic staging resulted in a 93% resectability rate for patients operated on with curative intent. CONCLUSIONS: We advocate staging laparoscopy as an important staging procedure for all patients with potentially resectable gastric cancer. The additional cost of laparoscopy should be more than offset by the decreased morbidity and expense of hospitalization for those patients who avoid an unnecessary laparotomy.