Impact of pasireotide on postoperative pancreatic fistulas following distal resections.

PURPOSE: Postoperative pancreatic fistula (POPF), a difficult complication after surgery, can cause peripancreatic fluid collection and infections in the operative area. In addition, pancreatic fluid is corrosive and can lead to postoperative bleeding. Clinically significant grade B and C fistulas (CR-POPF) increase postoperative morbidity, resulting in a prolonged hospital stay. Delaying adjuvant therapy due to fistula formation in cancer patients can affect their prognosis. In this study, we aimed to determine if pasireotide affects fistula formation, and the severity of other complications in patients following pancreatic distal resections. DATA AND METHODS: Between 2000 and 2016, 258 distal pancreatectomies were performed at Helsinki University Hospital and were included in our analysis. Pasireotide was administered to patients undergoing distal resections between July 2014 and December 2016. Patients received 900-µg pasireotide administered twice daily perioperatively. Other patients who received octreotide treatment were analyzed separately. Complications such as fistulas (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), reoperations, and mortality were recorded and analyzed 90 days postoperatively. RESULTS: Overall, 47 (18%) patients received pasireotide and 31 (12%) octreotide, while 180 patients (70%) who received neither constituted the control group. There were 40 (16%) clinically relevant grade B and C POPFs: seven (15%) in the pasireotide group, three (10%) in the octreotide group, and 30 (17%) in the control group (p = 0.739). Severe complications categorized as Clavien-Dindo grade III or IV were recorded in 64 (25%) patients: 17 (27%) in the pasireotide group, 4 (6%) in the octreotide group, and 43 (67%) in the control group (p = 0.059). We found no 90-day mortality. CONCLUSIONS: In this study, pasireotide did not reduce clinically relevant POPFs or severe complications following pancreatic distal resection.

Diagnosis, natural course and treatment outcomes of groove pancreatitis.

BACKGROUND: Groove pancreatitis (GP) is a rare form of chronic pancreatitis with limited data on its diagnostics and treatment outcomes. The aim of this study was to assess its diagnostics, natural course, and treatment options. METHODS: The study is a retrospective population-based study from Southern Finland, including all patients with suspected GP between January 2005 and December 2015. Two certified gastrointestinal radiologists re-reviewed the imaging studies. The radiological re-review, clinical judgment, and final histopathology confirmed the GP diagnoses. RESULTS: Out of 67 patients with possible GP, 39 patients were considered to have high radiological certainty of GP. Out of these 39, five patients had cancer instead. Thirty-three patients with confirmed GP formed the final study cohort. Patients with GP were mostly middle-aged (median 55 years) men. All had at least moderate alcohol consumption. No intervention was needed in 14 patients. In five-year follow-up all conservatively treated patients became asymptomatic, while 10 out of 16 patients undergoing at least one intervention were asymptomatic at five years. CONCLUSION: The radiological diagnosis of GP is difficult, and a low threshold for cancer suspicion should be kept. Symptoms of GP decrease with time and suggest conservative treatment as the first-line option.

The Role of Endoscopic and Surgical Treatment in Chronic Pancreatitis.

Chronic pancreatitis is a long-term illness leading to hospital admissions and readmission. This disease is often caused by heavy alcohol consumption and smoking. Patients with chronic pancreatitis suffer from acute or chronic pain episodes, recurrent pancreatitis, and complications, such as pseudocysts, biliary duct strictures, and pancreatic duct fistulas. Pancreatic duct strictures and stones may increase intraductal pressure and cause pain. Endoscopic therapy is aiming at decompressing the pressure and relieving the pain, most commonly with pancreatic duct stents and pancreatic duct stone retrieval. Early surgery is another option to treat the pain. In addition, endotherapy has been successful in treating complications related to chronic pancreatitis. The therapy should be individually chosen in a multidisciplinary meeting. Endoscopic therapy and surgery as treatment options for chronic pancreatitis are discussed in this review.

Differences in Prognostic Factors and Recurrence Patterns After Curative-Intent Resection of Perihilar and Distal Cholangiocarcinomas.

BACKGROUND: Perihilar cholangiocarcinoma and distal cholangiocarcinoma arise from the same tissue but require different surgical treatment methods. It remains unclear whether these cholangiocarcinoma types have different outcomes, prognostic factors, and/or recurrence patterns. METHODS: This retrospective study evaluated patients who underwent curative-intent resection for perihilar cholangiocarcinoma or distal cholangiocarcinoma at a tertiary academic hospital during 2000-2015. Survival and prognostic factors were identified using Kaplan-Meier and Cox regression analyses. RESULTS: The 90-day mortality rates were 0% for perihilar cholangiocarcinoma (36 patients) and 4% for distal cholangiocarcinoma (47 patients). There were no significant differences between perihilar cholangiocarcinoma or distal cholangiocarcinoma in median overall survival (30.9 vs 40.4 months) or median disease-free survival (14.2 vs 21.4 months). Among perihilar cholangiocarcinoma patients, age > 65 years was an independent predictor of poorer overall survival (hazard ratio: 2.45, 95% confidence interval: 1.07-5.64), while requiring bile duct re-resection was an independent predictor of disease-free survival (hazard ratio: 2.76, 95% confidence interval: 1.01-7.51). Among distal cholangiocarcinoma patients, a pN1 category independently predicted poorer overall survival (hazard ratio: 3.40, 95% confidence interval: 1.14-10.11), while preoperative CA19-9 levels >30 U/mL (hazard ratio: 2.51, 95% confidence interval: 1.09-5.79) and pN1 category (hazard ratio: 2.51, 95% confidence interval: 1.09-5.79) predicted a shorter disease-free survival. Local recurrence was more common with perihilar cholangiocarcinoma (50% of recurrences), while multiple synchronous sites were more common for distal cholangiocarcinoma (41% of recurrences). CONCLUSION: Perihilar cholangiocarcinoma and distal cholangiocarcinoma patients have similar survival outcomes. However, local control appears to be more prognostic for perihilar cholangiocarcinoma patients, while positive lymph nodes are critical prognostic factor for distal cholangiocarcinoma patients.

Outcomes of High-Frequency Gastric Electric Stimulation for the Treatment of Severe, Medically Refractory Gastroparesis in Finland.

BACKGROUND AND AIMS: Severe, medically uncontrollable gastroparesis is a rare entity, which can be treated using a high-frequency gastric electric stimulator implanted surgically. Previous follow-ups have proven positive outcomes with gastric electric stimulator in patients with gastroparesis. The aim of this study was to evaluate the efficacy and safety of gastric electric stimulator in patients, in whom gastroparesis could not be controlled by conservative means in our country. MATERIALS AND METHODS: This is a retrospective multi-center cohort comprising all patients who had been implanted gastric electric stimulator for severe, medically refractory gastroparesis during 2007-2015 in Finland. RESULTS: Fourteen patients underwent implantation of gastric electrical stimulator without any postoperative complications. Laparoscopic approach was used in 13 patients (93%). Prior implantation, all patients needed frequent hospitalization for parenteral feeding, 13 had severe nausea, 11 had severe vomiting, 10 had notable weight loss, and 6 had frequent abdominal pain. After operation, none of the patients required parenteral feeding, 11 patients (79%) gained median of 5.1 kg in weight (P < 0.01), and symptoms were relieved markedly in 8 and partially in 3 patients (79%). Of partial responders, two continued to experience occasional vomiting and one mild nausea. Five patients needed medication for gastroparesis after the operation. One patient did not get any relief of symptoms, but gained 6 kg in weight. No major late complications occurred. CONCLUSION: Gastric electrical stimulator seems to improve the nutritional status and give clear relief of the symptoms of severe, medically uncontrollable gastroparesis. Given the low number of operations, gastric electrical stimulator seems to be underused in Finland.

Early gastric cancer: clinical characteristics and results of surgery.

BACKGROUND: Early gastric cancer (EGC) is associated with better prognosis than advanced cancer of the stomach. Unfortunately, EGC accounts for a minority of operated gastric cancers in Europe. The aim of this study was to evaluate the clinical characteristics of EGC and the outcome after surgery. METHODS: The study group comprised 94 EGC patients having undergone surgery at Helsinki University Central Hospital between April 1983 and July 2007. RESULTS: The overall 5-year survival rate of EGC patients was 92.4%. Tumor location in the upper part of the stomach and mixed histological type impaired the prognosis (p = 0.043 and 0.008, respectively). The probability of lymph node metastasis was significantly higher when the tumor infiltrated gastric submucosa rather than mucosa (p = 0.012). Existence of lymph node or distant metastases decreased the survival rates (both p < 0.001). Total gastrectomy, pancreatic resection, and extended D2 lymph node dissection increased the complication rate, but did not have effect on survival. CONCLUSION: The overall prognosis of EGC is favorable. The survival rates of EGC decreased when the tumor was located in the upper part of the stomach or was of mixed histological type, or the patient had lymph node or distant metastasis.

Clinical outcome after D1 vs D2-3 gastrectomy for treatment of gastric cancer.

BACKGROUND: Clinical benefit from extended lymphadenectomy for gastric cancer remains controversial as a considerable variation exists between results of different studies. METHODS: 562 patients were treated at HUCH between 1987-2003, whereof 223 underwent gastrectomy with curative intent. Of these, 114 patients underwent subtotal/total gastrectomy with D1 (standard) lymphadenectomy and 109 patients had D2-3 (extended) lymph node dissection. The clinical outcome of these patients was analysed retrospectively. RESULTS: The incidence of surgical complications was 33.0% in D2-3 and 16.8% in D1 lymphadenectomy groups (p = 0.008). Abscess was the most common complication (11.0%) among D2-3 operated patients and haemorrhage (4.4%) in D1 group. Hospital mortality was 3.7% in D2-3 and 1.8% in D1 group (p = 0.438). The only statistically significant factor influencing the rate of complications was D2-3 lymphadenectomy (OR 2.620, 95% C.I. 1.375 to 4.991). D2-3 was associated with a longer postoperative hospital stay and operation time, greater blood loss and increased need for blood transfusions compared to D1. The 5-year survival was not statistically different between lymphadenectomy groups. CONCLUSION: It is justified to perform a D2-3 gastrectomy in Europe with a acceptable postoperative mortality but with a significant morbidity. Further studies are needed to assess the value of extended lymphadenectomy in gastric cancer.

Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer.

BACKGROUND: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high-energy phosphates. About half of the patients with breast cancer have a decrease in XOR expression. Patients with breast cancer with unfavourable prognosis are independently identified by the loss of XOR. AIM: To assess the clinical relevance of XOR expression in gastric cancer. METHODS: XOR levels were studied by immunohistochemistry in tissue microarray specimens of 337 patients with gastric cancer and the relation between XOR expression and a series of clinicopathological variables, as well as disease-specific survival, was assessed. RESULTS: XOR was moderately decreased in 41% and was undetectable in another 14% of the tumours compared with the corresponding normal tissue. Decreased XOR was associated with advanced stage, deep tumour penetration, diffusely spread tumour location, positive lymph node status, large tumour size, non-curative disease, cellular aneuploidy, high S-phase fraction and high cyclooxygenase-2 expression, but not with p53 expression or Borrmann classification. Down regulation of XOR was associated with unfavourable outcome, and the cumulative 5-year gastric cancer-specific survival in patients with strong XOR expression was 47%, compared with 22% in those with moderate to negative expression (p<0.001). This was also true in patients with stage I-II (p = 0.01) and lymph node-negative (p = 0.02) disease, as well as in patients with smaller (< or =5 cm) tumours (p = 0.02). CONCLUSION: XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer.

MMP-2 but not MMP-9 associated with COX-2 and survival in gastric cancer.

BACKGROUND AND AIM: Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. As cyclo-oxygenase-2 (COX-2) has been shown to activate MMPs, creating one of the COX-2-promoted pathways of tumour growth and metastasis, the prognostic role of MMP-2 and MMP-9 in gastric cancer was assessed and their association with COX-2 expression was evaluated. MATERIALS AND METHODS: Samples were collected from 342 consecutive patients operated on for gastric cancer, of which 315 were acceptable for MMP-2, MMP-9 and COX-2 immunohistochemistry. Specimens were stained with specific antibodies, evaluated and categorised by two interpreters, and then correlated with clinical data and survival. RESULTS: Epithelial MMP-2 immunoreactivity was associated with male sex, high stage, advanced penetration depth, non-curative surgery, high COX-2 expression and poor survival. Stromal MMP-2 expression correlated with high stage, intestinal type and non-curative surgery whereas MMP-9 correlated only with intestinal type. Stage, intent of surgery and COX-2 were independent prognostic factors. CONCLUSIONS: Epithelial MMP-2 expression in gastric cancer is associated with aggressive forms, COX-2 and poor survival, although MMP-2 was not an independent prognostic factor. In gastric cancer tumour growth is apparently induced by COX-2, and invasion is mediated by MMP-2.

High tissue expression of tumour-associated trypsin inhibitor (TATI) associates with a more favourable prognosis in gastric cancer.

AIMS: The tumour-associated trypsin inhibitor (TATI) is a 6-kDa protease inhibitor with potential inhibitory effects on tissue degradation. In serum, increased levels have been associated with adverse prognosis in different forms of cancer. We assessed the tumour tissue expression and prognostic value of TATI in a surgically treated, single-institution series of patients with gastric cancer. METHODS AND RESULTS: Using a monoclonal anti-TATI antibody, immunohistochemistry was performed on formalin-fixed paraffin-embedded tumour specimens from 336 patients. TATI expression was observed in 265 (79%) of the tumours. There was a significant association between high TATI expression and low stage (P = 0.007), superficial tumours (P = 0.005), and absence of nodal (P = 0.015) and of distant metastases (P = 0.022). In univariate analysis, patients with high TATI expression had a significantly more favourable 5-year cumulative survival compared with patients with negative to moderate immunostaining (43% and 28%, respectively, P = 0.006). On multivariate survival analysis stratified for estimated cure of surgery, stage (P < 0.0001) and age (P = 0.022) at the time of surgery were independent prognostic factors. CONCLUSIONS: High TATI expression in tumour tissue was detected more frequently in patients with early-stage gastric cancer and seems to correlate with a favourable outcome.

Genoprevalence in human tissues of TT-virus genotype 6.

TT virus (TTV) is a newly discovered human virus of high genotypic diversity. TTV is widely distributed among humans, but the possible genotype-related differences in TTV biology are not well known. The prevalence and amount of TTV-DNA, especially of genotype 6, was determined by nested-PCR in various human tissues, and human parvovirus B19, another ssDNA virus, was used as a reference. TTV DNA was detected simultaneously in bile, peripheral blood mononuclear cells (PBMC) and plasma of 77% subjects, in 38% skin samples, in 38% synovial samples and in all (100%) adenoids, tonsils and liver samples. The relative concentrations of TTV-DNA did not vary significantly among the different samples. Genotype 6 TTV-DNA was detected in bile and plasma of one subject (3%), in skin and serum of one subject (8%) and in one liver (5%). The overall prevalence of TTV genotype 6 was 4% in subjects and 4% in sera. TTV genotype 6 was shown to occur in human tissues with no obvious tissue-type or symptom specificity. Parvovirus B19 DNA was detected overall in 38% subjects, and bile was the only sample type tested that did not persistently harbour B19 DNA.

The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia.

BACKGROUND: There are few data on the natural course of Helicobacter pylori-related atrophic gastritis. AIM: To investigate the effect of H. pylori eradication on advanced atrophic gastritis in the corpus. METHODS: Twenty-two elderly men with H. pylori infection and moderate or severe atrophic corpus gastritis formed the study population. These men were under endoscopic surveillance because of the presence of indefinite or definite dysplastic gastric lesions in addition to atrophic corpus gastritis. The men were gastroscopically and bioptically examined four times before they received H. pylori eradication therapy (mean follow-up time, 7.5 years), and once again 2.5 years after eradication therapy. Serum levels of pepsinogen I and H. pylori antibodies were analysed at baseline, immediately before and 2.5 years after eradication therapy. RESULTS: During the 7.5-year period prior to eradication therapy, no significant changes were observed in the mean atrophy and intestinal metaplasia scores or in the mean serum level of pepsinogen I. However, a significant improvement occurred in the mean histological scores of inflammation (from 2.2 to 0.5), atrophy (from 2.2 to 1.2) and intestinal metaplasia (from 1.6 to 1.1) in the corpus mucosa after H. pylori eradication. In addition, the mean serum level of pepsinogen I increased from 16.3 to 25.7 microg/L (P=0.0071, Wilcoxon signed rank test) after eradication therapy. CONCLUSIONS: The results suggest that advanced atrophic corpus gastritis (and intestinal metaplasia) improves and may even heal after the eradication of H. pylori.

DNA copy number profiling in esophageal Barrett adenocarcinoma: comparison with gastric adenocarcinoma and esophageal squamous cell carcinoma.

We screened 18 specimens of Barrett adenocarcinoma for genetic alterations using comparative genomic hybridization (CGH) to analyze DNA copy number changes. The most common gains were at 20q (56%) and 17q (39%). High-level amplifications were observed in the same chromosomes. The most common losses were in chromosomes 4 (22%) and 5 (22%). Other recurrent changes were gains of chromosomes 8, 10q, and 13. We compared the copy number changes in Barrett adenocarcinoma and those previously reported in the intestinal type of stomach carcinoma. The similarities we found suggest a common molecular pathogenesis, whereas dissimilarities seen between Barrett adenocarcinoma and esophageal squamous cell carcinoma are in keeping with a well-known different etiology.

Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer.

The prognostic value of the immunohistochemical expression of epithelial and stromal syndecan-1 was evaluated in 296 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with mouse monoclonal antibody B-B4 against human syndecan-1. Loss of immunoreactivity (syndecan-1 immunoreactivity correlated with a higher stage of disease (stages II-IV), tumour location in the upper third of the stomach, nodal metastases (N1 or N2), positive stromal syndecan-1 staining, deep tumour penetration (to subserosa or deeper = T2-T4), larger tumour size (> or = 5 cm) and intestinal type of cancer. No correlation between epithelial syndecan-1 immunoreactivity and age, gender, distant metastases, grade of differentiation or Borrmann classification was observed. Positive stromal syndecan-1 immunoreactivity correlated with decreased epithelial syndecan-1 expression, intestinal type of cancer and Borrmann type I. Patients with low epithelial syndecan-1 expression in cancer cells had worse overall survival than patients with strong epithelial syndecan-1 staining (p = 0.0012). Stromal syndecan-1-positive patients had a worse outcome than patients with syndecan-1-negative stroma (p = 0.0193). In Cox multivariate analysis, stromal syndecan-1 immunoreactivity was a prognostic factor independent of TNM stage, surgery for cure and tumour size. Thus, the immunohistochemical expression of syndecan-1 might be a predictor of outcome in patients with gastric adenocarcinoma.

Survival of Helicobacter pylori From complement lysis by binding of GPI-anchored protectin (CD59).

BACKGROUND & AIMS: Although Helicobacter pylori is sensitive to complement lysis in vitro, chronic infection persists for years. We tested whether H. pylori acquires complement resistance by binding glycolipid-tailed inhibitors from the host. METHODS: Gastric biopsy specimens from H. pylori-infected patients (n = 10) and noninfected controls (n = 6) were analyzed for complement deposition and expression of the complement regulators protectin (CD59) and DAF. Protectin binding and complement sensitivity analyses were performed with the NCTC strain 11637 (CagA(+)) and 2 clinical isolates 9:0 (CagA(+)) and 67:20 (CagA(-)). RESULTS: In the noninfected mucosa, protectin was strongly expressed on the membranes of epithelial cells, but in the infected epithelia the expression was granular and more focused to the mucus. H. pylori bacteria in the gastric pits were often positive for protectin but negative for C5b-9. An opposite pattern was seen on the surface mucosa. In vitro analyses using (125)I-CD59 and bacteriolysis assays showed that protectin bound to H. pylori and protected CagA(+) strains against complement killing. In an enzyme-linked immunosorbent assay, the binding of CD59 correlated inversely with the appearance of the C5b-9 neoantigen. CONCLUSIONS: Binding of protectin inhibits membrane attack complex assembly on H. pylori and may thereby contribute to their survival on the gastric mucosa.

Gastric carcinoma in young adults.

Approximately 10% of gastric cancer cases are found in patients younger than 41 years old. Symptoms of gastric carcinoma are not different from those in the elderly, but because of its relatively uncommon presentation in the young age group, the diagnosis may be delayed. Most of the gastric cancer cases are of diffuse type, and are associated with superficial gastritis. No association is found with intestinal metaplasia. Some gastric cancer cases may, however, develop into histologically normal stomachs. Approximately 10% of young gastric cancer patients have positive family history. In practice, the treatment of gastric cancer is not different between age groups. The same kind of survival is also seen between the age groups after operation if the same tumor stages are compared.

Superior mesenteric and portal vein thrombosis following laparoscopic nissen fundoplication.

This case report describes superior mesenteric and portal vein thrombosis after laparoscopic Nissen fundoplication. As a thromboembolic prophylaxis, 2,500 IU of dalteparin was given preoperatively. After postoperative day 19, the patient experienced gradually increasing abdominal pain, mostly related to meals. Physical examination and laboratory tests were normal. CT scan revealed a portal and superior mesenteric vein thrombosis. Dalteparin and warfarin treatment was started, and symptoms relieved rapidly. In a control Doppler ultrasound 1 month after the onset of the treatment, a good flow in the portal and superior mesenteric vein was seen. Possible mechanisms are discussed.

Diagnosis of Helicobacter pylori infection in patients with atrophic gastritis: comparison of histology, 13C-urea breath test, and serology.

BACKGROUND: Atrophic gastritis, a risk factor for gastric cancer, is a late consequence of Helicobacter pylori infection in approximately one-third of the infected patients. It has been suggested that gastric cancer would develop less frequently if H. pylori were eradicated. However, the prevalence of H. pylori infection may be underestimated in patients with atrophic gastritis and intestinal metaplasia if only biopsy-based diagnostic methods are used. METHODS: We compared histology, 13C-urea breath test (13C-UBT), and serology in H. pylori diagnostics in 50 male patients with atrophic corpus gastritis. RESULTS: H. pylori was detected in 15 (30%) patients by histology and in 14 (28%) by 13C-UBT, whereas increased serum antibody levels indicating H. pylori infection were found in 41 (82%) patients (P < 0.0001 between serology and both histology and 13C-UBT). H. pylori infection was associated with atrophic corpus gastritis in 84% of the present patients (in one patient with normal antibody titres H. pylori was defined histologically). CONCLUSIONS: H. pylori infection would have been missed in most patients with atrophic gastritis without the analysis of H. pylori antibodies. Therefore, in patients with atrophic gastritis, the use of serology is encouraged in diagnosing H. pylori infection.

A prognostic value of syndecan-1 in gastric cancer.

BACKGROUND: Syndecan-1, a cell surface heparan sulphate proteoglycan, has a role in cell adhesion, maturation and proliferation. Syndecan-1 has been reported to be a promising prognostic marker in various cancer forms. MATERIALS AND METHODS: We analysed tumour specimens from 296 gastric cancer patients. Syndecan-1 expression was studied by immunohistochemistry. RESULTS: Syndecan-1 immunoreactivity was observed in 234 (79%) patients. The expression of syndecan-1 did not correlate significantly with the presence of lymph node metastases, distant metastases, peritoneal spreading, penetration depth, tumour size, tumour location, Borrmann's classification, Laurén's classification, age or gender. Syndecan-1 immunoreactivity correlated significantly with survival in the whole patient series (p = 0.0499) and also in the subgroup of patients with stage I cancer (p = 0.0417), but not in patients with stage II, III or IV disease. In multivariate survival analysis, stage of disease and tumour size emerged as the only independent prognostic factors. CONCLUSIONS: In conclusion, immunohistochemical expression of syndecan-1 is a potential prognostic factor in gastric cancer, especially in patients with stage I disease.

LKB1 somatic mutations in sporadic tumors.

Germline mutations of LKB1/Peutz-Jeghers syndrome gene predispose carriers to hamartomatous polyposis of the gastrointestinal tract as well as to cancer of different organ systems. Although Peutz-Jeghers syndrome patients frequently present with neoplasms of the colon, stomach, small intestine, pancreas, breast, ovaries, and cervix, somatic mutations appear to be rare in the sporadic tumor types thus far studied (colorectal, gastric, testicular, and breast cancers). To evaluate whether somatic mutations of LKB1 contribute to the tumorigenesis of yet unstudied tumor types, we screened 14 cell lines and 129 tumor specimens from different cancers for a genetic defect in LKB1. Six melanoma and eight myeloma cell lines were scrutinized for LKB1 somatic mutations by genomic sequencing. No changes were found in the coding LKB1 sequence and exon/intron boundaries. Next, we analyzed 12 pancreatic, 8 gastric, 12 ovarian granulosa cell, 26 cervical, 28 lung, 24 soft tissue, and 19 renal tumors by single-strand conformational polymorphism analysis. Three changes in LKB1 coding nucleotide sequence were identified. One base pair deletion at A957 and G958 substitution by T occurred in a cervical adenocarcinoma sample, resulting in a frameshift and premature stop codon at position 335. Substitution of A581 by T occurred in a lung adenocarcinoma sample, resulting in the change of aspartic acid at position 194 to valine. A loss of another allele was detected in this sample. One silent change, C1257T, was found in a pancreatic carcinoma sample. The changes were not present in the matched normal tissue DNA samples. Our results suggest that mutational inactivation of LKB1 is a rare event in most sporadic tumor types.