Evaluation of optimum classification measures used to define textbook outcome among patients undergoing curative-intent resection of gastric cancer.

BACKGROUND: Textbook outcome (TO) is a composite measure reflecting various aspects of services provided to patients with solid malignancies. We sought to evaluate the importance of various TO components previously proposed for gastric cancer. METHODS: Prospectively maintained electronic databases of 1,743 patients treated in two academic surgical centres were reviewed. Six candidate definitions of TO were evaluated based on their ability to accurately predict patients' prognosis by Cox proportional hazards modelling. RESULTS: TO definition combining 10 measures corresponding to complete tumour resection with an uneventful postoperative course showed the best goodness of fit by achieving the lowest values of Akaike (AIC) and Bayesian (BIC) information criteria and the best predictive performance based on the highest value of c-index. The overall median survival was significantly longer for patients with than without textbook outcome (69.0 vs 20.1 months, P < 0.001). TO maintained its prognostic value in a multivariate model controlling for age, sex, comorbidities, treatment, and tumour related variables and was associated with a 39% lower risk of death (HR 0.61, 95%CI 0.51 - 0.73, P < 0.001). Nine variables identified as predictors of TO were used to develop a nomogram showing very good correlation between the predicted and actual probability of achieving TO. The AUC of ROC obtained from the nomogram was 0.752 (95% CI 0.727 to 0.781). CONCLUSIONS: A uniform definition of textbook outcome provides clinically relevant prognostic information and could be used in quality improvement programs for gastric cancer patients.

Nomogram-Based Prognostic Evaluation of Gastric Cancer Patients with Low Counts of Examined Lymph Nodes Outperforms the Predictive Ability of the 7th and 8th Editions of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system has limited accuracy in predicting survival of gastric cancer patients with inadequate counts of evaluated lymph nodes (LNs). We therefore aimed to develop a prognostic nomogram suitable for clinical applications in such cases. METHODS: A total of 1511 noncardia gastric cancer patients treated between 1990 and 2010 in the academic surgical center were reviewed to compare the 7th and 8th editions of the AJCC staging system. A nomogram was developed for the prediction of 5-year survival in patients with less than 16 LNs evaluated (n = 546). External validation was performed using datasets derived from the Polish Gastric Cancer Study Group (n = 668) and the SEER database (n = 11,225). RESULTS: The 8th edition of AJCC staging showed better overall discriminatory power compared to the previous version, but no improvement was found for patients with < 16 evaluated LNs. The developed nomogram had better concordance index (0.695) than the former (0.682) or latest (0.680) staging editions, including patients subject to neoadjuvant treatment, and calibration curves showed excellent agreement between the nomogram-predicted and actual survival. High discriminatory power was also demonstrated for both validation cohorts. Subsequently, the nomogram showed the best accuracy for the prediction of 5-year survival through the time-dependent ROC curve analysis in the training and validation cohorts. CONCLUSIONS: A clinically relevant nomogram was built for the prediction of 5-year survival in patients with inadequate numbers of LNs evaluated in surgical specimens. The predictive accuracy of the nomogram was validated in two Western populations.

Differences in prognosis of Siewert II and III oesophagogastric junction cancers are determined by the baseline tumour staging but not its anatomical location.

BACKGROUND: The anatomical Siewert classification for adenocarcinoma of the oesophagogastric junction (OGJ) was dictated by the potential differences in tumour epidemiology and pathology. However, there are some uncertainties whether the distinction of true carcinoma of the cardia (type II) and subcardial gastric cancer (type III) is of clinical value. METHODS: Using a multicentre data set, we studied 243 patients with OGJ adenocarcinomas who underwent gastric resections between 1998 and 2008. Postoperative complications and long-term survival were compared to evaluate the potential differences in clinically relevant outcomes. RESULTS: A group of 109 patients with Siewert type II and 134 with Siewert type III OGJ adenocarcinoma was identified. Both groups showed similar baseline characteristics, including clinical symptoms and duration of diagnostic delay. However, the prevalence of node-negative cancers and superficial (T1-T2) lesions was significantly higher among type II tumours, i.e. 42% vs 21% (P = 0.003) and 43% vs 20% (P = 0.045), respectively. Morbidity and mortality rates were 25% and 3.7%, respectively, but types and incidence of postoperative complications were not affected by the anatomical location of the tumour. The overall median survival was significantly longer for Siewert type II tumours (42 vs 16 months; P < 0.001). However, only patients' age >70 years, depth of tumour infiltration, lymph node metastases, distant metastases, and radical resection were identified as independent prognostic factors using the Cox proportional hazards model. CONCLUSION: The topographic-anatomic sub-classification of OGJ adenocarcinomas does not correspond to relevant differences in clinical parameters of safety and efficacy of surgical treatment.

Non-curative gastrectomy for metastatic gastric cancer: rationale and long-term outcome in multicenter settings.

BACKGROUND: Metastatic gastric cancer remains a significant problem as the majority of Western patients are diagnosed with disseminated disease and no routine therapeutic regimen is accepted in such cases. METHODS: A cohort of 3141 patients with gastric cancer operated between 1990 and 2005 was evaluated using a multicenter data set held by the Polish Gastric Cancer Study Group to determine potential risks and benefits of non-curative gastrectomy for metastatic disease. Additionally, parameters of Quality of Life (QoL) were evaluated prospectively in 140 patients undergoing gastrectomy using the QLQ-C30 questionnaire. RESULTS: Gastrectomy was carried out in 2258 patients. Distant organ metastases were diagnosed in 951 patients, 415 of which underwent non-curative gastrectomy. The overall mortality rates were significantly higher in patients undergoing non-resectional surgery (10%) than either curative (3%, P < 0.001) or non-curative (4%, P = 0.002) gastrectomy. The overall median survival in patients with metastatic disease was significantly higher for non-curative gastrectomy (10.6 months, 95% confidence interval (CI) 9.3-11.9) than for non-resective operations (4.4 months, 95% CI 4.0 to 4.8, P < 0.001). The hazard ratio of death in patients subject to non-resectional surgery compared to those treated by gastrectomy was 2.923 (95% CI 2.473 to 3.454, P < 0.001). A gradual impairment in QoL parameters was found over 12 months after non-curative resections but changes did not reach statistical significance and individual parameters were similar to gastrectomy without distant metastases. CONCLUSION: Non-curative gastrectomy for metastatic gastric cancer is associated with significantly better survival compared to non-resective surgery and does not impair quality of life.

Implications of overweight in gastric cancer: A multicenter study in a Western patient population.

AIMS: The purpose of this study was to evaluate the effects of overweight on surgical and long-term outcomes in a Western population of patients with gastric cancer (GC). METHODS: An electronic database of all patients with resectable GC treated between 1986 and 1998 at seven university surgical centres cooperating in the Polish Gastric Cancer Study Group was reviewed. Overweight was defined as a body mass index (BMI) of 25 kg/m(2) or higher. RESULTS: Four hundred and ninety-two of 1992 (25%) patients were overweight. Postoperatively, higher BMI was associated with higher rates of cardiopulmonary complications (16% vs 12%, P = 0.001) and intra-abdominal abscess (6.9% vs 2.9%, P < 0.001). However, other complications and mortality rates were unaffected. The median disease-specific survival of overweight patients was significantly higher (36.7 months, 95% confidence interval (CI) 29.0-44.4) than those with BMI<25 kg/m(2) (25.7 months, 95%CI 23.2-28.1; P = 0.003). These differences were due to the lower frequencies of patients with T3 and T4 tumours, metastatic lymph nodes, distant metastases, and non-curative resections. A Cox proportional hazards model identified age, depth of infiltration, lymph node metastases, distant metastases, and residual tumour category as the independent prognostic factors. CONCLUSIONS: Overweight is not the independent prognostic factor for long-term survival in a Western-type population of GC.

Impact of anastomotic leakage on long-term survival after total gastrectomy for carcinoma of the stomach.

BACKGROUND: Recent studies suggest that anastomotic leak may adversely affect long-term survival in patients undergoing surgery for gastrointestinal malignancies. Data relating to total gastrectomy for gastric cancer are scarce. METHODS: An electronic database of all patients with resectable gastric cancer treated between January 1999 and December 2004 at seven university surgical centres cooperating in the Polish Gastric Cancer Study Group was reviewed. RESULTS: Anastomotic leakage was diagnosed in 41 (5.9 per cent) of 690 patients who underwent total gastrectomy. The prevalence of surgical and general complications, and mortality rates were significantly higher in patients diagnosed with anastomotic leakage. The only two independent risk factors for leakage were Eastern Cooperative Oncology Group performance status of 2 or 3 (odds ratio 5.09, 95 per cent confidence interval (c.i.) 2.29 to 11.32) and splenectomy (odds ratio 2.58, 95 per cent c.i. 1.08 to 6.13). Two Cox proportional hazards models including all the patients and excluding in-hospital deaths identified anastomotic leakage as an independent predictor of survival with hazard ratios of 3.47 (95 per cent c.i. 1.82 to 6.64) and 3.14 (1.51-6.53) respectively. CONCLUSION: The occurrence of anastomotic leakage was a major independent prognostic factor for long-term survival.

Adjuvant chemotherapy with etoposide, adriamycin and cisplatin compared with surgery alone in the treatment of gastric cancer: a phase III randomized, multicenter, clinical trial.

OBJECTIVE: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy with etoposide, Adriamycin and cisplatin (EAP) after potentially curative resections for gastric cancer. METHODS: After surgery, patients were randomly assigned to the EAP or control arm. Chemotherapy included 3 courses, administered every 28 days. Each cycle consisted of doxorubicin (20 mg/m(2)) on days 1 and 7, cisplatin (40 mg/m(2)) on days 2 and 8, and etoposide (120 mg/m(2)) on days 4, 5, and 6. RESULTS: Of 309 eligible patients, 141 were allocated to chemotherapy and 154 to the supportive care group. Four (2.8%) treatment-related deaths were recorded, including 3 due to septic complications of myelosuppression and 1 due to cardiocirculatory failure. Grade 3 or 4 toxicities were found in 17 (22%) patients. According to the intention-to-treat analysis, the median survival was 41.3 months (95% confidence interval, 24.5-58.2) and 35.9 months (95% confidence interval, 25.5-46.3) in the chemotherapy and control group, respectively (p = 0.398). Subgroup analysis revealed survival benefit from chemotherapy in patients with tumors infiltrating the serosa and in those with 7-15 metastatic lymph nodes. CONCLUSION: Three cycles of EAP regimen postoperatively offer no survival advantage in gastric cancer patients.

Ratio of metastatic to resected lymph nodes for prediction of survival in patients with inadequately staged gastric cancer.

BACKGROUND: Staging is inadequate in up to 70 per cent of patients with gastric cancer in Western countries owing to the small number of lymph nodes dissected during surgery. The aim was to determine whether using the ratio of metastatic to resected lymph nodes (LNR) might improve accuracy. METHODS: Data were analysed from patients with gastric cancer who had gastrectomy in several centres between 1986 and 1998, with dissection of 15 or fewer lymph nodes. LNRs and other prognostic factors were evaluated. RESULTS: From a total of 738 patients, the median number of resected nodes was 8 (range 1-15) and median LNR was 42.8 per cent. The number of metastatic nodes significantly affected survival only in univariable analysis. In a Cox proportional hazards model, patient age, depth of tumour infiltration, tumour location, and LNR were identified as independent prognostic factors. Compared with node-negative patients, the hazard ratio for an LNR of 0.1-40.0 per cent was 1.85 (P < 0.001), increasing to 2.93 (P < 0.001) when the LNR exceeded 40.0 per cent. CONCLUSION: The LNR cannot be used as a substitute for staging with adequate lymphadenectomy. It may help to stratify patients in terms of prognosis when the number of resected lymph nodes is limited.

The effects of preoperative chemotherapy on isolated tumour cells in the blood and bone marrow of gastric cancer patients.

Recent studies in breast cancer suggest that monitoring the isolated tumour cells (ITC) may be used as a surrogate marker to evaluate the efficacy of systemic chemotherapy. In the present study, we have investigated the effects of preoperative chemotherapy on ITC in the blood and bone marrow of patients with potentially resectable gastric cancer. After sorting out the CD45-positive cells, the presence of ITC defined as cytokeratin-positive cells was examined before and after preoperative chemotherapy. The patients received two courses of preoperative chemotherapy with cisplatin (100 mg m(-2), day 1) and 5-fluorouracil (1000 mg m(-2), days 1-5), administered every 28 days. Fourteen of 32 (44%) patients initially diagnosed with ITC in blood and/or bone marrow were found to be negative (responders) after preoperative chemotherapy (P<0.01). The incidence of ITC in bone marrow was also significantly (P<0.01) reduced from 97 (31 of 32) to 53% (17 of 32). The difference between patients positive for ITC in the blood before (n=7, 22%) and after (n=5, 16%) chemotherapy was statistically insignificant. The overall 3-year survival rates were 32 and 49% in the responders and non-responders, respectively (P=0.683). These data indicate that preoperative chemotherapy can reduce the incidence of ITC in patients with gastric cancer.

Outcome of gastric cancer surgery in elderly patients.

BACKGROUND/AIMS: The aim of the study was to review cases of gastric cancers in elderly adults (70 years of age and older), and compare demographic, clinical, pathologic features and outcomes of surgical treatment with younger patients (below 70 years of age). METHODOLOGY: The analysis included 3431 patients treated for gastric cancer between 1977 and 1998 at eight university surgical centers cooperating for the Polish Gastric Cancer Study Group (PGCSG). Patients were analyzed retrospectively according to data obtained from standardized forms and divided into two groups: group I--patients 70 years of age and over, group II--younger patients. RESULTS: There were no significant differences between these two groups in clinical symptoms at the time of diagnosis and tumor advancement. The incidence of the intestinal type according to Lauren (55.9% vs. 43.9%;p<0.05) and distally-located cancers (40.8% vs. 31.3%; p<0.05) was higher in group I. Total gastrectomies and extended lymph node dissection were performed more often in younger patients. There were no significant differences in postoperative complications between both groups, except the higher incidence of abdominal abscesses in the younger group. The overall 5-year survival was 24% and 35% for group I and II, respectively (p<0.05), and increased to 35% and 53% after radical resections, respectively. However, there were no statistically significant differences in stage-specific survival between both groups. CONCLUSIONS: Surgical resection is the method of choice in the treatment of gastric cancer. Age of the patients is not a contraindication to surgical treatment of gastric cancer.

[Patients with non-advanced pancreatic cancer benefit from extended lymphadenectomy]. / Patienten mit nicht-fortgeschrittenen Pankreaskarzinomen profitieren von der ausgedehnten Lymphadenektomie.

BACKGROUND: Despite improvements in surgical technique and adjuvant therapy models, the overall outcome for patients with pancreatic cancer has not significantly improved over the recent decades. The aim of the study was to assess the value of extended lymphadenectomy for pancreatic cancer. STUDY DESIGN: We performed a retrospective analysis of 136 patients with pancreatic cancer who underwent pancreatectomy and standard or extended lymph node dissection, to compare the rate of perioperative complications and 5-year survival. RESULTS: Of 136 patients treated, 43 (32 %) underwent standard (group I) and 93 (68 %) extended (group II) lymphadenectomy. Both groups were comparable with regard to various clinicopathological factors including patients' age, gender, tumour location, advancement and radicality of performed resection. The mean operative time in the extended group was longer (385 +/- 78 min) than in the standard group (359 +/- 62 min) but observed difference was insignificant. Similarly, there were no significant differences with respect to transfused blood and plasma units. The mean number of resected lymph nodes was significantly (p < 0.001) higher in group II (29.0 +/- 17.7) compared to I (13.0 +/- 7.4). The overall morbidity and mortality rates were 43 % and 6 %, respectively, without significant differences between both groups. The overall 5-year survival was 16.7 % and was similar regardless the type of performed lymphadenectomy. However, patients with node-negative pancreatic cancer following extended lymphadenectomy had significantly higher (p < 0.01) 5-year survival (48 %) compared to the standard resection (22 %). CONCLUSION: Extended pancreatoduodenectomy can be performed with similar morbidity and mortality rates as the standard procedure. However, only patients with non-advanced pancreatic cancer are likely to benefit of 5-year survival.

[Surgical palliation for pancreatic cancer. The 25-year experience of a single reference centre]. / Chirurgisch palliative Therapie beim Pankreaskarzinom - 25 Jahre Erfahrungen eines einzelnen Referenzzentrums.

BACKGROUND: In spite of dynamic development of modern diagnostic and therapeutic methods, the long-term results of surgical therapy in pancreatic cancer are still unsatisfying. The aim of this study was to analyse long-term results of surgical palliation for pancreatic cancer in a pancreatic surgery centre. METHODS: We performed a retrospective analysis of 418 patients who underwent non-resective, palliative procedures for pancreatic cancer between 1975 and 1999. In order to compare two consecutive periods of time, the patients were divided in 2 groups; group I treated from 1975 to 1990 (n = 204), and group II from 1991 to 1999 (n = 214). RESULTS: Of all patients qualified for surgery, 281 (67.2 %) underwent surgical bypass, 107 (25.6 %) laparotomy, and in 30 cases surgical intervention was limited to implantation of endoprosthesis. A significant tendency towards double (i. e. biliary and gastric) anastomosis was observed (32.3 % vs. 74.8 %; p < 0.01) in patients who underwent bypass procedures. The postoperative morbidity was 16.3 %. The postoperative mortality rate was 5.7 % and significantly (p < 0.01) decreased from 10.3 % (group I) to 1.4 % (group II). No differences neither in mortality nor morbidity related to the type of performed surgery were found. The mean time of hospital stay was 15.5 +/- 6.9 days and showed no differences related to the type of intervention. Jaundice or symptoms of gastric outlet obstruction were observed in 16 % of patients in the follow-up period and concomitantly performed biliary and gastric bypasses were associated with the lowest rate of the late gastrointestinal obstruction (4 %). The median survival time was 169 days and only 4 % of patients survived 12 months. The univariate analysis of prognostic factors showed that location and stage of the tumour, the type of surgical intervention and bypass procedure influenced 1-year survival. The multivariate analysis using Cox proportional hazard model proved that only stage and location of the tumour had independent prognostic value. CONCLUSION: Surgical palliation for pancreatic cancer can be performed with acceptable morbidity and mortality rates. For tumours located in the head and body of the pancreas combined biliary and gastric bypass should be preferred. For cancers located in the tail of the pancreas gastric bypass should be performed routinely. Because surgical palliation can prevent gastric outlet obstruction by gastroenterostomy, endoscopic biliary stenting should be only performed in patients with pancreatic head cancers and simultaneous evidence of distal metastases as well as in older patients with high comorbidity.

Long-term results of surgery for early gastric cancer.

BACKGROUND: Gastrectomy for early gastric cancer is widely accepted as an adequate therapeutic method. Recent developments of less invasive procedures require the identification of patients who will benefit from such an approach. METHODS: A retrospective study was undertaken of 238 patients with early gastric cancer who underwent gastrectomy from 1977 to 1999. Clinicopathological data relating to survival were evaluated. RESULTS: Analysis of 33 node-positive patients (14 per cent) revealed a tumour diameter greater than 20 mm (P = 0.011), depressed macroscopic type (P < 0.05), diffuse histological type (P < 0.001), poor tumour differentiation (P < 0.001) and infiltration of the submucosal layer (P < 0.002) as factors associated with lymph node metastasis. Multivariate analysis found diffuse histological type to be an independent risk factor. The overall 5-year survival rate was 87 per cent, and was significantly better in patients who underwent radical lymphadenectomy than in those who had regional lymph node dissection (92 versus 78 per cent; P < 0.01). Similarly, patients younger than 65 years had a more favourable 5-year survival rate (90 per cent) than older ones (77 per cent). Multivariate analysis with the Cox proportional hazards model confirmed patient age and type of lymphadenectomy as independent prognostic factors. CONCLUSION: The findings suggest that extended lymph node dissection may be beneficial for some patients with early gastric cancer, although randomized clinical trials are needed to evaluate this observation further.

Changing patterns of gastric carcinoma over the past two decades in a single institution: clinicopathological findings in 1557 patients.

BACKGROUND: Reported differences in clinicopathological patterns of gastric carcinoma (GC) suggest the presence of time-related changes of cancer biology. The aim of this study was to analyse any fluctuations of GC biology in a large series of patients from Poland, where morbidity and mortality rates for GC are relatively high. METHODS: Based on the prospectively collected data of 1557 GC patients treated surgically between 1977 and 1999, we analysed the differences in clinicopathological patterns for two consecutive periods: 1977-88 (group I) and 1989-99 (group II). Moreover, time-related trends of GC biology were assessed. RESULTS: The mean age of the patients was 59.1 years (range 20-93) and increased from 58.1 years in group I to 59.9 years in group II (P < 0.05). Early GC occurred in 6.2% of cases in group I and in 13.7% in group II (P < 0.001). The incidence of stage IV carcinomas according to the UICC classification significantly decreased from 70.9% to 53.6% (P < 0.001). The proportion of tumours located in the distal part of the stomach declined from 44.1% in group I to 37.6% in group II (P < 0.05). Analysis did not reveal differences in histological type (according to the Lauren classification) between groups; nevertheless, a significant trend toward lowering incidence of intestinal type GC was observed (P < 0.05). Overall, 5-year survival was 27.2% and increased over the period of study from 18.6% to 30.4% (P < 0.001). CONCLUSIONS: The patterns of GC stage, location and histology have changed during the analysed period of time. Observed differences are probably related to fluctuations in carcinogenic factors and have diagnostic as well as therapeutic implications.

Does extended lymphadenectomy improve survival of pancreatic cancer patients?

PURPOSE: Aim of the study was to assess the value of extended lymphadenectomy for pancreatic cancer. MATERIALS AND METHODS: A retrospective analysis of 201 patients with pancreatic and ampullary cancer who underwent pancreatectomy with standard or extended lymph node dissection were analysed in order to compare the rate of perioperative complications and 5-year survival. RESULTS: Of 201 patients treated, 65 (32%) underwent standard (group I) and 136 (68%) extended (group II) lymphadenectomy. These two groups were similar with regard to age, gender, tumour location, advancement and radicality of performed resection. The mean operating time in the extended lymphadenectomy group was longer (383 +/- 81 min) compared to the standard group (357 +/- 64 min) but observed difference was insignificant. Similarly, there were no significant differences with respect to transfused blood and plasma units. The mean number of resected lymph nodes was significantly (p < 0.001) higher in group II (29.0 +/- 17.7) compared to group I (13.0 +/- 7.4). The overall morbidity and mortality rates were 43% and 6.9%, respectively without significant differences between both groups. The overall 5-year survival for pancreatic and ampullary cancer was 16.7% and 67.6% respectively, and was similar regardless the type of performed lymphadenectomy. Patients with node-negative pancreatic cancer following extended lymphadenectomy had significantly higher (p < 0.01) 5-year survival (48%) compared to the standard resection (22%). CONCLUSIONS: Extended lymphadenectomy can be performed with similar morbidity and mortality rates compared to the standard resection. Benefits of 5-year survival can be achieved only in a limited group of patients with non-advanced pancreatic cancer.

IGF-I triple helix strategy in hepatoma treatment.

BACKGROUND/AIMS: To investigate the effect of gene therapy for hepatocellular carcinoma based on inhibition of cellular IGF-I expression, the technique of IGF-I triple helix was investigated in mice developing programmed hepatoma. METHODOLOGY: mhAT1F1 mouse hepatoma cell line was transfected in vitro with IGF-I triple helix expression vector (pMT-AG-TH) or with IGF-I antisense expression vector (pMT-Anti-IGF-I). 10 x 10(6) transfected cells of either triple helix or antisense type were inoculated intraperitonealy into transgenic ATIIITB6 mice developing genetically programmed hepatoma (mice die between the age of 6 and 7 months). In parallel, human cell cultures established from surgically removed hepatomas were investigated. RESULTS: mhAT1F1 and human primary cell cultures, transfected with pMT-AG-TH or pMT-Anti-IGF-I vectors resulted in total inhibition of IGF-I demonstrated by immunocytochemical and Northern blot techniques. Transfected cells changed their phenotype and recovered major histocompatibility complex I expression showed by fluorescence-activated cell sorting analysis and Western blot. Moreover, two phenomena were observed in IGF-I "antisense" or "triple helix" transfected cells: 1) the apoptosis, demonstrated by TUNEL technique; 2) the presence of IL-6 simultaneously with disappearance of tumor necrosis factor-alpha and IL-10, investigated by reverse transcriptase-polymerase chain reaction technique. In in vivo experiments, injection of murine transfected cells into mice in terminal-phase prolonged their survival 3-4 months in 100% of cases, as well in "antisense" group (8/8) as in "triple helix" group (10/10). CONCLUSIONS: Injection of hepatoma cells transfected with IGF-I triple helix expression vector, and showing immunogenic and apoptotic characteristics, can constitute an effective cellular therapy against hepatocellular carcinoma.

Prognostic factors of long-term survival after resective procedures for pancreatic cancer.

BACKGROUND/AIMS: Five-year survival rates following surgical resection of pancreatic cancer reported by the leading medical centers do not exceed 25%. It necessitates further extensive research in this area. The aim of the study was to determine prognostic factors of long-term survival after surgical treatment for pancreatic cancer. METHODOLOGY: From 1980 to 1999, 212 patients underwent surgical resection for pancreatic carcinoma. Statistical analysis of prognostic factors of long-term survival after pancreatic cancer surgery estimated by Kaplan-Meier method was carried out using multiple regression model. RESULTS: A group of 212 patients underwent surgery, where 98 had Whipple's resection, 50 Traverso, 35 total pancreatic resections, 25 left subtotal resections, and the remaining 4 segmental pancreatic body resections. Perioperative mortality was below 8%, 5-year survival approximately 15%, increasing to 65% in patients with early cancer. It was observed, that the following prognostic factors influenced the long-term survival rate: tumor size, localization, histopathologic type, and metastases to lymph nodes. The type and extent of surgery was of significance in the case of small neoplasms. CONCLUSIONS: Based on the analysis carried out, the authors conclude that the main prognostic factors for long-term survival after pancreatic cancer surgery are related to the tumor itself and show associations with the natural development biology.

Long-term results of pancreatic cancer surgery.

Despite of growing incidence of pancreatic cancer and dynamic development of modern diagnostic methods, long-term treatment results are still unsatisfying. The aim of the study is the assessment of long-term outcome of pancreatic cancer surgery. Group of 621 patients hospitalized between 1972-1999 was analyzed. Pancreatic resection was performed in 34.1% (n = 212) patients, and in 65.9% (n = 409) cases a palliative bypass procedure was carried out. Increased number of resective procedures (from 6.2% to 40.1%) in the recent years was observed with lower perioperative mortality rates (from 20% to below 5%). The analysis of the long-term results of surgical treatment for pancreatic cancer showed significant improvement of the overall 5-year survival from 4.2% to 17.1% in the recent years. Based on the carried out analysis the authors conclude, that pancreatic cancer surgery performed by the experienced surgeon improves long-term results lowering to minimum the rates of complications.

Molecular cloning and functional expression of a third isoform of the human calcitonin receptor and partial characterization of the calcitonin receptor gene.

We have cloned and expressed two isoforms of the human calcitonin (hCT) receptor. Primers designed from the published sequence of a CT receptor cloned from an ovarian small cell carcinoma line were used for the polymerase chain reaction amplification of related products from human breast carcinoma MCF-7 cells. Two complementary DNAs were isolated. One clone lacks a 16-amino acid insert in the first intracellular loop and is virtually identical to the receptor recently cloned from the T47D human breast carcinoma cell line. The second clone is another splice variant lacking both the 16-amino acid insert in the first intracellular domain as well as the first 47 amino acids of the amino-terminus extracellular domain. COS-7 cells transfected with either receptor isoform bound [125I]salmon CT with high affinity and responded to hCT with increases in cAMP. Tissue distribution studies revealed the truncated extracellular domain 1 isoform transcripts in human skeletal muscle, kidney, brain, and lung. Analysis of a hCT receptor genomic clone demonstrated an exon/intron organization similar to that of the porcine CT receptor gene, except for a distinct exon coding for the alternatively spliced insert in the first intracellular domain.