Lope Estevez-Schwarz

Prevalence of familial pancreatic cancer in Germany

Based on several case‐control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit‐model and the Kaplan‐Meier method. Twenty‐three of 479 (prevalence 4.8%, 95% CI 3.1–7.1) patients reported at least 1 first‐degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3–2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9–3.5) and by standardized interviews of first‐degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1–5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1–3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.

Gastric Cancer Surgery in Elderly Patients

BackgroundTo investigate the value of individual risk-adapted therapy in geriatric patients, we performed a consecutive analysis of 363 patients undergoing potentially curative surgery for gastric cancer.Patients and MethodsAll patients underwent extensive preoperative workup to assess surgical risk. The following criteria were evaluated in 3 age groups (< 60 years, 60–75 years, and > 75 years): comorbidity, tumor characteristics, type of resection, postoperative morbidity and mortality, recurrence rate, overall survival, and disease-free survival.ResultsThere was an increased rate of comorbidity in the higher age groups (51% vs 76% vs 83%; P < 0.05). Cardiovascular and pulmonary diseases were most common. There was a decrease in the rate of both total gastrectomy (74%, 54%, 46%; P < 0.05) and D2 lymphadenectomy (78%, 53%, 31%; P <0.05). The 30-day mortality in the 3 age groups was 0%, 1%, and 8%, respectively (P < 0.05). There was only a slight difference in tumor recurrence rate (35%, 37%, and 27%; P = 0.437), with no significant difference in 5-year cancer-related survival (61%, 53%, 61%; P = 0.199).ConclusionsPatient selection and risk-adapted surgery in elderly patients can result in acceptable therapeutic results comparable to younger patients. Limited surgery in elderly gastric cancer patients with high comorbidity does not necessarily compromise oncological outcome.

Surgical strategies for gastric cancer with synchronous peritoneal carcinomatosis

Gastric cancer frequently spreads to the peritoneal cavity. Whether laparoscopy is useful in planning therapy remains controversial. The aim of this study was to investigate the value of laparoscopy and to develop a therapeutic algorithm.

Analysis of DLC-1 expression in human breast cancer

The chromosome region 8p12-p22 shows frequent allelic loss in many neoplasms, including breast cancer (BC). The DLC-1 gene, located on 8p21-p22, might be a candidate tumor suppressor gene in this region. To evaluate the involvement of DLC-1 in breast carcinogenesis we studied DLC-1 mRNA expression in a panel of 14 primary human BC and the corresponding normal breast cells as well as 8 BC cell lines. Low levels or absence of DLC-1 mRNA were observed in 57% of primary BC and 62.5% of BC cell lines, respectively. We could not find any correlation between DLC-1mRNA expression and deletions at the DLC-1 locus. Transfection of the gene into DLC-1 deficient T-47D cells raised the DLC-1 mRNA level and resulted in inhibition of cell growth and reduced colony-forming capacity. Our results indicate a role of DLC-1 in BC carcinogenesis.

Subclassification of nerve sheath tumors by gene expression profiling

Nerve sheath tumors are the most common tumors of Neurofibromatosis type 1 (NF1) patients. Dermal neurofibromas develop in nearly all NF1‐patients, whereas plexiform neurofibromas are only observed in one‐third of the patients. NF1‐patients have about a 10% lifetime risk for developing malignant pheripheral nerve sheath tumors (MPNST). The origin of these tumors is thought to be the Schwann cell lacking functional neurofibromin. However, additional genetic alterations are likely to modulate tumor biology and to contribute to individual nerve sheath tumor entities. To gain insight into the molecular events and to determine whether these tumors can be classified according to gene expression profiles, we performed expression analysis applying cDNA array technology. Nine dermal neurofibromas, 7 plexiform neurofibromas, ten MPNST and two MPNST cell cultures were examined. All tumors but 6 sporadic MPNST were obtained from NF1‐patients. We detected significant differences in gene expression patterns between neurofibromas and MPNST and between dermal neurofibromas and plexiform neurofibromas. Tumor class prediction agreed in all but one case with histological and clinical classification. NF1‐associated and sporadic MPNST could not be distinguished by their gene expression patterns. We present a panel of discriminating genes that may assist subclassification of nerve sheath tumors.

Body Mass Index Does Not Affect Systematic D2 Lymph Node Dissection and Postoperative Morbidity in Gastric Cancer Patients

AbstractBackground: The extent of standard lymph node dissection (D1, D2, or D3) in gastric cancer patients is still controversial. Several prospective European trials attained contradictory results. A generally increased body mass index (BMI) of the European patients was assumed to be one of the major causes for postoperative morbidity. Methods: We evaluated the effect of BMI on the quality of routine D2 lymph node dissection and on postoperative morbidity in patients with gastric cancer who underwent a potentially curative total gastrectomy. A total of 199 consecutive gastric cancer patients who underwent a total gastrectomy and a routine D2 lymph node dissection between 1992 and 2001 were included in the study. According to BMI, they were assigned to three groups: group A, with BMI <25 kg/m2 (normal body weight); group B, with BMI of 25 to 30 kg/m2 (overweight); and group C, with BMI >30 kg/m2 (obesity). Parameters such as complete histopathological staging, intraoperative blood loss, length of operation, and surgical and nonsurgical morbidity were recorded and correlated within the different groups. Results: No significant differences were found with regard to the number of examined lymph nodes, blood loss, length of operation, surgical complications, or length of stay in the intensive care unit. Conclusions:In contrast to comparable Japanese studies, our analysis reveals that even for overweight patients, a standard D2 lymph node dissection is justified without significantly increased morbidity.

Detailed deletion mapping in sporadic breast cancer at chromosomal region 17p13 distal to the TP53 gene: association with clinicopathological parameters

Chromosome 17p is among the most frequently deleted regions in a variety of human malignancies including breast cancer. This study has further refined the localization of a putative tumour suppressor gene (TSG) at 17p13 distal to the TP53 gene in breast carcinomas. It was found that 73% (37 of 51) of the breast tumours exhibited loss of heterozygosity (LOH) at one or more loci at 17p13. The allelic loss patterns of these tumours suggest the presence of at least seven commonly deleted regions on 17p13. The three most frequently deleted regions were mapped at chromosomal location 17p13.3–17p13.2 between the markers D17S831 and D17S1845 (56% LOH), at 17p13.1 between D17S1810 and D17S1832 (53% LOH), and at 17p13.1 between D17S938 and TP53 (55% LOH). A significant correlation was found between loss at 17p13 and tumour grade, size, proliferative activity, and oestrogen receptor (ER) status. Losses at 17p13 were seen more frequently in large and poorly differentiated tumours with high proliferative activity. These data support and extend previous reports on the presence of a putative TSG(s) at chromosomal region 17p13 distal to the TP53 gene and show that different subsets of LOH are associated with more aggressive tumour behaviour. Copyright

Wolf in sheep's clothing: spilled gallstones can cause severe complications after endoscopic surgery.

Bile concrements may remain intraperitoneally after laparoscopic cholecystectomy. Previously, this was considered harmless, a view supported by some experimental studies. Recently, however, spilled gallstones have been identified as a source of rare but potentially serious complications. We report a case of a retrohepatic abscess and dorsal fistulation after laparoscopic cholecystectomy. Healing was achieved only by repeated surgery, including abscess drainage, stone removals, and fistula excision. Since 1990, 73 cases with gallstone-related complications after laparoscopic cholecystectomy have been reported in the literature. Among these complications, intra-abdominal abscesses and transabdominal fistulas were predominant. The interval between the cholecystectomy and the appearance of complications ranged from 4 days to 29 months, with a peak incidence at 4 months. Spillage of small bile concrements or fragments is, with the exception of multiple irremovable stones, not commonly an indication for conversion to an open procedure. However, the patient needs to be warned about the risk of gallstone loss and its associated complications at the time when informed consent is obtained. Furthermore, if gallstone loss has occurred, the patient should be informed, and the occurrence should be documented.

Prognostic Value of Cytokeratin-Positive Bone Marrow Cells of Gastric Cancer Patients

BackgroundEpithelial cells in the bone marrow of patients with gastric cancer suggest tumor dissemination; however, their prognostic implications are controversial. We prospectively evaluated the correlation of bone marrow findings, recurrence rate, and disease-free survival after long-term follow-up.MethodsBone marrow were aspirated from both iliac crests and stained with monoclonal cytokeratin (CK)-18 antibody in 209 patients before their initial operation. Patients were followed up for a median of 56 months.ResultsOverall, 39 (19%) of 209 patients and 15 (14%) of 109 R0-resected patients had CK-positive cells. CK-positive patients had more local, regional, and distant recurrence than CK-negative patients (P < .05). We found a significantly shorter disease-free survival (P < .05) in the patients with >2 CK-positive cells per 2 × 106 bone marrow cells (mean, 35 months) than in patients with ≤2 CK-positive cells per 2 × 106 bone marrow cells (mean, 70 months) or in patients with no CK-positive cells (mean, 86 months). Multivariate analysis confirmed that >2 CK-positive cells per 2 × 106 bone marrow cells was an independent prognostic factor for tumor-related death (P < .05).ConclusionsNot only the mere presence of CK-positive epithelial cells in bone marrow, but also the cell number, correlates with prognosis. Our findings suggest that classifying CK-positive bone marrow cells in these patients will facilitate future studies.