Biomedical subjects

Matthias Rothmund

Publications and source records attributed to Matthias Rothmund.

At least 19 recordsLinked to original sources

PubMed2006

Cystadenocarcinoma of the gallbladder.

Biliary cystadenocarcinomas are a very rare set of neoplasms that occur in the liver, the extrahepatic bile duct system, and occasionally in the gallbladder. We report on a 75-year-old man with a cystadenocarcinoma of the gallbladder who presented with mild abdominal discomfort and a palpable mass in the right upper abdomen. The diagnostic workup included ultrasound, magnetic resonance tomography, and fine needle core biopsy and revealed a multicystic tumor 16 cm in diameter. The patient underwent multivisceral resection of the tumor with a resection of the right colon, a partial resection of the stomach and the liver, and a lymph node dissection. The resected specimen weighed 2500 g and the final histopatholical diagnosis was a primary, moderately differentiated cystadenocarcinoma of the gallbladder with two lymph node metastases and invasion of the right colon. The patient remains without evidence of recurrence 12 months after surgery. The clinical presentation, diagnosis, therapeutic options, and classification of hepatobiliary cystadenocarcinomas are discussed.

Aged↗

PubMed2006

Improvement of surgical skills after a three-day practical course for laparoscopic surgery.

OBJECTIVES: Currently, skills labs are becoming increasingly important in the field of medical education. This study aims to objectively assess psychomotor skills acquisition of residents attending a three-day laparoscopic course. MATERIALS AND METHODS: 44 participants (test group) of the sixth practical course for Visceral Surgery of German surgical societies (Deutsche Gesellschaft für Chirurgie; DGCH and Berufsverband Deutscher Chirurgen; BDC) in Warnemuende with various degree of experience in laparoscopic surgery (18 advanced residents performing more than 50 laparoscopic operations and 26 novices performing less than 10 laparoscopic operations) and 6 consultants attending as tutors of the course (gold standard) were recruited as subjects. 20 medical students in their final year (camera holder) were chosen as a second control group (naive). Both control groups had no training during the practical course. The virtual reality simulator LapSim was used to assess laparoscopic skills of participants before and after the course. Time to complete the tasks, error score, and economy of motion parameters (path length and angular path) were analysed. RESULTS: After the practical course the advanced participants of the test group completed the task significantly faster (p = 0.019), with smaller error score (p = 0.023), and more economy of motion [path length (p = 0.014) and angular path (p = 0.049)] than before the course. The novices of the test group and both control groups showed no significant improvement of their performance parameters (p >0.05). CONCLUSION: A three-day practical course for laparoscopic surgery improved laparoscopic skills of residents. However, advanced residents benefit most from the course.

Adult↗

PubMed2006

Supervised surgical trainees perform thyroid surgery for Graves' disease safely.

BACKGROUND: There is little information about the effect of operative experience and supervision of trainees on long-term outcomes after thyroid resection for Graves' disease (GD). The aim of this study was to compare the morbidity rate after thyroid resection performed by trainees vs consultant surgeons. METHODS: Based on a cross-sectional design analysis with a median follow-up of 96 months (range, 12-216 months), long-term outcomes for 111 patients operated on by consultants were compared with those of 42 patients operated on by supervised trainees in an academic teaching hospital between 1987 and 2002. RESULTS: Of the 111 patients operated on by the consultants, there were 25 (21.6%) cases of transient and 12 (10.8%) cases of permanent hypocalcemia and 10 (9.0%) cases of transient and 1 (0.9%) case of permanent recurrent laryngeal nerve (RLN) palsy. Of the 42 patients operated upon by the supervised trainees, there were 8 (21.4%) cases of transient and no permanent hypocalcemia, 3 (7.1%) cases of transient, and 1 (2.3%) case of permanent RLN palsy. Permanent complication rate of the entire group was low, and the grade of the primary surgeon made no difference in the occurrence of complications (P>0.05). CONCLUSION: Supervised trainees can perform thyroid surgery for GD safely if a standardized surgical teaching program is available.

Adolescent↗

PubMed2006

Novices in surgery are the target group of a virtual reality training laboratory.

BACKGROUND: This study aims to establish which physicians represent the suitable target group of a virtual training laboratory. METHODS: Novices (48 physicians with fewer than 10 laparoscopic operations) and intermediate trainees (19 physicians who performed 30-50 laparoscopic operations) participated in this study. Each participant performed the basic module 'clip application' at the beginning and after a 1-hour short training course on the LapSim. The course consisted of the tasks coordination, lift and grasp, clip application, cutting with diathermy and fine dissection at increasing difficulty levels. The time taken to complete the tasks, number of errors, and economy of motion parameters (path length and angular path) were analyzed. RESULTS: Following training with the simulator, novices completed the task significantly faster (p = 0.001), demonstrated a greater economy of motion [path length (p = 0.04) and angular path (p = 0.01)]. In contrast, the intermediate trainees showed a reduction of their errors, but without reaching statistical significance. They showed no improvement in economy of motion and completed the task significantly slower (p = 0.03). CONCLUSION: Novices, in comparison to intermediate trainees, tend to benefit most during their first exposure to a laparoscopy simulator.

Adult↗

PubMed2006

An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors.

OBJECTIVE: To evaluate the outcome of reoperations in patients with duodenopancreatic neuroendocrine tumors (PETs) in a tertiary referral center. SUMMARY BACKGROUND DATA: The management of reoperations in PETs is still controversial. METHODS: A total of 125 patients with PETs that underwent surgery between 1987 and 2004 at our institution were retrospectively evaluated. The diagnosis of PETs was based on clinical symptoms, biochemical tests, and histopathology. Patients with at least one reoperation were analyzed regarding clinical characteristics, pathology, operations, and long-term follow-up. RESULTS: A total of 33 patients with a median age of 42 years were identified for this study: 13 patients had gastrinomas, 12 patients had nonfunctional islet cell tumors, 6 patients had insulinomas, and 2 patients had vipomas; 24 patients had sporadic NETs, 9 patients had a MEN-1-syndrome; 27 patients had histologically verified malignant tumors; 33 initial operations and 50 reoperations were performed. The initial procedures comprised 27 resections of the primary tumor and 6 explorative laparotomies; 28 of all reoperations were resections of distant metastases, including 15 liver resections; 19 resections of the pancreas or duodenum were performed during reoperations. The overall morbidity and mortality was 45% and 4.8%, respectively. After a median follow-up of 124 months (range, 16-384 months), 27 of 33 patients are still alive, 12 without evidence of disease. All 6 patients with benign tumors are still alive. The 5-, 10-, and actuarial 25-year survival rate for patients with malignant tumors were 81%, 72%, and 36%, respectively. The survival rate was significantly related to the patients age at time of initial operation and better in patients younger than 50 years compared with patients older than 50 years (P = 0.0007), and the presence or development of metastases (none or lymph node metastases versus distant metastases: P = 0.01). CONCLUSION: We show that an aggressive surgical approach leads to long-term survival in patients with malignant PETs. Although long-term cure can only be achieved in a proportion of patients with malignant PETs, significant long-term palliation can be achieved.

Adult↗

PubMed2005

The Study Centre of the German Surgical Society--rationale and current status.

BACKGROUND: The concept of evidence-based medicine was introduced into surgery in the mid-1990s, initially focussing on the integration of best research evidence, surgeons' expertise and patients' value. The lack of relevant external evidence [randomised controlled trials (RCTs), systematic reviews] in favour of surgical procedures has led to the need for a new approach in clinical research. DESIGN: Development and implementation of the Study Centre of the German Surgical Society (SDGC) in order to design, perform and analyse multicentre randomised controlled trials in surgery. RESULTS: The German Surgical Society has recently initiated four surgical RCTs within the SDGC in order to improve the national infrastructure for clinical research and its international scientific standing. All surgical trials focus on procedures in various fields (thyroid and parathyroid diseases, pancreatic surgery, abdominal wall closure) and are designed to fit the specific needs of each study (blinding of patients and assessors, ranking of endpoints, patients' perspective). Additionally, in a nationwide survey of 1,274 surgical departments in Germany, 307 replied, of which 237 (19%) were willing to participate in multicentre projects. CONCLUSION: Evidence-based medicine has changed surgical practice, leading to an increase in demand for RCTs and requiring a new infrastructure in surgical departments and scientific societies.

Clinical Trials as Topic↗

PubMed2005

Peripyloric lymph node metastasis is a rare condition in carcinoma of the pancreatic head.

OBJECTIVES: Pylorus preserving pancreatoduodenectomy (PPPD) was introduced to achieve a better functional result compared with the conventional Kausch-Whipple procedure (PD). In PPPD, peripyloric and perigastric lymphatic tissue is not removed compared with PD. The aim of this prospective study was to identify the frequency of peripyloric and perigastric lymph node metastases in ductal adenocarcinoma of the pancreatic head (PC). METHODS: Fifty specimens following Kausch-Whipple procedure including partial gastric resection for PC were analyzed for peripyloric and perigastric lymph node metastases by a standardized clearing technique. All lymph nodes of the specimens were counted, discriminating between those not removed ("group A") and those removed ("group B") in pylorus preserving resection of the pancreatic head. Additionally, the duodenal wall and paraduodenal tissue at a potential duodenal resection margin 2 cm distal of the pylorus were investigated histologically. RESULTS: Three of the 50 specimens (6%) carried peripyloric lymph node metastases, whereas 32 of the 50 specimens (64%) contained lymph node metastases in total. Four of 362 group A and 90 of 748 group B lymph nodes showed metastatic spread of the carcinoma. The 4 lymph node metastases in group A could be identified exclusively in 88 peripyloric lymph nodes but in none of the 274 perigastric lymph nodes at the lesser or greater curvature. In 2 of the 3 patients with peripyloric lymph node metastases, these lymph nodes were the only lymph nodes with metastatic involvement in the entire specimen. In 1 specimen, a small tumor nest of less than 2 mm in diameter was detected at a distance of less than 1 mm to the pylorus, although pyloric involvement was not suspected intraoperatively. The potential PPPD resection margin of the duodenal wall was not infiltrated by intramural tumor spread in any specimen. CONCLUSION: In a minority of 6%, PC metastasizes in peripyloric lymph nodes. Lymph nodes of the lesser and greater curvature of the stomach are not involved in patients with PC. Thus, we conclude by the data of this prospective study that the limited benefits of the extended lymph node dissection in a conventional Kausch-Whipple resection are far outweighed by the disadvantages construed by this procedure.

Aged↗

PubMed2005

Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1.

OBJECTIVE: To evaluate the outcome of an aggressive surgical approach for duodenopancreatic neuroendocrine tumors (PETs) associated with multiple endocrine neoplasia type 1 (MEN1). SUMMARY BACKGROUND DATA: The management of PETs is still controversial in the setting of the autosomal dominant inherited MEN1 syndrome. METHODS: MEN1 patients that had either biochemical evidence of functioning PETs or visualized nonfunctioning PETs larger than 1 cm in size on imaging were operated. Since 1997, patients were followed annually by biochemical testing and imaging studies. RESULTS: Twenty-six genetically confirmed MEN1 patients underwent duodenopancreatic resection for functioning (n = 17) or nonfunctioning (n = 9) PETs. Ten (38%) patients had malignant PETs as characterized by the presence of lymph node (10 patients) and/or distant metastases (2 patients). The surgical approach was selected based on the type, location, and size of PETs. Four Zollinger-Ellison syndrome (ZES) patients required pylorus preserving pancreaticoduodenectomy (PPPD) as initial or redo procedure, 20 patients underwent other duodenopancreatic resections, and 2 patients had simple enucleations of PETs. After median 83 months (range, 5-241 months), 24 patients were alive and 2 patients died of an unrelated cause. All patients with insulinoma or vipoma and 7 of 11 patients with ZES were biochemically cured, including the ZES patients who underwent PPPD. However, 19 of 26 (73%) patients developed new small PETs (<1 cm) in the pancreatic remnant, but no patient had yet detectable metastases on imaging. CONCLUSIONS: Early and aggressive surgery of PETs in MEN1 patients prevents the development of liver metastases, which are the most life-threatening determinant. PPPD might be the procedure of choice for MEN1-ZES, which has to be proven in large scale studies.

Adolescent↗

PubMed2004

Prospective evaluation of imaging procedures for the detection of pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1.

Early identification of pancreaticoduodenal endocrine tumors (PETs) in multiple endocrine neoplasia type 1 (MEN-1) is mandatory, because these tumors represent the most common cause of death within the syndrome. The diagnostic value of imaging procedures has therefore been evaluated in a prospective observational study. Between December 1997 and June 2003 twenty-two MEN-1 patients with genetically confirmed disease were followed for PETs using a standardized screening program with serum hormone measurements, endoscopic ultrasonography (EUS), computed tomography (CT), and somatostatin-receptor scintigraphy (SRS). Results could be validated by surgery and histopathology in 13 patients during 18 operations. In 12 asymptomatic patients with tumors measuring 10 mm or less, who have not yet undergone operation, PETs were detected by EUS in 12/12, by CT in 1/12, and by SRS in 2/11 cases. In 13 patients who have undergone surgical exploration EUS, CT, and SRS were true positive in 12 of 16, 7 of 13, and 12 of 17 cases, respectively, although the number of tumors detected by each imaging procedure alone was lower than the number detected intraoperatively and histopathologically in almost every case. A solitary liver metastasis in one patient and a nonfunctioning PET recurrence in another were identified only by SRS. Endoscopic ultrasonography is the most sensitive imaging procedure for the detection of small (< or = 10 mm) PETs in MEN-1, whereas SRS is the procedure of choice for the identification of metastases of MEN-1 PETs-i.e., for staging. Detection of PETs at an early stage by an aggressive screening program using EUS may lead to prompt surgical intervention and improved prognosis of MEN-1 PETs.

Adolescent↗

PubMed2004

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.

Adult↗

PubMed2004

Assessing the site of recurrence in patients with secondary hyperparathyroidism by a simplified Casanova autograftectomy test.

Patients with recurrent secondary hyperparathyroidism (rSHPT) following total parathyroidectomy and autotransplantation were prospectively studied by a modified Casanova test to discriminate between the graft-bearing arm and the neck as the site of the recurrence. The test measures intact parathyroid hormone (PTH) in blood obtained from the non-graft-bearing arm before an ischemic period and from the arm bearing the parathyroid graft during an ischemic period caused by an Esmarch bandage. The aim of this study was to evaluate the time course of PTH levels during the test and to establish an abbreviated procedure. A series of 30 patients with rSHPT who were admitted for reoperative surgery between 1994 and 2002 were studied. Systemic PTH levels were determined prior to suprasystolic exclusion of the graft-bearing arm as well as 2, 4, 6, 8, 10, 20, and 30 minutes during it and at 10 minutes afterward. Results were interpreted with a simple algorithm that suggested graft-dependent recurrence (GDR) whenever PTH levels dropped by more than 50% and neck-dominated recurrence (NDR) whenever the PTH levels dropped to less than 20%. Patients were operated on accordingly. Biochemical normalization of calcium and PTH was defined as success. Altogether, 15 patients had GDR and were cured after graft explantation. All of these patients were identified within 4 minutes of starting the test. Another 12 patients had NDR and were cured by excising overlooked or supernumerary glands. PTH levels were indeterminate in three patients (10%). Clinically, NDR is likely in all of these cases, but the test results were firmly established with 100% accuracy 8 minutes after the start of the test procedure. This abbreviated form of the Casanova test is advantageous for accurately determining the site of recurrence in the presence of rSHPT. It is less time-consuming, satisfactory in an ambulatory setting, equally effective, and less invasive than the original Casanova procedure.

Adult↗

PubMed2003

Clinical value of parathyroid scintigraphy with technetium-99m methoxyisobutylisonitrile: discrepancies in clinical data and a systematic metaanalysis of the literature.

There is a considerable discrepancy in the literature concerning the sensitivity of parathyroid scintigraphy (PS) with 99mTc-MIBI. We therefore analyzed our own data and compared them to the literature in a metaanalysis. All patients who received 99mTc -MIBI scintigraphy and subsequent surgery in our department for the detection of enlarged parathyroid glands in primary (pHPT) or secondary (sHPT) hyperparathyroidism between 1991 and 1999 were included in our retrospective analysis. The results of surgery served as the gold standard. For a true positive result, the scintigraphy had to predict the exact location of parathyroid adenoma (PA) or parathyroid hyperplasia (PH). We then compared these data to the results of a nonstatistical systematic metaanalysis of the literature. Patients (178) underwent PS between 1991 and 1999; 139 were operated on and included in this study. Of these, 109 had pHPT and 30 had sHPT. The sensitivity and specificity of the PS were found to be 45%/94% for pHPT and 39%/40% for sHPT. Fifty-two studies concerning PS were included in the metaanalysis. Sensitivities reported varied from 39% to >90%. Consideration of the different possible techniques used for PS could not explain these discrepancies. Our data show that the sensitivity of PS in clinical routine may be lower than expected from the literature. Our data are consistent with other studies and with partially unpublished clinical observations from other university hospitals. We believe that a well-designed and properly conducted prospective study is necessary to evaluate the reasons for the differences observed.

Follow-Up Studies↗

PubMed2003

BRCA2 germline mutations in familial pancreatic carcinoma.

BACKGROUND: Although as many as 10% of pancreatic cancer cases may have an inherited component, familial pancreatic cancer has not been linked to defects in any specific gene. Some studies have shown that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer. To study these relationships in more detail, we examined whether BRCA2 germline mutations are associated with familial pancreatic cancer. METHODS: We identified 26 European families in which at least two first-degree relatives had a histologically confirmed diagnosis of pancreatic ductal adenocarcinoma. We sequenced genomic DNA isolated from peripheral blood lymphocytes obtained from participating family members to identify germline mutations in BRCA2. RESULTS: Three (12%, exact 95% confidence interval [CI] = 2% to 30%) families carried germline frameshift mutations in the BRCA2 gene that are predicted to result in a truncated BRCA2 protein. Two additional families harbored mutations previously designated as unclassified variants of BRCA2. Thus, 19% (exact 95% CI = 7% to 39%) of the families in our study had either a frameshift mutation or an unclassified variant of BRCA2. None of the families in our study met the criteria for familial breast or ovarian cancer. CONCLUSIONS: Our data support an important role for BRCA2 germline mutations in a subpopulation of families with familial pancreatic cancer. BRCA2 mutation analysis should be included in molecular genetic testing and counseling strategies in families with at least two first-degree relatives affected with ductal adenocarcinoma of the pancreas.

Adult↗

PubMed2003

Relation between severe illness and non-completion of quality-of-life questionnaires by patients with rectal cancer.

Quality of life (QoL) is an important outcome measure in clinical studies, but interpretation is hindered by incompleteness of data. We addressed this issue in a population-based cohort study of 146 patients with newly diagnosed rectal cancer. QoL was assessed by means of European Organization for the Research and Treatment of Cancer questionnaires at discharge from hospital after primary treatment and then every 3 months for 2 years. In parallel, objective clinical data were documented. Analyses were conducted in three steps: participants versus non-participants with QoL-assessment; poor compliers who filled in only one or two questionnaires (n=20) versus good compliers who filled in all or nearly all questionnaires (n=18); and the proportion of missing forms and critical (very poor) QoL scores in risk patients versus non-risk patients over the course of 2 years. Non-participants and poor compliers were older, were more likely to receive palliative (rather than curative) treatment, and had worse scores for physical status. Tumour progression and therapeutic interventions were more frequent in poor compliers than in good-compliers. Patients with risk factors (age 475 years, poor physical status, palliative treatment) were more likely to have missing questionnaires and critical QoL scores in respect of physical functioning and global quality of life over the course of 2 years. Missing values for QoL have clinical as well as methodological implications, because QoL scores can enhance a clinician's insight. Unwillingness to fill in a questionnaire is an indicator of serious illness. Studies that report sample statistics without specifying compliance rates and the characteristics of non-compliers will give a misleadingly positive picture.

Adult↗

PubMed2002

Quality of life and patient satisfaction after reoperation for primary hyperparathyroidism: analysis of long-term results.

Morbidity after reoperation for persistent or recurrent primary hyperparathyroidism (pHPT) is higher than after primary surgery. According to our experience, there is a contrast between postoperative normalization of laboratory parameters and the quality of life/patient satisfaction after reoperation. Therefore the aim of the study was to analyze the outcomes of reoperations in comparison to primary surgery. We evaluated the patients' reported quality of life using the SF-36 (an accepted health status assessment tool) and complete prospectively documented perioperative and follow-up data including postoperative complications. Additionally, we searched for reasons why primary surgical intervention did not succeed. In a prospective cohort study the perioperative data of 653 consecutive patients with pHPT, including 75 reoperated patients (11.5%) who underwent parathyroidectomy between 1987 and 1999, were evaluated by uni- and multivariate analysis. At a median 78 months (6-156 months) postoperatively, all patients underwent a planned follow-up that included the SF-36, physical examination, and laboratory investigations. A total of 51 reoperated patients were available for follow-up. Postoperative alleviation of symptoms or being symptom-free was reported by 70.6%. Patients after reoperation had lower SF-36 scores in all health domains postoperatively than patients after a primary operation. Of the reoperated patients, 19.6% stated that after evaluating the development of their complaints they would not consent to reoperation again. Subgroup analysis showed that 80% of patients with postoperatively persistent pHPT, 60% of those who did not observe symptom alleviation, and 44% of those after sternotomy were in the group of dissatisfied patients. Surprisingly, none of the patients with more than one reoperation, only two of the five patients with permanent recurrent laryngeal nerve injury, and only one of the four patients with persistent hypoparathyroidism were dissatisfied overall. Parathyroidectomy resulted in normocalcemia in 90.2% of the reoperated patients, with an operative morbidity of 27.4% and no mortality. After an unsuccessful operation for pHPT, patients should be treated at an expert center to avoid persistent hypercalcemia. Reoperations necessitating sternotomy should be restricted to patients with severe symptoms and signs.

Aged↗

PubMed2002

Adrenal involvement in multiple endocrine neoplasia type 1.

Adrenal lesions belong to the spectrum of multiple endocrine neoplasia type 1 (MEN-1) syndrome. However, the prevalence of adrenal involvement, the characteristics, and the clinical management of adrenal lesions have not yet been clearly defined. A total of 66 patients with confirmed MEN1 germline mutations and 1 additional patient with typical manifestations in three organ systems were monitored in a regular screening program that included evaluation of the adrenals (median follow-up 96 months; range 12 to 300 months). Age at the diagnosis of MEN-1 and of adrenal tumors and the clinical characteristics, genotype, treatment, and follow-up of adrenal disease were analyzed. Adrenal lesions were identified in 18 of 67 (26.8%) MEN-1 patients and were diagnosed 5 years later than MEN-1. The median tumor diameter at diagnosis was 3.0 cm (range 1.2-15.0 cm), with most tumors being 3 cm or smaller. Eight patients had bilateral tumors. Ten patients had nonfunctional benign tumors, three had benign adrenal Cushing syndrome, and one patient had a pheochromocytoma. Four patients developed adrenocortical carcinomas (ACCs), three of which were functional. Nine adrenalectomies and one subtotal adrenalectomy were performed in six patients. Three patients with ACC died owing to the tumor. Patients with mutations in exons 2 and 10 developed adrenal tumors significantly more often than patients with other mutations (p <0.01). Adrenal tumors are a common feature of MEN-1 but occur later in the course of the disease. The lesions are often small and nonfunctional and can therefore be managed by close surveillance; others have significant malignant potential and should be considered for surgery when they are 3 cm or larger.

Adolescent↗

PubMed2002

p16INK4a is a prognostic marker in resected ductal pancreatic cancer: an analysis of p16INK4a, p53, MDM2, an Rb.

OBJECTIVE: To identify the prognostic relevance of the G1/S cell cycle regulator genes p16INK4a, p53, MDM2, and Rb in patients with resected ductal pancreatic cancer (PC). SUMMARY BACKGROUND DATA: The tumor suppressor genes p16INK4a, p53, and Rb are altered in PC in 27% to 95%, 40% to 70%, and 5%, respectively. The role of MDM2 is not clearly defined in PC. The prognostic value of these cell cycle regulators has not been clarified. METHODS: Sixty-two patients with PC with complete follow-up who underwent potentially curative resections were included in the study. An extreme group analysis was performed including the 20 patients with the shortest survival and the 20 patients with the longest survival. Protein expression of p16, p53, MDM2, and Rb was investigated, and mutation analysis of p16INK4a and p53 was performed. p16INK4a promoter hypermethylation was examined by methylation-specific polymerase chain reaction. RESULTS: Significantly more tumors in the shortest-surviving patients had p16INK4a alterations compared with tumors of the longest-surviving patients. In contrast, the frequency of p53 alterations was not significantly higher in the shortest-surviving versus the longest-surviving groups. Stabilization of MDM2 and loss of Rb expression were identified in a minority of tumors, independent of survival length. CONCLUSIONS: The presence of p16INK4a alterations in resected tumors of patients with PC is connected with a worse prognosis, indicating patients that might benefit from adjuvant therapy regimens. p53 alterations, MDM2 overexpression, and loss of Rb expression could not be identified as prognostic markers from this study, but a larger study with greater statistical power might show a different result with regard to p53.

Biomarkers, Tumor↗

PubMed2002

CDKN2A germline mutations in familial pancreatic cancer.

OBJECTIVE: To evaluate the prevalence of mutations in the CDKN2A gene encoding p16 and p14 in familial pancreatic cancer (FPC). SUMMARY BACKGROUND DATA: The genetic basis of FPC is still widely unknown. Recently, it has been shown that germline mutations in the p16 tumor suppressor gene can predispose to pancreatic cancer. The presence of p14 germline mutations has yet not been determined in this setting. METHODS: Eighteen families with at least two first-degree relatives with histologically confirmed pancreatic cancer and five families with at least one patient with pancreatic cancer and another first-degree relative with malignant melanoma of the German National Case Collection for Familial Pancreatic Cancer were analyzed for CDKN2A germline mutations including p16 and p14 by direct DNA sequencing. All participating family members were genetically counseled and evaluated by a three-generation pedigree. RESULTS: None of 18 FPC families without malignant melanoma revealed p16 mutations, compared to 2 of 5 families with pancreatic cancer and melanoma. Truncating p16 germline mutations Q50X and E119X were identified in the affected patients of pancreatic cancer plus melanoma families. None of the 23 families revealed p14 germline mutations. CONCLUSIONS: CDKN2A germline mutations are rare in FPC families. However, these data provide further evidence for a pancreatic cancer-melanoma syndrome associated with CDKN2A germline mutations affecting p16. Thus, all members of families with combined occurrence of pancreatic cancer and melanoma should be counseled and offered screening for p16 mutations to identify high-risk family members who should be enrolled in a clinical screening program.

Adenocarcinoma↗