C. Nies

Laparoscopic Versus Open Adrenalectomy for Adrenocortical Carcinoma: Surgical and Oncologic Outcome in 152 Patients

BACKGROUND The role of laparoscopic adrenalectomy in the treatment of patients with adrenocortical carcinoma (ACC) is controversial. OBJECTIVE Our aim was to compare oncologic outcome in patients with ACC who underwent either open adrenalectomy (OA) or laparoscopic adrenalectomy (LA) for localised disease. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective analysis of 152 patients with stage I-III ACC with a tumour < or =10 cm registered with the German ACC Registry. INTERVENTION Patients were stratified into two groups according to the surgical procedure (LA or OA). For comparison, we used both a matched pairs approach by selecting for each patient from the LA group (n=35) one corresponding patient from the OA group (n=117) and multivariate analysis in all 152 patients. MEASUREMENTS Disease-specific survival was chosen as the predefined primary end point. Secondary end points were recurrence-free survival, frequency of tumour capsule violation and postoperative peritoneal carcinomatosis, and incidence and reasons for conversion from LA to OA. RESULTS AND LIMITATIONS LA and OA did not differ with regard to the primary end point using either the matched pairs approach (hazard ratio [HR] for death: 0.79; 95% confidence interval [CI], 0.36-1.72; p=0.55) or multivariate analysis (HR for death: 0.98; 95% CI, 0.51-1.92; p=0.92). Similarly, adjusted recurrence-free survival was not different between LA and OA (HR: 0.91; 95% CI, 0.56-1.47; p=0.69). Frequency of tumour capsule violation and peritoneal carcinomatosis were comparable between groups. In 12 of 35 patients of the LA group, surgery was converted to open surgery with no impact on the clinical outcome. CONCLUSIONS For localised ACC with a diameter of < or =10 cm, LA by an experienced surgeon is not inferior to OA with regard to oncologic outcome.

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.

Conventional bilateral cervical exploration versus open minimally invasive parathyroidectomy under local anaesthesia for primary hyperparathyroidism

Minimally invasive parathyroidectomy (MIP) has been introduced for the treatment of patients with primary hyperparathyroidism (pHPT). Thus far, only one randomized trial has compared video‐assisted MIP with conventional bilateral cervical exploration (BCE). The value of open MIP is therefore not known.

Surgical treatment of pheochromocytomas : Laparoscopic or conventional?

AbstractBackground: The use of minimally invasive techniques in the surgical treatment of pheochromocytoma is controversial because of possible intraoperative excessive hormone release resulting in cardiovascular instabilities. Methods: Laparoscopic adrenalectomy was performed in nine patients with a total of 10 pheochromocytomas. Conversion was required in two cases. The relevant data were prospectively documented and compared with a historical group of nine patients who had undergone conventional transabdominal adrenalectomy for unilateral pheochromocytoma. Results: The laparoscopic operations lasted significantly longer than the conventional procedures (median 243 min vs. 100 min, p < 0.01). Intraoperative cardiovascular instabilities (tachycardia, hypertension) occurred in seven laparoscopically and eight conventionally treated patients. All were easily controlled. Blood transfusions were necessary in four patients in the conventional and one patient in the laparoscopic group. Postoperative hospital stay and duration of analgetic treatment were significantly shorter after laparoscopic adrenalectomy. Conclusions: Laparoscopic adrenalectomy is a safe procedure for patients with pheochromocytoma.

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.

Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma.

Objective: Adrenocortical carcinoma (ACC) is a rare malignancy with an unfavorable prognosis. The impact of a locoregional lymph node dissection (LND) has never been defined in this disease. We report the disease-specific outcome of patients treated with or without LND during primary adrenalectomy. Methods: The medical records of patients followed by the German ACC Registry were retrospectively reviewed. Patients with incomplete resection or distant metastases were excluded. Only if the histologic analysis retrieved 5 or more lymph nodes, an intended LND was assumed (LND group). The predefined primary end point of the study was disease-specific survival. Results: Of 283 included patients, 47 patients (16.6%) were treated with LND, whereas 236 patients (83.4%) underwent surgery without LND. Patients who underwent LND had a larger median tumor size (12.0 cm, range: 2.3–30 cm vs 10.0 cm, range: 4.0–39 cm, P = 0.007) and were more often treated by multivisceral resection (LND: 47.8% vs no-LND: 18.1%; P < 0.001). The other baseline characteristics (age, sex, endocrine activity, Weiss score, Ki-67 index, and adjuvant treatment) did not differ significantly. Median follow-up of all patients still alive was 40 months (range: 6–326). Multivariate analysis adjusted for age, tumor stage, multivisceral resection, adjuvant treatment, and lymph nodes status on preoperative imaging demonstrated a significantly reduced risk for tumor recurrence (hazard ratio: 0.65; 95% confidence interval: 0.43–0.98; P = 0.042) and for disease-related death (hazard ratio: 0.54; 95% confidence interval: 0.29–0.99; P = 0.049) in LND patients when compared with no-LND patients. Conclusions: Our retrospective data indicate that locoregional LND improves tumor staging and leads to a favorable oncologic outcome in patients with localized ACC.

K-ras oncogene mutations indicate malignancy in cystic tumors of the pancreas.

OBJECTIVE To evaluate clinical parameters, presurgical diagnostic tests, histologic findings, and the presence of K-ras oncogene mutations in cystic tumors of the pancreas to determine which best predict malignancy. SUMMARY BACKGROUND DATA Because presurgical, intraoperative, and final pathologic differentiation is difficult in cystic tumors of the pancreas, it would be a major benefit to identify markers that accurately predict malignancy in these rare tumors. The role of K-ras oncogene mutations as an indicator of malignancy has not been determined in these tumors. METHODS Nineteen patients with cystic tumors of the pancreas were evaluated, including K-ras mutation analysis based on polymerase chain reaction and restriction digestion assays and direct DNA sequencing, to screen for parameters that accurately predict malignancy. RESULTS All malignant cystic pancreatic tumors (five cystadenocarcinomas and three mucin-producing adenocarcinomas) harbored K-ras mutations at codon 12 or 13. K-ras mutations were also detected in the percutaneous fine-needle aspirates of two of these patients. In contrast, none of nine benign cystadenomas or the solid-papillary neoplasm had K-ras mutations. None of the patients with a benign tumor carrying K-ras wild-type sequences developed recurrent disease after a mean follow-up of 50 months. Seven of the 8 malignant cystic pancreatic tumors, but none of the 11 benign tumors, showed dilatation of the main pancreatic duct on computed tomography or endoscopic retrograde cholangiopancreatography. CONCLUSIONS K-ras mutation analysis seems to be a powerful tool to determine the malignant potential of cystic pancreatic tumors before and after surgery. Dilatation of the main pancreatic duct on computed tomography or endoscopic retrograde cholangiopancreatography is highly suggestive for malignancy in these rare tumors.

Second Step: Testing—Outcome Measurements

Despite worldwide enthusiasm for endoscopic surgery, this new technology is now on the top of McKinlays “product life circle curve.” Critical questions are being asked about its benefits and burdens, but the concepts applied and the methodologies used for technology assessment are in a similar position as endoscopic surgery and need a critical evaluation. (1) There are incorrect and outdated concepts for the scientific basis of surgery (surgical theory) including the basic sciences involved; biomedicine still dominates, but assessment of outcome after operations is no longer possible without clinical epidemiology and social psychology. (2) Based on an outdated scientific theory for surgery, an outdated concept of disease is still propagated. It is denoted as mechanical and is based solely on biomedicine. Human subjects are reduced to biologic machines, and outcomes measurement excludes most dimensions of functioning and well-being. To achieve a valid result for outcome measures, a hermeneutic approach must be combined with the mechanical approach. (3) Based on an outdated model of disease, the outcomes used in endoscopic surgery rely too much on traditional measures, such as mortality rate, complication rate, hospital stay, and especially an endless list of biochemical mediators. Their alterations during the perioperative period have not yet been shown to be related to clinical or hermeneutic outcomes. A new method of assessment for clinical trials in endoscopic surgery and for other surgical problems is outlined, such as for surgical infections and for surgical oncology. It includes an index of recovery and objective health status assessed by the doctor, a quality-of-life self-report by the patient, and the true endpoint concept as a critical weighting of both types of outcome by patients and doctors.

Expectations and quality of life of cancer patients undergoing radiotherapy.

Summary Expectations, real or false, affect the way patients respond to their illnesses. We assessed therapy-related expectations in relation to global quality of life in 55 cancer patients before and after radiotherapy. Factor analysis indicated that therapy-related expectations come into three broad categories—pain/emotional control, healing and tumour/symptom control. 35 patients expected ‘healing’ even though curative treatment was intended in only 19 and all patients had been fully informed. The expectation of healing was associated with high quality of life, and the same was true of perception of healing after radiotherapy. In the group as a whole, quality of life was little altered by radiotherapy, but it became substantially worse in those patients who had expected healing but perceived that this had failed, even though physician-assessed Karnofsky status did not change. These findings indicate that the expectation of healing, in cancer patients, is a component of a good global quality of life, whereas more limited expectations (pain control, tumour control) relate to lower quality of life. Patients’ expectations deserve further study as a novel approach to improving care.

Localization, Malignant Potential, and Surgical Management of Gastrinomas

Abstract. Between 1987 and 1996 a total of 25 patients with proved Zollinger-Ellison syndrome (ZES) have been treated in our department. If preoperative imaging studies did not show diffuse metastatic disease, patients were scheduled for operation with a standardized surgical approach including thorough exploration and intraoperative ultrasonography (IOUS) of the pancreas and a longitudinal duodenotomy, with separate palpation of the anterior and posterior walls. Postoperatively, patients were followed up by physical examination, fasting gastrin levels, and the secretin stimulation test. Altogether 10 patients had duodenal wall gastrinoma, 14 patients pancreatic gastrinoma, and the tumor was not found in 1 patient. Only 15 tumors (60%) (2 duodenal wall and 13 pancreatic gastrinomas) could be visualized preoperatively. Intraoperatively, 24 of 25 primary gastrinomas were localized. The mean size of duodenal wall gastrinomas (9.6 mm) was significantly smaller than that of pancreatic gastrinomas (28.7 mm) (p < 0.05). At the time of surgical exploration, five duodenal and seven pancreatic gastrinomas had metastasized. The incidence of lymph node metastases was similar for both tumor sites, whereas patients with pancreatic gastrinomas more frequently had liver metastases. The presence of liver metastases was the most important determinant for survival. Four patients (40%) with duodenal and seven with pancreatic (50%) gastrinomas (mean follow-up 5.2 years) were biochemically cured by operation. Of the remaining patients, eight are still alive with recurrent disease. Our results suggest that preoperative localization of gastrinomas often fails despite all modern imaging methods. Therefore a standardized surgical exploration of the pancreas including IOUS and a duodenal exploration should be performed to achieve optimal results. Preoperative diagnostic imaging tests should include computed tomography, ultrasonography, and somatostatin receptor scintigraphy to exclude diffuse metastases. In contrast to liver metastases, lymph node metastases do not have a significant influence on survival.