Search

BACKGROUND: In the 90s, digital human manikins (DHMs) were introduced in planning of workstations, by static or semi-static simulations. Modern DHMs can simulate dynamic work and offer a rapid way for a virtual pre-production ergonomic evaluation. Work-related musculoskeletal disorders may affect surgical performance and patient safety. A prototype of an open console, which is contrary to the conventional closed consoles and may be seen as a representative for a new generation, has been designed to reduce workload for robotic surgery surgeons. OBJECTIVE: The aim of this project was to test a new DHM tool with improved usability to evaluate the ergonomics of a console of a robotic surgical system in a pre-production stage. METHODS: The DHM tool IMMA was used together with a 3D model of the prototype console. Twelve manikins who represented females and males from two national populations were introduced. Manikin-console distances, after console adjustments per manikin, were compared with a US checklist and Swedish standard for VDU work. RESULTS: The DHM tool was useful for this case, but the distances of the checklist and the standard were needed to be obtained “manually”. The automatic functions of the DHM worked smoothly but were not optimized for VDU work. The prototype fulfilled most, but not all, of the ergonomic criteria of the checklist and the standard. CONCLUSIONS: There is room for improvements of the adjustable ranges of the console prototype. DHMs may facilitate rapid pre-production evaluation of workstations for static work; if ergonomic assessment models for VDU work are built-in, there may be a revival of DHMs in static work situations.

Background: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking. Methods: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3. Results: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98). Conclusion: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms.

Background Work-related pain and discomfort experienced by surgeons is widely reported in the literature. A survey was, therefore, conducted to explore this issue among members of the European Association for Endoscopic Surgery (EAES). Methods The survey was emailed to 2980 EAES members in 2017 enquiring about their working practice, musculoskeletal (MSK) pain and burnout. Results A total of 569 (19%) surgeons responded, of whom 556 were practicing surgeons; 86% were consultants, 84% were male, and 94% were right-handed. Respondents operated on average 3.3 days/week with 27% of their procedures lasting longer than 3 h. The 386 endoscopists surveyed reported performing an average of 5.3 procedures/day with 83% performing endoscopy at least once per week. Over half of practicing surgeons (62%) reported their worst pain score was 3 or higher (10-point scale) in the past 7 working days, encompassing 71% of their open, 72% laparoscopic, 48% robot-assisted cases and 52% of their endoscopies. Of the 120 surgeons who had ever sought medical help for aches, pain or discomfort, 38% were currently in pain and 16% had considered leaving surgery due to their MSK pain, 26% had reported work-related pain to their employer, 26% had been on short-term disability during their career and 4% long-term disability due to MSK disorders. A significant proportion of the respondents (49%) felt their physical discomfort would influence the ability to perform or assist with surgical procedures in the future. These surgeons reported significantly lower satisfaction from their work (p = 0.024), higher burnout (p = 0.005) and significantly higher callousness toward people (p

Background: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. Methods: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. Results: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. Conclusion: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.

Background Poorly differentiated anal neuroendocrine carcinomas (ANECs) are rare lesions with poor prognosis, and the molecular etiology is only partially understood. Case presentation At our institution, we have treated and followed a patient with such a rare ANEC. He had primarily surgery followed by three rounds of repeated surgery for loco-regional recurrences. He also received three different combinations of chemotherapy and external beam radiation. At last follow-up 13 years since the primary diagnosis, the patient had been in complete remission for nine years. The patient’s medical files were re-examined, including laboratory, radiology and clinical examinations. Histopathology was re-assessed, and expanded immunohistochemistry was performed from tissue specimens from the four surgical procedures. In addition, the molecular genetic status was evaluated through next-generation sequencing. The initial tumor was consistent with a 59 mm small cell neuroendocrine cancer with a Ki-67 index of 80%. Regional lymph node metastases were evident, and immunohistochemistry supported a neuroendocrine origin. A PCR screening detected human papilloma virus type 45 DNA (high-risk subtype), and focused next-generation sequencing found a missense mutation in the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene. In tissues representing subsequent recurrences, the Chromogranin A expression was lost, and the Ki-67 index increased to 90%. Conclusions For the first time, we report the detection of HPV45 in a case of ANEC. To our belief, PIK3CA mutations have also not been previously demonstrated in this tumor entity. In highly malignant ANECs, cure can in rare cases be achieved. Although speculative, expression of HPV45 and/or the PIK3CA mutation may have contributed to the favorable outcome.

Purpose Many pheochromocytomas and paragangliomas (PPGLs) are nowadays diagnosed as incidentalomas or by screening. This may have changed outcomes. Methods We reviewed 110 consecutive cases of PPGLs. Two cases with concurrent ectopic ACTH-syndrome were excluded. Results Sixty-five percent had presented as incidentalomas, 30% as symptomatic PPGLs, and 5% had been screened (previously diagnosed MEN2A). Doxazosin was used in 79%, phenoxybenzamine in 18%, intravenous phentolamine in 1%, and no alpha-blockade in the rest. Laparoscopic surgery was performed in 70%, but 11% were converted to open surgery. Complications of surgery were seen in 20%, and length of stay after surgery was 4 days (2–8) with no correlation with alpha-blockade dose or time. In the whole cohort glycemic disturbances decreased by surgery (47% vs. 9%, P 2% n = 2; KI67 ≤ 1% n = 3; tumor size ≥ 95 mm n = 4), and 13% died (metastatic pheochromocytoma n = 2, hypertensive crisis n = 1, heart failure n = 2, other malignancies n = 5, and unclear n = 4). Surgery improved blood pressure and glycemic disturbances in the incidentaloma and the symptomatic PPGL. Recurrence was more common in the screening group. The symptomatic PPGL group was more likely to die of a PPGL-related cause. Surgery was more challenging in the paragangliomas, with less improvement in glycemic control than in the pheochromocytoma group. However, blood pressure and long-term outcomes were similar. Conclusion The outcomes seemed slightly better than previous studies. Long-term prognosis was similar between pheochromocytomas and paragangliomas.

Plasma Protein Kallikrein-14 Strongly Predicts Pronounced Chromogranin A (CgA) Response in Small Intestinal Neuroendocrine Tumor (NET) Patients after Somatostatin Analog (SSA) Treatment : The Nordic EXPLAIN Biomarker Study

Background With the increasing access to imaging more pheochromocytomas are diagnosed in the workup of adrenal incidentalomas. This may have changed the occurrence of the classic presentation with hypertension and the classic triad (headaches, sweating and palpitation). Methods We reviewed 94 consecutive cases of pheochromocytomas. Two cases of ectopic ACTH-syndrome were subsequently excluded. Results Of the 92 cases included 64% had presented as an incidentaloma, 32% as a suspected pheochromocytoma and 4% had been screened because of previously diagnosed MEN2A. Those screened were youngest while those with incidentalomas were oldest. The females were more common in the incidentaloma and the screening groups, and males in the suspected pheochromocytoma group. Measurements of noradrenaline/normetanephrine levels were highest in the suspected pheocromocytoma group and lowest in the screening group. Hypertension was present in 63% of the incidentalomas, 79% of suspected pheochromocytomas and in none of the screening group. Paroxysmal symptoms were present in almost all with suspected pheochromocytoma while only in half of the other groups. The suspected pheocromocytoma group had most symptoms and the screening group least. The classic triad was present in 14% of the incidentalomas, in 28% of the suspected and in none of the screening group, while no symptoms at all was present in 12%, 0% and 25%, respectively. Pheochromocytoma crisis occurred in 5%. There was a positive correlation between tumor size vs hormone levels, and catecholamine levels vs blood pressure. Conclusion Clinicians need to be aware of the modern presentation of pheochromocytomas since early identification can be life-saving.

Clinical Practice PointsRenal cell carcinoma (RCC) has a poor prognosis and is difficult to treat because of its ability to spread asymptomatically and its resistance to chemotherapy.In this patien ...

To compare long-term outcomes in patients with adrenal incidentalomas (AIs) with the response to a 1 mg overnight dexamethasone suppression test (DST). Consecutive patients with “non-functional” AIs (n = 365) were examined. Patients with overt hormone excess, adrenocortical cancer and known malignancy had been excluded. Patients were classified to normal cortisol secretion group (n = 204, DST ≤ 50 nmol/l), possible autonomous cortisol secretion group (n = 128, DST 51–138 nmol/l) and autonomous cortisol secretion group (n = 33, DST ≥ 138 nmol/l). Thirty-seven patients (10.1%) deceased during the follow-up period (5.2 ± 2.3 years): 16(7.8%) in the non-secreting group (time from diagnosis to death: 3.9 ± 2.9 years), 15 in the possible autonomous cortisol secretion group (11.7%, 3.2 ± 1.8 years) and 6 in the autonomous cortisol secretion group (18.2%, 2.3 ± 1.5 years), respectively (P = 0.019). Multivariate analysis only found significant association with age and the tumour size but if cortisol levels post-DST were analysed as a continuous variable it was significant as well. All deaths in autonomous cortisol secretion group were due to cancer not related to adrenal glands. Hypertension, cardiovascular disease and medications were more common in the possible and autonomous cortisol secretion group, especially in the former. More bilateral AIs and larger AI size were found in the two latter groups. Patients with autonomous cortisol secretion had higher mortality than those with non-functioning AIs though cortisol levels post-DST as a continuous variable, age and tumour size were better predictor of mortality. Cardiovascular disease and osteoporosis medication seemed more prevalent in the possible and autonomous cortisol secretion groups, especially in the former.

The purpose of this study was to investigate if the ProMIS™ simulator could serve as a training platform for the da Vinci® surgical system and if this constellation could prove construct validity.The da Vinci system was connected to the ProMIS simulator, which registered objective data concerning how the surgeon performed in the box environment related to time, path, and smoothness. Five experienced robotic surgeons passed four different surgical tasks with progressive difficulty. A novice group-constituted of 13 consultants and 6 residents, none of them with any previous experience in the da Vinci system-passed the same tasks and the data were compared with the results from the expert group.A statistically significant difference between experts and novices was demonstrated in all tasks concerning time and smoothness. For the parameter path, significant difference was only noted in the more complex tasks.Our study showed that ProMis could differentiate between experienced robotic surgeons and novices, thereby proving construct validity. Smoothness appeared to be the most sensitive objective parameter in our study. Tasks with high complexity are recommended when designing the program for robotic training.

Adenomas of the adrenal cortex cause different disorders depending on the main steroid synthesized and released. The aim of this research is to increase our understanding of the pathophysiology of steroidogenesis in adrenocortical disorders by comparing the release of steroids from adrenocortical adenomas in vitro with the messenger RNA (mRNA) expression of steroid synthesizing enzymes. Fourteen patients with adrenal tumors were included in the present study; nine were diagnosed with primary aldosteronism and three with Cushing's syndrome. Two patients had an adrenal tumor discovered on computed tomography (CT) during workup for an unrelated disease. Serum cortisol, plasma aldosterone, and urinary catecholamines were normal. Tissue was taken for in vitro steroid release, and aldosterone and cortisol in the medium after a 1-hour incubation were determined. Oligonucleotide probes with sequences complementary to mRNAs encoding for the steroid synthesizing enzymes 11 beta-hydroxylase (CYP11B1), 18-hydroxylase (CYP11B2), 17 alpha-hydroxylase (CYP17), and 21-hydroxylase (CYP21) were synthesized (Genset, Paris, France) and in situ hybridization was performed. Moderate expression of CYP11B2 and low expression of CYP11B1 were seen in the zona glomerulosa. The zona fasciculata of the control adrenals expressed a high signal of CYP11B1, whereas the expression of CYP11B2 was very low. There was considerable variation in aldosterone release from the aldosteronomas, whereas the tumors from the Cushing patients showed no detectable release of aldosterone. In contrast, tumors from patients with primary aldosteronism, Cushing's syndrome, and no hyperfunction all had the ability to synthesize and release cortisol in vitro. The highest cortisol release was found in tumors from patients with Cushing's syndrome, but also the nonhyperfunctioning tumors and some of the aldosteronomas released significant amounts of cortisol. The two patients with highest release of aldosterone in vitro showed the highest expression of CYP11B2 and the lowest expression of CYP11B1 and CYP17. The remaining aldosteronomas had low expression of CYP11B2, similar to the two other groups. Expression of CYP11B1 was high as expected in the Cushing adenomas, but also the two nonhyperfunctioning tumors and some of the aldosteronomas showed a moderate expression. Adenomas from Cushing's syndrome, nonhyperfunctioning adenomas, and some of the aldosterone-producing adenomas had moderate to high expression of CYP17. This paper presents new means for functional characterization of adrenocortical tumors. Diagnosis of an aldosteronoma is often difficult, and with the advent of these methods it is possible to determine the functional capacity of a tumor, once it is removed. This is of special interest if the patient remains hypertensive postoperatively, and it is not clear whether the patient indeed had a functioning tumor.

Invasive breast cancer varies widely in biologic aggressiveness, from fairly indolent tumors to rapidly disseminating carcinomas. Matrix metalloproteinases have enzymatic activity and assist in tumor invasion by degrading basement membranes and extracellular matrix. The extracellular matrix metalloproteinase inducer EMMPRIN is thought to stimulate fibroblasts to produce the zymogen pro-gelatinase A. The membrane type 1-matrix metalloproteinase (MT1-MMP) is thought to assist in tumor invasion and metastasis by activating pro-gelatinase A, which shows enhanced expression in various tumors. Overexpression of gelatinase A has shown to correlate with a malignant phenotype in many tumor forms. The aim of the study was to investigate the mRNA expression pattern of MT1-MMP, gelatinase A, and EMMPRIN in breast tumors. Formalin-fixed paraffin-embedded breast tissue samples from 18 patients operated on with breast-conserving surgery for invasive breast carcinoma20 mm between 1977 and 1985 were analyzed using the mRNA in situ hybridization technique. Most of the patients were node-negative (15/18) and underwent postoperative irradiation to the breast (16/18). The median age at diagnosis was 52 years (21-83 years). At the time of the study 11 patients were alive, 4 without recurrence; 7 patients had been operated for ipsilateral breast tumor recurrences, and 2 had distant metastases. The median follow-up was 112 months (102-193 months). Seven patients died of disseminated breast cancer; their median follow-up was 43 months (22-116 months). (35)S-labeled antisense and sense mRNA probes transcribed from linearized plasmids containing cDNA for the matrix metalloproteinases gelatinase A and MT1-MMP and the glycoprotein EMMPRIN were hybridized to 5 microm paraffin-embedded tissue sections. Several invasive carcinomas were surrounded by normal tissue and carcinoma in situ lesions. Gelatinase A, MT1-MMP, and EMMPRIN mRNA expression were detected in all of the carcinomas. The gelatinase A mRNA expression was mainly localized to stromal cells at moderate to high levels surrounding the invading carcinoma cells but was also seen in single cells at low levels in in situ lesions and in some normal glandular cells. MT1-MMP and EMMPRIN were expressed in all of the carcinomas and were mainly localized to tumor cells; but they were also seen to some extent in single cells at low levels in in situ lesions and in normal glandular cells. No differences in levels of expression for gelatinase A, MT1-MMP, or EMMPRIN were seen in patients who survived compared to patients who died from metastatic disease. The co-expression of gelatinase A, MT1-MMP, and EMMPRIN mRNA in invasive breast carcinoma supports the theory that these proteins interact and are important for the invasive phenotype in breast carcinoma. Hence EMMPRIN may be a central factor for stimulation of gelatinase A activation. Specific inhibition for individual MMP members could in the future be target-specific events in breast tumor progression. Inhibition of EMMPRIN could be such a target.

OBJECTIVE The development and progression of sporadic adrenocortical tumours are poorly understood. In autopsy studies adrenocortical tumours are found in between 2 and 9% of the general population. In congenital adrenal hyperplasia (CAH), decreased production of cortisol leads to increased secretion of ACTH from the pituitary, resulting in hyperplasia of the adrenals. More than 95% of all cases of CAH are due to steroid 21-hydroxylase deficiency, resulting from mutations in the CYP21 gene. In subjects homozygous and heterozygous for CYP21 mutations, adrenocortical tumours have been found in a high frequency compared to the general population, suggesting that chronic ACTH stimulation may play a role in the development of this tumour form. In order to test whether mild undiagnosed CAH is a common predisposing factor, we screened 27 patients with sporadic adrenocortical tumours for CYP21 mutations. DESIGN A retrospective study. PATIENTS We screened 27 patients with sporadic adrenocortical tumours, representing both benign and malignant as well as hormonally active and silent lesions. MEASUREMENTS Mutation analyses of the CYP21 gene was performed by allele-specific PCR on high molecular weight DNA. The method used detects the nine CYP21 mutations that are responsible for 95% of all disease-causing alleles in CAH. RESULTS No mutations were detected in any of the 23 DNA samples that were prepared from leucocytes. In 4 cases where no leucocyte DNA was available, tumour tissue was analysed. In one of these tumours, two CYP21 mutations, V281 L and L307insT, were found in heterozygous form. CONCLUSION Our data indicate that mild undiagnosed congenital adrenal hyperplasia is not a common underlying factor predisposing to adrenocortical tumours, at least not in the Swedish population.

Surgery is the only curative treatment for primary hyperparathyroidism. Focused surgical techniques are being practiced with increasing frequency. Preoperative imaging, such as scintigraphy, is a prerequisite for focused surgery. There is controversy about which preoperative imaging method should be used. The sensitivity reported for parathyroid scintigraphy varies considerably. This study was designed to determine the accuracy of the preoperative imaging routinely used at our institution. This retrospective study included consecutive patients who underwent a routine dual-phase sestamibi-SPECT (single photon emission computed tomography) scintigraphy and subsequent operation with follow-up. Scintigraphy results were evaluated by comparing the results to surgical findings and histopathology. Two hundred and sixty-four individuals entered the study. Sensitivity for scintigraphy was 84%, specificity 91%, positive predictive value 91%, and negative predictive value 84%. Sestamibi-SPECT scintigraphy is a sensitive preoperative modality with high positive predictive value. Scintigraphy is a good indicator for when to perform a focused surgical approach and could often correctly guide the actual operation.

Somatostatin analogues (SSAs) are well established in the treatment of neuroendocrine tumors (NETs), including small intestinal NET (SI-NET) due to their tumor growth arrest and symptom relieving characteristics. Here we determined the direct effects of lanreotide treatment on NET cell lines and a primary SI-NET culture. The cell lines HC45 and H727 were treated with a pharmacological concentration of 10 nM lanreotide for different time periods and the proteome, analyzed by in-depth HiRIEF LC-MS/MS, was compared with the proteome of non-treated cells. We quantified 6 451 and 7 801 proteins in HC45 and H727. Differential expression of the candidate proteins APC, BIRC5/survivin, BMPER, C14orf142, FYN, INSM1 and SPAG16 was confirmed by Western blotting. The possible direct anti-proliferative effect of lanreotide was evaluated in the primary SI-NET culture and the HC45, H727 and BON1 cell lines, which showed only a slight inhibition of proliferation. However, based on proteomics driven pathway analysis a significant synergy in anti-proliferative effect of lanreotide was observed when the small molecule IGF1R inhibitor, NVP-AEW541, was combined with lanreotide .This effective combination also represents an indirect model of suppressed IGF1 activity in the NET patients treated with SSA. Targeting of survivin with the small molecule YM155 dramatically reduced the proliferation of HC45. We also studied the effect of lanreotide alone or in combination with IGF-1R inhibitor on signaling pathways PI3K/Akt, Erk1/2 and P38. P38, Erk1/2 and GSK3β phosphorylation was equally increased by lanreotide and/or NVP-AEW541, however, lanreotide-induced AktS473 dephosphorylation was reversed after6 hours, unlike consistent AktS473 dephosphorylation after treating with NVP-AEW451 alone or in combination. In conclusion, we report growth inhibitory and potential feedback pro-growth signaling of the SSA lanreotide on NET cells, highlighting the role of SSAs in modulation of IGF1 in NET cell growth arrest and propose combination treatment candidate targets for improved efficacy of this agent. Citation Format: Omid Fotouhi, Hanna Kjellin, Jamileh Hashemi, Ming Lu, Christofer Juhlin, Anders Höög, Jan Zedenius, Catharina Larsson, Janne Lehtiö, Magnus Kjellman. Proteomic profiling reveals novel targets for combination treatment with lanreotide in neuroendocrine tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3462. doi:10.1158/1538-7445.AM2015-3462

The increasing occurrence of incidentally discovered benign adrenocortical tumors has become a clinical dilemma because of the difficulties in differentiating them from their malignant counterpart. Adrenocortical tumors are associated with familial cancer syndromes such as the Beckwith-Wiedemann syndrome, the Li-Fraumeni syndrome, the Carney complex, multiple endocrine neoplasia type 1, congenital adrenal hyperplasia, and the McCune-Albright syndrome. Genetic events are known to take place on the chromosomal and gene level in sporadic adrenocortical tumors.

In an attempt to understand the mechanism behind the invasion and metastasis in adrenocortical cancer we performed mRNA in situ hybridization on 30 tumors for three matrix metalloproteinases (MMPs): gelatinase A, membrane type 1 matrix metalloproteinase (MT1-MMP), and collagenase-3. All are known to participate in the invasion and metastasis of other tumor forms by degrading the extracellular matrix. Thirteen of sixteen cancers, but only one of fourteen benign lesions showed expression of gelatinase A, which was localized in stromal cells. MT1-MMP is thought to assist in tumor invasion and metastasis by activating the zymogen gelatinase A. Of 14 malignant tumors analyzed, 12 showed MT1-MMP mRNA expression, which in 7 cases was detected in both neoplastic and stromal cells. The benign tumors showed MT1-MMP expression in only 3 of 11 cases, and it was restricted to tumor cells. Fourteen tumors (11 cancers, 3 adenomas) were also analyzed for collagenase-3 mRNA, but no expression was detected. In conclusion, our data show that gelatinase A mRNA is expressed in most malignant adrenocortical tumors but not in the benign tumors. Gelatinase A mRNA expression is restricted to stromal cells, whereas its activator, MT1-MMP, is expressed in both stromal and neoplastic cells. Inhibition of gelatinase A and other proteinases may in the future become important as a form of cancer treatment.

The incidental detection of small benign adrenocortical tumors has increased in patients who are investigated with imaging techniques in the upper abdomen. Because these benign lesions are difficult to differentiate from their rare malignant counterparts, the interest to find better tumor markers ha

Objective: To evaluate the results of a modern surgical approach in patients with primary hyperparathyroidism. Design: Retrospective analysis. Setting: University hospital, tertiary care center. Patients: One hundred patients consecutively operated on for suspected primary hyperparathyroidism. Patients were available for follow-up 1 month (n=100) and 1 year (n=96) after surgery. Intervention: Cervical exploration. Surgical strategy was to remove enlarged parathyroid glands only and perform a biopsy on no more than one normal gland. Main Outcome Measures: Surgical morbidity and normocalcemia. Results: No operative mortality or wound infection occurred in any patient. Postoperative vocal cord paralysis was recorded in two patients; both recovered fully. Two patients underwent a second operation. (One patient experienced subcutaneous bleeding and the second patient, previously operated on for toxic goiter, experienced persistent hypercalcemia and was operated on 5 days after the initial operation. A second abnormal gland was then found on the contralateral side, not initially surgically explored.) At follow-up, 97 patients were normocalcemic; three patients had hypoparathyroidism: two of these patients, with multiglandular disease, were normocalcemic and received a low dose of vitamin D (1α[OH]D 3 ), and one patient, who had had a single adenoma removed, was slightly hypocalcemic, however, asymptomatic. Conclusions: More than 90% of patients with primary hyperparathyroidism can be operated on without complications occurring. This supports a liberal attitude to operation. (Arch Surg. 1994;129:237-240)