Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma.

AIMS: No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker. METHODS: We monitored a 15-year-old boy diagnosed to have FLHCC by measuring the common markers alanine aminotransaminase, alkaline phosphatase, lactate dehydrogenase, and bilirubin, as well as vitamin B12 (B12), and the forms of the B12 binding proteins. Tumour biopsies were examined immunohistologically. DNA and RNA were extracted from tumour and normal tissue and examined for content of HC DNA and mRNA. RESULTS: The only markers indicative of disease progression were HC and (B12), levels of which were markedly elevated to 84 (11) nmol/L at the time of diagnosis and returned to values within the reference interval (0.43 (0.33) nmol/L) after an apparently radical removal of the tumour. The disappearance rate of HC followed a biphasic curve, the unsaturated protein displaying a half-life of 2.8 days and B12 and saturated HC one of 13 days. Before each diagnosed relapse, an increased concentration of HC was observed. We found a strong immunoreaction against HC in tumour tissue and a high mRNA expression of HC supporting the notion that HC was tumour derived. CONCLUSIONS: Plasma HC proved to be a useful tumour marker in a patient with FLHCC, and we suggest the use of this protein as a marker of disease progression in these patients.

Endoscopic ultrasound-guided fine-needle marking of lymph nodes.

BACKGROUND AND STUDY AIMS: No previous studies have evaluated the ability of endoscopic ultrasonography to describe the anatomic location of lymph nodes on the basis of a node-to-node comparison. The aim of this study was to assess the feasibility and safety of a new endoscopic ultrasound (EUS)-guided fine-needle technique for marking lymph nodes. PATIENTS AND METHODS: Twenty-five patients with suspected or confirmed malignancies of the upper gastrointestinal tract were prospectively included. EUS-guided fine-needle marking (EUS-FNM) was performed with a silver pin with a diameter that allowed it to fit into a 19-gauge needle. The position of the pin was verified by EUS. End points were the ability to identify and isolate the marked lymph node during surgery and a comparison between the location of the pin as suggested by EUS and the actual location found in the resected specimen. RESULTS: Twenty-three lymph nodes were marked. Nineteen intended surgical isolations were performed. The lymph nodes were isolated in the resection specimens in 18 patients (95 %). In 2 out of 20 cases the pin was not localized by laparoscopic ultrasonography. In 89 % of the cases the marked lymph node was in the same location as described by EUS. One pin (5 %) was not retrieved. In three cases, a small hematoma was observed. There was no sign of long-term complications. CONCLUSION: EUS-FNM with a silver pin in lymph nodes is feasible and safe. EUS-FNM seems to be a suitable tool for evaluating lymph nodes on the basis of a node-to-node comparison.

Impact of endoscopic ultrasonography (EUS) on surgical decision-making in upper gastrointestinal tract cancer: an international multicenter study.

BACKGROUND: Endoscopic ultrasonography (EUS) is an integrated part of the pretherapeutic evaluation program for patients with upper gastrointestinal (GI) tract cancer. Whether the clinical impact of EUS differs between surgeons from different countries is unknown. The same applies to the potential clinical influence of EUS misinterpretations. The aim of this study was to evaluate the interobserver agreement on predefined treatment strategies between surgeons from four different countries, with and without EUS, and to evaluate the clinical consequences of EUS misinterpretations. METHODS: One hundred patients with upper GI tract cancer were randomly selected from all upper GI tract cancer patients treated at Odense University Hospital between 1997 and 2000. Based on patient records and EUS database results, a case story was created with and without the EUS result for each patient. Four surgeons were asked to select the relevant treatment strategy in each case, at first without knowledge of the EUS and thereafter with the EUS result available. Interobserver agreement and impact of EUS misinterpretations were evaluated using the actual final treatment of each patient as reference. RESULTS: Three of four or all four surgeons agreed on the same treatment strategy for nearly 60% of the patients with and without the EUS results. Treatment decisions were changed in 34% based on the EUS results, and the majority of these changes were toward nonsurgical and palliative treatments (85%). Interobserver agreement was relatively low, but overall EUS increased kappa values from 0.16 ("poor") to 0.33 ("fair"), thus indicating increased overall agreement after the EUS results were available. EUS conclusion regarding stage or resectability was wrong in 17% of the cases, but only one serious event would have been the clinical result of EUS misinterpretations. CONCLUSION: Despite being used in different ways by different surgeons, EUS did change patient management in one third of the cases. The impact of EUS misinterpretations seemed very low, and this study confirmed one of the strongest clinical possibilities of EUS, i.e., the ability to detect nonresectable cases. EUS is an important imaging modality for oncosurgeons from different countries.

Combined preoperative endoscopic and laparoscopic ultrasonography for prediction of R0 resection in upper gastrointestinal tract cancer.

BACKGROUND: This study evaluated the ability of combined endoscopic and laparoscopic ultrasonography to predict R0 resection and avoid unnecessary surgery in patients with upper gastrointestinal tract cancer (UGIC). METHODS: A total of 411 consecutive patients with UGIC (182 pancreatic cancers, 134 gastric cancers and 95 oesophageal cancers) treated between January 2002 and May 2004 were analysed prospectively. The allocation of patients into resectability groups by endoscopic ultrasonography (EUS) and laparoscopic ultrasonography (LUS) was compared with the treatment actually undertaken. RESULTS: The combination of EUS and LUS correctly predicted R0 resection in 90.6 per cent, R1-R2 in 91 per cent and irresectability in 91.4 per cent of patients. Ten patients (2.4 per cent) had explorative laparotomy only. There were no complications associated with the EUS and LUS procedures. CONCLUSION: The routine use of EUS and LUS before surgery predicted R0 resection in nine of ten patients and reduced the number of unnecessary laparotomies to less than 3 per cent.

Combined endoscopic and laparoscopic ultrasound as preoperative assessment of patients with pancreatic cancer.

BACKGROUND: An accurate pre-therapeutic assessment of the resectability in pancreatic cancer patients is essential to reduce the number of futile surgical explorations. The aim of this study was to assess the combination of endoscopic ultrasound (EUS) and laparoscopic ultrasound (LUS) regarding the detection of patients with non-resectable tumours. PATIENTS AND METHODS: From 2002 to 2004, 179 consecutive patients with pancreatic cancer referred for surgical treatment were eligible. Thirty-one (17%) patients were excluded due to co-morbidity and poor performance status. Two patients (1%) were excluded due to metastasis seen on CT scans prior to referral. Thus, 146 patients entered the study. Patients were first examined with EUS followed by LUS, if EUS found no signs of non-resectability. Only patients with tumours found to be resectable or possibly resectable at EUS and LUS were offered surgical treatment. Resectability criteria were defined prior to the study. RESULTS: In all, 108 (74%) patients had non-resectable tumours by the pre-defined criteria. EUS identified 68 (63%) patients and LUS identified an additional 26 (24%) patients. Thus, a total of 94 (87%) patients were non-resectable at either EUS or LUS. Fifty-two (36%) patients underwent surgery. Six patients had surgical exploration and three patients had palliative surgery. Forty-three patients (29%) were resected with curative intention, of whom 38 (88%) had an R0 resection and 5 (12%) had a palliative resection. DISCUSSION: The combination of EUS and LUS is accurate in identifying the non-resectable patients and has a high predictive value for complete resection.

Prospective evaluation of patient tolerability, satisfaction with patient information, and complications in endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: Prospective data are lacking on the safety of endoscopic ultrasonography (EUS) and on patient satisfaction with the procedure. We prospectively recorded complications related to EUS in order to establish morbidity and mortality. In addition the levels of patient satisfaction were evaluated, with regard to the tolerability of the procedure (pain, discomfort, and anxiety levels) and the provision of information. PATIENTS AND METHODS: 3324 consecutive patients who underwent EUS were studied with regard to complications. During the study period 300 patients were interviewed and followed up in detail as part of the evaluation of patient satisfaction. RESULTS: Ten patients (0.3 %) suffered from a complication related to the EUS procedure, and two patients died (0.06 %). There were no significant differences between the complication rates for EUS-guided fine-needle aspiration (EUS-FNA) and for EUS, but both fatal cases related to EUS-FNA/EUS-guided intervention. Nine of the ten patients with complications (90 %) had a diagnosis of malignancy, and esophageal perforation accounted for half of all complications. Although the majority of patients with nonlethal complications were managed well on conservative regimens, only one case, of self-limiting acute pancreatitis, could be classified as a mild complication. With regard to patient tolerability, only minor incidents occurred during the EUS procedure (tracheal suction 5 %, vomiting 0.3 %, aspiration 0.3 %) and no intervention was necessary. During the procedure, 80 % of the patients had no or only slight pain and more than 95 % experienced only slight or no anxiety, whereas more than half of the patients experienced moderate to severe discomfort. More than 90 % of the patients were satisfied or very satisfied with the information provided to them before and after the EUS, and the same number of patients were ready without hesitation to undergo an additional EUS examination if necessary. CONCLUSIONS: EUS, EUS-FNA and EUS-guided intervention are safe techniques, but severe and lethal complications do occur. The EUS procedures can be performed with a high level of patient satisfaction and with low levels of pain, discomfort and anxiety.

A new method for three-dimensional laparoscopic ultrasound model reconstruction.

BACKGROUND: Laparoscopic ultrasound is an important modality in the staging of gastrointestinal tumors. Correct staging depends on good spatial understanding of the regional tumor infiltration. Three-dimensional (3D) models may facilitate the evaluation of tumor infiltration. The aim of the study was to perform a volumetric test and a clinical feasibility test of a new 3D method using standard laparoscopic ultrasound equipment. METHODS: Three-dimensional models were reconstructed from a series of two-dimensional ultrasound images using either electromagnetic tracking or a new 3D method. The volumetric accuracy of the new method was tested ex vivo, and the clinical feasibility was tested on a small series of patients. RESULTS: Both electromagnetic tracked reconstructions and the new 3D method gave good volumetric information with no significant difference. Clinical use of the new 3D method showed accurate models comparable to findings at surgery and pathology. CONCLUSIONS: The use of the new 3D method is technically feasible, and its volumetrically, accurate compared to 3D with electromagnetic tracking.

Initial experience with new dedicated needles for laparoscopic ultrasound-guided fine-needle aspiration and histological biopsies.

BACKGROUND AND STUDY AIMS: Laparoscopic ultrasonography (LUS) is an important imaging modality during laparoscopic staging of intra-abdominal malignancies, but LUS-assisted biopsy is often difficult or impossible. We report a newly developed inbuilt biopsy system for direct LUS-guided fine-needle aspiration (FNA) and Tru-cut biopsies. PATIENTS AND METHODS: LUS-guided biopsy was performed in 20 patients with upper gastrointestinal tract tumors. The biopsied lesions had either not been previously detected by other imaging modalities or had been inaccessible, or the biopsy sample had been inadequate. Primary diagnosis, duration of biopsy procedure, needle monitoring (visibility, penetration, and deviation), complications, technical failures, and pathological findings were prospectively recorded. RESULTS: 44 biopsies were performed with 25 needles (19, 20, and 22-G). Needle monitoring and penetration were good or acceptable in 18 patients (90%). Slight needle deviation (<10 mm) was seen in eight patients (40%). The LUS-guided biopsy specimen was sufficient for analysis in 13 patients (65%). In two additional patients, adequate material was obtained, but pathological examination was impossible owing to incorrect handling of the specimen. The biopsy procedures lasted 16.3 minutes (range 10-20 minutes) and no complications were seen. CONCLUSIONS: LUS-guided fine-needle aspiration or Trucut biopsy is possible using this newly developed biopsy system. These preliminary data suggest that LUS-guided biopsy may further improve the diagnostic possibilities of LUS.

[Curative treatment of ventricular cancer]. / Kurativ behandling af cancer ventriculi.

Extended lymphadenectomy on connection with the surgical treatment of gastric cancer is gaining access in western centres especially since Japanese centres have shown an ever increasing rate of survival over several decades, coupled with the fact that operative procedures have become more sophisticated. The latest prospective studies in the west seem to confirm the value of lymphadenectomy in some patients. Furthermore, correct staging demands extended lymphadenectomy. For patients with gastric cancer, adjuvant preoperative chemotherapy is probably an asset.

[The value of intravenous cholangiography prior to elective laparoscopic cholecystectomy]. / Vaerdien af intravenøs biligrafi forud for elektiv laparoskopisk kolecystektomi.

Thirty-eight patients admitted for elective cholecystectomy were preoperatively evaluated by means of liver function tests, ultrasonographic examination and intravenous cholangiography (IVC). Common bile duct stones (CBS) were found in four patients (11%, 95% confidence limits 3-25%). Due to a history of jaundice and/or elevated liver function tests, CBS were suspected in three of these patients, and unexpected in one. Totally, CBS were suspected in eight patients, either because of their history and/or elevated liver function tests. No side effects were observed during or after the IVC procedure. It can be concluded that IVC is a lenient procedure for radiological assessment of the common bile duct prior to elective laparoscopic cholecystectomy. It can be recommended as an alternative to diagnostic endoscopic retrograde cholangiography in patients in whom CBS are suspected.

[Surgical treatment of goiter at a central hospital. A consecutive study with special emphasis on surgical complications]. / Kirurgisk behandling af struma på et centralsygehus. En konsekutiv opgørelse specielt med henblik på kirurgiske komplikatoiner.

The aim of this study was to analyse the frequency of permanent and transient complications following thyroid gland surgery. During a period of four years, from 1991 to 1995, 129 patients were treated operatively for thyroid disease. Sixteen patients were operated for thyrotoxicosis and 113 for nontoxic goitre. Nine patients underwent reoperation for recurrent goitre. Thyroid malignancy was found in two patients. The frequency of permanent complications was 0.7%. Transient unilateral pareses developed postoperatively in two patients. There were no permanent vocal cord paralyses. One patient developed permanent hypoparathyroidism. Five patients had transient postoperative hypocalcaemia requiring calcium supplements. Other complications were haemorrhage (3.8%), wound infection (0.7%) and other postoperative complications (1.5%). It is shown that uncomplicated thyroid surgery may be performed at a district hospital that has a special interest in patient evaluation, indications for surgery and up to date surgical technique.

[Duodenal cancer--illustrated by 5 cases, with special consideration to symptomatology, diagnosis and treatment]. / Cancer duodeni--belyst ved fem sygehistorier, specielt med henblik på symptomatologi, diagnostik og behandling.

Over a period of 30 months we have seen five patients with duodenal cancer (four adenocarcinomas and one carcinoid-tumour). All patients are presented with a brief history of vague and non-specific symptoms. Diagnosis was established by endoscopy and biopsies. In one case, a Whipple's procedure was performed, and the patient is without evidence of tumour recurrence eight months later. Three patients could only be offered palliative surgery, of these, one is still alive two years after the operation, one (the patient with a carcinoid tumour) died three months postoperatively, and the third has only just recently been operated. The fifth patient died ten days after the diagnosis was confirmed, without any specific treatment. The different diagnostic methods available as well as the treatment and prognosis of duodenal cancer are discussed. We conclude that: 1) despite improved diagnostic procedures, the diagnosis of duodenal cancer is still difficult and delayed due to vague and non-specific symptoms, 2) the diagnostic procedure is endoscopy and biopsy. 3) the treatment is surgery and 4) the prognosis is poor in the majority of patients.

The fate of impacted lower third molars after the age of 20. A four-year clinical follow-up.

Seventy dental students (mean age: 20 years) with 130 asymptomatic, non-ectopic, impacted mandibular 3rd molars were followed for 4 years. At the initial visit 26 were impacted in soft tissue, 30 were partially impacted in bone, and 74 were completely impacted in bone. The following items were registered at each visit: regional pocket depths, signs and symptoms of pathology, degree of impaction, presence of upper 3rd molar. No signs or symptoms of pathology were observed in any of the subjects at the 2 visits. The 4-year visit revealed that 49 3rd molars had been removed, the reason being pericoronitis or caries in 30%, mild symptoms in 39% and for prophylactic reasons in 31%. Of the remaining 81 3rd molars: 71% of the soft tissue impactions, 25% of partial bony impactions, and 8% of complete bony impactions showed complete and normal eruption. The remaining 3rd molars were either static or had advanced in the degree of eruption. It is concluded that non-ectopic, impacted 3rd molars in the given age group may have a chance to completely erupt. The treatment for asymptomatic impacted 3rd molars in young adults, therefore, might be observation instead of prophylactic removal.

Transurethral prostatotomy versus transurethral prostatectomy in benign prostatic hypertrophy. A prospective randomised study.

Transurethral prostatotomy (TUT) in 24 patients was compared with transurethral prostatectomy (TUR) in 25 patients in a prospective randomised trial. All patients were aged 60 years or more and presented with symptomatic benign hypertrophy. One half of the patients had acute retention. Shorter operative time and less post-operative bleeding were found in the TUT group, which included 3 failures. No difference was found in post-operative duration of catheterisation or duration of hospitalisation. No significant differences were seen after 1 year's follow-up in the number of patients with positive urinary culture or urinary flow rate. One patient in the TUT group had a recurrence of symptoms, thus giving a total of 4 failures and a success rate of 82%. One patient became incontinent after TUR and 4 developed a stricture. The success rate after TUR was 78%. It was concluded that TUT and TUR produce similar functional results in cases where the gland is not too large.

Incomplete distal denervation and recurrent ulcer after parietal cell vagotomy.

Twenty-five patients with chronic duodenal ulcer and subjected to parietal cell vagotomy were evaluated as either underdenervated or optimally denervated, depending on whether parietal cells were present distal to the last branch of Latarjet's nerve. A 5-year follow-up study demonstrated recurrent ulcer in three of five judged as underdenervated. In addition to the possible technical error of distal and proximal dissection, the importance of the inborn error of incomplete distal denervation is confirmed.

Long-term observation following perforation and rupture of the esophagus.

A follow-up study of 35 patients was performed 1.5 to 22 years after simple closure and drainage of the esophagus for nonmalignant intrathoracic perforation or rupture, with special attention to dysphagia. Of the seven patients with spontaneous rupture, only one required supplementary postoperative treatment, for severe reflux esophagitis. None of the eight patients with iatrogenic lesion and no prior esophageal disorder had any dysphagia postoperatively. Postoperative swallowing problems were absent in 13 of the 20 patients with perforation caused by examination or treatment of an already diseased esophagus. Four required repeated esophageal dilation and three underwent further surgery. Simple closure and drainage of nonmalignant intrathoracic perforation or rupture of the esophagus is concluded to be a safe procedure in regard to late postoperative dysphagia.

The antral gastrin-producing cells in duodenal ulcer patients. A study of preoperative G-cell densities, fasting serum-gastrin, pre- and postoperative gastric acid secretion and outcome after parietal cell vagotomy.

Antral gastrin-producing cell densities, as well as serum gastrin and gastric acid secretion were obtained prior to parietal cell vagotomy from 60 patients suffering from chronic duodenal ulcer disease. Acid secretion was also measured postoperatively. The patients were followed for five years. The ulcer recurrence rate was 20%. No differences were found in the G-cell densities, fasting serum-gastrin or gastric acid secretion preoperatively between the two groups: recurrence and non-recurrence. The acid secretion was higher postoperatively in patients with recurrent ulcer as compared to those without recurrence of the ulcer, suggesting that incomplete vagotomy is a reasonable explanation of the recurrence, even though post-operative G-cell abnormality cannot definitely be ruled out.

The antral gastrin-producing cells in duodenal ulcer patients. A light microscopic and ultrastructural study during long-term, low dose treatment with cimetidine.

The antral mucosa has been examined in four duodenal ulcer patients before and during long-term, low dose treatment with cimetidine (given a total dose of between 472 g and 894 g). No convincing changes were found in the number or the volume of G cells. Signs of inactivity were demonstrated ultrastructurally, with small granules of intermediate type, a reduced amount of granular endoplasmatic reticulum and Golgi complex, mostly showing no signs of granulogenesis. The occurrence of bundles of cytoplasmic microfilaments, not observed before treatment and the reduced number of D cells may also be signs of inactivity. Hyperplasia and/or neoplasia were not seen in other antral endocrine cells.

Morphometric investigation of the human thyroid gland. With special reference to the methods and to nontoxic goiter.

A study was carried out to (1) evaluate methods for the quantitative morphologic description of the human thyroid gland and (2) investigate the relationship between the morphology and the functional state of the gland in patients with nontoxic goiter. Analysis of sampling variance showed a high contribution of biologic variation between individuals, a low contribution from the variance within individuals and a negligible contribution from the stereologic procedure itself to the overall variation. The optimal numbers of sections per gland and fields of vision were found to be 2 and 17, respectively. The only constant relationship between the morphology and the functional state, either before or after resection, was a positive correlation between the epithelial cell volume left behind and the se-"free" thyroxine index 12 months postoperatively. It is concluded that quantitative morphologic description of the human thyroid gland is possible without being too time-consuming but that the value of such investigations is clinically doubtful in cases of nontoxic goiter.