Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality.

OBJECTIVES: To compare a low-tube-voltage with or without high-iodine-load multidetector CT (MDCT) protocol with a normal-tube-voltage, normal-iodine-load (standard) protocol in patients with pancreatic ductal adenocarcinoma (PDAC) with respect to tumour conspicuity and image quality. METHODS: Thirty consecutive patients (mean age: 66 years, men/women: 14/16) preoperatively underwent triple-phase 64-channel MDCT examinations twice according to: (i) 120-kV standard protocol (PS; 0.75 g iodine (I)/kg body weight, n = 30) and (ii) 80-kV protocol A (PA; 0.75 g I/kg, n = 14) or protocol B (PB; 1 g I/kg, n = 16). Two independent readers evaluated tumour delineation and image quality blindly for all protocols. A third reader estimated the pancreas-to-tumour contrast-to-noise ratio (CNR). Statistical analysis was performed with the Chi-square test. RESULTS: Tumour delineation was significantly better in PB and PA compared with PS (P = 0.02). The evaluation of image quality was similar for the three protocols (all, P > 0.05). The highest CNR was observed with PB and was significantly better compared to PA (P = 0.02) and PS (P = 0.0002). CONCLUSION: In patients with PDAC, a low-tube-voltage, high-iodine-load protocol improves tumour delineation and CNR leading to higher tumour conspicuity compared to standard protocol MDCT. KEY POINTS: • Low-tube-voltage high-iodine-load MDCT improves pancreatic cancer conspicuity compared to a standard protocol. • The pancreas-to-tumour attenuation difference increases significantly by reducing the tube voltage. • The radiation exposure dose decreases by reducing the tube voltage.

Computed tomography staging of pancreatic cancer: a validation study addressing interobserver agreement.

BACKGROUND/OBJECTIVES: Ductal adenocarcinoma in the head of the pancreas (PDAC) is usually unresectable at the time of diagnosis due to the involvement of the peripancreatic vessels. Various preoperative classification algorithms have been developed to describe the relationship of the tumor to these vessels, but most of them lack a surgically based approach. We present a CT-based classification algorithm for PDAC based on surgical resectability principles with a focus on interobserver variability. METHODS: Thirty patients with PDAC undergoing pancreaticoduodenectomy were examined by using a standard CT protocol. Nine radiologists, representing three different levels of expertise, evaluated the CT examinations and the tumors were classified into four categories (A-D) according to the proposed system. For the interobserver agreement, the Intraclass Correlation Coefficient (ICC) was estimated. RESULTS: The overall ICC was 0.94 and the ICCs among the trainees, experienced radiologists, and experts were 0.85, 0.76, and 0.92, respectively. All tumors classified as category A1 showed no signs of vascular invasion at surgery. In category A2, 40% of the tumors had corresponding infiltration and required resection of the superior mesenteric vein/portal vein (SMV/PV). One of two tumors in category B2 and two of three in category C required SMV/PV resection. All six patients in category D had both arterial and venous involvement. CONCLUSION: There is almost perfect agreement among radiologists with different levels of expertise in regards to the local staging of PDAC. For tumors in a more advanced preoperative category, an increased risk for vascular involvement was noticed at surgery.

Preoperative pancreas CT/MRI characteristics predict fistula rate after pancreaticoduodenectomy.

BACKGROUND: Pancreatic fistula (PF) is considered to be the main cause of morbidity after pancreaticoduodenectomy (PD). A recent study from our institution suggested the risk for pancreatic fistula after distal pancreatectomy to be closely related to the pancreatic remnant volume (PRV). The hypothesis was formulated that after PD the PRV is an important determinant of the risk for PF formation. METHOD: All patients undergoing PD between September 2007 and November 2010 at the Karolinska University Hospital Stockholm were included. Preoperative multidetector computed tomography (CT) or magnetic resonance imaging (MRI) was used to calculate the PRV and the pancreatic duct width (PDW) at the alleged resection line. RESULTS: A total of 182 patients (median age 67 years) undergoing PD were included. The diagnosis was malignant in 144 patients (79.1 %) and benign in 38 (20.9 %). Pancreatic fistula defined according to the International Study Group on Pancreatic Fistula (ISGPF) criteria was diagnosed in 37 patients (20.3 %). The median PRV was 35.2 cm(3) and the median PDW was 3.9 mm. In a univariate analysis a large calculated volume of the pancreatic remnant increased the subsequent risk of PF (odds ratio [OR], 3.71; 95% confidence interval [95% CI], 1.58-8.71; P < 0.01), as did a small duct width (OR, 8.46; 95% CI, 3.11-23.04; P < 0.01). According to the multivariate analysis, the size of the pancreatic remnant and the width of the pancreatic duct maintained their impact on leakage risk. CONCLUSIONS: A large pancreatic volume and small pancreatic duct increase the risk of PF. Preoperative CT and/or MRI therefore are useful in predicting fistula formation before pancreaticoduodenectomy.

Liver vessel enhancement by Gd-BOPTA and Gd-EOB-DTPA: a comparison in healthy volunteers.

BACKGROUND: A thorough understanding of magnetic resonance (MR) contrast media dynamics makes it possible to choose the optimal contrast media for each investigation. Differences in visualizing hepatobiliary function between Gd-BOPTA and Gd-EOB-DTPA have previously been demonstrated, but less has been published regarding differences in liver vessel visualization. PURPOSE: To compare the liver vessel and liver parenchymal enhancement dynamics of Gd-BOPTA (MultiHance) and Gd-EOB-DTPA (Primovist). MATERIAL AND METHODS: The signal intensity of the liver parenchyma, the common hepatic artery, the middle hepatic vein, and a segmental branch of the right portal vein was obtained in 10 healthy volunteers before contrast media administration, during arterial and portal venous phases, and 10, 20, 30, 40, and 130 min after intravenous contrast medium injection, but, due to scanner limitations, not during the hepatic venous phase. The doses of contrast media were 0.1 mmol/kg for Gd-BOPTA and 0.025 mmol/kg for Gd-EOB-DTPA. RESULTS: Maximum enhancement of liver parenchyma was observed from the portal venous phase until 130 min after Gd-BOPTA administration and from 10 min to 40 min after Gd-EOB-DTPA. There was no difference in maximum enhancement of liver parenchyma between the two contrast media. When using Gd-BOPTA, the vascular contrast enhancement was still apparent 40 min after injection, but had vanished 10 min after Gd-EOB-DTPA injection. The maximum difference in signal intensity between the vessels and the liver parenchyma was significantly greater with Gd-BOPTA than with Gd-EOB-DTPA (P<0.0001). CONCLUSION: At the dosage used in this study, Gd-BOPTA yields higher maximum enhancement of the hepatic artery, portal vein, and middle hepatic vein during the arterial and the portal venous phase and during the delayed phases than Gd-EOB-DTPA does, whereas there is no difference in liver parenchymal enhancement between the two contrast agents.

Detection of cholangiocarcinoma with magnetic resonance spectroscopy of bile in patients with and without primary sclerosing cholangitis.

BACKGROUND: Early detection of cholangiocarcinoma (CC) is very difficult, especially in patients with primary sclerosing cholangitis (PSC) who are at increased risk of developing CC. PURPOSE: To evaluate 1H magnetic resonance spectroscopy ((1)H-MRS) of bile as a diagnostic marker for CC in patients with and without PSC. MATERIAL AND METHODS: The institutional review board approved the study, and all patients gave informed consent. Bile from 49 patients was sampled and investigated using 1H-MRS. MR spectra of bile samples from 45 patients (18 female; age range 22-87 years, mean age 57 years) were analyzed both conventionally and using computerized multivariate analysis. Sixteen of the patients had CC, 18 had PSC, and 11 had other benign findings. RESULTS: The spectra of bile from CC patients differed from the benign group in the levels of phosphatidylcholine, bile acids, lipid, and cholesterol. It was possible to distinguish CC from benign conditions in all patients with malignancy. Two benign non-PSC patients were misclassified as malignant. The sensitivity, specificity, and accuracy were 88.9%, 87.1%, and 87.8%, respectively. CONCLUSION: With 1H-MRS of bile, cholangiocarcinoma could be discriminated from benign biliary conditions with or without PSC.

Contrast-enhanced magnetic resonance cholangiography with Gd-BOPTA and Gd-EOB-DTPA in healthy subjects.

PURPOSE: To evaluate the biliary enhancement dynamics of the two gadolinium chelates Gd-BOPTA (MultiHance) and Gd-EOB-DTPA (Primovist) in normal healthy subjects. MATERIAL AND METHODS: Ten healthy volunteers were evaluated with both agents by magnetic resonance (MR) imaging at 1.5T using a breath-hold gradient-echo T1-weighted VIBE sequence. The relative signal intensity (SI) differences between the common hepatic duct (CHD) and liver parenchyma were measured before and 10, 20, 30, 40, 130, 240, and 300 min after contrast medium injection. RESULTS: Biliary enhancement was obvious 10 min post-injection for Gd-EOB-DTPA and was noted at 20 min for Gd-BOPTA. At 40 min delay, Gd-BOPTA reached its peak biliary enhancement, but at neither 30 nor 40 min delay was there any significant difference compared with that of Gd-EOB-DTPA. At later delays, the contrast between CHD and liver continued to increase for Gd-EOB-DTPA, whereas it decreased for Gd-BOPTA. CONCLUSION: The earlier onset and longer duration of a high contrast between CHD and liver for Gd-EOB-DTPA facilitates examination of hepatobiliary excretion. Therefore, Gd-EOB-DTPA may provide adequate hepatobiliary imaging within a shorter time span than Gd-BOPTA and facilitate scheduling at the MR unit. Further studies in patients are required to compare the imaging advantages of Gd-EOB-DTPA and Gd-BOPTA in clinical practice.

Low-intensity conditioning and hematopoietic stem cell transplantation in patients with renal and colon carcinoma.

We have evaluated whether allogeneic hematopoietic stem cell transplantation (HSCT) could induce an antitumor effect in patients with metastatic solid tumors. A total of 12 HLA-identical siblings and 6 HLA-A-, -B- and -DR beta 1-compatible unrelated grafts were used. Diagnoses were adenocarcinoma of kidney (n=10), colon (n=6), breast (n=1) and cholangiocarcinoma (n=1). Conditioning was fludarabine 30 mg/m(2)/day for 3 days and 2 Gy of total body irradiation. Recipients of unrelated HSCT were also given thymoglobuline and two additional days of fludarabine. The median CD34+ cell dose was 7.5 x 10(6)/kg. Immunosuppression was mycophenolate mofetil and cyclosporin. Among all, 12 patients became complete donor chimeras within a median of 28, 29 and 65 days for B, myeloid and T cells, respectively. Two patients rejected the grafts, one developed marrow aplasia and three were mixed chimeras. The probability of grades II-IV acute graft-versus-host-disease (GVHD) was 57%. Regression of all tumor metastases was seen in one patient with colon carcinoma. Another patient with colon and two with renal carcinoma had regression of lung metastases, but progression of metastases in the liver and/or bone. Necrosis of lung metastasis was found in one further patient with renal carcinoma who died of graft-versus-host-disease (GVHD). In all, 10 patients died; four of transplant-related complications, one of trauma and five of progressive disease. Thus, progression was common after allogeneic HSCT in unselected patients with advanced solid tumors. However, the regression of some metastases associated with GVHD provides suggestive evidence that the GVHD effect may occur in renal and colon adenocarcinoma using reduced intensity conditioning.

Cystic tumors of the pancreas.

The discovery of a cystic lesion in the pancreas implies a challenge for the physician. Approximately 10% are cystic tumors, benign to highly malignant, or true cysts, showing all stages of cellular differentiation, from benign to highly malignant tumors. Malignant cystic tumors are rare and comprise only about 1% of all pancreatic malignancies, they are potentially curable. Therefore, correct diagnosis and treatment of these lesions are of great importance. It is usually not possible to separate a pseudocyst from a benign cyst or a cystic tumor, but there are some signs and findings that could be helpful in the clinical decision. The diagnosis of a cystic pancreatic tumor requires different imaging techniques, including ultrasonography, computerized tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography, but to distinguish a pseudocyst or a benign cyst from a potentially malignant lesion can be very difficult. The usefulness of blood tests and investigations of cyst fluid can be questionable. Today, surgical treatment of cystic pancreatic tumors can be performed with low morbidity. Therefore, we conclude that an active strategy with resection of cystic tumors of the pancreas should be recommended.

A graft-versus-colonic cancer effect of allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (ASCT) has proved to have an important immune-mediated anti-tumour effect in patients with haematologic malignancies. There is also evidence of such an effect in patients with malignant tumours. We studied this effect of ASCT in a patient with colorectal cancer. A 77-year-old man having a primarily resected colonic cancer with disseminated lymph node involvement received ASCT from his HLA-identical sibling as the only treatment. Mixed haematopoietic chimerism was monitored using PCR-amplification of variable number tandem repeats and tumour size, assessed by repeated CT scans. Recipient leucocytes were gradually replaced by donor cells for 1 month. Continuous resolution of lymph node metastases was seen together with clinical graft-versus-host disease (GVHD). The patient died of pneumonia and cardiac insufficiency 4 months after transplantation. At autopsy, most of the metastases were necrotic, with few remaining tumour cells. Clinical and histopathological postmortem results showed a graft-versus-colorectal cancer effect.

Decalcification by perfusion. A new method for rapid softening of temporal bones.

We describe a new technique, decalcification by perfusion, for the softening of bony tissue. The blood circulatory system was perfused in 16 rats via a cannula through the left heart ventricle with a fixative followed by New Decalc (an acidic demineralizer) for 30-240 minutes. Perfusion decalcification for 120 minutes softened all heads and middle ear specimens could be easily sampled and prepared for studies by both light and electron microscope. For comparison, a conventional immersion technique required 72 hours of decalcification to accomplish softening. The perfusion technique considerably reduced the time needed to decalcify the tissue and preserved the morphology better than did the immersion procedure.

Hyaluronan applied to the middle ear mucosa prior to fixation improves the morphological quality.

In a previous study, it was noted that immersion-fixed middle ear mucosa appeared better preserved if treated with hyaluronan (hyaluronic acid, HA) prior to fixation. The present study showed that HA instilled into the middle ear caused the epithelial cells to emerge more brilliant--when stained with toluidine blue--but did not hinder minor autolytic changes from occurring. The precise molecular or biochemical event or events that cause the brilliance are not known at present. HA did not cause any severe structural alterations of the mucosa.

Middle ear mucosa in rats and humans.

The purposes of the study were to review thoroughly the literature and summarize it in a standardized fashion; to study the mucosa, including the distribution of mast cells, in all parts of the middle ear cavity in rats; and to compare the experimental findings with those known in humans. Adult, healthy rats were studied by light, scanning electron, and transmission electron microscopic techniques. The ciliated and secretory cells of the rat tympanic cavity are confined to two tracts, one anterior and one inferoposterior to the promontory. The tracts connect the epitympanum with the eustachian tube. The pars flaccida exhibits the highest density of mast cells, but mast cells are also distributed in the subepithelial layer of the tracts and in the floor of the tympanic bulla. The structure of the rat mucosa shows striking similarities to that of humans. Thus, from a morphological point of view, the rat seems to be a suitable model for middle ear studies. However, to be able to compare results obtained in different species and/or different laboratories, the areas of the middle ear from which the specimens have been taken must be carefully defined and presented in a standardized manner.

The vascular supply of the rat tympanic membrane.

The vascular supply of the rat tympanic membrane (TM) was studied by means of otomicroscopy, angiography, acrylic casts, and light microscopy. The branches of the external carotid artery in the external auditory meatus were found to vascularize 1) the pars flaccida, 2) the manubrial part of the pars tensa, and 3) the junction between the fibrocartilaginous ring of the TM and the tympanic sulcus of the temporal bone. The TM vessels of areas 1 and 2 were found beneath the squamous epithelium, close to mast cells and nerve bundles. Vessels originating from the tympanic cavity (also probably emanating from the external carotid artery) supplied the periphery of the pars tensa with minute branches, localized immediately beneath the tympanal epithelium. The portion of the pars tensa between the manubrial part and the periphery lacked a vascular system. Upon mechanical stimulation (gentle pressure on the handle of the malleus), the normally visible vessels dilated and minute branches appeared. This dilation may be caused, at least partly, by a release of vasoactive substances from mast cells and/or nerves in its vicinity. Even under mechanical stimulation, a large portion of the pars tensa seemed to be devoid of vessels. The nutrition of this part may be served by diffusion, with nutrients originating from the vessels in the tympanal rim and along the handle of the malleus. The architecture of the attachment of the fibrocartilaginous ring to the bony sulcus of the temporal bone is quite unique. Thus, the flow in the dense vascular network between these structures may be affected by an altered tension in the pars tensa.

Mast cells and middle ear effusion.

The mast cell--an important component of connective tissue--carries in its cytoplasmic granules various biologically active substances, such as heparin, histamine, and a broad spectrum of enzymes. This cell type plays a prominent role in inflammatory and allergic conditions. In the middle ear, the mast cells are mainly localized in the pars flaccida of the tympanic membrane and beneath the tracts of secretory and ciliated cells in the middle ear mucosa. Degranulation of the mast cells by the histamine liberator compound 48/80 causes histamine-rich effusion material to accumulate in the middle ear. Plugging of the eustachian tube and/or tympanic isthmus will bring about a similar accumulation. It would thus seem that mast cells in some way participate in the production of middle ear effusion, probably via their potent mediators.

Pharmacological characterization of receptors on blood vessels in the tympanic membrane involved in otitis media.

Acetylcholine dropped onto the meatal surface of the tympanic membrane evoked vasodilatation and a vascular leakage to the middle ear cavity. The vasoreactions were atropine-resistant. Substance P and vasoactive intestinal polypeptide (VIP) injected intravenously caused a marked vascular leakage and VIP also vasodilatation. These blood vessel changes seem to be regulated by the parasympathetic nerves as they were inhibited by vagotomy. Constriction of the tympanic membrane vessels was mediated through alpha-receptors.

The anatomy of the Eustachian tube.

Most important for opening/closure mechanisms of the Eustachian tube (ET) in rat is probably the mucosal part with its nasopharyngeal orifice, which consists of two lips of soft tissue. From this part of the tube the tensor veli palatini, the levator veli palatini and the salpingopharyngeus muscles originate. The macro- and microanatomy of the rat ET seems to correspond well with that described for man. Hence the rat seems to be an adequate model for continuing experimental studies on the ET.

Fatal accidental hypothermia and alcohol.

A series of 51 fatal cases of accidental hypothermia in northern Sweden has been reviewed. The cases conform well to previous investigations with respect to the mean age of the victims (48 years) and a predominance of males. The cases occurred mainly during the winter months and on Saturdays. Most cases succumbed at temperatures below -10 degrees C. The most frequent necropsy findings were areas of frostbite with purple discoloration of the skin, reddish lividity and superficial erosions of the gastric mucosa. Paradoxical undressing was present in more than half of the cases. About two thirds of the cases were under the influence of alcohol with a mean blood alcohol concentration of 1.6 g/l. Furthermore, at least half of the cases could be considered habitual drunkards. In conclusion, the present series shows two main groups of fatal hypothermia victims: one group of elderly persons, mostly chronic abusers and under the influence of alcohol (approximately two-thirds of the series), and another of younger and sober persons, performing recognised sporting activities (approximately one-fourth of the series).

The anatomy of the eustachian tube in the rat: a macro- and microscopical study.

The rat eustachian tube (ET), from the nasopharyngeal orifice to the tympanal orifice, is about 4.5 mm long, of which the naso-medial membranous part (the nasopharyngeal orifice) measures about 1.5 mm and the occipito-lateral bony portion about 3 mm. The nasopharyngeal orifice is surrounded by two soft, lip-like, mucosal swellings--one ventral and one cranial--both easily mobile. The muscles related to the tubal opening mechanisms are the salpingopharyngeus, the tensor veli palatini and the levator veli palatini muscles. The salpingopharyngeus muscle originates partly from the cranial lip, whereas the palatal muscles originate partly from the ventral lip. The tympanal two thirds of the mucosal lining of the ET is cranially guided by a cartilage and incompletely framed by bony structures. The tympanal orifice is situated in the nasal part of the medial wall, well above the floor of the bulla. The tensor tympani muscle does not seem to take part in the opening and closing mechanisms of the ET. The mucosal lining of the ET consists of a respiratory epithelium with numerous glands in the lamina propria. It is suggested that the tubal muscles control the passage through the ET by moving the lip-like folds of the nasopharyngeal orifice. The anatomy of the rat ET is comparable to that described in Homo and it can be concluded that the rat ET might be a good model for studying the function of the human ET.

The stapedial artery in the rat. A microscopical study under normal conditions and in otitis media with effusion.

Arteria stapedialis in the rat was studied in healthy rats and in experimental otitis media with effusion (OME). The mean diameters of the vessel was calculated to approximately 460 microns (healthy) and 430 microns (otitic) (no significant difference). The tunica intima consisted of an endothelium and a well-developed elastica interna. The tunica media was composed of 2-3 layers of smooth muscle cells. The adventitia was thicker than the media and consisted of bundles of collagen fibers. The artery in the middle ear cavity was quite naked covered only with the middle ear mucosa. The stapedial artery did not appear to be involved in the production of effusion in experimentally induced OME.

Clearance of effusion material from the attic space--an experimental study in the rat.

Rat serum with Evan's blue added as a tracer was instilled into the attic through a pars flaccida perforation in rats. At intervals the drainage of the effusion-like material was observed through a hole in the tympanic bulla. The distribution of ciliary cells was studied in the middle ear using light microscopic and scanning electronmicroscopic techniques. It was noted that the effusion material was propelled from the attic to the inlet of the Eustachian tube mainly by hydrostatic forces. It is also concluded that this mechanism might apply in Homo sapiens and that the drainage position of the head may be of importance in preventing and treating otitis media with effusion (OME).