Diagnosis and Treatment of Autoimmune Pancreatitis Types 1And 2

Original article

Diagnosis and treatment of autoimmune pancreatitis types 1and2

S. Fritz1, F. Bergmann2, L. Grenacher3,M.Sgroi1, U. Hinz1,T.Hackert1, M. W. Büchler1 and J. Werner4

Departments of 1General, Visceral and Transplantation Surgery, 2Pathology and 3Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, and 4Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilians University of Munich, Munich, Germany Correspondence to: Dr S. Fritz, Division of Pancreatic Surgery, Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany (e-mail: [email protected])

Background: Autoimmune pancreatitis (AIP) is characterized by diffuse or focal swelling of the pancreas. AIP has been divided into types 1 and 2. The aim of the study was to evaluate and compare the clinicopathological characteristics, therapy and outcome of patients with AIP. Methods: The medical records of patients diagnosed with AIP between January 2003 and July 2011 were reviewed. Characteristics of patients with AIP types 1 and 2 were compared with those of patients with pancreatic ductal adenocarcinoma (PDAC). Results: AIP was classified as type 1 in 40 patients and type 2 in 32 according to the HISORt (Histology, Imaging, Serology, Other organ involvement, Response to therapy) criteria. Patients with histologically confirmed AIP type 2 were younger than those with type1(P = 0⋅005). Some 30 of 32 patients with AIP type 2 were found to have a localized tumour-like pancreatic mass and underwent pancreatectomy, compared with only 16 of 40 with type 1 (P < 0⋅001). Three of 25 patients with AIP type 2 presented with raised serum levels of IgG4 compared with 21 of 38 with type 1 (P < 0⋅001). There was no difference in symptoms and involvement of other organs between AIP types 1 and 2. Presentation with weight loss was more common among patients with PDAC than those with AIP, but there was no difference in pain or jaundice between the groups. Raised serum carbohydrate antigen 19-9 levels were more prevalent in patients with PDAC. Conclusion: Patients with AIP type 2 frequently present with abdominal pain and a tumour-like mass. Differentiating AIP from PDAC is difficult, so making the clinical decision regarding operative versus conservative management is challenging.

Paper accepted 24 April 2014 Published online 22 July 2014 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9574

Introduction During the international AIP consensus meeting in 20099, the need to differentiate between two subtypes During the past decade, recognition of autoimmune pan- of AIP was outlined10–13. AIP types 1 and 2 differ with creatitis (AIP) as a distinct clinical entity has increased , regard to treatment response and relapse rate. Type 1 worldwide1 2. AIP accounts for approximately 5 per cent fits the classical criteria of AIP and is associated with of all patients with chronic pancreatitis3. The aetiology and pathogenesis remain poorly understood4.Patients a histological pattern of lymphoplasmacytic sclerosing 1,14 –16 with AIP frequently present with diffuse or focal swelling pancreatitis . Affected patients usually present with of the pancreas with or without jaundice owing to extra- abdominal pain, weight loss, anorexia and jaundice. There hepatic cholestasis5. Even with use of modern thin-slice is frequently diffuse swelling of the pancreas, often associ- 17 abdominal imaging the differential diagnosis between ated with an irregular narrowing of the pancreatic duct . AIP and a malignant pancreaticobiliary tumour remains Some 75 per cent of patients with AIP type 1 present with challenging6,7. Consequently, affected patients are fre- raised serum levels of IgG418. AIP type 1 is frequently , , quently referred for surgery and undergo pancreatic associated with other autoimmune-related diseases6 19 20. resection to exclude definitely the risk of harbouring a AIP type 2 is characterized by a so-called idiopathic malignant pancreatic tumour8. duct-centric pancreatitis and pathognomonic ‘granulocyte

epithelial lesion (GEL)-positive pancreatitis’21,22. First described by Ectors and colleagues23, GELs are characterized by focal detachment, disruption and destruction of the epithelium of interlobular ducts24. Although the histo- morphology of AIP type 2 has been described in various reports, little is known about the clinical characteristics and outcome of these patients11. The diagnosis of AIP type 1 can usually be made on clinical grounds, by imaging25 and laboratory tests1,19,26, whereas histological proof is mandatory for the definite diagnosis of AIP type12 2 ,27,28. The aim of the study was to evaluate the clinicopathological characteristics, therapy and outcome of patients with AIP types 1 and 2.

Methods

All patients seen at the Pancreas Centre of the Depart- ment of Surgery, University of Heidelberg, who fulfilled Fig. 1 Typical sausage-shaped pancreas of a 51-year-old man with the HISORt (Histology, Imaging, Serology, Other organ autoimmune pancreatitis type 1. Multidetector computed involvement, Response to therapy) criteria29 for AIP tomography in the portal-venous phase shows diffuse swelling of between January 2003 and July 2011 were eligible for the entire pancreas (arrows) the study. Following the HISORt classification system, AIP was diagnosed when patients met at least one of This study and the questionnaire used were approved by the following criteria: histologically confirmed diagnosis the local ethics committee of the University of Heidelberg. of AIP following surgical resection or biopsy (HISORt diagnostic criteria group A); typical radiological features Imaging studies (such as diffusely enlarged sausage-shaped gland with All patients underwent either multidetector computed irregular narrowing of the main pancreatic duct) and tomography (MDCT), magnetic resonance imaging associated serological changes (HISORt diagnostic criteria (MRI) and/or magnetic resonance cholangiopancreato- group B); and typical radiological features of AIP and an graphy (MRCP). Endoscopic retrograde pancreatogra- imaging-confirmed response to steroid therapy (HISORt phy and endoscopic ultrasonography were considered diagnostic criteria group C). Patients with AIP type 2 were for evaluation of pancreatic morphology when avail- diagnosed exclusively based on histology. If histology was able. Radiological features characteristic of AIP included not available, but the patient met the HISORt criteria, the diffusely enlarged pancreas with loss of normal lob- patient was assigned to the AIP type 1 cohort19. ularity (sausage-like appearance) (Fig. 1), delayed and Patients with known risk factors for chronic pancreatitis, low-density ‘rim’ enhancement, and a dilated main pan- such as alcohol consumption exceeding 60 g/day, pancreas creatic duct together with focal or diffuse narrowing25. divisum, history of necrotizing pancreatitis or abdominal ‘Tumour-like lesion’ was used to describe a focal trauma, were excluded from the study. mass-forming lesion resembling a pancreatic malig- A standard record form, including details of age and sex, nancy (Fig. 2). Thin-slice imaging was also used to symptoms, other organ involvement, abdominal imaging, exclude potential metastatic disease and to assess whether blood tests, treatment and quality of life, was filled out there were abdominal extrapancreatic autoimmune-related by the physician at each visit. Any specific information lesions. relevant to the study (recurrent disease, surgical procedures, complications) were documented. Evaluation of Blood tests the patients’ medical history focused on pancreaticobiliary diseases, previous pancreatic surgery, autoimmune-related Serum concentrations of IgG and IgG4 were determined diseases including sclerosing cholangitis, sclerosing at the time of diagnosis by automated immunonephelo- sialoadenitis, involvement of lacrimal glands or kidneys, metry. In all patients who underwent primary surgery for retroperitoneal fibrosis, and allergic manifestations such as suspected pancreatic cancer, IgG levels were determined allergic rhinitis, atopic dermatitis or bronchial asthma30. as soon as the final histological diagnosis of AIP was

Histopathology Haematoxylin and eosin staining, and immunohisto- chemistry for IgG4-positive plasma cells was carried out routinely in all resected specimens and biopsies. Diagnos- tic criteria for AIP included periductal lymphoplasmocytic infiltrate, periductal concentric fibrosis (Fig. 3a)and detection of vasculitis (Fig. 3c)13. AIP type 2 was diagnosed when an idiopathic duct-centric pancreatitis with typical GELs was present (Fig. 3b) in combination with absent or rare IgG4-positive plasma cells (10 or fewer per high-power field (HPF)). AIP type 1 was characterized by lymphoplasmacytic sclerosing pancreatitis including dense fibrosis with rich lymphoplasmacytic infiltration (‘storiform fibrosis’), and obliterative phlebitisFig. ( 3c). In addition, numerous IgG4-positive plasma cells (more a Axial plane than 10/HPF) were identified in AIP typeFig. 1( 3d)27. Histopathological diagnoses were made in accordance with the 2011 international consensus diagnostic criteria for autoimmune pancreatitis28.

Follow-up All patients, whether managed conservatively or by surgery, were seen in the outpatient clinic after 3 months. There- after the interval for future visits was determined on an individual basis depending on clinical symptoms or other complaints. The date of last follow-up was July 2011. Follow-up data were obtained in the outpatient clinic or b Coronal view from the patient’s last visit to the general physician. Eval- uation included the current status of the disease, as well as Fig. 2 Multidetector computed tomography with intravenous the occurrence or relapse of pancreatic or extrapancreatic contrast showing tumorous lesion in the pancreatic head of a manifestations. patient with autoimmune pancreatitis type 2: a axial plane (note endoprosthesis in distal part of bile duct) and b coronal view Comparison of autoimmune pancreatitis available. Levels of IgG of at least 16⋅0 g/l, and IgG4 of with pancreatic ductal adenocarcinoma 140 g/l or more, were considered raised31. The following autoantibodies were used as markers for autoimmune All patients with AIP type 1 or 2 who presented with a local- disease; levels were considered to be raised when values ized lesion suspicious for malignancy were matched with were above the upper limit of normal (in parentheses): controls with pancreatic ductal adenocarcinoma (PDAC). antinuclear antibody (ANA; more than 1 : 80), rheumatoid The following parameters were used to match one patient factor (RF; over 25 units/ml), antineutrophil cytoplas- with AIP (case) with two patients with PDAC (controls): mic antibodies (ANCA; more than 1 : 10), male germ age (± 5 years), sex and site of disease. All controls were cell-associated kinase antibody (MAK; over 60 units/ml), identified from the institutional database of pancreatic thyroid-stimulating hormone receptor antibodies (TRAK; cancer. over 1⋅00 units/ml), lactoferrin antibody (antibody ratio less than 10), carbonic anhydrase 1 antibodies (positive), Statistical analysis carbonic anhydrase 2 antibodies (positive), extractable nuclear antigens (ENA; more than 6⋅3 units/l) and soluble The records of all patients diagnosed with AIP were interleukin 2 receptor (sCD25; over 900 units/ml). ANA, entered into a database. Continuous data are presented ANCA, MAK, TRAK, ENA, RF and sCD25 levels were as median (range), unless indicated otherwise. The dis- determined using enzyme-linked immunosorbent assays. tribution of age was compared between groups using the

a Periductal fibrosis and infiltrates b Granulocytic intraepithelial lesions

c Venulitis d IgG4-positive plasma cells

Fig. 3 Histological features of autoimmune pancreatitis: a periductal concentric fibrosis (arrow) and periductal infiltrates of lymphocytes and plasma cells (dotted arrow) (haematoxylin and eosin stain, original magnification ×18); b granulocytic intraepithelial lesions (arrow) in type 2 autoimmune pancreatitis (haematoxylin and eosin stain, original magnification ×72); c venulitis (arrow) (haematoxylin and eosin stain, original magnification ×72); d increased number of immunohistochemically IgG4-positive plasma cells (stained red) in autoimmune pancreatitis type 1 (methylene blue counterstain, original magnification ×72)

Mann–Whitney U test. Fisher’s exact test was used for biopsy for preoperative diagnosis. A total of 47 patients analysis of categorical variables. All tests were two-sided had a pancreatic resection. AIP type 1 was diagnosed and statistical significance was assumed at the 5 per cent in 40 patients, and in 25 the diagnosis was established level. Statistical evaluation was performed using the SAS® by clinical presentation, imaging and serology (HISORt version 9.1 for Windows® (SAS Institute, Cary, North diagnostic criteria group B and C) (Fig. 1). In 15 patients, Carolina, USA). histopathological examination of the resection specimen was performed (HISORt diagnostic criteria group A). Results There were 32 patients with AIP type 2, all diagnosed after pancreatectomy. Some 72 patients (52 men, 20 women) with AIP were Characteristics of the patients with AIP types 1 and 2 are included in the study. None of the patients underwent core summarized in Ta b l e 1 . Patients presented with abdominal

Table 1 Characteristics of patients with autoimmune pancreatitis Table 2 Indications for surgery, procedures and outcomes types 1 and 2 AIP type 1 AIP type 2 AIPtype1 AIPtype2 (n = 40) (n = 32) (n = 40) (n = 32) P‡ Indication for surgical treatment Age (years)* 52 (18–74) 44⋅5 (20–75) 0⋅267§ Pancreatic resection to exclude malignancy 924 Sex ratio (M : F) 29 : 11 23 : 9 > 0⋅999 (tumour-like mass) Clinical presentation Pain following conservative management of 23 Abdominal pain 32 25 > 0⋅999 pancreatitis Jaundice 13 12 0⋅804 Unsuccessful steroid therapy 0 1 Diarrhoea/steatorrhoea 14 8 0⋅444 Pancreatic duct stenosis* 0 2 Acute or recurrent acute 20 12 0⋅344 Cystic pancreatic lesion suspicious for IPMN 1 1 pancreatitis Total pancreatectomy for suspected total 01 Weight loss 9 7 > 0⋅999 gland disease Site of disease Cholestasis suspicious for malignant 30 obstructive process Head/body 12 27 < 0⋅001 Operative procedure Tail 1 4 0⋅164 Pancreaticoduodenectomy 11 23 Entire gland 27 1 < 0⋅001 Duodenum-preserving pancreatic head 24 Imaging resection Diffuse pancreatic swelling 26 1 < 0⋅001 Total pancreatectomy 1 1 Tumour-like pancreatic mass 16 30 < 0⋅001 Distal pancreatectomy 1 4 (suspicious for malignancy) Outcomes Serology Death 0 0 Raised IgG (≥16 g/l) 8 of 38 2 of 24 0⋅048 Mean hospital stay (days) 9⋅510 Raised IgG4 (≥140 g/l) 21 of 38 3 of 25 < 0⋅001 Reoperation (postop. bleeding) 0 1 Raised ANA 12 of 38 8 of 25 0⋅792 Delayed gastric emptying 3 4 Other raised autoimmune 20 of 38 10 of 25 0⋅150 antibodies Pancreatic fistula 0 1 Autoimmune-related diseases 13 9 0⋅799 Lymphatic fistula 0 1 Psoriasis 0 2 0⋅194 Cholangitis 0 1 Rheumatism 5 1 0⋅217 Intra-abdominal abscess 1 0 Autoimmune gastritis 3 2 > 0⋅999 Surgical-site infection 1 0 Hashimoto’s thyroiditis 1 2 0⋅581 Pneumonia 0 1 Hepatitis, SLE 2 2 > 0⋅999 Urinary tract infection 1 0 Sjögren’s syndrome 3 1 0⋅624 *Pancreatic resection for pancreatic duct stenosis following previous ⋅ Inflammatory bowel disease 02 194 pancreatic surgery (duodenum-preserving pancreatic head resection and Initial therapy† left pancreatic resection). AIP, autoimmune pancreatitis; IPMN, < ⋅ Pancreatic resection 13 31 0 001 intraductal papillary mucinous neoplasm. Corticosteroids 16 1 < 0⋅001 Best supportive care 11 0 < 0⋅001 laboratory and imaging data were comparable between *Values are median (range). †First 2 weeks after diagnosis. AIP, autoimmune pancreatitis; ANA, antinuclear antibody; SLE, systemic types 1 and 2. lupus erythematosus. ‡Fisher’s exact test, except §Mann–Whitney U test. Treatment of autoimmune pancreatitis pain and a medical history of acute or recurrent acute Most patients with AIP type 1 were treated conservatively pancreatitis. One-third were jaundiced and nine of the 32 in the first 3 weeks after diagnosis with corticosteroids or patients with AIP type 2 had associated autoimmune dis- best supportive care, whereas the majority with AIP type eases. Patients with AIP type 2 were younger than patients 2 underwent surgical resection (Ta b l e 1 ). Fifteen of the 40 with type 1 (P = 0⋅267), and more often showed a local- patients with AIP type 1 eventually underwent pancrea- ized pancreatic mass on imaging (30 of 32 versus 16 of 40; tectomy. The indications for surgical treatment, type of P < 0⋅001). Patients with AIP type 2 had a lower preva- operation and outcome within 28 days are summarized in lence of raised serum levels of IgG (2 of 24 versus 8 of 38; Ta b l e 2 . P = 0⋅048) and IgG4 (3 of 25 versus 21 of 38; P < 0⋅001). Comparing only histologically confirmed AIP type 1 (15 Clinical course after surgery for autoimmune patients) with type 2 (32 patients), a higher proportion of pancreatitis patients with AIP type 1 had raised levels of IgG4 (8 of 13 versus 3 of 25; P = 0⋅002). Patients with AIP type 2 were Follow-up was available for at least 6 months after surgery significantly youngerP ( = 0⋅005), but all other clinical, for all but one patient with AIP type 2. After operation, all

Table 3 Comparison between autoimmune pancreatitis and pancreatic ductal adenocarcinoma for each subtype of autoimmune pancreatitis

AIP type 1 PDAC AIP type 2 PDAC (n = 16) (n = 32) P (n = 30) (n = 60) P†

Age (years)* 63 (24–71) 64 (39–71) 0⋅956 45 (16–79) 46 (33–79) 0⋅327‡ Sex ratio (M : F) 16 : 0 32 : 0 – 21 : 9 42 : 18 1⋅000 Site of disease 1⋅000 1⋅000 Head/body 14 (88) 28 (88) 27 (90) 54 (90) Tail 2 (12) 4 (12) 3 (10) 6 (10) Pain 10 (63) 15 (47) 0⋅369 23 (77) 40 (67) 0⋅465 Jaundice 11 (69) 21 (66) 1⋅000 13 (43) 37 (62) 0⋅114 Weight loss 4 (25) 24 (75) 0⋅002 6 (20) 40 (67) < 0⋅001 Acute pancreatitis 5 (31) 2 (6) 0⋅033 11 (37) 8 (13) 0⋅015 Tumour markers CA19-9 > 37 units/ml 2 (13) 24 (75) < 0⋅001 5 (17) 47 (78) < 0⋅001 CEA > 2⋅5 μg/l 5 of 15 (33) 19 (59) 0⋅125 5 (17) 23 of 59 (39) 0⋅052

Values in parentheses are percentages unless indicated otherwise; *values are median (range). AIP, autoimmune pancreatitis; PDAC, pancreatic ductal adenocarcinoma; CA, carbohydrate antigen; CEA, carcinoembryonic antigen. †Fisher’s exact test, except ‡Mann–Whitney U test. patients with AIP type 2 showed a decrease in abdominal which was successful. Weight loss was more com- pain. Typicaldisease relapse was characterized by recurrent mon among patients with PDAC than those with AIP. episodes of pain and pancreatitis. Six patients with AIP type Raised serum CA19-9 levels were more prevalent among 2 received corticosteroid therapy. Five patients received patients with PDAC. There was no difference in pain or corticosteroids after operation, including four patients with jaundice. recurrent disease. Recurrence developed within a median of 34 (3–50) months. One patient received corticosteroids Discussion 4 weeks after surgery as prophylactic therapy and one before surgery as initial treatment. Although there have been consensus conferences in Asia Among the patients with AIP type 1 who underwent and the USA to establish an exact definition for the diag- pancreatic resection, nine complained of abdominal pain nosis of AIP, no clear characterization and classification before the operation. Four of these patients had raised of the different subtypes is yet available. To determine serum levels of carbohydrate antigen (CA) 19-9 (at least the correct classification for diagnosis of AIP, the Japanese 38 units/ml) and/or carcinoembryonic antigen (5 μg/l or criteria32, HISORt criteria29, consensus Asian criteria26, more) in preoperative investigations. Seven of 15 patients Korean criteria33 and the M-ANNHEIM classification34 had a raised total serum bilirubin level (1⋅5 mg/dl or more). were reviewed. Although all classifications have overlap- After surgical resection, seven of nine patients experi- ping criteria, there are important differences. According to enced relief of pain, two reported unchanged pain intensity the Japanese diagnostic criteria, typical imaging is manda- after surgery, and one experienced new-onset mild abdom- tory for the diagnosis of AIP. In the present study of pre- inal pain. dominantly surgical patients with a histological diagnosis, preoperative imaging was not specific for AIP in many patients. These patients would not have been diagnosed Comparison between autoimmune pancreatitis with AIP using the Japanese criteria. It has been shown and pancreatic ductal adenocarcinoma that the HISORt criteria have the highest sensitivity (92 Ta b l e 3 shows a comparison of patients with AIP and per cent) for the diagnosis of AIP35. These criteria are in matched patients with PDAC. Seven of those with accordance with the 2011 international consensus diagnos- AIP aged between 15 and 32 years were matched with tic criteria for AIP28 and seemed most appropriate for the patients with PDAC up to 20 years older. One 48-year-old present study. man presented with a mass-forming tumour in the tail The most feared scenario is PDAC misdiagnosed as AIP. of the pancreas that was suspected to be a neoplastic Recent advances in MDCT, MRI and/or MRCP imaging tumour, but had features suggestive of AIP. Owing to techniques have led to high-quality image acquisition his relatively young age and preference, he received that has improved the ability confidently to recognize conservative therapy with corticosteroids for 2 weeks, typical features of AIP17. However, it remains a challenge

to differentiate between AIP and pancreatic cancer, was there a difference in extrapancreatic manifestations particularly in patients with AIP type 2 who present with a between AIP types 1 and 2. Therefore, this study cannot suspected malignant lesion. In these patients, late enhance- confirm the widely held belief that AIP type 1 is a systemic ment seems to be a key feature and is best detected with IgG4-related disease, whereas type 2 is exclusively confined MRI. With regard to symptoms, patients with PDAC more to the pancreas20. frequently presented with weight loss than those with AIP Beside IgG4 serum levels, there seems to be a differ- in the present study. However, no weight loss occurs in ence between AIP types 1 and 2 with regard to mor- one in three patients with pancreatic cancer, particularly in phology and location of the inflammatory mass. In the the earlier stages. Thus, this clinical variable does not seem present study, patients with AIP type 1 more frequently to be helpful in discriminating between PDAC and AIP showed diffuse swelling of the entire pancreas, whereas a in individual patients. Likewise, in patients with a lesion tumour-like mass mimicking pancreatic cancer was found suspicious for AIP and normal serum tumour marker levels in the majority of patients with AIP type 2. Thus, in (particularly CA19-9), PDAC cannot be excluded reliably, contrast to Maire and colleagues40, who reported that because a raised level of CA19-9 is found in only 75 per surgery was performed more often in AIP type 1, the cent of patients with PDAC36. present results indicate that AIP type 1 can more fre- It has been reported that the serum IgG4 level is raised quently be diagnosed without histology and surgical resec- in 94 per cent of patients with AIP37. In the present study, tion, because this type is usually associated with typical only 55 per cent of patients (21 of 38) with AIP type 1 features of AIP according to the Asian or HISORt crite- and 12 per cent (3 of 25) with type 2 had raised IgG4 ria. In contrast, in patients with AIP type 2 the indication levels, in accordance with a recent report38. IgG4 levels for operative versus conservative therapeutic management may be raised in up to 10 per cent of subjects without remains challenging. AIP, which further complicates the differential diagnosis of pancreatic cancer39. Therefore, IgG4 is not a good marker Disclosure with which to identify patients with AIP. Surgical resection is warranted if there is any doubt about the diagnosis and The authors declare no conflict of interest. a tumour-like pancreatic mass is present. Alternatively, corticosteroid therapy can be given for 2 weeks to patients with typical AIP morphology on MRI, followed by further References MRI to evaluate the response to steroids. However, the 1 Finkelberg DL, Sahani D, Deshpande V, Brugge WR. treatment response always must be evaluated critically, and Autoimmune pancreatitis. NEnglJMed2006; 355: it has to be kept in mind that serum IgG4 levels may 2670–2676. ‘improve’ with steroid therapy even though the underlying 2 Pearson RK, Longnecker DS, Chari ST, Smyrk TC, disease is pancreatic cancer6. Okazaki K, Frulloni L et al. Controversies in clinical The present study has confirmed that histology should pancreatology: autoimmune pancreatitis: does it exist? Pancreas 2003; 27: 1–13. be the standard, not only for the diagnosis of AIP, 3 Kim KP, Kim MH, Song MH, Lee SS, Seo DW, Lee SK. but also to differentiate between the two subtypes. In Autoimmune chronic pancreatitis. 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Snapshot quiz

Snapshot quiz 14/13

Question: What does this photograph of the perineum and abdominal CT show?

The answer to the above question is found on p. 1279 of this issue of BJS.

Al-Choule H, IlumL,Sparre P, Olaison G: Department of Surgery, Holbaek Hospital, Smedelundsgade 60, Holbæk 4300, Denmark (e-mail: [email protected])

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