Cystic neoplasms of the pancreas: conservativeor operative treatment? B. Akan, K. Sahora, H. Puhalla, M. Gnant, R. Jakesz, P. Götzinger Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria Received November 17, 2007; accepted after revision July 15, 2008 Zystische Tumore des Pankreas: Konservative oder of diagnosis. 33 (78%) underwent operative treatment, whereas 10 (22%) were treated conservatively. Malignancywas found in nine (27%) operated patients. Seven patients Zusammenfassung. Grundlagen: Die modernen bildge- (78%) with malignant cystic neoplasm and 15 patients benden Verfahren haben zu einem Anstieg der Inzidenz (63%) with a benign cystic neoplasm had symptoms.
der prima¨r zystischen Pankreastumore gefu Median cyst size was 3.5 cm (1.5–12). There was one case die chirurgische Behandlung obligat. Nach Art und Gro¨ße of malignancy within cystic lesion smaller than 3 cm.
des Tumors kann jedoch auch ein konservativer Ansatz Conclusions: Therapy can be tailored depending on size and character of the pancreatic cyst. Surgical treat- Ergebnisse: Von 43 zystischen Neoplasmen wur- Keywords: Pancreas, intraductal papillary mucinous den 11 (33 %) zufa¨llig entdeckt, 22 (77 %) Patienten hatten neoplasm, serous cystic neoplasms, mucinous cystic neo- Symptome zum Zeitpunkt der Diagnose. 33 (78 %) Pat- ienten wurden operativ, 10 (22 %) Patienten jedoch kon-servativ behandelt. Bei neun (27 %) Patienten wurdeMalignita¨t festgestellt. Sieben (78 %) mit malignen und 15 (63 %) mit benignen Pankreastumor hatten Symptome.
Cystic pancreatic neoplasms are diagnosed in 0.7% of Die mediane Zystengro¨ße lag bei 3,5 cm (1,5–12).
patients among 24,000 CT or MRI scans [1] and represent Schlussfolgerungen: Die Therapie kann, nach Gro¨ße less than 10% of pancreatic neoplasms [2]. Non-neoplas- und Charakter der Pankreaszyste, adaptiert werden.
tic, inflammatory cysts found in patients with a history of Die chirurgische Behandlung allein ist nicht mehr die pancreatitis represent the vast majority of cystic lesion of einzige Behandlungsmo¨glichkeit der prima¨r zystischen the pancreas, originate on necrosis and have no malig- ¨sselwo¨rter: Pankreas, IPMN, SCN, MCN, zystische The most common neoplastic type of cyst, the mu- cinous cystic neoplasm (MCN) represented 44–49% [3, 4].
MCNs occur typically in middle-aged women and are usu- Summary. Background: Owing to modern imaging tech- ally located in the body or the tail region. Often the diam- niques, the incidence of primary cystic neoplasms of the eter exceeds 5 cm at the time of diagnosis, containing pancreas is increasing. During the past decades all pan- areas of malignant transformation in 10% of all patients.
creatic cysts were treated operatively. Depending on type Typical cystic architecture is built of large multi-locular and size a more conservative approach can be advocated.
cysts, with extensive mucin production without any com- Method: Review of the literature and presentation of munication to the pancreatic duct. They can be charac- terized benign, borderline or malignant. The prognosis of Results: From 43 patients, 11 (33%) were discovered patients with resected mucinous cystadenocarcinoma is incidentally and 22 (77%) had symptoms at the time slightly better than patients with ductal adenocarcinoma,with 5-year survival of approximately 50% [3–8].
The second most common primary cystic neoplasm Correspondence: Klaus Sahora, M.D., Division of General Surgery, of the pancreas is serous cystadenoma (SCA), represent- Department of Surgery, Medical University of Vienna, Waehringer- ing 30% [3, 4]. SCAs are predominantly located in the guertel 18-20, 1090 Vienna, Austria.
head of the gland and also mostly diagnosed in middle Fax: þþ43-1-40400 5641E-mail: aged women (35 vs. 65%) They are built of multiple smal- 220 5/2008 Cystic neoplasms of the pancreas: conservative or operative treatment? ler cysts of different diameter, presenting a tumorous Medical University of Vienna, Department of Surgery, mass often greater than 7 cm when they are discovered.
were recorded within a database designed for this pur- A typical radiomorphologic finding is a star-like shaped pose. Patient information was anonymized and recorded scar in the center of whole cyst. The cystic fluid does not according to law and IRB regulations. The clinicopatho- contain mucin. They are classified as benign even if there logic findings during hospital stay were analyzed. Follow- are some reports on very rare cases of serous cystad- up of these patients was performed by telephone and=or enocarcinoma [3, 6, 7, 9]. In most cases, symptoms are query of the systematic Statistic Austria Database on depending from size of the cystic neoplasm and lesions patient’s date of death, executed annually by institution, larger than 4 cm tend to cause symptoms [9].
thus providing follow-up data on 100% of patients.
The intraductal papillary mucinous neoplasm Patients who presented only once at time of diagnosis (IPMN) represents 20–25% of all cystic neoplasms. IPMN are not listed in the database. Patient data were collected is more frequently seen in the head of the pancreas and at the outpatient clinic inspection and retrospectively can be of benign, borderline or malignant character [3, 6].
with the assistance of the ‘‘clinical information system’’ Unlike other cystic neoplasms, it occurs more often in of the hospital, providing an archive of all patient-specific men than in women (55 vs. 45%). The pancreatic head reports, leading to completeness of data. Surgery reports, is the area of predominance. The cystic tumor is formed discharge letters, histology reports and chemotherapy by papillary formations rising from the ductal epithelium treatment records were evaluated for every single patient.
and always communicates with the main or branch duct All results of the patients are reported in median (range) of the pancreas. Cystic fluid contains mucin, and is held back because of duct occlusion. IPMNs are potentiallymalignant and are classified like MCN in benign, border-line or malignant. At the time of diagnosis, an invasive carcinoma is found in about 40% of patients. Five-yearsurvival after the resection of malignant IPMN is 45%.
Between 1997 and 2007, 43 patients were diagnosed with Solid and cystic papillary neoplasms also called primary cystic lesions of the pancreas. The mean age was Franz- or Hamoudi-tumors occur primarily in women of 68 years (24–82) and there were 32 (74%) female and 11 all age. They are seen in all regions of the pancreas and (26%) male patients included. Forty seven per cent of consist of solid, cystic and papillary components. Most of cystic neoplasms were discovered incidentally and 53% the patients are cured even after resection, vascular inva- due to symptoms. The radiographic method most com- sion and metastases have been reported.
monly used was CT (n ¼ 29, 67%) and MRI (n ¼ 13, 30%).
Within the majority of patients, cystic neoplasms of The average cyst diameter was 3 cm (0.5–12). Thirty three the pancreas are not symptomatic and are often inciden- out of 43 patients underwent surgical resection at our tal findings [1–3]. The standard diagnostic methods to institution and 10 were treated conservatively.
distinguish between benign and malignant cysts are mul-tislice computed tomography (CT) and magnetic reso-nance images (MRI) [3]. There is no reported difference in the superiority of neither CT nor MRI. MRI tends to be Patient and cyst characteristics are summarized in more sensitive in smaller lesions (<2 cm) and offer the Table 1. The median age of nine male (27%) and 24 fe- opportunity of non-invasive cholangiopancreaticography.
male patients (73%) was 65 years (24–85). Five (15%) Endosonography may offer additional information after patients had a positive family anamnesis of neoplasms, inconclusive CT or MRI scan. There is low evidence on 17 (52%) had history of nicotine abuse and 20 (61%) of the therapy of primary cystic neoplasms because of the alcohol abuse. Six Patients had at least one episode of small number of patients in studies and limited therapy pancreatitis, five (15%) diabetes mellitus and seven options. Today the most common approach in all cystic (21%) suffered from a second neoplasm.
pancreatic lesions is curative resection [1–3, 10, 11]. De- The standard radiographic method was CT (n ¼ 23, pendent on size, symptoms, solid component and septa- 70%). Eighteen out of 23 histopathologic results con- tion, some authors claim that selected patients with cystic firmed the findings of CT prior to surgery (sensitivity lesions <3 cm should be followed radiographically. Al- 50%). Endoscopic retrograde cholangiopancreatography though malignant transformation is possible at low risk, (ERCP) was performed in 11 (33%) with a correct histo- mortality after pancreatic resection exceeds this level, pathologic correlation within four patients, eight (24%) even in high volume centers [10, 11].
patients underwent abdominal ultrasonography with four The aim of this report is to review patients with correlating diagnostic results, nine (27%) patients had cystic neoplasms who underwent operative treatment at MRIs with six correct diagnostic results and performed a single institution, to review literature and to define an endosonography correlated in four (12%) patients.
algorithm in decision making of either conservative oroperative treatment.
Symptomatic vs. asymptomatic patientsin the operative group Eleven patients (33%) were discovered incidentally and 22 During the period 1997 to 2007, all patients diagnosed (77%) had symptoms at the time of diagnosis. The most with primary cystic neoplasms of the pancreas at the common symptom was upper abdominal pain (n ¼ 14, Cystic neoplasms of the pancreas: conservative or operative treatment? Tab. 1: Clinic pathologic features of all patients and comparison of patients with malignant and benigncystic neoplasms of the pancreas in the operated group 42%). Six patients (18%) reported weight loss and four (12%) had cholestasis. Other symptoms were abdominal Thirty-three patients underwent surgical treatment. Thir- pain, diarrhea and emesis. Symptomatic patients had an teen patients (39%) underwent distal pancreatectomy, 8 average age of 66 years and asymptomatic patients of 63 patients (24%) had pylorus-preserving pancreaticoduode- years (Fig. 1). Seven patients (78%) with a malignant cys- nectomy and 6 patients (18%) classical whipple pancrea- tic neoplasm reported symptoms at the time of diagnosis ticoduodenectomy. Histopathologic findings were 12 and 15 patients (63%) died within the group of benign MCNs (37%), 11 IPMNs (33%) and 10 SCAs (30%).
All three types of cystic neoplasms of the pancreas occurred predominantly in women. There was no signifi-cant difference concerning patient’s age. Patients withSCAs reported the largest cyst size with a median of4.2 cm (2–10 cm). Further details of MCNs, SCAs andIPMNs are reported in Table 2.
There was no significant difference between median agesof patients with benign or malignant cystic neoplasms (68[59–83] vs. 67 [24–85] years). Five malignant (56%) and 19benign neoplasms (79%) were detected in women. Biliru-bin, CEA and CA 19-9 were more likely to be higher inpatients with malignant neoplasms. Benign and malig-nant cystic lesions are compared in Table 1.
Fig. 1: Symptoms and character of disease: Seven (78%) patients The median age of two male and eight female patients with malignant cystic neoplasms had symptoms at diagnosis versus15 (63%) of patients with benign cystic neoplasms was 68 years (42–82) (Table 3). Two of 10 patients had 222 5/2008 Cystic neoplasms of the pancreas: conservative or operative treatment? Tab. 2: Comparison between intraductal papillary mucinous neoplasm, mucinous cystic neoplasmand serous cystic neoplasm (operated group) SD Standard deviation; MCN mucinous cystic neoplasms; SCA serous cystadenoma; IPMN intraductal papillary mucinous neoplasm.
Tab. 3: Demographics, cyst characteristics and therapy of 10 patients with conservative treatment symptoms and eight were discovered incidentally. The another patient an intra-abdominal abscess. During fol- standard radiographic method was CT and MRI. An en- low-up seven (21%) patients had a relapse of the cystic doscopic fine needle aspiration was performed in five (50%) patients, with negative cytology. Also two patients All 10 patients who had conservative treatment from 10 had cyst drainage. The median cyst size was 3 cm were alive at the end of the study and did not report any (1.5–12). The median radiographic follow-up time was 4.5 years (1–10). No patient reported a progredience, eightpatients had a constant cyst size and in two the size de-creased. Radiographic characteristics were without a solid component, septation and infiltration.
Owing to modern imaging techniques, the incidence andimpact of primary cystic neoplasms of the pancreas isincreasing. In the past all patients underwent surgical resection on behalf of this uncertain diagnosis leading The 30-day mortality in the operative group was 0%. Five to surgical overtreatment in some of them. Up to now (15%) patients suffered from postoperative complications.
the problem is focused on missing consensus guidelines Two patients developed pancreatic fistula: one patient concerning diagnosis and treatment modalities for had relaparotomy because of secondary hemorrhage, patients suffering from cystic pancreatic lesions. Even one patient developed an anastomotic dehiscence and modern imaging and interventional techniques are able Cystic neoplasms of the pancreas: conservative or operative treatment? Fig. 2: Algorithm of how to manage patients with pancreatic cystic neoplasms. Operation should be performed in symptomatic patients or in caseof insecure diagnosis. Serous cystic neoplasms (SCN) smaller than 4 cm, no symptoms, can be followed conservatively. Intraductal papillarymucinous neoplasms (IPMN) of the main duct and mucinous cystic neoplasms (MCN) should be resected. IPMNs of a branch duct less than 1 cmcan be observed until growth occurs to provide almost secure diagnosis in many patients; intervals. According to the low perioperative mortality in there are still numerous depending on surgical resection centers of pancreatic surgery, they should be resected to to verify the correct pathologic finding. Depending on avoid the potential risk of malignancy, if diagnosis is not cyst size, architecture and symptoms, within a defined 100% clear and the patient is young or in good physical group of patients, the physician is confronted with the condition. Some also claim that cysts greater than 4 cm nearly equal risk of operative mortality and the risk of indicate operation, because the median growth rate of under diagnosed malignancy. The right decision to ob- the neoplasms is significantly greater in larger lesions serve or operate exceptionally depends on the correct (0.12 cm=year for lesions <4 cm versus 1.98 cm=year for diagnosis based on radiological imaging supported by biopsy and cytology [12]. In particular small asymptom- Mucinous cystic neoplasms are of unsecured dignity atic lesions which potentially can be treated conservative and have a high potential of malignancy or malignant are the most difficult to differentiate because of the ab- transformation. Patients should undergo resection after sence of clear pathognomonic findings (Fig. 2).
diagnosis is secured, regardless of cyst size.
Until now the greatest series of 369 conservatively Intraductal papillary mucinous neoplasms are also treated patients is reported by Allen et al. [10]. In this of high potential of malignancy but IPMN involving the study the presence of a solid component was the stron- main duct have a higher risk than the branch duct (64% gest factor leading to surgical resection, followed by cyst vs. 19%) [14]. Therefore, IPMN with main duct disease size, age and symptoms. All non-operative treated should be resected and IPMN with branch duct disease patients had small cysts, mean being 2.4 cm, without a <1–3 cm can be observed, if there is no enlargement of solid component. Twenty nine of them underwent resec- cyst size, symptoms or solid component of the lesion.
tion, due to changes during follow-up. Adenocarcinoma During the diagnostic process, there are cases was found in 8 of these patients, median follow-up was 24 where it is not possible to determine the type of the cystic pancreatic lesion. This makes decision in conser- Similar results are reported by Walsh et al. [13] on vative or operative treatment difficult. Table 4 shows treatment strategy of pancreatic cystic lesions from ac- Serous cystic neoplasms are benign lesions. If diag- tual literature presenting the largest number of cases nosis is clear, cysts do not contain a solid component and the patient is asymptomatic, they may be managed con- Treatment recommendations are differing. There servatively. These cysts can be followed by computer to- are comments that with some selected patients, cyst size mography or magnet resonance tomography at regular smaller than 3 cm without solid component, do not need 224 5/2008 Cystic neoplasms of the pancreas: conservative or operative treatment? Tab. 4: Treatment strategy of pancreatic cysts from different authors Smaller than 3 cm without solid component does not operate Symptoms, size, age are not sufficiently reliable indetermining the malignant potential operate if increasing, symptomatically and in fit elders operate symptomatically SCAs, all MCN, all unclear cystic neoplasms SCA Serous cystadenoma; MCN mucinous cystic neoplasm.
the strict strategy of operating. This group of patients have a low risk of malignancy, which approximate the risk [1] Spinelli KS, Fromwiller TE, Daniel RA, Kiely JM, Nakeeb A, Komorowski RA, Wilson SD, Pitt HA. Cystic pancreatic neo- Other investigators advocate surgical treatment for plasms: observe or operate. Ann Surg 2004;239:651–7; discus- all primary cystic lesions of the pancreas. Characteristics [2] Brugge WR, Lauwers GY, Sahani D, Fernandez-del Castillo C, such as cyst size, age and symptoms are not precise Warshaw AL. Cystic neoplasms of the pancreas. N Engl J Med enough to determine the malignant potential [15]. Malig- nant or premalignant pancreatic cysts were found in 47% [3] Sakorafas GH, Sarr MG. Cystic neoplasms of the pancreas; what of asymptomatic patients. They argue that cyst size smal- a clinician should know. Cancer Treat Rev 2005;31:507–35.
[4] Compagno J, Oertel JE. Mucinous cystic neoplasms of the ler than 2 cm does not predict malignant or benign po- pancreas with overt and latent malignancy (cystadenocarci- tential. Within patients older than 70 years, the indication noma and cystadenoma). A clinicopathologic study of 41 cases.
of surgical treatment is more difficult. There is no rep- [5] Sarr MG, Carpenter HA, Prabhakar LP, Orchard TF, Hughes S, orted higher risk for malignancy, within these patients, van Heerden JA, DiMagno EP. Clinical and pathologic correla- but an increased risk of operation and short life expectan- tion of 84 mucinous cystic neoplasms of the pancreas: can one cy after resection. Therefore a conservative approach may reliably differentiate benign from malignant (or premalignant)neoplasms? Ann Surg 2000;231:205–12.
be acceptable for the elderly patient. Finding the best [6] Kosmahl M, Pauser U, Anlauf M, Sipos B, Peters K, Luttges J, treatment modality for each patient, they also claim that Kloppel G. Cystic pancreas tumors and their classification: correct preoperative diagnosis is achieved only in 22% of features old and new. Pathologe 2005;26:22–30.
[7] Goh BK, Tan YM, Yap WM, Cheow PC, Chow PK, Chung YF, Wong WK, Ooi LL. Pancreatic serous oligocystic adenomas: In the present study, we found similar results. Neither clinicopathologic features and a comparison with serous micro- cyst size nor symptoms predict malignancy. Cyst size of cystic adenomas and mucinous cystic neoplasms. World J Surg malignant neoplasms ranged from 2 to 12 cm in the pres- ¨ gger R. Pancreatic carcinoma. Eur Surg 2006;38:112–17.
ent analysis. Comparable to investigations by Fernandez [9] Tseng JF, Warshaw AL, Sahani DV, Lauwers GY, Rattner DW, et al., we could not find a significant correlation between Fernandez-del Castillo C. Serous cystadenoma of the pancreas: cyst size and malignancy [16]. Two (18%) from 11 with tumor growth rates and recommendations for treatment. Ann incidental found cysts and seven (31%) from 22 symptom- Surg 2005;242:413–9; discussion 419–21.
[10] Allen PJ, D’Angelica M, Gonen M, Jaques DP, Coit DG, atic cysts were malignant neoplasms (p <0.05). Malignan- Jarnagin WR, DeMatteo R, Fong Y, Blumgart LH, Brennan cy was observed only in patients older than 61 years MF. A selective approach to the resection of cystic lesions of compared to patients with benign lesions, who ranged the pancreas: results from 539 consecutive patients. Ann Surg2006;244:572–82.
from 24 to 85 years. Age was, however, not reported as a [11] Allen PJ, Jaques DP, D’Angelica M, Bowne WB, Conlon KC, prognostic factor in larger trials and patients’ number with- Brennan MF. Cystic lesions of the pancreas: selection criteria in this study is too small to make further conclusions.
for operative and nonoperative management in 209 patients.
J Gastrointest Surg 2003;7:970–7.
CT and MRI are the best imaging modalities for [12] Wrba F. Oncological surgery and standards in surgical patholo- detection, characterization and follow-up of cystic neo- plasm [17, 18], but they are not 100% reliable in the [13] Walsh RM, Vogt DP, Henderson JM, Zuccaro G, Vargo J, Dumot diagnosis of pancreatic cysts. CT is able to reliably differ- J, Herts B, Biscotti CV, Brown N. Natural history of indetermi-nate pancreatic cysts. Surgery 2005;138:665–70; discussion entiate between serous, mucinous and intraductal papil- lary cystic neoplasms of the pancreas [19]. Preoperative [14] Serikawa M, Sasaki T, Fujimoto Y, Kuwahara K, Chayama K.
CT can also be used to different malignant intraductal Management of intraductal papillary-mucinous neoplasm ofthe pancreas: treatment strategy based on morphologic classi- papillary neoplasms. Signs like dilated main duct, mural fication. J Clin Gastroenterol 2006;40:856–62.
nodules or thickness of cyst wall can predict malignancy [15] Goh BK, Tan YM, Cheow PC, Chung YF, Chow PK, Wong WK, Ooi [20]. In the present report we had five from 23 CTs that LL. Cystic lesions of the pancreas: an appraisal of an aggressive resectional policy adopted at a single institution during 15 years.
Am J Surg 2006;192:148–54.
In conclusion, decision making in conservative or [16] Fernandez-del Castillo C, Targarona J, Thayer SP, Rattner DW, operative treatment should depend on size, symptoms, Brugge WR, Warshaw AL. Incidental pancreatic cysts: clinico- patient age and reliable secure diagnosis. In the case of pathologic characteristics and comparison with symptomaticpatients. Arch Surg 2003;138:427–34; discussion 433–34.
uncertain cyst character, surgical resection is indicated [17] Sahani DV, Kadavigere R, Saokar A, Fernandez-del Castillo C, Brugge WR, Hahn PF. Cystic pancreatic lesions: a simple imag- Cystic neoplasms of the pancreas: conservative or operative treatment? ing-based classification system for guiding management.
noma and intraductal papillary mucinous tumor. Am J [18] O’Toole D, Palazzo L, Hammel P, Ben Yaghlene L, Couvelard A, [20] Chiu SS, Lim JH, Lee WJ, Chang KT, Oh DK, Lee KT, Lee JK, Choi Felce-Dachez M, Fabre M, Dancour A, Aubert A, Sauvanet A, SH. Intraductal papillary mucinous tumour of the pancreas: Maire F, Levy P, Ruszniewski P. Macrocystic pancreatic cystade- differentiation of malignancy and benignancy by CT. Clin noma: the role of EUS and cyst fluid analysis in distinguishing mucinous and serous lesions. Gastrointest Endosc 2004;59:823–9.
[21] Le Borgne J, de Calan L, Partensky C. Cystadenomas and [19] Kim SY, Lee JM, Kim SH, Shin KS, Kim YJ, An SK, Han CJ, Han JK, cystadenocarcinomas of the pancreas: a multiinstitutional ret- Choi BI. Macrocystic neoplasms of the pancreas: CT differenti- rospective study of 398 cases. French Surgical Association. Ann ation of serous oligocystic adenoma from mucinous cystade- 226 5/2008 Cystic neoplasms of the pancreas: conservative or operative treatment?


Microsoft word - msd.qa0.10039.00000.02.doc

MATERIAL SAFETY DATA SHEET JRS PHARMA LP 2981 Route 22, Suite 1, Patterson, NY, USA 12563-2359 Tel: + (845) 878-3414; Fax: + (845) 878-3484 Church House, 48 Church Street, Reigate, Surrey, RH2 OSN, U.K. Tel: +(44) 1737 222323; Fax: +(44) 1737 222545 1. PRODUCT Pruv® Sodium stearyl fumarate, NF 2. PRODUCT INFORMATION 3. HAZARDS IDENTIFICATION May be harmful if in

Innovator duty of care in the pharmaceutical industry

Innovator duty of care in the pharmaceutical industryDoes the inventor or “innovator” of a brand-name drug have a duty of care to the consumers of that drug’s generic equivalent manufactured by a competitor? The Ontario Superior Court of Justice considered this question in the recent case of Goodridge v Pfizer Canada1 and determined that, for now, no such duty exists. In that decision, th

© 2010-2014 Pdf Medical Search