Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010

Table 1 Summary of the terms used singly or in combination for evidence acquisition

Primary MeSH terms	Secondary MeSH terms (epidemiology, diagnosis)	Secondary MeSH terms (treatment, palliation)
Pancreatic neoplasm(s)	Epidemiology	Pancreaticoduodenectomy
Adenocarcinoma(s)	Classification	Resection
Carcinoma(s)	Diagnosis	Therapeutic(s)
Pancreatic diseases	Differential diagnosis	Treatment outcome(s)
Pancreas	Risk factor(s)	Surgery
Carcinoma, pancreatic ductal	Diagnostic imaging	Surgical procedures
Pancreatic duct(s)	Magnetic resonance imaging	Clinical trial(s)
Humans	Endosonography	Controlled clinical trial(s)
Adult	Ultrasonography	Randomized controlled trial(s)
	Emission computed tomography	Clinical trial (phase I)
	Radionuclide imaging	Clinical trial (phase II)
	Positron emission tomography	Clinical trial (phase III)
	Tomography	Clinical trial (phase IV)
	X-ray computed	Drug therapy
	Biopsy (fine needle)	Chemotherapy
	Biopsy (needle)	Neoadjuvant therapy
	Cytology	Adjuvant
	Cytodiagnosis	Antineoplastic combined chemotherapy protocols
	Tumor markers (biological) antigen(s)	Antineoplastic agent(s)
	Carcinoembryonic antigen	Antimetabolites, antineoplastic
	Ca 19-9 antigen	Combined modality therapeutic antineoplastic
	Ca 125 antigen	Combined chemotherapy protocols neoadjuvant
	Antigens, tumor-associated, carbohydrate	Therapy
	Endoscopic retrograde cholangiopancreatography	Radiotherapy
	Computed assisted image processing	Drainage
	Sensitivity and specificity	Cholestasis
	Endoscopy	Obstructive jaundice
		Celiac plexus
		Autonomic nerve block
		Nerve block
		Ethanol
		Injections, intralesional
		Cisplatin
		Deoxycytidine
		Epidermal growth factor
		Fluorouracil
		Endostatin
		Biological products
		Neoplasm proteins
		Immunotherapy
		Antibodies, monoclonal

Table 2 Known risk factors for pancreatic cancer

Age (more than 60 yr)

Smoking

Diabetes

Type II

Gestational diabetes

Impaired glucose tolerance

Alcohol

Pancreatitis

Acute

Chronic

Genetic predisposition

Family history

Hereditary disorders

Hereditary pancreatitis

Puetz-Jeghers syndrome

FAMMM

Familial breast and ovarian cancer

Li-Fraumeni syndrome

Fanconi anaemia

Ataxia-telangiectasia

Familial adenomatous polyposis

Cystic fibrosis

HNPCC

Lynch syndrome

Obesity

FAMMM: Familial atypical multiple mole melanoma; HNPCC: Hereditary non polyposis colon cancer.

Table 3 clinico-pathological features of the most frequent classes of pancreatic cancer

Classification	Frequency (%)	Author	yr	Survival (5-yr survival after surgical resection)
DIA (incidence per 100 000 patients at risk = 8.37)[69]	85-90[1]	Conlon et al[70]	1996	10%
		Winter et al[71]	2006	18%
		Poultsides et al[72]	2010	19%
SPPN (incidence per 100 000 patients at risk = NA)[69]	0.1-3[73]	Papavramidis et al[74]	2005	95%
IPMN (incidence per 100 000 patients at risk = 0.03)[69]		Shin et al[76]	2010	Benign: 95%
				Malignant: 64%
IPMN with simultaneous DIA: (incidence per 100 000 patients at risk = NA)[69]	5[75]	Poultsides et al[72]	2010	42%
		Fan et al[77]	2010	57%
		Sohn et al[78]	2004	43%
Pancreatoblastoma (incidence per 100 000 patients at risk = NA)[69]	0.50[79]	Dhebri et al[80]	2004	50%
		Saif et al[79]	2007	80%
Undifferentiated (incidence per 100 000 patients at risk = 0.03)[69]	2-7[81]	Paal et al[82]	2001	3% (3-yr survival)
		Connolly et al[83]	1987	5 mo (average survival)
Medullary carcinoma (incidence per 100 000 patients at risk = NA)[69]	NA	Wilentz et al[84]	2000	11%
				14 mo (average survival)
Mucinous cystadenocarcinoma (incidence per 100 000 patients at risk = 0.43)[69]	1	Ridder et al[85]	1996	56%
Adenosquamous carcinoma (incidence per 100 000 patients at risk = 0.05)[69]	4	Madura et al[86]	1999	5-7 mo (median survival)
		Mulkeen et al[87]	2006
Acinar cell carcinoma (incidence per 100 000 patients at risk = 0.02)[69]	2	Holen et al[88]	2002	38 mo after surgical resection (median survival)
				14 mo for unresectable disease (median survival)

DIA: Ductal infiltrating adenocarcinoma; SPPN: Solid pseudo-papillary neoplasm; IPMN: Intraductal papillary nucinous neoplasm; NA: Not applicable.

Table 4 Presenting symptoms of advanced pancreatic cancer

Symptom	Percentage
Abdominal pain	78-82
Anorexia	64
Early satiety	62
Jaundice	56-80
Sleep disorders	54
Weight loss	66-84
Diabetes	97
Back pain	48
Nausea and weight loss	50-86

Table 5 Summary of the performance characteristics of serum tumor markers for the diagnosis of pancreatic cancer

Serum tumor marker	Author	Yr	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)
CA19-9	Boeck et al[141]	2006	70-90	43-91	72	81	67
	Ni et al[142]	2005
	Steinberg et al[143]	1990
	Safi et al[144]	1997
	Mu et al[162]	2003
CEA in pancreatic juice	Ozkan et al[155]	2003	NA	NA	77	95	85
	Futakawa et al[154]	2000
	Ni et al[142]	2005
CEA in serum	Boeck et al[141]	2006	45	75	NA	NA	NA
CA19-9 + CEA	Ni et al[142]	2005	37	84	91	90	89
	Ozkan et al[155]	2003
	Ma et al[163]	2009
CA 242	Nilsson et al[160]	1992	60	76	63	61	71
	Röthlin et al[164]	1993
	Carpelan-Holmström et al[165]	2002
	Pålsson et al[166]	1993
CEA + CA 242	Ni et al[142]	2005	34	92	67	90	87
	Ozkan et al[155]	2003
	Hall et al[167]	1994
CA19-9 + CA 242	Ni et al[142]	2005	59	77	65.3	87.8	65.1
	Röthlin et al[164]	1993
	Jiang et al[158]	2004
CA19-9 + CA 242 + CEA	Ni et al[142]	2005	29	96	NA	NA	NA

PPV: Positive predictive value; NPV: Negative predictive value; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; CA 242: Carbohydrate antigen 242; NA: Not applicable.

Table 6 Sensitivity, specificity and accuracy of computed tomography findings in pancreatic cancer patients

CT finding	Sensitivity (%)	Specificity (%)	Accuracy (%)
Hypoattenuation	75	84	81
Ductal dilatation	50	78	70
Ductal interruption	45	82	70
Distal pancreatic atrophy	45	96	81
Pancreatic contour anomalies	15	92	70
CBD dilatation	5	92	67

CT: Computed tomography; CBD: Common bile duct.

Table 7 Summary of the performance characteristics of imaging tests for the diagnosis of pancreatic cancer

Diagnostic modality	Author	Yr	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)
US	Giovannini et al[176]	1994	48-95	40-91	92	100	46-64
	Böttger et al[177]	1998
	Rösch et al[178]	1991
	Niederau et al[179]	1992
	Palazzo et al[180]	1993
	Tanaka et al[231]	1996
Doppler US	Candiani et al[232]	1998	50-94	80-100	79	88	81-95
	Casadei et al[184]	1998
	Calculli et al[233]	2002
EUS	Akahoshi et al[234]	1998	98	97	94	100	90
	Legmann et al[235]	1998
Contrast enhanced US	Dietrich et al[185]	2008	90	100	100	86	93
CT	Bronstein et al[196]	2004	77	100	NA	NA	73
	Megibow et al[197]	1995
MDCT	Park et al[214]	2009	83-91	63-75	80	87	85-95
	Vargas et al[202]	2004
	Diehl et al[203]	1998
	Schima et al[208]	2002
MRI-MRCP	Andersson et al[212]	2005	83-92	63-85	95	79	89
PET	Maemura et al[217]	2006	87-100	67-77	94	100	85-95
	Delbeke et al[221]	1999

PPV: Positive predictive value; NPV: Negative predictive value; US: Ultrasound; EUS: Endoscopic ultrasound; CT: Computed tomography; MDCT: Multi detector computed tomography; PET: Positron emission tomography; NA: Not applicable; MRI: Magnetic resonance imaging.

Table 8 American Joint Committee on Cancer staging of pancreatic cancer

AJCC 6th edition TNM staging system for pancreatic cancer
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	Carcinoma in situ
T1	Tumor limited to the pancreas, 2 cm or less in greatest diameter
T2	Tumor limited to the pancreas, greater than 2 cm at greatest diameter
T3	Tumor extends beyond pancreas but no involvement of celiac axis or superior mestenteric artery
T4	Tumor involves the celiac axis or the superior mestenteric artery (unresectable)
NX	Regional nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Regional lymph node metastasis
MX	Distant metastasis cannot be assessed
M0	No distant metastasis
M1	Distant metastasis
Stage grouping
Stage 0	Tis N0 M0	Localized within pancreas
Stage IA	T1 N0 M0	Localized within pancreas
Stage IB	T2 N0 M0	Localized within pancreas
Stage IIA	T3 N0 M0	Locally invasive, resectable
Stage IIB	T1, 2, or 3 N1 M0	Locally invasive, resectable
Stage III	T4 Any N M0	Locally advanced, unresectable
Stage IV	Any T Any N M1	Distant metastases

AJCC: American Joint Committee on Cancer.

Table 9 Stage distribution of pancreatic cancer and 5-year relative survival by stage at diagnosis for 1999-2006, all races and both sexes (SEER registries)

Stage at diagnosis	Stage distribution (%)	5-yr relative survival (%)
Localized (confirmed to primary site)	8	22.5
Regional (spread to regional LNs)	26	8.8
Distant (cancer had metastasized)	53	1.9
Unknown (unstaged)	14	5

SEER: Surveillance Epidemiology and End Results.

Table 10 Published results on laparoscopic pancreaticoduodenectomies

Author	Yr	Patient No.	Morbidity (%)	Pancreatic fistula (%)	Mean hospital stay	Mortality (%)
Kendrick et al[323]	2010	62	42	18	7	1.6
Palanivelu et al[324]	2007	42	28.6	7.1	10.2	2.4
Dulucq et al[325]	2006	25	31.8	4.5	16.2	0
Pugliese et al[326]	2008	19	31.6	15.8	18	0

Table 11 Survival data after resection of pancreatic cancer

Author	Yr	Resection (n)	R0 resection (n)	Overall 5-yr survival (%)	R0 5-yr survival (%)	Median survival (mo)
Fatima et al[371]	2010	617	468	17.4	20	18
Kato et al[376]	2009	138	115	9.9	13.2	12.3
Raut et al[373]	2007	360	300	NA	NA	24.9
Cameron et al[258]	2006	1000	NA	18	23	33
Shimada et al[372]	2006	88	66	19	26	22
Howard et al[375]	2006	126	158	4	67	18
Moon et al[374]	2003	81	20	10.8	67.8	11.8

NA: Not applicable.