t8-ovarian mass - cdn.ymaws.com€¦ · pag & ped surg (22 sx ped surg primary surgical...

3/28/2016

1

The Ovarian Mass: the What, Why and How Why and How about Management

NASPAG 2016 Workshopp

Dr. Lisa Allen, Section Head Pediatric Gynecology, SickKids; Associate Professor, University of Toronto

Dr. Furqan Shaikh, Pediatric Hematology/Oncology, SickKids; Assistant Professor, University of Toronto

Dr. J. Ted Gerstle, Director, Surgical Oncology Program, SickKids; Associate Professor, University of Toronto

ObjectivesAt th l i f th t ti tt d ill b At the conclusion of the presentation, attendees will be

better able to:

Discuss the appropriate investigations for an ovarian mass in children and adolescents

Incorporate into their practice an “appropriately” conservative approach to benign adnexal masses

Identify features that suggest a malignancy in an ovarian mass in children and adolescents

Discuss the surgical and oncologic management of malignant germ cell tumors

Increase ovarian conservation in their institution by involving a multidisciplinary team of health care providers

3/28/2016

2

Approach With 3 illustrative cases: Build an algorithm for the

approach to the mass

3/28/2016

3

Why does it matter? The goal of the prediction rule is to ensure that:

Benign tumors can receive appropriately conservative management (observation, laparoscopy, cystectomy).

Malignant tumors can receive appropriately Malignant tumors can receive appropriately aggressive management (complete resection, avoidance of spillage, delivery of intact capsule, full staging, correct assignment of adjuvant therapy).

41.2% expectant management58.8% operative procedure

Kirkham Y, Lacy L, Kives S, Allen L JOGC;2011;33(9):935-943

3/28/2016

4

Authors Non neoplastic(%)

Neoplasticbenign (%)

Neoplasticmalignant (%)

Brown (91, Philadelphia 1993)

38.5 40.6 21Philadelphia, 1993)Cass (106, Texas,2001)

46.3 44.3 9.4

Rogers (126, Toronto, 2014)

37 50 13

Kirkham (67, Toronto, 2011)*

35.8 62.2 11.9

De Silva (134 59 32 8 8 2

* 7% Malignancy Rate Overall

De Silva (134, Melbourne, 2004)

59 32.8 8.2

Cribb (219, New Zealand, 2014)

59.4 32.8 7.8

Michelotti (231, Pittsburg, 2010)

69 24 5

3/28/2016

5

Case 111 ld i l f d t l 11 year old girl referred to gynecology

Thelarche 1 year ago

No menarche to date

Left sided pelvic pain, intermittent, lasts for a few hours, sufficiently severe to present to the emergency department on 1 occasion

N iti No nausea, no vomiting

Otherwise healthy, overweight (BMI 29)

Pelvic ultrasound – simple cyst 4.9 cm in size, right ovarian

Case 1

3/28/2016

6

Pediatric RMICharacteristic Odds Ratio (CI)Age 1 – 8 yrs 3.02 (1.33 - 6.86)Symptom Mass 4.84 (2.48 – 9.45)Symptom Prec Pub 5.67 (1.60 – 20.30)Size > 8 cm 19.0 (4.42 – 81.69)Solid 39 0

Oltmann SC et al J Pediatr Surg 2010;45:130-134

Solid 39.0

Tumor markers, while stat associated with malignancy (hCG, AFP, CA125), positive or negative not conclusive

N=42415 yr retrospective review1 d to 19 yrs (mean 12.5)

3/28/2016

7

Pathology # Pts Percent of Total

Non-neoplastic 47 37

Simple or follicular 16 12.4

Paratubal 15 11.6

Hemorrhagic 10 7.8

Corpus luteum 5 3.8

Neoplastic-Benign 63 50

Mature teratoma 41 31.8

Cystadenoma 20 15.5

Endometrioid 2 1.5

Struma ovarii 1 0.8

Neoplastic-Malignant 16 13

Borderline tumor 5 3.8

Immature teratoma 4 3.1

Retrospective review 2001 – 2006 126 masses managed surgicallyPAG & Ped Surg(22 Sx Ped Surg primary surgical service)

Mixed germ cell tumor 2 1.5

Juvenile granulose cell 2 1.5

Dysgerminoma 1 0.8

Yolk sac tumor 1 0.8

Embryonal 1 0.8

Rogers E, Casadiego G, Lacy J, Gerstle T, Kives S, Allen L. JPAG 2014 27(3);125-128

Benign Malignant p-value PPV NPV

Pain 83/113 (73.5%) 12/16 (75%) 1.00 4.65% 72.15%

<=8 years old 17/113 (15%) 5/16 (31.2%) 0.107 39.71% 95.21%

Abnormal Markers 9/49 (18 4%) 9/16 (56 2%) 0 003 17 05% 94 39%Abnormal Markers 9/49 (18.4%) 9/16 (56.2%) 0.003 17.05% 94.39%

LDH 7/9 (77.7%) 4/9 (44.4%) 0.335 15.89% 56.23%

βHCG 0/9 (0%) 2/9 (22.2%) 0.471 98.64% 79.74%

AFP 2/9 (22.2%) 6/9 (66.7%) 0.153 49.96% 87.8%

CA‐125 1/9 (11.1%) 2/9 (22.2%) 1.00 41.76% 77.98%

Complex Cyst 76/113 (67.3%) 16/16 (100%) 0.006 15.48% 100%

≥8 cm 60/113 (53.1%) 16/16 (100%) 0.0001 21.05% 100%

≥ 10 cm 34/113 (30.1%) 9/16 (56.2%) 0.038 17.08% 89.78%

No simple cysts of any size were malignantNo Malignancies were less than 8 cm in size

≥8 cm + Complex Cyst 41/113 (36.3%) 16/16 (100%) 0.0001 37.1% 100%

Table 2: Comparison of benign vs malignant adnexal masses – Pediatric patients adnexal mass cases were stratified based on their pre-operative mass characteristics as identified by either ultrasound imaging, history, or biochemical markers. A Fisher’s exact test comparing the two cohorts identifies the significant differences between benign and malignant masses (p ≤ 0.05). Using the sensitivity and specificity of these pre-operative characteristics, the positive predictive value (PPV) and negative predictive value (NPV) of these criteria were also calculated.


Note: 7/16 malignant cases were 8 – 10 cm in size

3/28/2016

8

NPV 100% PPV 37.1%

Case 1 What is likelihood of resolution with serial follow

up?

Would you prescribe her an oral contraceptive pill to aid resolution?

Would you order any additional testing?

A th f t hi t t Are there any features on history or assessment that could help you decide if mass more likely to be managed expectantly successfully?

3/28/2016

9

Functional cysts (Hemorrhagic CystsFollicular Cysts)

Pathologic Cysts ((Cystadenomas, Paratubal/ParaovarianCysts, Dermoids < 8 cm, Endometriomas < 8 cm)


41.2% expectant management58.8% operative procedure

Retrospective review114 pts presenting to PAG (ER or ambulatory clinic) with an adnexal massMean age 12.7+/-3.9 years (neonate to 18)Jan 2003-Jan 2006

Expectant management

n=47


Prescribed CHC

12 (25.5%)

No CHC35 (74.5%)

3/28/2016

10

Desogestrel and 30 ug EE 84% (31/37) resolution by 10 – 12 weeks on U/S

Expectant 77% (30/39)

Levonorgestrel and EE

2/3 to ¾ resolve by 3 months

Not affected by OCP 64% (37/58) resolution by 2 to 3 mo on U/S

Expectant 61% (33/54)

Cochrane Review – Oral Contraceptives for Functional Ovarian Cysts (2014)

Do symptoms guide us?

Pain 73% Incidental Increased Precious puberty

Nausea and

*all patients with these symptoms went to

Pain 73% 8.8% girth 7.9% puberty 1.8%* vomiting

3.5%*surgeryOnly symptom that differed inc abdl girth


3/28/2016

11

*All patients with nausea/vomiting and precocious puberty underwent surgical therapy



Size Range:Surgical group 4.0 to 35 cmConservative group 2.5 to 9.8 cm

Size matters

Largest cyst managed without surgery 10 cm

3/28/2016

12

Age matters

67% no surgery

18.2% no surgery

47.6% no surgery


Features associated with expectant management:

Neonate/Postmenarcheal

Size of mass (< 9.8cm)

No:•Increased girth•Precocious puberty•Nausea and vomiting

3/28/2016

13

3 months later: Are you going to offer surgery?If so what surgical approach?

CystadenomasParatubal/Paraovarian CystsDermoids < 8 cmEndometrioma


3/28/2016

14

Case 1LaparoscopyParatubal Cystectomy



Benign Masses: 50/59 preservation ovary (84%)

Malignancies: 3/8 cystectomy

3/28/2016

15

Benign Cyst Cystectomy Rate

n= 2126 pts

13 – 16 yrs OR 1.36 (1.03-1.75)Surgeons OR 0.51 (0.38 – 0.68)

Overall Laparoscopy rate 62%Benign Laparoscopy rate 69%


3/28/2016

16

Advantages Laparoscopy Visibility of abdominal cavity

Shorter length of stay/shorter recovery


Less postoperative pain

Cosmesis

Safe: 2/158 cases, minor complications (1.2%)Rieger et al JPAG2015;157-162

35 benign laparotomies Reduced to: only 21 (40%

reduction)


3/28/2016

17

L L t PLaparoscopy Laparotomy P

Malignancy 2 (3%) 14 (29 %) <.001

Borderline tumor 0 (0%) 5 (36%) 1

Immature teratoma 1 (50%) 3 (21%) .45

Mixed germ cell tumor 0 (0%) 2 (14%) 1

Juvenile granulosa cell 1 (50%) 1 (7%) .24

Dysgerminoma 0 (0%) 1 (7%) 1

Yolk sac tumor 0 (0%) 1 (7%) 1

Embryonal 0 (0%) 1 (7%) 1

Benign 78 (97%) 35 (71%) <.001

Simple cyst 42 (54%) 10 (29%) .02

Mature teratoma 26 (33%) 15 (43%) .4

Cystadenoma 9 (12%) 10 (29%) .03

Endometrioma 1 (1%) 0 (0%) 1


Case 1 – if this was imaging?

Does this change your thoughts on thoughts on how to manage this patient?

3/28/2016

18

Mature Cystic TeratomaRisk of spillage

Cyst Rupture Chemical PeritonitisTempleman 2000 (n=14 l/s) 92.8% 0%Savasi 2009 (n=23 l/s) 100% 0%Nezhat 1999 (n-470 adults) 66% 0.2%

Nezhat CR eta al JSLS 1999;179-84Templeman CL et al Hum Reprod 2000;15:2669-72

Savasi, Lacy, Gerstle, Stephens, Kives, Allen JPAG 2009;22(6):360-4

Mature Cystic TeratomaRecurrence rate

Overall recurrencerate

Laparoscopy Open Requringsurgery

Laberge 2006 (n=245) 0% 7.6%* 4.2 vs 0%*Rogers 2014 (n=66) 10.6% 15% 3.8% 3%Harada 2013 (n=382) 4.2% 2.9%

*stat significant

All new dermoids were identified on first postsurgical u/s(209.7 +/- 135.5 days)

Rogers EM, Allen LM, Kives S JPAG 2014;JPAG:24(4)222-226

Recommend single ultrasound at 6- 12 mo post-op

3/28/2016

19

Predictive factors for dermoidrecurrence

Factor HR 95% CI P valueAge < 30 2.98 1.04-8.62 0.043Large (>8 cm) 2.75 1.03-7.37 0.044Bilateral 2.88 1.07-7.76 0.036Multiplicity 2.42 0.90-6.51 0.086Intraop spill 1.96 0.71-5.43 0.195L/ 3 23 0 42 24 6 0 257

n=382L/s 3.23 0.42-24.6 0.257

Overall recurrence rate 4.2% (16/382)21.0% recurrence if young, large and

bilateral3.4% if none

Harada M Eur J Obstet Gynecol Reprod Biol 2013;171:325-328

23% bilateral28% multipleIntraop spill

47%88% l/s


Improved decision making with consensus

3/28/2016

20

Simulated Impact of Pelvic

Marro A, Allen L, Kives S, Moineddin R, Chavhan G Accepted/In Press, Pediatr Radiol

Impact of Pelvic MRI in

Treatment Planning for

Paediatric Adnexal Masses

21/32 cases after MRI: discordance in at least 1 aspect of management

11 in oophorectomy vs cystectomycategory

Consensus reading Discrepancy less in suspicion for malignancy vs

choices of surgical approach in the benign mass Is cystectomy viable in the very large ovarian mass?

Surgeon A Surgeon B Consensus

•Oophorectomies13

•Oophorectomies4

•Oophorectomies4

Marro A, Allen L, Kives S, Moineddin R, Chavhan G Accepted/In Press, Pediatr Radiol

3/28/2016

21

Ovary Size: pre and postop cystectomy

Residual ovarian tissue in cystectomy specimens

2

3

4

5

6

Affected OvaryContralateral O

30 pts (6 – 16 yrs, median 9.1), 18 l/s, 12 laparotomy

86.7% no ovarian tissue in the cystectomy specimen

13.3% (2 l/s, 2 laparotomy) ti f d 1 l

0

1

Size (cm) Volume (cm3)

Ovary tissue found, < 1mm, onlywith endometriotic cysts

Reddy J Laufer M Fertil Steril 2009;91:1941 Palmara J Pediatr Surg 2012;47:577-580

3/28/2016

22

Case 2 15 year old girl referred to gynecology and

oncology

Bloating and abdominal distention x weeks, fever x days

Menses at 13y, regular q monthly. No OCP. Not sexually active.

Ultrasound showed large complex, mixed solid-cystic heterogenous mass, 10 x 12 x 13 cm.

Case 2 AFP 700 B-HCG 2 LDH 960

3/28/2016

23

3/28/2016

24

AFP HCG INH LDH CA125 Test/Est CEA

TUMOUR MARKERS IN OVARIAN MALIGNANCY

Dysgerminoma - -/+ - -/+ -/+ - -

Yolk sac tumor ++ - - -/+ -/+ - -

Immature teratoma -/+ - - - - - -

Embryonal Ca -/+ -/+ - - - - -

Choriocarcinoma - ++ - - - - -

Mixed MGCT -/+ -/+ - -/+ -/+ - -

Granulosa cell + + Granulosa cell - - + - - + -

Sertoli-Leydig - - -/+ - - + -

Epithelial - - - - -/+ - -/+

From Shaikh et al. Paediatric extracranial germ-cell tumours: Review. Lancet Oncology, April 2016

3/28/2016

25


Pain 83/113 (73.5%) 12/16 (75%) 1.00 4.65% 72.15%

<=8 years old 17/113 (15%) 5/16 (31.2%) 0.107 39.71% 95.21%


LDH 7/9 (77.7%) 4/9 (44.4%) 0.335 15.89% 56.23%

βHCG 0/9 (0%) 2/9 (22.2%) 0.471 98.64% 79.74%

AFP 2/9 (22.2%) 6/9 (66.7%) 0.153 49.96% 87.8%

CA‐125 1/9 (11.1%) 2/9 (22.2%) 1.00 41.76% 77.98%

Complex Cyst 76/113 (67.3%) 16/16 (100%) 0.006 15.48% 100%

≥8 cm 60/113 (53.1%) 16/16 (100%) 0.0001 21.05% 100%

≥ 10 cm 34/113 (30.1%) 9/16 (56.2%) 0.038 17.08% 89.78%

≥8 cm + Complex Cyst 41/113 (36.3%) 16/16 (100%) 0.0001 37.1% 100%




Pain 83/113 (73.5%) 12/16 (75%) 1.00 4.65% 72.15%

<=8 years old 17/113 (15%) 5/16 (31.2%) 0.107 39.71% 95.21%


LDH 7/9 (77.7%) 4/9 (44.4%) 0.335 15.89% 56.23%

βHCG 0/9 (0%) 2/9 (22.2%) 0.471 98.64% 79.74%

AFP 2/9 (22.2%) 6/9 (66.7%) 0.153 49.96% 87.8%

CA‐125 1/9 (11.1%) 2/9 (22.2%) 1.00 41.76% 77.98%

Complex Cyst 76/113 (67.3%) 16/16 (100%) 0.006 15.48% 100%

≥8 cm 60/113 (53.1%) 16/16 (100%) 0.0001 21.05% 100%

≥ 10 cm 34/113 (30.1%) 9/16 (56.2%) 0.038 17.08% 89.78%

≥8 cm + Complex Cyst 41/113 (36.3%) 16/16 (100%) 0.0001 37.1% 100%



3/28/2016

26

MRI second level exam•MRI second level exam

•Greater specificity to characterize the benign mass

•Useful to differentiate non adnexal masses

•Used in our institution for

ACOG Practice Bulletin 2007

Used in our institution for staging vs CT to decrease radiation

3/28/2016

27

Complex vs ComplexLesion DescriptionHemorrhagic cyst Various stages of hemorrhage,

acute, clot formation, retraction (fibrin strands, retracting thrombus, fluid levels

Mucinous cystadenoma Different densities of fluid (layering of mucin)

Mature Teratoma Fat/Fluid levels calcifications with Mature Teratoma Fat/Fluid levels, calcifications with posterior echogenic shadowing, fine echogenic bands hyperechoicmural module

Indicators of malignancy Solid components > 2cm in size, thick septations, multiple papillary projections ,ascites, high dopplercontent

3/28/2016

28

Surgical Staging in AdultsAd t d f d lt i ith ith li l i Adapted from adult experience with epithelial ovarian cancer

Adult staging generally comprehensive Peritoneal cytology and biopsies Omentectomy Retroperitoneal lymphadenectomy (bilat pelvic, para-aortic nodes) Removal of any suspicious tissue, with tumor reductive surgery to be

f d i th t f di i t d diperformed in the event of disseminated disease Bivalve and bx of contralateral ovary

Is the same comprehensive staging required in pediatric ovarian malignancies?

i i ( ) 2 intergroup trials undertaken by POG and CCG (1990-1996)

131 girls with primary ovarian MGCTs

Staging was as per adult recommendations, but compliance, yield and utility of each step examined.

i f ( ) Complete staging almost never performed (3/131) No bilateral node sampling (97%), no biopsy contralateral ovary

(60%), no omentectomy (36%), no peritoneal cytology (21%).

6-year survival >93% for all stages

3/28/2016

29

Component FindingsTumor Capsule Visual assessment of capsule integrity

incorrect ~20%Ascites 23/100 positive cytology

5 upstaged based solely on cytologyPeritoneal implants

0/7 normal areas positive (for malignancy)18/29 abnormal areas positive

Omentum 1/23 normal areas positive7/45 abnormal areas positive

Lymph nodes 0/18 grossly normal nodes positive19/46 grossly abnormal nodes positive

Contralateral ovary

0/21 normal-appearing ovaries positive11/21 abnormal positive

3/28/2016

30

Excerpts from COG AGCT1531 Surgical Guidelines (draft version)

The approach for ovarian tumors with known malignancy ti l h hi t i ll b b t h i preoperatively has historically been by open technique.

The current study will expand the guidelines to allow tumors less than 10 cm in diameter by imaging to be approached laparoscopically if desired. This will require the tumor to be placed into a retrieval bag without capsule violation; and if a cystic component is decompressed it must be done with the neck of the bag exteriorized through the incision to avoid any possibility of spill. All other staging criteria must still be completed.

it is important to avoid capsular disruption intraoperatively and the tumor must be provided to the pathologist intact to allow thorough assessment of the tumor capsule.

If removal would require en bloc removal of structures in addition to ovary and tube, only a biopsy should be done.

Case 2 Surgical pathology showed teratoma with yolk

sac tumor

Evidence of capsule rupture, ascites cytology positive, peritoneal implant and omental biopsies negative.

Staging? Further treatment?

3/28/2016

31

Who needs adjuvant chemotherapy?

Until recently, all patients with ovarian malignant germ cell tumors or stromal tumors received adjuvant chemotherapy (four cycles of Peb; cisplatin, etoposide, bleomycin).

Recently, it has been noted that a strategy of close surveillance ft i iti l f t I ti t (Fi t I d Ib) after initial surgery for stage I patients (Figo stage Ia and Ib) can

allow at least half of all patients to avoid chemotherapy.

This has made strict staging maneuvers all the more important.

3/28/2016

32

Half the patients eventually required chemotherapy (which means half did not).

All patients who recurred on surveillance had elevated AFP, and recurred within 9 months (median 2 months).

Nearly all patients could be salvaged with adjuvant chemotherapy started at recurrence.

One patient died, but this patient had chemo-refractory disease, and hence final outcome may not have been different.

3/28/2016

33

Pooled analysis of pediatric and adult clinical trials

179 patients with pure immature teratomas

Adult patients (N=91, GOG) Pediatric patients (N=98, COG) Surgery alone 0 5y EFS 87% OS 93%

Surgery alone 90 5y EFS 91% OS 99%

Grade 1: no relapses, regardless of age or stage

Grade 2: only one adult relapse, stage IIIc

Grade 3:

3/28/2016

34

Case 3i i i f f 14 year old girl with 4 week history of shortness of

breath, transferred from northern community

2 week history of abdominal pain

Recent decrease in appetite

Menses at 13y, regular q monthly. No OCP.

i i X-ray ordered by primary care provider: calcifications seen

PE: large, palpable abdominal mass extending above the umbilicus

3/28/2016

35

Case 3 AUS demonstrated a large abdominal-pelvic

mass: 19 x 8.6 x 21cm, complex solid-cystic mass with calcification

Case 3 How should this case be managed?

Any additional investigations?

3/28/2016

36

Case 3 AFP=1

Beta HCG<1

CA125= 97 (upper limit 35)

LDH 711 (elevated)

MRI – 20 x 15 x 11 cm solid 5 7 x 5 1 with ascites MRI – 20 x 15 x 11 cm, solid 5.7 x 5.1, with ascites, peritoneal seeding, second mass 11 x 8 cm *thought to be bilateral

3/28/2016

37

Repeat MRI

3/28/2016

38

Case 3 Surgical approach?

3/28/2016

39

Case 3 Surgical approach: lower midline laparotomy

Left salpingo-oopherectomy complete staging per algorithm

Intra-operative findings: pre-operative rupture of the tumour capsule and multiple peritoneal implants

Case 3 Pathology: mature teratoma with rupture of the

capsule and gilomatosis

Is adjuvant therapy required?

3/28/2016

40

Ovarian Teratoma and Gliomatosis Peritonei (GP) Gliomatosis peritonei: a clinicopathologic and

immunohistochemical study of 21 cases; Li Liang, Yifen Zhang, Anais Malpica, et al; MD Anderson Cancer Center, Houston, TX; Mod Pathol. 2015 December; 28(12):1613–1620

Mature ovarian teratoma with gliomatosisperitonei – A case report; Das CJ, Sharma R, Thulkar S, et al; All India Institute of Medical Sciences New Delhi India; et al; All India Institute of Medical Sciences, New Delhi, India; Indian Journal of Cancer, July - September 2005, Volume 42, Issue 3

Ovarian Teratoma and Gliomatosis Peritonei (GP) Rare condition often associated with immature ovarian

teratoma, but can be associated with mature ovarian teratoma and mixed germ cell tumours

Characterized by the presence of mature glial tissue in the peritoneum

Diagnosed commonly at time of initial surgery for ovarian mass (71%) but can develop secondarily (29%)

Age range: 5-42 yrs (mean 19 yrs); < 18 yrs = 30%

May co-exist with metastatic immature and/or mature teratoma

3/28/2016

41

Ovarian Teratoma and Gliomatosis Peritonei (GP) GP is considered grade 0 teratoma and is usually associated

with favorable prognosis and managed conservatively

On rare occasions, malignant transformation to a glial neoplasm

Can be part of growing teratoma syndrome, characterized by increasing growth of metastatic mass that is composed of mature teratoma (especially in patients who have received chemotherapy for malignant germ cell tumor)chemotherapy for malignant germ cell tumor)

Paradoxically, patients who have immature ovarian teratomas in association with GP appear to have an improved prognosis

Ovarian Teratoma and Gliomatosis Peritonei (GP) At laparotomy: all peritoneal, omental, diaphragmatic

surfaces must be extensively sampled

If no other teratomatous elements or malignant glial tissue is found in the implants, the mature glial implants can be ignored

Therapy should be directed by the stage and grade of the primary ovarian tumor and not by the mature glial implants

3/28/2016

42

SummaryM i t ill l ith t i l Many ovarian cysts will resolve without surgical management

Only a small proportion of patients with ovarian tumors are malignancies.

A prediction rule can allow the best balance in conservative vs oncologic management.

Tumors known or suspected to be malignant require i l h th t ll l t i t t a surgical approach that allows complete intact

resection and full staging.

Stage I ovarian tumors can be treated with surveillance alone, with chemotherapy reserved for recurrence.

t8-ovarian mass - cdn.ymaws.com€¦ · pag & ped surg (22 sx ped surg primary surgical...

Documents