Transcript Bowel Obstruction in Advanced or Recurrent Ovarian Cancer

Bowel Obstruction in
Advanced or Recurrent
Ovarian Cancer
The 6th Chinese Conference on Oncology
The 9th Cross-strait Academic Conference on Oncology
Ming-Shyen Yen M.D.
Chief, Division of Gynecology
Department of Obstetrics and Gynecology
Taipei Veterans General Hospital
National Yang-Ming University
May, 21, 2010
title
台北榮民總醫院Taipei Veterans General Hospital
主講：張文瀚
台灣男女性十大癌症 (95年)
Age-standardized incidence of top 10 cancers
for females over a 5-year period (2002-2006)
Age-standardized mortality rate for top 10 cancers
for females over a 5-year period (2003-2007)
Breast and Malignancies of
Female Genital Tracts in Taiwan (2006)
No. of new cases
No. of deaths
Breast
6895(49.99)*
1439(10.41)*
Cervix
(invasion)
1828(13.18)*
792(5.61)*
Corpus
1159(8.45)*
135(1.00)*
Ovary
1000(7.47)*
380(2.78)*
Others
117(0.83)*
39(0.27)*
Total
10999(79.92)*
2785(20.07)*
*age-adjusted incidence per 100,000 women
台灣歷年卵巢癌症發生率(一)
85年~95年上皮性卵巢癌型態分佈圖
803
(15.3﹪)
1336
(25.5﹪)
Mucinous
Serous
988
(18.8﹪)
EM
TOTAL：5249
2122(40.4﹪)
台灣歷年卵巢癌症發生率(二)
Clear
Ovarian Cancer

Patterns of Spread:
1. Direct extension to adjacent organs
2. By exfoliation and dissemination of
clonogenic tumor cells throughout the
peritoneal cavity
3. Via lymphatic system
General Treatment Strategy for
Ovarian Cancer
Cytoreductive Surgery
 Chemotherapy
 Therapy for relapse :






Secondary debulking
2nd-line chemotherapy
Intraperitoneal chemotherapy
IP P32
Whole-abdominal radiation (WAR)
Patterns of Recurrence

Serologic relapse
 Rising CA-125 only evidence of disease
Localized recurrence
 Disseminated intraperitoneal disease
 Extraperitoneal metastases
 Recurrences can be symptomatic or
asymptomatic

Treatment Considerations
in Recurrent Ovarian Cancer

Goals of therapy
 Palliate symptoms
 Prevent symptom development
 Maintain quality of life
 Increase progression-free survival
 Prolong overall survival
Therapeutic Goals in Recurrent
Ovarian Cancer
Manage symptomatic patients
 Delay progression of disease
 PFS
 Increase survival
 Maintain quality of life

Controversies in Recurrent
Ovarian Cancer
 Management
of an asymptomatic rise in CA-125 in
patients without evidence of disease on CT scan
or on physical examination
 Role of secondary cytoreduction
 Optimal chemotherapy
 Platinum-sensitive disease
 Platinum-resistant disease
 Use of in vitro sensitivity resistance assays
 Determine length of treatment
 Role
of biologic/targeted therapy
Chemotherapy Principles in Recurrent
Ovarian Cancer

Multiple agents have clinical activity
Activity superior in platinum-sensitive patients
Combinations are superior to single-agent
platinum in platinum-sensitive patients
 No established role for combinations in
platinum-resistant disease
 Management considerations

 Length of treatment and “drug holidays”
 Choice of combination in platinum-sensitive patients
 Choice of drug in platinum-resistant patients
Surgical Management of
Recurrent Ovarian Cancer

Secondary cytoreductive surgery
 The standard management of patients with recurrence, particularly
the role of surgery, remains poorly defined because of the absence of
prospective randomized data. (wait GOG #213)
 The longer the PFI, or the less residual disease after primary
treatment, the better the patient’s performance status, the more
likely that the patient will benefit from 2nd cytoreductive surgery.

Palliative surgery
 The most common indication is malignant intestinal obstruction.
 The management of malignant obstruction is challenging, not only
because it usually occurs in the setting of recurrent, often drugresistant, but also because there is a high morbidity and mortality
associated with surgery.
JCO, 25:2873-2883, 2007
Criteria for Consideration of
Secondary Cytoreductive Surgery (SCRS)
 Complete clinical response with a disease-free interval
≥6 months
 Rising CA125 level and/or radiographic or physical
findings suggestive of recurrence
 Absence of unresectable extra-abdominal or hepatic
metastases
 Patient acceptance of post-SCRS adjuvant therapy
 Absence of medical contraindications to SCRS
 Performance status score ≤3
Eisenkop SM et al. Cancer 2000; 88: 144.
Secondary Cytoreductive Surgery
Royal Hospital for Women, U.K.
Survival Benefit - Risk Ratio Analysis
Tay EH et al. Obstet Gynecol 2002; 99: 1008.
AGO DESKTOP- I OVAR Study: Surgery in
Recurrent Ovarian Cancer (retrospective)
Arbeitsciemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group
2000-2003
N= 267
Median survival 45.2 vs. 19.7 mos
Hazard Ratio (HR)= 3.71;
95% CI 2.27-6.05; P < 0.0001.
No residual
Residual > 10mm
Residual 1-10mm
Harter P, et al, Ann Surg Oncol. 2006
Role of Surgery in Ovarian Cancer
 Category I Surgery:
Initial surgical cytoreduction
Interval surgical cytoreduction
Cytoreduction after neoadjuvant chemotherapy
 Category II Surgery:
2-look surgical reassessment
Extent-of-disease surgical reassessment
Secondary cytoreduction
Palliative surgery
Surgery for palliation
Palliative surgery combined with local
irradiation:
 Cutaneous lesion:

Supraclavicular or inguinal-node metastasis
Abdominal wall metastasis
 Resection of an involved organ:
Liver, brain, lung to relieve pain or improve function

Surgery considered to relieve obstruction of
the urinary tract or intestine
The most common problem:
“ Intestinal Obstruction ”
Malignant Bowel Obstruction (MBO)
MBO is a complex problem occurring particularly in cancer
patients with advanced gynecological and gastrointestinal
cancer
1. Epidemiology:
Ovarian cancer – 5.5 to 42%
Colorectal cancer – 4.4 to 24%
Breast cancer, lung cancer, melanoma – 3 to 15%
2. Etiology:
Benign – adhesions, radiation enteritis
Malignant – single site, multiple sites, diffuse disease
3. Considerations:
Single site vs Multiple sites
Partial vs Complete
Small intestine vs Large intestine
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer
 Epidemiology:
 Exact incidence: unknown
 Retrospective studies: 20 – 50 %
 Related to disease and result of prior therapy
 Incidence from causes other than cancer: 5 – 24 %
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer
 Etiology:
Progressive intra-abdominal tumor growth that leads to
extrinsic occlusion of bowel lumen
Intraluminal occlusion due to pelvic recurrences or
mesenteric or omental masses
Intestinal motility problems with functional obstruction
due to the infiltration of the mesentery or bowel muscle
and nerves (extensive intraperitoneal carcinomatosis)
Result of prior therapy :
adhesion from prior previous surgery, IP C/T, or R/T
Causes of Symptoms in MBO
Partial or complete
bowel obstruction
Continuous pain
Distension,
Tumor mass,
Hepatomegalia
↑ Bowel contractions to
surmount the obstacle
↑ Colicky pain
Reduction or stop of throughmovements of intestinal contents
Bowel distension
lumen contents
Gut epithelial surface area
Bowel secretions of H2O,Na,Cl
Damage of intestinal epithelium
Bowel inflammatory response with
edema, hyperemia and production of
PG,VIP,nociceptive mediators
Nausea and/or
vomiting
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer
 Diagnosis:
 History
 Clinical symptoms
 Physical findings
 Supine and upright X-ray
 Radiographic contrast of the small and/or large intestine
 Abdominal CT scan
 Ultrasound
Management of Patients with MBO

Influenced by :





Level of obstruction
Pattern of disease
Clinical stage of cancer related to prognosis
Prior anticancer treatments
Patient’s health

One of the most challenging clinical scenarios

Balancing the advantages and disadvantages of
intervention with :
 Their prognosis
 Tumor biology
 Quality of life
Management of Patients with MBO
Diagnosis and Initial Management
 Problems with the Literature



When Not to operate:
MBO form Generalized Carcinomatosis
Surgical Decision-Making in MBO :
 Patient factors
 Disease factors
 Operative facotrs
 Other treatment approaches
 Stenting
 Percutaneous decompression

Decision-Making in Palliative Care
Management of Patients with MBO
Patient presenting with symptoms of bowel
obstruction and a history of cancer
Clinical assessment
• Patient acutely ill: surgical
emergency. Most patients
with MBO ≠ surgical emergency
• History of symptom
Patient factors
Radiology assessment :
CT +/- MRI
• Diagnosis and cause of obstruction
• Site: single vs multiple
Large vs small bowel
Partial (Most MBO) vs complete
Surgical decision making
Decision-making with patient and family
Technical factors
Management of Patients with MBO
Patient factors
Technical factors
 Age : biologic / physiologic
 Performance status
 Stage of cancer:
previous treatments, any
anticancer treatment options
 Malnutrition / cachexia
 Concurrent illness
 Ascites
 Degree of invasiveness
Interventional radiology
Endoscopy
Open laparotomy / laparoscopy
 Anesthetic requirements
 Risk of post-procedure
complications
Management of Patietns with MBO

Surgical decision making :

Identify the symptom
Identify a surgical cause for the symptom:
mechanical vs functional obstruction
Assess the realistic ability of an intervention to alleviate the symptom
Formulate recommendations:
No obligation to recommend futile therapy




Decision-making with patient and family :

What do they understand about the disease?
What do they expect from the surgery?
Explain clearly the expected potential benefits of the intervention:
Is this something that would be worth it to them given the risks?
Does this procedure fit with the goals of care?



Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer
 Conservative
treatment:
 Nasogastric tube drainage
 Intravenous fluid hydration
 Medical management:
hyoscine butybromide, haloperidol,
corticosteroids,
somatostatin, morphine,
parenteral nutrition for perioperative period
 Percutaneous endoscopic gastrostomy (PEG)
 Stents
Pharmacological treatment
in inoperable MBO
Drugs to control nausea and vomiting in MBO
Antisecretory drugs
Antiemetics
Prokinetic drug
Anticholingergic drug
Hyoscine butylbromide 40-120 mg/D SC,IV or
Hypscine hydrobromide 0/8-2.0 mg/D SC or
Glycopyrrolate 0.1-0.2 mg t.i.d SC or IV
and/or
Somatostatin analogue
Octreotide 0.2-0.9 mg/day SC
Metoclopramide 60-240 mg/D SC in
p’ts with partial occlusion and no colic
Neuroleptic drug
Haloperidol 5-15mg/D SC or
Methotrimeprazine 6.25-50 mg/D SC or
Prochlorperazine 25mg 8h PR or
Chlopromazine 50-100 mg 8h PR or IM
or
Antihistamine drug
Cyclizine 100-150 mg/D 8h PR or
Dimenhydrinate 50-100 mg SC prn
Pharmacological treatment
in inoperable MBO
Indications for the use of symptomatic drugs
Indications
Problems
Antiemetics
Symptom control
Metoclopramide
Functional
subobstruction
Steroids
Subobstructive states Symptom
control
Hyoscine
Symptom control
Octreotide
Subobstructive states Symptom
control
Short-term NG
Pts unresponsive to
pharmacological
treatment
Stop in definitive or
complete obstruction
Temporary
measure
Uncomfortable for
long-term use
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer (I)
Conservative treatment

Percutaneous endoscopic gastrostomy (PEG) :
 Symptomatic relief from a NG tube, not necessary for PEG
 Only to patients with symptoms poorly controlled with
medications and to those who are not imminently dying
 Ascites as a relative contraindication, but no adverse events if ascites
draine-out before placement of the PEG
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer (II)
Conservative treatment

Stents :
 Self-expanding metallic stent via fluoroscopy with or without
endoscopy
 Palliation for patients with single colonic obstruction in the
left colon
 Varying degrees of success for gastrodudenal, duodenal, and
small bowel obstruction from malignant disease
 No good published criteria to aid in the decision to stent on
patients with MBO
 The choice of treatment depending on patient factors, tumor factor,
and a history of any surgery and/or treatment
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer (III)
 Goal
of treatment:
 Palliative rather than curative measures
 Improving the QoL with a limited life expectancy
 Decision to attempt surgery: Extremely difficulty
 Considered:
 Successful palliation
 Risk of repeat obstruction
 QoL after the surgery
 Ability for further chemotherapy
 Rates of operative morbidity and mortality
 Obstipation vs constipation ?
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer

Types of procedure:
Depending on intra-operative findings at surgery
Options included both intestinal bypass and resection

Poor characteristics of ideal surgical
candidates:
 Bulky carcinomatosis
 Rapidly progressive disease
 Multiple sites of obstruction
 Poor performance status
 Heavy treatment of multiple chemotherapy agents or
radiation therapy
 Massive ascites?
Management for intestinal obstruction
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer

Successful palliative surgery defined:
 Survival > 60 days from surgery

Peri-operative mortality defined:
 Death within 30 days
Operative morbidity: 7 - 64 %
 Operative mortality: 4- 32 %
 Median survival: 5 - 33 weeks

 Heterogeneous
 More dependent on response to chemotherapy than the
surgery itself
Bowel Obstruction in Advanced or
Recurrent Ovarian Cancer

A through discussion with the patient and her family

No prospective randomized trial in this setting

No strict, clear-cut guidelines for management

The most challenging decisions, and the decision to
operate in gynecologic oncologist
Reoperative Surgery for MBO
Preoperative Consideration ( I )

Distorted Anatomy and Loss of Normal Tissue Planes
 A thorough knowledge of normal anatomy
 Depending on the prior surgery – distored fascial planes, thick
adhesions, walled-off fluid collections, a Gordian knot-like configuration
of small bowel, and ectopic positions of ureters
 A thorough review of the prior operative reports
 Knowledge of any prior postoperative complications

Potential Pitfalls and Complications
 Timing of reoperative surgery
 Enterotomies -- only one possible complication
 Nutrition
 Immuno-supplements -- enteral feeding, formulas rich in arginine,
glutamine, and omega-3 fatty acids
Reoperative Surgery for MBO
Preoperative Consideration ( II )
 Preoperative Adjuncts
 A thorough knowledge of prior surgeries and
postoperative courses
 Tumor markers and additional preoperative imaging
studies
 Place bilateral ureteral stents routinely
 Operative Technique
 Positioning of the patient
 Dilators or other long blunt instrument be placed
transvaginally
 Exposure in visualizing anatomy and proceeding
safely through the exploration
 Enter the peritoneal cavity in virgin territory
Reoperative Surgery for MBO
Preoperative Consideration ( III )

Literature review and retrospective studies:
 Patients received benefits in both survival and QoL
when operation is chosen and successful for MBO.
 When pursuing surgical exploration, it is important to keep in
mind all of the different options, including bowel resection
with anastomoses, intestinal bypass, creation of stoma, lysis of
adhesions, placement of gastrostomy or jejunostomy tubes, or
any combination of these.
 Unfortunately, there are times that carcinomatosis is so
extensive that the only option is to open and close in order to
avoid extensive iatrogenic injury.
Multiple authors have tried to define parameters
to help determine which patients will likely
benefit from palliative surgical intervention.
270 patients with epithelial ovarian cancer (1984 – 2005)
75 patients (28%) developed bowel obstruction
University of Brescia, Venice, Italy
<< Krebs score >>
• Age
• Nutritional status
• Tumor spread
• Presence of ascites
• Type
• Previous chemotherapy
• Previous radiation
therapy
This score system
benefit from surgical
intervention, 1983
Bowel Obstruction and Survival in
Patients with Advanced Ovarian Cancer
Analysis of Prognostic Variables
Parameters
0
1
2
Age
< 45
45 - 65
> 65
Free interval
>2
1-2
<1
> 30
25 - 30
< 25
> 3.06
2.55 – 3.06
< 2.55
< 1350
< 1125
< 900
y (from Dx to onset)
Hematocrit
%
Albumin
g/dL
Lymphocytes
cell/mm3
Bowel Obstruction and Survival in
Patients with Advanced Ovarian Cancer
Analysis of Prognostic Variables
Parameter
0
1
2
< 10
10 - 25
> 25
> 80
60 - 70
< 60
Standard
Others
None
Previous R/T
None
R/T to pelvis
R/t to
abdomen
Previous C/T
None
Single drug
Multiple
drugs
Weight change
%
Performance
status (PSK)
Previous operations
Bowel Obstruction and Survival in
Patients with Advanced Ovarian Cancer
Analysis of Prognostic Variables
Parameters
0
1
2
Tumor status
NO palpable
Palpable
Distant
0.1 - 1
1.1 - 3
>3
Large bowel
Small bowel
Both
Vomiting
No
Occasional
Persistent
Pain
No
-
Yes
Ascites, L
Site of obstruction
New score
15 Prognostic
parameters
MSKCC 1994 - 1999
G O 89, 2003: 306-311
Palliative surgery for bowel obstruction
in recurrent ovarian cancer
Survival based on
successful palliation
Survival based on
postoperative chemotherapy
Palliative surgery for bowel obstruction in
recurrent ovarian cancer
Comparison of survival by
type of obstruction
Palliative surgery for bowel obstruction in
recurrent ovarian cancer
Survival based on whether
surgical correction is possible
Survival based on whether surgical
correction is possible, successful
palliation no possible, surgical
correction not possible
Palliative surgery for bowel obstruction in
recurrent ovarian cancer
 Results
and Conclusions:
 If surgery resulted in successful palliation, median
survival 11.6 months vs 3.9 months for all other
patients ( P < 0.01).
 The extension of survival compared with prior
studies may be attributable to improved patient
selection for surgery and perhaps the ability to
tolerate chemotherapy after surgery.
Conclusions ( I )

MBO is a complex problem in patients with ovarian
cancer, but it is a severe complication affecting survival and,
moreover, quality of life (QoL).

The exact incidence is unknown and retrospective review
show 20-50% of patients with ovarian cancer present with
symptoms of MBO.

The etiology of MBO is varied, including progressive intraabdominal tumor growth, intra-luminal occlusion, intestinal
motility problem, and result of prior therapy.

The treatment of MBO, surgical or medical, is not decided
based on a fixed protocol, but the choice of therapy is
individualized.
Conclusions ( II )

The goal of treatment of MBO are palliative rather than
curative measures, improving the QoL with a limited life
expectance, and the decision to attempt surgery is
extremely difficulty that is one of the most challenging
clinical scenarios.

When such a decision is under consideration, one must
taking into account of the change of successful palliation,
risk of repeat obstruction, QoL for patient after the
surgery, ability to administer further chemotherapy, as well
as the rates of operative morbidity and mortality.

If the surgery resulted in successful palliation, median
survival was longer than all other patients with MBO.
Thank you for your attention !!