bowel obstruction in advanced or recurrent ovarian cancer
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Bowel Obstruction in Advanced or Recurrent Ovarian Cancer. The 6 th Chinese Conference on Oncology The 9 th Cross-strait Academic Conference on Oncology. Ming-Shyen Yen M.D. Chief, Division of Gynecology Department of Obstetrics and Gynecology Taipei Veterans General Hospital - PowerPoint PPT PresentationTRANSCRIPT
Bowel Obstruction in Bowel Obstruction in Advanced or Recurrent Advanced or Recurrent Ovarian CancerOvarian Cancer
Ming-Shyen Yen M.D.Chief, Division of Gynecology
Department of Obstetrics and GynecologyTaipei Veterans General Hospital
National Yang-Ming University
The 6th Chinese Conference on Oncology
The 9th Cross-strait Academic Conference on Oncology
May, 21, 2010
台北榮民總醫院Taipei Veterans General Hospital 主講:張文瀚
title
台灣男女性十大癌症 台灣男女性十大癌症 (95(95 年年 ))
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 Breast and Malignancies of Female Genital Tracts in Taiwan Female Genital Tracts in Taiwan
(2006)(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 )
1336
2122
988
803
85年~95年上皮性卵巢癌型態分佈圖
Mucinous
Serous
EM
Clear
(25.5﹪)
(40.4﹪)
(18.8﹪)
(15.3﹪)
TOTAL :5249
台灣歷年卵巢癌症發生率 ( 二 )
Ovarian CancerOvarian Cancer
Patterns of Spread:1. Direct extension to adjacent
organs2. By exfoliation and dissemination of
clonogenic tumor cells throughout the peritoneal cavity
3. Via lymphatic system
General Treatment Strategy for General Treatment Strategy for Ovarian CancerOvarian Cancer
Cytoreductive Surgery Chemotherapy Therapy for relapse :
Secondary debulking 2nd-line chemotherapy Intraperitoneal chemotherapy IP P32
Whole-abdominal radiation (WAR)
Patterns of RecurrencePatterns of Recurrence
Serologic relapse Rising CA-125 only evidence of disease
Localized recurrenceDisseminated intraperitoneal
diseaseExtraperitoneal metastasesRecurrences can be symptomatic
or asymptomatic
Treatment ConsiderationsTreatment Considerationsin Recurrent Ovarian Cancerin 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 Therapeutic Goals in Recurrent Ovarian CancerOvarian Cancer
Manage symptomatic patientsDelay progression of disease
PFSIncrease survivalMaintain quality of life
Controversies in Recurrent Controversies in Recurrent Ovarian CancerOvarian 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 cytoreductionOptimal chemotherapy
Platinum-sensitive diseasePlatinum-resistant diseaseUse of in vitro sensitivity resistance assaysDetermine length of treatment
Role of biologic/targeted therapy
Chemotherapy Principles in Chemotherapy Principles in Recurrent Ovarian CancerRecurrent Ovarian Cancer
Multiple agents have clinical activityActivity 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 Surgical Management of Recurrent Ovarian CancerRecurrent Ovarian CancerSecondary 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 surgeryThe 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 drug-resistant, 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)
Eisenkop SM et al. Cancer 2000; 88: 144.
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
Secondary Cytoreductive SurgeryRoyal 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 AGO DESKTOP- I OVAR Study: Surgery in Recurrent Ovarian Cancer Recurrent Ovarian Cancer (retrospective)(retrospective)
Arbeitsciemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group
Harter P, et al, Ann Surg Oncol. 2006
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
Role of Surgery in Ovarian Role of Surgery in Ovarian CancerCancer 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 palliationSurgery 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 Malignant Bowel Obstruction (MBO)(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 Bowel Obstruction in Advanced or Recurrent Ovarian Canceror 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 Bowel Obstruction in Advanced or Recurrent Ovarian Canceror 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
Damage of intestinal epithelium
Bowel inflammatory response with edema, hyperemia and production of PG,VIP,nociceptive mediators
Partial or complete bowel obstruction ↑ Bowel contractions to
surmount the obstacle
↑ Colicky pain
Nausea and/or vomiting
Reduction or stop of through-movements of intestinal contents
Continuous pain Distension, Tumor mass, Hepatomegalia
Causes of Symptoms in MBOCauses of Symptoms in MBO
Bowel distension lumen contents
Gut epithelial surface area
Bowel secretions of H2O,Na,Cl
Bowel Obstruction in Advanced Bowel Obstruction in Advanced or Recurrent Ovarian Canceror 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 Management of Patients with MBOMBO 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 Management of Patients with MBOwith MBODiagnosis and Initial ManagementProblems with the Literature
When Not to operate: MBO form Generalized CarcinomatosisSurgical Decision-Making in MBO :
Patient factorsDisease factorsOperative facotrsOther treatment approaches
Stenting Percutaneous decompression
Decision-Making in Palliative Care
Management of Patients with Management of Patients with MBOMBO
Patient presenting with symptoms of bowel obstruction and a history of cancer
Decision-making with patient and family
Surgical decision making Technical factorsPatient factors
Clinical assessment• Patient acutely ill: surgical emergency. Most patients with MBO ≠ surgical emergency
• History of symptom
Radiology assessment : CT +/- MRI
• Diagnosis and cause of obstruction• Site: single vs multiple
Large vs small bowel Partial (Most MBO) vs complete
Management of Patients with Management of Patients with MBOMBO
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 invasivenessInterventional radiologyEndoscopyOpen laparotomy / laparoscopy
Anesthetic requirements Risk of post-procedure complications
Management of Patietns with Management of Patietns with MBOMBO
Surgical decision making : Identify the symptom Identify a surgical cause for the symptom: mechanical mechanical vs functional obstructionfunctional 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 Bowel Obstruction in Advanced or Recurrent Ovarian Canceror 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 Pharmacological treatment
in inoperable MBOin inoperable MBODrugs to control nausea and vomiting in
MBO
Somatostatin analogue
Octreotide 0.2-0.9 mg/day SC
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
Prokinetic drug
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
Antihistamine drug
Cyclizine 100-150 mg/D 8h PR or Dimenhydrinate 50-100 mg SC prn
or
Antisecretory drugsAntiemetics
Indications Problems
Antiemetics Symptom control
Metoclopramide
Functional subobstruction
Stop in definitive or complete obstructionSteroids Subobstructive
statesSymptom control
Hyoscine Symptom control
Octreotide Subobstructive states
Symptom control
Short-term NG Pts unresponsive to pharmacological treatment
Temporary measure
Uncomfortable for long-term use
Indications for the use of symptomatic drugs
Pharmacological treatment Pharmacological treatment in inoperable MBOin inoperable MBO
Bowel Obstruction in Advanced Bowel Obstruction in Advanced or Recurrent Ovarian Cancer (I)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
Conservative treatment Stents :
Self-expanding metallic stent via fluoroscopy with or without
endoscopyPalliation for patients with single colonic obstruction
in the left colonVarying 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 Bowel Obstruction in Advanced or Recurrent Ovarian Cancer or Recurrent Ovarian Cancer (II)(II)
Bowel Obstruction in Advanced or Bowel Obstruction in Advanced or Recurrent Ovarian Cancer (III)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 Bowel Obstruction in Advanced or Recurrent Advanced or Recurrent Ovarian CancerOvarian Cancer
Types of procedure:Depending on intra-operative findings at surgeryOptions included both intestinal bypass and
resectionPoor 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 Bowel Obstruction in Advanced or Recurrent Advanced or Recurrent Ovarian CancerOvarian 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 Bowel Obstruction in Advanced or Recurrent Advanced or Recurrent Ovarian CancerOvarian 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 MBOPreoperative Consideration ( I )
Distorted Anatomy and Loss of Normal Tissue PlanesA thorough knowledge of normal anatomyDepending 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 reportsKnowledge of any prior postoperative complications
Potential Pitfalls and ComplicationsTiming of reoperative surgeryEnterotomies -- only one possible complicationNutrition 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
• Age
• Nutritional status
• Tumor spread
• Presence of ascites
• Type
• Previous chemotherapy
• Previous radiation therapy
<< Krebs score >>
This score system benefit from surgical intervention, 1983
Bowel Obstruction and Survival in Bowel Obstruction and Survival in Patients with Advanced Ovarian Patients with Advanced Ovarian CancerCancer
Parameters 0 1 2
Age < 45 45 - 65 > 65
Free interval y (from Dx to onset)
> 2 1 - 2 < 1
Hematocrit %
> 30 25 - 30 < 25
Albumin g/dL
> 3.06 2.55 – 3.06 < 2.55
Lymphocytes cell/mm3
< 1350 < 1125 < 900
Analysis of Prognostic Variables
Bowel Obstruction and Survival in Bowel Obstruction and Survival in Patients with Advanced Ovarian Patients with Advanced Ovarian CancerCancer
Parameter 0 1 2
Weight change%
< 10 10 - 25 > 25
Performancestatus (PSK)
> 80 60 - 70 < 60
Previous operations
Standard Others None
Previous R/T None R/T to pelvis R/t to abdomen
Previous C/T None Single drug Multiple drugs
Analysis of Prognostic Variables
Parameters 0 1 2
Tumor status NO palpable
Palpable Distant
Ascites, L 0.1 - 1 1.1 - 3 > 3
Site of obstruction Large bowel
Small bowel Both
Vomiting No Occasional Persistent
Pain No - Yes
Analysis of Prognostic Variables
Bowel Obstruction and Survival in Bowel Obstruction and Survival in Patients with Advanced Ovarian Patients with Advanced Ovarian CancerCancer
15 Prognostic parameters
New score
G O 89, 2003: 306-311
MSKCC 1994 - 1999
Palliative surgery for bowel Palliative surgery for bowel obstruction in recurrent ovarian obstruction in recurrent ovarian cancercancer
Survival based on successful palliation
Survival based on postoperative chemotherapy
Palliative surgery for bowel Palliative surgery for bowel obstruction in recurrent ovarian obstruction in recurrent ovarian cancercancer
Comparison of survival by type of obstruction
Palliative surgery for bowel Palliative surgery for bowel obstruction in recurrent ovarian obstruction in recurrent ovarian cancercancer
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 Palliative surgery for bowel obstruction in recurrent ovarian obstruction in recurrent ovarian cancercancer
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 intra-abdominal 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 !!