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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 !!