Epithelial Ovarian Cancer and Pseudomyxoma Peritonei
¢Â Epithelial Ovarian Cancer
1. Pathology : Ovarian cancerÀÇ 90%´Â epithelium or mesothelium orign
¨ç Invasive Cancer
: Serous type (75%), mucinous (20%), endometrioid (2%),
: Clear cell, Brenner, and undifferentiated carcinoma (<1%)
¨è Borderline Tumors
- Tumor of low malignant potential
- Confined to the ovary for long periods,
- Predominantly in premenopausal women
: 30~50´ë¿¡ ÈçÇÔ invasive carcinoma´Â 50-70´ë¿¡ ÈçÇÔ
- Good prognosis
- Metastatic implants
: noninvasive vs invasive form
: invasive formÀÌ peritoneal cavity¿¡ progressive, proliferative disease¸¦ ¹ß»ý½ÃÄÑ intestinal obstruction, death¿¡ À̸¦ °¡´É¼ºÀÌ ´õ ³ô´Ù
- 20~25% : spread beyond the ovary
2. Etiology
¨ç Associated with low parity, infertility, early menarche and late menopause
=> Suppression of ovulation°ú °ü·Ã¼º ÀÖ´Ù´Â °¡¼³À» µÞ¹Þħ
=> Repetitive disruption and repair of surface epithelium -> higher probability of spontaneous mutations
3. Prevention
¨ç Having at least one child (risk reduction of 0.3 to 0.4)
¨è Oral contraceptive (>5 year) : only documented method of chemoprevention
¨é Fenretinide(4-hydroxyretinoic acid) -> ÇöÀç trial Áß
¨ê Prophylactic oophorectomy : reduce risk of ovarian cancer, but not eliminate peritoneal carcinoma
4. Screening
¨ç TV-USG : >95% sensitivity for the detection of early-stage
¨è CA-125 : sensitivity - 50% of stage I
- 60% of stage II
=> µÎ°¡Áö ¸ðµÎ false positive ¶§¹®¿¡ cost effective ÇÏÁö ¾Ê°í routineÀ¸·Î ÀÌ¿ëµÇÁö ¾Ê´Â´Ù.
5. Symptoms and Signs
- Most of pts has no symptoms
`¨ç In early-stage disease
- Irregular menses, urinary frequency or constipation, lower abdominal distension, pressure, pain(such as dyspareunia)
- Acute Sx : pain secondary to rupture or torsion
¨è In advanced-stage disease
- Related Sx with ascites, omental metastases, and bowel metastases
; abdominal distention, bloating, constipation, nausea, anorexia, or early satiety
- Premenopausal women : Irregular or heavy mense
- Postmenopausal women : vaginal bleeding
¨é Sign
- Pelvic mass on P/E ; solid irregular, fixed mass
- Upper abdominal mass or ascites
6. Diagnosis
- DDx with benign neoplasm, functional cysts of the ovaries, pelvic inflammatory disease, endometriosis, pedunculated uterine leiomyomas, diverticulitis, colonic mass, pelvic kidney
- CA125 : distinguishing malignant from venign pelvic mass
: postmenopausal pts¿¡¼ >95 U/ml À̸é 96% positive predictive value for malignancy
- Cystic mass > 8cm : tumor °¡´É¼º ³ôÀ½
- Preoperative evaluation
: Chest radiography, IVP,
: CT, MRI - pelvic mass°¡ definiteÇϸé ÇÊ¿äÄ¡ ¾ÊÁö¸¸, ascites°¡ Àְųª pelvic mass°¡ ¾ø¾î liver or pancreatic tumor¸¦ ã¾Æº¼ ¶§ ½ÃÇà °¡´É
: ovarian metastasisÀÇ primary originÀ» ã±â À§ÇØ
- 45¼¼ ÀÌ»óÀÇ È¯ÀÚ´Â colonoscopy½ÃÇàÇϰí, gastric symptomÀÌ ÀÖ´Â °æ¿ì¿¡´Â E.G.D ½ÃÇàÇÑ´Ù. breast mass°¡ ¸¸Á®Áö´Â °æ¿ì mammography ½ÃÇàÇϰí PAP smear¿Í ÇÔ²² irregular mense ¶Ç´Â postmenopausal vaginal bleedingÀÌ ÀÖÀ» °æ¿ì EM Ca¸¦ È®ÀÎÇϱâ À§ÇØ endocervical curettage & EM Bx ½ÃÇà
7. Patterns of Spread
¨ç Transcoelomic : Exfoliation of cells that implant along the surfaces of the peritoneal cavity
¨è Lymphatic : pelvic and paraaortic LN
-> lymphatic channels of the diaphragm and retroperitoneal LN
-> supraclavicular LN
¨é Hematogenous : lung and liver (only 2-3%)
: diaphragm À§ÂÊÀ¸·Î ħ¹üÀÌ Áø´ÜµÈ ȯÀÚÀÇ ´ëºÎºÐÀº right pleural effusion ÀÖÀ½
8. Prognostic Factors
¨ç Pathologic Factors
1) Hystologic type : Clear cell carcinoma - poor prognosis
2) Hystologic grade : Grade°¡ ³ôÀ»¼ö·Ï ¿¹Èİ¡ ³ª»Ý
¨è Biologic Factors
1. Ploidy : low-stage cancer -> tend to be diploid
: high-stage cancer -> tend to be aneuploid
2. Protooncogenes : HER-2/neu oncogene -> poor prognosis
: p53 mutation
¨é Clinical Factors
: Stage
: Extent of residual disease after primary surgery
: Volume of ascites
: Patient age
: Performance status
9. Treatment of Early stage disease
¨ç Surgical staging(Exploratory laparotomy)
: FIGO staging based on findings at surgical exploration
- FIGO stage
¨è Stage I
1. Borderline Tumors
- Surgical resection of the primary tumor
- No subsequent chemotherapy or radiation therapy
- For preservation of ovarian function
-> ȯÀÚ ¿øÇϸé unilateral oophorectomy ½ÃÇà °¡´É
-> 2-18³â »çÀÌ¿¡ 8%Á¤µµ Àç¹ß
2. Stage Ia and Ib, grade 1
- TAH + BSO
- ȯÀÚ ¿øÇϸé unilateral oophorectomy °¡´É
3. Stage Ia and Ib, grade 2 or 3 & Stage III
- Adjuvant chemotherapy
; carboplatin and paclitaxel for 3-6 cycles
; older women - short course of a single agent(carboplatin or paclitaxel)
10. Treatment of Advanced stage disease
¨ç Cytoreductive Surgery(=Debulking surgery)
- Remove as much of the tumor and its metastases as possible
- TAH + BSO + complete omentectomy + resection of any metastatic lesions
- Effects of debulking surgery
: eliminate areas that are most likely to be relatively resistant to treament
(bulky tumor -> poorly vascularized & small growth fraction -> chemotherapy or radiation¿¡ ´ëÇÑ ¹ÝÀÀ ÀûÀ½)
: removal of the bulky tumor -> ¡éascites
: removal of the omental cake -> ¡énausea and early satiety
: removal of the intestinal metastasis -> improvement of overall nutritional status
- Goal of debulking surgery
: removal of all of the primary cancer and metastatic disease
: all metastatic nodules < 1.5 cm in maximal diameter (=> Optimal cytoreduction)
¨è Chemotherapy
1) Paclitaxel+Carboplatin vs Paclitaxel+Cisplatin
- Efficacy and survivals were similar
- More acceptable toxicity in carboplatin-containing regimen
2) Intraperitoneal(IP) Chemotherapy
- Value in the primary treatment of optimally respected stage III ovarian cancer remains unclear
3) Neoadjuvant chemotherapy
- 2~3 cycles of chemotherapy prior to cytoreductive surgery may be helpful in patients with massive ascites and large pleural effusion
* Chemotherapeutic Recommendation
1) Combination chemotherapy with carboplatin and paclitaxel : the treatment of choice
- Carboplatin(starting dose AUC=5~6) + Paclitaxel(175mg/m2)
: over 3 hours every 3 weeks for six cycles
2) In patients who cannot tolerate the combination
- single-agent carboplatin(AUC = 5~6)
3) In patients who have a hypersensitivity to paclitaxel
- alternative active drug (e.g. cyclophosphamide or topotecan)
4) In patients who cannot tolerate IV CTx
- oral alkylating agent
¨ê Immunotherapy
1) Interferon-, interferon-, and interleukin-2
2) Monoclonal antibody
- Antibodies directed toward CA125, HMFG (Human milk fat globulin)
- Herceptin: HER-2/neu oncogene
- Antibodies against mutated p53 tumor suppressor gene
11. Treatment assessment
- Second-look operation
: tumor marker³ª radiologic assessment´Â sensitivity°¡ ³Ê¹« ³·¾Æ subclinical disease¸¦ ³õÄ¥ ¼ö ÀÖ´Ù.
- CA125
: Ä¡·á½ÃÀÛ ½Ã¿¡ Áõ°¡µÇ¾î ÀÖ´Ù¸é ´ëüÀûÀ¸·Î second-look operation°ú correlation Àß µÇ¹Ç·Î Ä¡·á¹ÝÀÀÀ» º¼¶§ ½±°Ô ÀÌ¿ëÀÌ °¡´É
* Second-Look Operations
¨ç Performed on a patient who has no clinical evidence of disease
¨è Determine the response to therapy.
¨é Essentially identical to that for the staging laparotomy
12. Second-line Therapy
¨ç Secondary Cytoreduction
- Candidates : persistent or recurrent pelvic and abdominal tumors after primary therapy
- Suitable patient
: Reasonable chance of either prolonging life of resulting in significant palliation of symptoms
- Goal
: Remove all residual gross tumor, reduce the metastatic tumor burden <5mm maximal dimension
¨è Second-Line Chemotherapy
- The response rates for second-line chemotherapies : 15~35%
- Cisplatin, carboplatin, paclitaxel, docetaxel(Taxotere), topotecan, gemcitabine, etoposide(VP-16), doxorubicin (Doxil), vinorelbine (Navelbine), ifosfamide, 5-FU with leucovorin, hexamethylmelamine
¨é Platinum-sensitive Versus Platinum resistant
- Cisplatin sensitive tumor : Carboplatin (Response rates : 20-30%)
- Platinum- or paclitaxel- sensitive tumor : retreatment with a platinum or paclitaxel
(Response rate : 20-25%)
- Cisplatin-refractory tumor : response rates to second-line carboplatin : < 10%.
- Platinum-resistant tumor
: non-cross-resistant agent with different anticancer mechanism (Response rate : 8-28%)
: Topoisomerase inhibitors (topotecan, etoposide), anthracycline (doxorubicin), alkylating agents (ifosfamide), or other agents (hexamethylmelamine)
- Several new combination
: Gemcitabine and platinum
: Topotecan and platinum
¨ê Intraperitoneal Therapy
- Candidates : complete responses with minimal residual disease(<5mm)
; Cisplatin, 5-FU, Ara-C, etoposide, mitoxantrone (Response rates : 20-40%)
; interferon-, interferon-, TNF and IL-2 (Response rate : 30-50%)
¨ë Hormonal Therapy
- Tamoxifen
- GnRH agonist (Leuprolide acetate, Lupron)
- Aromatase inhibitors (e.g., Arimidex)
¨ì Radiation Therapy
- Whole-abdominal radiation -> relatively high morbidity (30%- intestinal obstruction)
13. Prognosis
¢Â Pseudomyxoma peritonei
- Mucinous cyst
-> perforate and initiate intra-abdominal transformation of the peritoneal mesothelium to a mucin-secreting epithelium
-> gradual accumulation in the peritoneal cavity of huge amounts of gelatinous material
(pseudomyxoma peritonei)
- 13 cases of pseudomyxoma
: 10 cases - originated in benign ovarian tumors
: 2 cases - originated in malignant ovarian tumors
: 1 case - originated in appendiceal mucocele
- Treatment
: Repeatedly surgery, because of the recurrent nature of the lesion
: Intraperitoneal alkylating agents -> little success
: Radiation, mucolytic agents -> disappointing
- Prognosis
: 45 % of 5-year survival
: 40% of 10-year survival
1. Pathology : Ovarian cancerÀÇ 90%´Â epithelium or mesothelium orign
¨ç Invasive Cancer
: Serous type (75%), mucinous (20%), endometrioid (2%),
: Clear cell, Brenner, and undifferentiated carcinoma (<1%)
¨è Borderline Tumors
- Tumor of low malignant potential
- Confined to the ovary for long periods,
- Predominantly in premenopausal women
: 30~50´ë¿¡ ÈçÇÔ invasive carcinoma´Â 50-70´ë¿¡ ÈçÇÔ
- Good prognosis
- Metastatic implants
: noninvasive vs invasive form
: invasive formÀÌ peritoneal cavity¿¡ progressive, proliferative disease¸¦ ¹ß»ý½ÃÄÑ intestinal obstruction, death¿¡ À̸¦ °¡´É¼ºÀÌ ´õ ³ô´Ù
- 20~25% : spread beyond the ovary
2. Etiology
¨ç Associated with low parity, infertility, early menarche and late menopause
=> Suppression of ovulation°ú °ü·Ã¼º ÀÖ´Ù´Â °¡¼³À» µÞ¹Þħ
=> Repetitive disruption and repair of surface epithelium -> higher probability of spontaneous mutations
3. Prevention
¨ç Having at least one child (risk reduction of 0.3 to 0.4)
¨è Oral contraceptive (>5 year) : only documented method of chemoprevention
¨é Fenretinide(4-hydroxyretinoic acid) -> ÇöÀç trial Áß
¨ê Prophylactic oophorectomy : reduce risk of ovarian cancer, but not eliminate peritoneal carcinoma
4. Screening
¨ç TV-USG : >95% sensitivity for the detection of early-stage
¨è CA-125 : sensitivity - 50% of stage I
- 60% of stage II
=> µÎ°¡Áö ¸ðµÎ false positive ¶§¹®¿¡ cost effective ÇÏÁö ¾Ê°í routineÀ¸·Î ÀÌ¿ëµÇÁö ¾Ê´Â´Ù.
5. Symptoms and Signs
- Most of pts has no symptoms
`¨ç In early-stage disease
- Irregular menses, urinary frequency or constipation, lower abdominal distension, pressure, pain(such as dyspareunia)
- Acute Sx : pain secondary to rupture or torsion
¨è In advanced-stage disease
- Related Sx with ascites, omental metastases, and bowel metastases
; abdominal distention, bloating, constipation, nausea, anorexia, or early satiety
- Premenopausal women : Irregular or heavy mense
- Postmenopausal women : vaginal bleeding
¨é Sign
- Pelvic mass on P/E ; solid irregular, fixed mass
- Upper abdominal mass or ascites
6. Diagnosis
- DDx with benign neoplasm, functional cysts of the ovaries, pelvic inflammatory disease, endometriosis, pedunculated uterine leiomyomas, diverticulitis, colonic mass, pelvic kidney
- CA125 : distinguishing malignant from venign pelvic mass
: postmenopausal pts¿¡¼ >95 U/ml À̸é 96% positive predictive value for malignancy
- Cystic mass > 8cm : tumor °¡´É¼º ³ôÀ½
- Preoperative evaluation
: Chest radiography, IVP,
: CT, MRI - pelvic mass°¡ definiteÇϸé ÇÊ¿äÄ¡ ¾ÊÁö¸¸, ascites°¡ Àְųª pelvic mass°¡ ¾ø¾î liver or pancreatic tumor¸¦ ã¾Æº¼ ¶§ ½ÃÇà °¡´É
: ovarian metastasisÀÇ primary originÀ» ã±â À§ÇØ
- 45¼¼ ÀÌ»óÀÇ È¯ÀÚ´Â colonoscopy½ÃÇàÇϰí, gastric symptomÀÌ ÀÖ´Â °æ¿ì¿¡´Â E.G.D ½ÃÇàÇÑ´Ù. breast mass°¡ ¸¸Á®Áö´Â °æ¿ì mammography ½ÃÇàÇϰí PAP smear¿Í ÇÔ²² irregular mense ¶Ç´Â postmenopausal vaginal bleedingÀÌ ÀÖÀ» °æ¿ì EM Ca¸¦ È®ÀÎÇϱâ À§ÇØ endocervical curettage & EM Bx ½ÃÇà
7. Patterns of Spread
¨ç Transcoelomic : Exfoliation of cells that implant along the surfaces of the peritoneal cavity
¨è Lymphatic : pelvic and paraaortic LN
-> lymphatic channels of the diaphragm and retroperitoneal LN
-> supraclavicular LN
¨é Hematogenous : lung and liver (only 2-3%)
: diaphragm À§ÂÊÀ¸·Î ħ¹üÀÌ Áø´ÜµÈ ȯÀÚÀÇ ´ëºÎºÐÀº right pleural effusion ÀÖÀ½
8. Prognostic Factors
¨ç Pathologic Factors
1) Hystologic type : Clear cell carcinoma - poor prognosis
2) Hystologic grade : Grade°¡ ³ôÀ»¼ö·Ï ¿¹Èİ¡ ³ª»Ý
¨è Biologic Factors
1. Ploidy : low-stage cancer -> tend to be diploid
: high-stage cancer -> tend to be aneuploid
2. Protooncogenes : HER-2/neu oncogene -> poor prognosis
: p53 mutation
¨é Clinical Factors
: Stage
: Extent of residual disease after primary surgery
: Volume of ascites
: Patient age
: Performance status
9. Treatment of Early stage disease
¨ç Surgical staging(Exploratory laparotomy)
: FIGO staging based on findings at surgical exploration
- FIGO stage
¨è Stage I
1. Borderline Tumors
- Surgical resection of the primary tumor
- No subsequent chemotherapy or radiation therapy
- For preservation of ovarian function
-> ȯÀÚ ¿øÇϸé unilateral oophorectomy ½ÃÇà °¡´É
-> 2-18³â »çÀÌ¿¡ 8%Á¤µµ Àç¹ß
2. Stage Ia and Ib, grade 1
- TAH + BSO
- ȯÀÚ ¿øÇϸé unilateral oophorectomy °¡´É
3. Stage Ia and Ib, grade 2 or 3 & Stage III
- Adjuvant chemotherapy
; carboplatin and paclitaxel for 3-6 cycles
; older women - short course of a single agent(carboplatin or paclitaxel)
10. Treatment of Advanced stage disease
¨ç Cytoreductive Surgery(=Debulking surgery)
- Remove as much of the tumor and its metastases as possible
- TAH + BSO + complete omentectomy + resection of any metastatic lesions
- Effects of debulking surgery
: eliminate areas that are most likely to be relatively resistant to treament
(bulky tumor -> poorly vascularized & small growth fraction -> chemotherapy or radiation¿¡ ´ëÇÑ ¹ÝÀÀ ÀûÀ½)
: removal of the bulky tumor -> ¡éascites
: removal of the omental cake -> ¡énausea and early satiety
: removal of the intestinal metastasis -> improvement of overall nutritional status
- Goal of debulking surgery
: removal of all of the primary cancer and metastatic disease
: all metastatic nodules < 1.5 cm in maximal diameter (=> Optimal cytoreduction)
¨è Chemotherapy
1) Paclitaxel+Carboplatin vs Paclitaxel+Cisplatin
- Efficacy and survivals were similar
- More acceptable toxicity in carboplatin-containing regimen
2) Intraperitoneal(IP) Chemotherapy
- Value in the primary treatment of optimally respected stage III ovarian cancer remains unclear
3) Neoadjuvant chemotherapy
- 2~3 cycles of chemotherapy prior to cytoreductive surgery may be helpful in patients with massive ascites and large pleural effusion
* Chemotherapeutic Recommendation
1) Combination chemotherapy with carboplatin and paclitaxel : the treatment of choice
- Carboplatin(starting dose AUC=5~6) + Paclitaxel(175mg/m2)
: over 3 hours every 3 weeks for six cycles
2) In patients who cannot tolerate the combination
- single-agent carboplatin(AUC = 5~6)
3) In patients who have a hypersensitivity to paclitaxel
- alternative active drug (e.g. cyclophosphamide or topotecan)
4) In patients who cannot tolerate IV CTx
- oral alkylating agent
¨ê Immunotherapy
1) Interferon-, interferon-, and interleukin-2
2) Monoclonal antibody
- Antibodies directed toward CA125, HMFG (Human milk fat globulin)
- Herceptin: HER-2/neu oncogene
- Antibodies against mutated p53 tumor suppressor gene
11. Treatment assessment
- Second-look operation
: tumor marker³ª radiologic assessment´Â sensitivity°¡ ³Ê¹« ³·¾Æ subclinical disease¸¦ ³õÄ¥ ¼ö ÀÖ´Ù.
- CA125
: Ä¡·á½ÃÀÛ ½Ã¿¡ Áõ°¡µÇ¾î ÀÖ´Ù¸é ´ëüÀûÀ¸·Î second-look operation°ú correlation Àß µÇ¹Ç·Î Ä¡·á¹ÝÀÀÀ» º¼¶§ ½±°Ô ÀÌ¿ëÀÌ °¡´É
* Second-Look Operations
¨ç Performed on a patient who has no clinical evidence of disease
¨è Determine the response to therapy.
¨é Essentially identical to that for the staging laparotomy
12. Second-line Therapy
¨ç Secondary Cytoreduction
- Candidates : persistent or recurrent pelvic and abdominal tumors after primary therapy
- Suitable patient
: Reasonable chance of either prolonging life of resulting in significant palliation of symptoms
- Goal
: Remove all residual gross tumor, reduce the metastatic tumor burden <5mm maximal dimension
¨è Second-Line Chemotherapy
- The response rates for second-line chemotherapies : 15~35%
- Cisplatin, carboplatin, paclitaxel, docetaxel(Taxotere), topotecan, gemcitabine, etoposide(VP-16), doxorubicin (Doxil), vinorelbine (Navelbine), ifosfamide, 5-FU with leucovorin, hexamethylmelamine
¨é Platinum-sensitive Versus Platinum resistant
- Cisplatin sensitive tumor : Carboplatin (Response rates : 20-30%)
- Platinum- or paclitaxel- sensitive tumor : retreatment with a platinum or paclitaxel
(Response rate : 20-25%)
- Cisplatin-refractory tumor : response rates to second-line carboplatin : < 10%.
- Platinum-resistant tumor
: non-cross-resistant agent with different anticancer mechanism (Response rate : 8-28%)
: Topoisomerase inhibitors (topotecan, etoposide), anthracycline (doxorubicin), alkylating agents (ifosfamide), or other agents (hexamethylmelamine)
- Several new combination
: Gemcitabine and platinum
: Topotecan and platinum
¨ê Intraperitoneal Therapy
- Candidates : complete responses with minimal residual disease(<5mm)
; Cisplatin, 5-FU, Ara-C, etoposide, mitoxantrone (Response rates : 20-40%)
; interferon-, interferon-, TNF and IL-2 (Response rate : 30-50%)
¨ë Hormonal Therapy
- Tamoxifen
- GnRH agonist (Leuprolide acetate, Lupron)
- Aromatase inhibitors (e.g., Arimidex)
¨ì Radiation Therapy
- Whole-abdominal radiation -> relatively high morbidity (30%- intestinal obstruction)
13. Prognosis
¢Â Pseudomyxoma peritonei
- Mucinous cyst
-> perforate and initiate intra-abdominal transformation of the peritoneal mesothelium to a mucin-secreting epithelium
-> gradual accumulation in the peritoneal cavity of huge amounts of gelatinous material
(pseudomyxoma peritonei)
- 13 cases of pseudomyxoma
: 10 cases - originated in benign ovarian tumors
: 2 cases - originated in malignant ovarian tumors
: 1 case - originated in appendiceal mucocele
- Treatment
: Repeatedly surgery, because of the recurrent nature of the lesion
: Intraperitoneal alkylating agents -> little success
: Radiation, mucolytic agents -> disappointing
- Prognosis
: 45 % of 5-year survival
: 40% of 10-year survival