Case Conference April 5th 2017

05-Apr-2017, Divisi Ginekologi Onkologi RSCM

Mrs. X

 

Left mucinous ovarium carcinoma

CASE DESCRIPTION ( March 29^th ,2017)

 

-       Patient complained of having abdominal pain since the second pregnant. This began when she had first pregnant, she did examination ultrasonography. The result is she got cyst about 7 cm and this size is enlargement in the second pregnant until 14 cm. Then on 15 February 2017 she did labor by section cecaria and continued with salpingooofrectomy sinistra. Post-operative pathology result was left mucinous ovarium carcinoma. Left tuba is separated from malignancy tumor cell. Then she was referred to RSCM to get further therapy.

 

Physical examination on March 29^th, 2017:

General status:

CM. BP: 136/80mmHg, HR: 76 bpm, RR: 20x/m, T:36.3^oC, Height 152cms, Weight 60,5 kgs

Head: Pale conjungtiva (-/-)

Neck: supraclavicula lymph nodes (-/-)

Axilla: lymph nodes (-/-)

Thorax: symmetry shape

Cardia: no murmur, no gallop

Abd: flat, no palpable mass

Extremity: inguinal lymph nodes (-/-)

Gyn state: 

Inspection: normal external genitalia organ

Inspeculum: smooth portio, fluor (-) fluxus (-)

RVT: anteflexi corpus uteri with normal shape and size.  parametrium within normal limit, no palpable mass in both adnexa. TSA normal, rectal mass (-).

 

 

 

 

Hystophatology (20/02/2017)

Macroscopic

Received an ovarian tissue likes cyst that have been split in the size of 13 x 10 x 6 cm. In lamelation looked white solid mass likes jelly. Partially looked as white fragile solid mass with diameter size is  4 cm, wall thickness is 0.3 cm. Tuba is not found.

 

Microscopic

Preparation of left ovarian surgery is tumor mass which consist of round cells, oval which  growing hyperplastic, groups, partially forming glandular structures, partially papillifer, polimorfic cell nucleus, hiperkromatic, partially vesicular, clear small nucleus, founded mitosis. Partially fibrocolagen connective tissue stroma run into hyalinitation, spreaded lymphocyte inflammatory cells and hemorrhage with dilatation of blood vessels. In another part looked formed  extracellular mucin colom and wall of epithelial cyst coated torax cell with goblet which partly erosive, nucleus cell within normal limit, nothing seemed invasion of tumor cells into the underlying stroma.

Preparation of tuba like rugae mucosa which coated torac epitelial that partly erosive, the nucleus of cells within normal limits. In subepithelial looked connective tissue stroma fibromuscular with spreaded inflammatory cells including lymphocytes cell inflamation and bleeding with dilatation and blood vessels. Not visible sign of malignant.

 

Conclusion

Left mucinous ovarium carcinoma.

Left tuba is separated from malignancy tumor cell

 

USG 31/03/2017

 

Retrofleksi uterus with shape and size within normal limit. Homogeneous myometrium.

Uterine cavity  doesn’t contain abnormal mass.

Reguler basalis stratum endometrium, thin <2 mm.

Portio and endocervix within normal limit.

Right ovarium with shape and size within normal limit.

Nonvisual left ovarium (post SOS)

No abnormality mass in both adnexa

No looked enlargement of paraaorta and parailiaka lymphe nodes

Post SOS. No abnormality of organic interna genitalia

Liver and both renal are normal limit

Conclusion

POST SOS. No organic abnormality on interna genitalia

 

 

Introduction

 

Mucinous carcinoma accounts for 3 to 4 percent of primary ovarian cancers. These neoplasms most often present in perimenopausal women in their late 40s to early 50s, although they have been reported in patients as young as 14 and old as 87. Nearly all mucinous carcinomas of the ovary present with early stage disease, usually stage I.

When including all types of mucinous neoplasms, they account for 10 to 15 percent of all ovarian neoplasms. Approximately 80 percent are benign mucinous cystadenomas, and the majority of the rest are mucinous borderline neoplasms.

Primary ovarian mucinous carcinoma and borderline neoplasms are often seen together in the same tumor. In addition, it is not unusual to see a mucinous borderline neoplasm with high-grade intraepithelial neoplasia adjacent to invasive mucinous carcinoma. Consequently, primary ovarian mucinous carcinomas are thought to arise from mucinous borderline neoplasms.

 

CLINICAL QUESTION

 

What is appropriate management for Patient with ovarian carcinoma post incomplete surgical staging?

 

METHODS

 

Search strategy

The search was conducted on Pubmed, Science Direct, and Cochrane  on April 4^th 2017, using the search tool containing the keyword “Ovarian Carcinoma post Incomplete surgical staging, complete surgical staging, chemotherapy, overall survival ” (Table 1).

 

Search results were filtered by the engine according to the following criteria : articles published in the past 10 year, human species, and English language. Search strategy, result, and the inclusion and exclusion criteria are shown in the flowchart 

The titles of the filtered results from Pubmed, Science Direct, and Cochrane were screened using the inclusion criteria. A second screening was conducted by reading the abstract, and finally 5 articles were found.

 

 

 

Critical Appraisal

 

Two article from Ingrid Ramirez, MD; Hye Sook Chon, MD; Sachin M. Apte, MD, MS., 2011., The Role of Surgery in the Management of Epithelial Ovarian Cancer and Tien Le, M.D., 2002. The Benefits of Comprehensive Surgical Staging in the Management of Early-Stage Epithelial Ovarian Carcinoma

Discussion

A gynecologic malignancy is estimated to complicate four to eight of every 100,000 pregnancies. Unfortunately, the data on the effects of antineoplastic drugs administered during pregnancy have largely been derived from case reports, small case series, and collected reviews of pregnant women treated for a variety of cancers. There are even less data on long-term outcomes in offspring.

The finding of early-stage epithelial ovarian cancer (EOC) is occasionally made during surgery for an emergent (eg, torsion) or benign (ie, ovarian cystectomy) indication. In these cases, women will not have undergone surgical staging and technically speaking would be considered to have apparent early but unstaged ovarian cancer. For women with unstaged apparent early EOC, we suggest staging because both prognosis and adjuvant treatment options are tied to disease stage. Often this surgery can be performed through a minimally invasive approach. Alternatively, some evidence suggests that surgery may not be required if adjuvant chemotherapy is administered:

·         As described above, the Adjuvant Chemotherapy in Ovarian Neoplasm (ACTION) trial of adjuvant chemotherapy versus observation highlighted the importance of complete surgical staging in patients with early stage EOC. In this trial, the benefit of adjuvant chemotherapy was limited to patients with incomplete staging:

·         For the 297 women who were not completely staged, adjuvant chemotherapy was associated with significant improvement in recurrence-free survival (Hazard Ratio [HR] 1.78, 95% CI 1.15-2.77) and overall survival (HR 1.75, 95% CI 1.04-2.95) compared with observation.

·         For the 224 women enrolled in to the observation arm, complete staging was associated with a significant improvement in recurrence-free (HR 1.82, 95% CI 1.02-3.24) and overall survival (HR 2.31, 95% CI 1.08-4.96) over incomplete staging.

·         For the 151 women who were completely staged, chemotherapy was not associated with a recurrence-free or overall survival advantage over observation.

·         In a retrospective study of 88 patients with early stage ovarian cancer (36 unstaged), all of whom received adjuvant chemotherapy, there was no difference in outcomes among women who underwent staging after a diagnosis of EOC and those who did not undergo a second surgery for staging. The estimated rates of five-year progression free survival were 85 and 80 percent, respectively, with corresponding rates of overall survival of 85 and 88 percent.

·         In a separate series of 138 patients with tumor confined to the ovary, 53 underwent adjuvant chemotherapy (34 after staging, 19 without staging performed). The relapse rate at a median follow-up of 58 months was 32 percent among staged patients and 42 percent among unstaged patients.

While these underpowered studies suggest that it might be safe to omit formal surgical staging after a woman has been diagnosed with apparent EOC, prospective studies are needed to confirm this finding before incorporating this into standard practice. For women who choose not to undergo formal surgical staging, we recommend adjuvant chemotherapy. With grade 3 or clear cell tumors, where chemotherapy will be administered regardless of staging outcome, there may be less impetus for a secondary procedure.

There are several different histologic types of malignancy that can arise within the ovary including epithelial ovarian cancer (EOC), ovarian germ cell tumors, and sex-cord stromal tumors. In some series of women presenting with an ovarian malignancy while pregnant, germ cell tumors predominate, while others report a higher frequency of EOC.

Following surgery, the indications for adjuvant treatment of epithelial ovarian cancer (EOC) are similar for pregnant and non-pregnant women. However, administration of chemotherapy during the first trimester should be avoided. We recommend chemotherapy for:

·         Women with early-stage EOC,  if any of the following high-risk features is present: stage IA/IB, grade 2/3; stage IC or II (any histology); serous or clear cell carcinoma (stage IA, IB, IC, or II)

The standard treatment for women begins with surgical staging. Stage is known to be an important predictor of survival with women having stage I disease achieving the best prognosis. Estimated 5-year survival is reported to be between 70% and 90 %, compared with less than 30% for those advaed disease. For those presenting advanced disease, studies have shown that surgical resection is associated with survival with women achieving a  complete cytoreduction having best chance survival. Given significance of surgical staging, the Gynecologic Oncol- ogy Group has specified a formal staging procedure for women with gynecologic malignancies, which applies to both early and advanced stage ovarian cancer The standard treatment of ovarian cancer is the combination of debulking surgery and chemotherapy. There is an ongoing discussion on which treatment is best: primary debulking surgery (PDS) or neoadjuvant chemotherapy with interval debulking (NACT-IDS). Even a large randomized trial has not settled this issue.

Surgical evaluation is indicated for most women with known or suspected EOC. The goals of the initial surgery are to obtain a pathologic diagnosis, accurately determine the extent of disease and, when feasible, optimally cytoreduce the ovarian cancer. Accurate surgical staging is particularly important for apparent early-stage disease, ie, women with an ovarian cancer that appears grossly confined to the ovary.

Diagnosis of early-stage epithelial ovarian carcinoma without all the information needed to assign an accurate surgical stage. Incomplete surgical staging, making treatment recommendations difficult. The most common missing pieces of information are the status of the omentum, the status of the retroperitoneal nodes, and peritoneal/diaphragmatic biopsies. Approximately 25% to 30% of women with apparent early-stage disease will be upstaged upon thorough surgical staging.

Steinberg et al. studied 109 omenta in 159 patients with ovarian cancers; 22% of the normally looking omenta did carry macroscopic tumor deposits with a mean tumor diameter of 6.7 mm. Dexeus et al. Documented 15% positive pelvic nodes and 5.5% isolated paraaortic nodal involvement in 68 patients. Lang studied, The incidence of microscopic lymphatic metastasis was 10.3%.

Kolomainen et al. reported that the outcomes of patients with early-stage ovarian cancer who relapsed following a policy of no adjuvant chemotherapy are similar to those of patients with stage III ovarian cancers who are given chemotherapy at the time of diagnosis.

Patients with early-stage ovarian cancer should undergo a comprehensive staging surgery to guide postoperative management. adjuvant chemotherapy statistically significantly improved recurrence-free survival, but no improvement was seen in overall survival. Tumor grade, histologic cell type, and completeness of surgical staging were independent prognostic factors. adjuvant chemotherapy is not effective in optimally staged patients.

Adjuvant chemotherapy in early-stage ovarian cancer is predominantly effective in patients with occult residual disease Starting adjuvant chemotherapy between 21 and 35 days after primary debulking surgery for ovarian cancer is associated with increased survival. The optimal time period for chemotherapy initiation is between 25 and 29 days, although this brief window is not statistically different from the larger two-week interval of 21–35 days. Close clinical follow-up women with higher risk for chemotherapy delay.

Conclusion

Based on the current state of the evidence, we purpose to complete surgical staging

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