Corresponding author: Nicolae Bacalbaæa, MDDimitrie Racoviåã Street, no. 2, Bucharest, Romaniae-mail: nicolae_bacalbasa@yahoo.ro

Modern Medicine. 2015, Vol. 22, No. 2 : 172- Copyright© Celsius

Case Report

Modern Medicine. 2015, Vol. 22, No. 2 : 172-176 Copyright© Celsius

Cytoreductive Surgery for Peritoneal Carcinomatosis fromEndometrial Cancer - A Case Report and Literature ReviewN. Bacalbaæa1, C. Anghel2, I. Barbu2, I. Dudus2, M.I. Ionescu2, M. Pautov2, M. Motthor2, Irina Bãlescu3, V. Braæoveanu2,4

1“Carol Davila” University of Medicine and Pharmacy Bucharest, Romania2“Dan Setlacec” Department of General Surgery and Liver Transplantation Fundeni Clinical Institute, Bucharest, Romania3“Ponderas” Hospital, Bucharest, Romania4„Titu Maiorescu” University, Faculty of Medicine, Bucharest, Romania

REZUMAT

Citoreducåie chirurgicalã pentru carcinomatoza peritonealã din cancerul endometrial - prezentare de cazæi revizia literaturiiNeoplasmul de endometru reprezintã una din cele mai fercvente malignitati ale tractului genital feminin,prezentând incidenåã în creætere mai ales din cauza cresterii numarului de persoane supraponderale. În timpce cazurile diagnosticate æi operate în stadii precoce ale bolii au evoluåie favorabilã, lucrurile stau cu totul altfel în cazurile diagnosticate în stadii avansate. În orice caz, pacientele care prezintã diseminãri peritonealela momentul diagnosticului beneficiazã de un abord chirurgical agresiv, similar cu cel practicat în neoplasmulovarian avansat. Prezentãm cazul unei paciente de 67 ani diagnosticatã cu carcinomatozã peritonealã de origine endometrialã la care principiile chirurgiei citoreductive au fost aplicate cu success.

Cuvinte cheie: neoplasm endometrial, carcinomatozã peritonealã, citoreducåie

ABSTRACTEndometrial cancer is one of the most common malignancies of the female reproductive tract, with increasingincidence particularly due to the increase proportion of the overweight persons. While cases diagnosed in anearly stage of the disease report an excellent outcome, things significantly change when it comes to advancedstages. However it seems that women who already present peritoneal seeding at the moment of diagnosis benefit most from an aggressive surgical approach, similar to the one performed in advanced stage ovarian cancer. We present the case of a 67 year old patient diagnosed with peritoneal carcinomatosis from endometrial cancer in which the principles of cytoreductive surgery were successfully applied.

Key words: endometrial cancer, peritoneal carcinomatosis, cytoreductive surgery

Cytoreductive Surgery for Peritoneal Carcinomatosis from Endometrial Cancer 173

INTRODUCTION

Endometrial cancer is one of the most commonmalignancies of the genital tract in women, with anincreasing incidence in the last few years. The reported incidence in the United States surpassed40.00 cases/year while the death rate reached almost7500 deaths/year (1,2). The most important prognos-tic factors are thought to be diabetes, estrogen secreting tumors, nulliparity and the higher numberof overweight persons (2). While up to 70% ofpatients are diagnosed in an early stage of the diseaseand report an excellent outcome (5 year overall survival of 90%), patients diagnosed in an advancedstage of the disease have a poor prognosis associated with low rates of survival - 67% and 23%,respectively, for cases with regional or distant disease(3). However, in these cases it seems that an aggressive surgical approach similar to the one performed in advanced ovarian cancer is perfectlyjustified (2,4).

CASE REPORT

A 67 year old, nulligesta, nullipara, obese patientpresented for abdominal and pelvic diffuse pain asso-ciated with vaginal bleeding. Local examinationrevealed the presence of a distended slightly painfulabdomen, with no palpable tumor mass. A biopticuterine curettage was performed and the histopatho-logical findings revealed a poorly differentiatedendometrial adenocarcinoma. Abdomino-pelviccomputed tomography revealed the presence of disseminated tumor masses all over the peritonealsurface. The patient was submitted to surgery; intra-operatively a large uterine tumor and diffuse peritoneal carcinomatosis were found, so the patientwas operated according to the principles of ovariancytoreductive surgery. A radical total hysterectomyen bloc with bilateral adnexectomy, total omentec-tomy, total colectomy, pelvic and parietal peritonec-tomy, pelvic and lymph node dissection were performed (Fig. 1-9). The histopathological findingsconfirmed the presence of a poorly differentiatedendometrial adenocarcinoma.

DISCUSSIONS

The efficacy of debulking surgery and minimalresidual disease after cytoreductive surgery in ovarian cancer encouraged the surgeons to apply the

same principles in other advanced abdominal malignancies in order to obtain a better outcome in

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Figure 1. Initial aspect – disseminated peritoneal tumors associatedwith an uterine tumor

Figure 2. Cmplete mobilization of the uterine body

Figure 3. Tumoral nodules involving the mesosigmoid

Figure 4. Tumoral nodules involving the transverse mesocolon Figure 5. Performing parietal peritonectomy

Figure 6. The final aspect after resection, pelvic and para-aorticlymph node dissection Figure 7. Parietal peritonectomy

Figure 8. The final aspect of the pelvic cavity after resection

Figure 9. The specimens: total hysterectomy with bilateral adnexectomy, total colectomy and total omentectomy

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terms of survival. Several studies demonstrated theefficacy of cytoreductive surgery associated withother therapeutic strategies such as hypertermicintraperitoneal chemotherapy (HIPEC) in coloncancer and endometrial cancer (2, 4-6).

Delotte et al included in their study 13 patientsdiagnosed with advanced stage endometrial cancerwith peritoneal disseminations who were submittedto complete resection and HIPEC. During cytoreductive surgery, an average of 2 organs wereresected, the most frequently performed resectionsbeing bowel resection, atypical hepatectomies,splenectomies, partial cystectomy or partial frenectomy. They reported a disease free survival of11,4 months and a median overall survival of 19,4months. An important conclusion of this study wasthat association of HIPEC was able to offer a significant increase of survival when compared tocytoreduction alone (19,4 months vs. 12 months) (2).Some other studies also consider that aggressivecytoreduction remains the most important prognos-tic factor related to an increased overall survival,while other authors consider that the evolution ofthese cases in strongly correlated to histopathologicalfeatures and to the initial extent of the disease (7,8).Bakrin et al reported a case series of 5 patients withadvanced endometrial cancer with peritoneal carcinomatosis treated by the same principles andreported improved outcomes: 2 patients were free ofdisease after 2 and 3 years while the other 2 patientswere living with recurrence after 1 and 3 years (4).

Abu Zaid et al included in their study 6 patientsdiagnosed with advanced stage endometrial cancerwho were treated by cytoreductive surgery andHIPEC from November 2010 to August 2013.Cytoreductive surgery consisted of peritonectomyand visceral resections in order to provide a complete elimination of the tumor masses from theabdomino-pelvic Cavity while HIPEC was performed with Cisplatin and Doxorubicin at 41 to42,2°C for 90 minutes. Postoperatively all patientswere submitted to systemic chemotherapy based oncarboplatin and paclitaxel regimens. Two casesdeveloped recurrent disease during the next 6months, one of them being dead because of the disease 5 months after surgery, while the other 4patients were alive and free of any recurrence at7,34,35 and 19 months (9).

There are authors who consider that endometrialcancer consist in fact of two different tumor types:type 1 endometrial cancer has a primary lymphatic

spread by pelvic lymph nodes especially obturatoryfossa lymph nodes and only secondarily to iliac lymphnodes, while type 2 has a peritoneal pattern of spread(10). According to these two different patterns ofspread, studies have shown that for type 1 stage IVendometrial cancer complete debulking can beachieved only in 44-72% and only patients with goodbiological status should be candidates for this surgicalapproach (11,12,13). Bristow et al conducted a studyon 65 patients diagnosed with advanced endometrialcancer who were submitted to surgery between January 1990 and December 1998. Complete R0cyotreduction was defined as the absence of residualdisease larger than 1 cm; they demonstrated that theoverall survival was significantly higher in cases submitted to R0 resection (34,3 months) when compared to those with >1 cm residual disease (11months, p=0,0001). Other factors associated withimproved outcomes were higher performance status,age under 58 years, adjuvant chemo-irradiation. Onmultivariate analysis age (p=0,023), performance status (p=0,043) and residual disease (p=0,0001)were independent predictors of survival (13).

When it comes to patients in whom type 2 stageIV endometrial cancer is encountered, it seems thatthis subtype resembles most with advanced ovariancancer and its propagation via transperitoneal route;in consequence, these patients should benefit mostfrom an aggressive surgical approach similar withdebulking surgery in advanced stage ovarian cancer(14-21). In order to increase the rate of completecytoreduction some authors recommended theadministration of 3 cycles of neo-adjuvant chemo-therapy (22); however patients who report a poorresponse to neoadjuvant treatment might also notbenefit from cytoreductive surgery too (23).

When it comes to association of adjuvant treat-ments such as radiotherapy, studies have shown thatit might be useful in the postoperative course.Administrated pre-operatively, radiation therapyseems to interfere with the adequate tumor stagingwithout improving the outcomes (23,24). In order toincrease the overall survival, adjuvant chemotherapycan be associated; most authors sustain the association of taxanes- platinum salts regimens (25-27). Randall et al included in their study 388 patientsdiagnosed with stage IV endometrial cancer whowere submitted first to cytoreductive surgery (withmaximum residual disease < 2 cm); after surgery,the patients were randomly assigned to doxorubicinand cisplatin chemotherapy for seven courses or

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whole-abdominal radiotherapy with 30 Gy in 20 fractions and a pelvic boost of 15 Gy. Although therecurrence rate was similar (55%) in the pelvis andabdomen in both groups, 2-year progression-free survival was better with chemotherapy (59% vs 46%)as was the overall survival (70% vs 59%; p_0·01) (27).

However, the largest meta-analysis conducted onthe subject of advanced stage endometrial cancer andrecurrent endometrial cancer, performed by Barlin etal on 14 studies came to demonstrate that improvedsurvival was positively associated with complete surgical cytoreduction (each 10% increase improvedsurvival by 9.3 months, p = 0.04) and receiving post-operative radiation therapy (each 10% increaseimproved survival by 11.0 months, p= 0.004); thesame meta-analysis concluded that an increasing proportion of patients receiving chemotherapy wasnegatively associated with survival (each 10%increase decreasing survival by 10.4 months, p=0.007) (28).

CONCLUSIONS

The most appropriate therapeutic protocol inadvanced endometrial cancer is not well establisheddue to the paucity of data and due to the limitednumber of patients included in the studies published on this topic so far. However, almost allstudies come to sustain the benefit of cytoreductivesurgery as part of an aggressive surgical approach;similarly to advanced ovarian cancer, in advancedendometrial cancer one of the most important prognostic factors is the absence of macroscopicresidual disease at the end of resection. Other therapies such as HIPEC seem to improve the out-comes without increasing the early postoperativemorbidity and mortality. Association of adjuvantchemo-irradiation might also play a role but furtherstudies are still needed.

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