Pelvic bone cancer

Advanced abdominal and pelvic malignancy represents a major challenge to the surgical oncologist. Usually patients receive palliative surgery or systemic chemotherapy with only minor responses and little or no survival benefit. To optimize the utilization of the chemotherapeutic drugs, alternative approaches have been developed such as regional chemotherapy and high-dose chemotherapy with bone marrow support. The former consists of tumor targeting by direct administration of higher dosages of chemotherapeutic agents into the blood vessels feeding the tumor area. The latter uses systemic myeloablative doses of chemotherapy followed by rescue with either bone marrow or peripheral blood cell precursors (stem cells).

Isolation of the pelvic vasculature to treat pelvic malignancies is a technique that has evolved over the last 40 years. Intra-arterial chemotherapy with nitrogen mustard was initiated in the 1950s. Currently, alkylating agents, such as phenylalanine mustard is used more commonly for intra-arterial chemotherapy regimens. Regional perfusion by extra-corporeal circuit was introduced separately by Creech and Stehlin in the late fifties.1-3 Since that time, approximately 20 studies have described the use of isolated pelvic perfusion in 377 patients of whom 39% had colorectal cancer, 36% had gynecologic malignancy and the remaining few had soft tissue tumors (5%), melanomas (4%), urinary tract cancer (3%) and male genital tract cancer (2%). Isolated pelvic perfusion achieves high drug level in the pelvis (pelvic:systemic ratio of 2.8-13.3:1) by isolating the pelvic vasculature with occlusion of the large abdominal vessels with intra-vascular balloons and external thigh tourniquets.

Our team has utilized the minimally invasive procedure of isolated pelvic perfusion using the balloon occlusion technique both in the palliative and curative setting.4,5 While palliative perfusions may ameliorate the quality of life, the neo-adjuvant approach has the potential of facilitating the effectiveness of a curative resection. Our last report of neo-adjuvant isolated pelvic perfusion included 10 patients with unresectable pelvic colorectal cancer. Almost all patients underwent 2 courses of pelvic perfusion and 8 of them received curative surgery. An R0 resection was possible in 3 of theses 8 patients. Overall, 2 patients were alive without disease at 16 and 32 months, one is alive at 12 months with disease, and seven have died of disease 5-20 months thereafter.5 Long-term survival has also been achieved for soft tissue tumors and cancer of the cervix.6,7

The current report describes the use of isolated chemotherapeutic perfusion of the pelvis and upper abdomen for advanced recurrent endometrial cancer combined with stem cell support to counteract the myelotoxicity from high-dose chemotherapy administered during the perfusion. The patient was subsequently resected of all disease, and remains with no evidence of disease two and a half years after resection.

CASE REPORT

A 70-year-old female with a history of endometrial cancer treated with 500 cGy of radiation and total hysterectomy bilateral salpingoopherectomy, remained disease free for 18 years. Two and a half years ago she presented to her primary care physician with a complaint of increased abdominal girth. On physical exam, a mid-abdominal mass was palpated and a computed tomography (CT) scan revealed multiple large abdominal masses. Biopsies demonstrated well-differentiated, ER and PR positive, adenocarcinoma consistent with recurrent endometrial carcinoma. The patient began a course of chemotherapy, paclitaxel 175 mg/m^sup 2^ and carboplatin 235 mg/m^sup 2^ every 21 days for three cycles, and presented to our office for options of further treatment modalities.

HISTORY AND PHYSICAL EXAMINATION

Medical history was significant for left upper lobe lung cancer, resected by lobectomy 10 years prior, GERD, peptic ulcer disease, arthritis, hypertension and hypercholesterolemia. Surgical history also included appendectomy, parotid tumor resection, cholecystectomy, knee repair, hysterectomy. Medications included a combination of bisprolol, hydrochlorothiazide, atorvastatin, lorazepam, and non-steroidal anti-immune drugs (NSAIDS) for arthritis. The patient quit smoking 10 years prior. Family history was significant for maternal ovarian cancer. Review of systems was significant for a 15 Ib (7 Kg) weight loss over the past six months. Physical exam revealed healthy appearing obese woman in no apparent distress. Her weight was 191 lb (89 Kg), afebrile with normal vital signs. The abdomen was protuberant and non-tender with a 15 cm mass in the mid-abdomen with some right pelvic fullness. The pelvic exam revealed a foreshortened vaginal cuff and a mass in the anterior pelvic vault that extended to the right side. The rectal exam was guaiac negative with no masses felt in the pouch of Douglas. The rest of the physical exam was unremarkable.

LABORATORY DATA

CT scan of the abdomen, chest and pelvis revealed several hepatic lesions, the largest measuring 3 cm. There were multiple masses in the peritoneal cavity, a 5 x 4 cm mass obstructing the right ureter and uretrovessical junction, a 7 cm mass in the right lower quadrant and a 5 x 14 cm mass along the undersurface of the transverse colon that was invading into the rectus abdominis anteriorly. Pelvocaliectasis and ureterectasis due to obstructing mass in the pelvis were also noted. (Figure 1A).

CLINICAL COURSE

After she completed three cycles of systemic chemotherapy (paclitaxel/carboplatin), a CT scan showed progression of disease. A cystourethroscopy with right retrograde pyelogram was done and a right ureteral stent was placed to relieve the tumor obstruction. Biopsies of the lesion invading the bladder revealed poorly differentiated adenocarcinoma with squamous and heterologous mesenchymal components consistent with carcinosarcoma. (Figure 2A) The tumor was estrogen and progesterone receptor (ER/PR) positive, cytokeratin (CK-7) positive and CK-20 negative.

Bone marrow was harvested from the patient immediately prior to high dose neoadjuvant pelvic chemotherapy using isolated pelvic perfusion with balloon occlusion technique and extra corporeal bypass (110 mg/m^sup 2^ l-phenylalanine mustard and 44 mg/m^sup 2^ paclitaxel in four divided doses over 60 minutes). During the initial 5 minutes of the procedure, a portion of the total drug dose was given with the occlusive balloons above the renal artery branches. The remainder of the drug dose was given with the balloons below the renal artery branches, protecting the kidneys from the chemotherapy and isolating the infra-renal and pelvic viscera. A left groin node taken at this time was negative for neoplasm. The patient received the rescue autologous bone marrow transplant one day following the chemotherapy procedure. She tolerated the procedure well with estimated blood loss of 300-400 cc but had a prolonged hospital stay (61 days) due to prolonged neutropenia and mental status changes attributed to high dose chemotherapy.

The CT scan obtained after pelvic perfusion showed a questionable 1 cm low attenuation hepatic mass. There was also a 3.5 x 9 cm heterogeneous mass that extended below the level of the iliac crest. Bilateral hydronephrosis was also noted. (Figure 1B)

Two months after pelvic perfusion, an exploratory laparotomy with lysis of adhesions and resection of intra-abdominal metastasis, transverse colon, ileum, cecum and omentum was done. Two tissue expanders were placed in anticipation of radiation therapy. The multiple specimens included a mass invading the transverse colon with attached omental carcinomatosis, one invading the right ureter, one with retro-peritoneal and peri-ureteral extension and one with right iliac side wall invasion. Pathological examination of the surgical specimen revealed poorly differentiated endometrial adenocarcinoma with focal elements of carcinosarcoma in the omentum. (Figure 2B) The tumor was approximately 30-40% necrotic. The patient was hospitalized for 36 days with postoperative complications including aspiration pneumonia and tracheitis requiring tracheostomy and episodes of encephalopathy attributed to anesthesia hypersensitivity. After discussion at our institution's tumor board meeting, a consensus was formed that further treatment should be an alternate to traditional chemotherapy, given the patient's previous hypersensitivity reaction and positive hormone receptors. A regimen of tamoxifen and medroxyprogesterone was started.

Four months postoperatively, hyperfractionated radiation treatment totaling 3000 cGy was completed in a 2week interval and the tissue expanders were removed. Follow up CT scan of the abdomen at this time revealed the hepatic lesion no longer seen, improved right hydronephrosis with no soft tissue mass or adenopathy.