Advanced Pelvic Malignancies Research Articles

Total pelvic clearance for advanced pelvic malignancy

Objective: Advanced pelvic tumours require multidisciplinary care to improve outcome. This is an audit of one specialist unit's experience.Method: Consecutive patients referred from 2001 to 2005 for consideration of pelvic clearance were evaluated by retrospective review.Results: Of 100 patients assessed, 55 were considered unsuitable for surgery. Exclusions included unresectable pelvic side‐wall disease (25), widespread disease (23) and severe co‐morbidity (7). Forty‐five patients were operated on; 22 had locally advanced disease, 14 had recurrence and nine had residual disease following previous surgery. The primary cancers were colorectal in 24, gynaecological in 10 and urogenital in 10; one patient had non‐neoplastic disease. Preoperatively 39 (87%) had examination under anaesthetic (87%) and all had MR and CT imaging. Neoadjuvant radiotherapy and chemotherapy was given in 27 and 18 patients respectively. Following resection by a multi‐speciality team, surgery was considered curative in 40 (90%) of cases as judged by a histologically negative margin. All patients received level 2 care postoperatively with only two requiring level 3 care. There was no 30‐day mortality but there were 17 complications treated conservatively and five that required surgery.Conclusion: Advanced pelvic tumours require careful multidisciplinary assessment and treatment. This study shows that this can be performed safely with high levels of histological clearance of tumour.

37: Laparoscopic Anterior Exenteration for Advanced Pelvic Malignancies—Review of 10 Consecutive Cases

Anterior exenteration has a definite role in the management of advanced pelvic malignancies. Our own publication in the journal of pelvic surgery shows the benefit in palliative as well as curative settings. This is a technically difficult procedure associated with morbidity. We have done the same procedure laparoscopically with intracorporeal ureterosigmoidostomy and wish to present our experience of 10 cases. This paper deals with the indication for anterior exenteration as well as the prerequisites for doing the same. The entire procedure is done laparoscopically including the urinary diversion. The study period is from September 2003 to March 2005. All the patients were operated by the same team. Ten patients have been operated. All had advanced pelvic cancers. Eight patients had cervical cancers and two had bladder tumor with uterine involvment. Six patients had received previous chemotherapy or radiation. Thus only 4 patients were operated primarily out of which two were bladder tumors. All the patients had ureterosigmoidostomy as the preferred method of urinary diversion and thus the entire procedure was completed laparoscopically. All patients had the routine preoperative investigations in addition to CT scan, MRI and cystoscopy with examination under anesthesia. The average time taken for the procedure was 200 minutes and the average blood loss was 100ml. The average hospitalization was 4 days. One patient had urinary leak and one had intestinal obstruction. Both were treated conservatively. Four patients have completed 15 months follow up and are disease free. Laparoscopic anterior exenteration, though technically complicated can be performed. Besides the technical feasibility it decreases the morbidity and hospitalization. The oncologic safety is the same as that in open surgery.

Exenterative pelvic surgery—eleven year experience of the Swansea Pelvic Oncology Group

To review indications for surgery and outcomes of patients with complex locally advanced pelvic malignancies treated by a multidisciplinary Pelvic Oncology Group. Between March 1992 and March 2003, 130 patients were jointly assessed in a monthly clinic involving urological, gynaecological, colorectal and plastic surgeons, an oncologist and nurse specialists. Seventy-six patients proceeded to exenterative surgery. Rectal carcinoma and gynaecological cancers were the two most common indications for surgery. Median follow-up was 14 months (range 1-120 months). There were no deaths within 30 days of surgery. The morbidity rate was 28%. Predicted 5 years survival was 53% in cases with clear histological margins and no lymph node metastasis. With careful patient selection and multi specialty care pelvic exenteration is a safe and effective option in the treatment of complex locally advanced pelvic malignancy.

Balloon catheter hypoxic pelvic perfusion with mitomycin C and melphalan for locally advanced tumours in the pelvic region: A phase I—II trial

To investigate the feasibility of hypoxic pelvic perfusion (HPP), using balloon catheter techniques as treatment modality for locally advanced pelvic malignancies. In a phase I--II study, 16 patients with various non-resectable pelvic tumours were treated with two HPP with MMC and melphalan, followed by radiotherapy (25 Gy) and surgical resection if feasible. Toxicity and procedure related complications were documented. Tumour responses were assessed by MRI or CT. Pain reductive effects were assessed by evaluation of pain registration forms. HPP resulted in augmented regional drug concentrations with relatively low systemic levels. Some severe systemic toxicity was observed. One procedure related death occurred. Pain reduction effects were short-lived. Ten patients had radiological NC, two PD and one PR. In 11 patients surgical resection was performed, which was microscopically radical in six cases. Mean survival was 26.8 months (range 1--86). The seemingly favorable pharmacokinetic profiles observed with HPP in this and other studies can still lead to severe systemic toxicity. In terms of survival, local (re-)recurrence and pain reduction there seems no benefit of addition of HPP to pre-operative radiotherapy. HPP with MMC and melphalan, does not seem a therapeutic option in patients with locally advanced pelvic tumours.

Radical cystectomy in patients aged ≥ 75 years: an updated review of patients treated with curative and palliative intent

To evaluate the morbidity and mortality of radical cystectomy in a group of unselected patients aged > or = 75 years who were treated with curative and palliative intent. We retrospectively analysed 53 patients aged 75-90 years (median 78.8 years) who had radical cystectomies between May 1994 and July 2002. The patients were divided into two groups: 46 were treated with curative intent (group A) and seven with palliative intent (group B). The indications for cystectomy in group A were recurrent and otherwise therapy-resistant bladder cancer, severe irritative voiding symptoms, and recurrent macrohaematuria. The indications in group B were advanced pelvic malignancy with severe irritative voiding symptoms, severe pain, and recurrent macrohaematuria requiring blood transfusions. Patients were categorized according to the American Society of Anesthesiologists classification, with a score of II in 28 patients, III in 21 and IV in four. Complications and mortality before, during and after surgery, and the duration of hospital stay and clinical outcome, were assessed. RESULTS; The early mortality rate in group A was 4% (2/46); in group B two patients died after prolonged complications. The median (range) hospital stay was 28 (6-56) days, and was significantly longer in patients with complications, at a median (range) of 36 (6-70) days. The complication rates early and late after surgery in group A were 22% and 11%, respectively, and in group B, five of seven (early). The total median survival was 2 (0.33-7) years. Elderly people undergoing radical cystectomy have a greater risk of perioperative morbidity and mortality, especially those with very advanced pelvic malignancies who have had cystectomy with palliative intent. The incidence of early and late complications in patients treated with curative intent is acceptable, but the hospital stay is prolonged.

Malignant Arterio-enteric Fistulae: Endovascular Treatment by Covered Stent-graft

Surgery is less attractive in arterio-enteric fistulae secondary to advanced malignancy. We describe stent-grafting as a safer alternative than iliac ligation and extra anatomical bypass in a case of a life threatening bleed from an ilio-enteric fistula secondary to advanced pelvic malignancy.

Malignant Arterio-enteric Fistulae: Endovascular Treatment by Covered Stent-graft

Surgery is less attractive in arterio-enteric fistulae secondary to advanced malignancy. We describe stent-grafting as a safer alternative than iliac ligation and extra anatomical bypass in a case of a life threatening bleed from an ilio-enteric fistula secondary to advanced pelvic malignancy.

Phase I trial of concomitant vinorelbine, cisplatin, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies

To determine the maximum tolerated dose (MTD) of vinorelbine in combination with weekly cisplatin and pelvic radiation therapy (RT). Eligible patients included those with bulky or locally advanced cervical cancer. Women with other advanced gynecologic malignancies were also eligible. All patients received cisplatin 40 mg/m(-2)/week (maximum dose, 70 mg) during pelvic RT. Vinorelbine was administered on the same day as cisplatin at a starting dose of 10 mg/m(-2)/week and escalated in 5 mg/m(-2)/week increments. Dose-limiting toxicity (DLT) was defined as: grade 3-4 non-hematologic toxicity, grade 4 hematologic toxicity, or any toxicity which required > or =1 week delay in RT or an omission of >1 dose of chemotherapy. Between April 2001 and September 2002, 12 women with pelvic malignancies (11 cervical, 1 recurrent ovarian) were enrolled. Cohorts of 3, 6, and 3 patients were treated at 10, 15, and 20 mg/m(-2)/week dose levels of vinorelbine. At the 20 mg/m2 level, DLT was observed. Two of three patients missed >1 cycle of chemotherapy secondary to predominantly hematologic toxicity. One patient at the 20 mg level developed a creatinine clearance <50 ml/min and missed 1 dose of cisplatin. Another developed transient grade 3 diarrhea. No grade 4 toxicities were observed. The MTD of vinorelbine in combination with cisplatin and pelvic RT in patients with cervical cancer is 15 mg/m(-2)/week.

How to treat the persistent perineal sinus after rectal excision.

As surgery for more advanced and complex pelvic malignancies continues to expand to include larger and more exenterative techniques, dealing with the resulting pelvic and perineal defect has become an increasingly frequent necessity. The goal is both to close the defect and to accomplish complete healing. Methodology for managing the perineal wound, which results after proctocolectomy for cancer and more recently, after exenterative resection of the rectum, sacrum, uterus, vagina, bladder and larger areas of soft tissue (i.e. perineum), varies between simple closure on one hand and creation of complex gluteal and rectus abdominus flaps on the other. We examined these methodologies in terms of indications, technical details, complications and outcomes. Finally, the newest techniques for eliminating persistent perineal sinus tracts are detailed.

Therapeutic transcatheter arterial embolization in the management of intractable haemorrhage from pelvic urological malignancies: preliminary experience and long‐term follow‐up

To evaluate the feasibility, efficacy and complications of internal iliac artery embolization as a palliative measure in the control of intractable haemorrhage from advanced pelvic urological malignancies. Six patients (mean age 80 years, range 76-87) with advanced pelvic malignancies (three each with bladder carcinoma and prostate carcinoma) underwent embolization between September 1997 and July 2001, using permanent coils in the anterior division of internal iliac artery bilaterally. All patients had undergone conservative treatment before embolization for a mean of 2 days. The mean requirement for transfusion before embolization was 3.2 units. All patients except one were successfully embolized in a single setting with no complications. Bleeding was successfully controlled in one patient at the second attempt of embolization. There were minor complications, e.g. nausea, vomiting or fever, for a mean of 2 days, responding well to conservative treatment. At a mean follow-up of 22 months, no patient had a recurrence of bleeding. Internal iliac artery embolization is a feasible, effective and minimally invasive option in managing advanced pelvic urological malignancies presenting with intractable bleeding; it should be bilateral and permanent.

Is There Still a Role for Open Cordotomy in Cancer Pain Management?

For a small number of cancer patients, good pain control remains difficult to achieve despite adequate assessment and medical management. In nine cases, effective control of intractable pain from malignant pelvic disease was achieved by open thoracic cordotomy. The technique was well tolerated, with no major complications. Eight of the nine patients decreased their median daily oral morphine requirement from 560 mg (range 360-2600 mg) to 160 mg (range 40-1000 mg). Maximal survival time post-cordotomy was 830 days, with a median of 107 days. No patient experienced recurrent pain in the initially painful site. For patients with intractable pain associated with advanced pelvic malignancy, the use of an open cordotomy should be considered when satisfactory pain control is not achieved by medical or minimally invasive methods.

Transureteroureterostomy: an adjunct to the management of advanced primary and recurrent pelvic malignancy.

The surgical management of advanced primary or recurrent rectal cancer may involve the lower ureter or ureterovesical junction. With unilateral involvement, reconstruction of the ureters with salvage of the ipsilateral renal function should be considered. With optimal exposure both ureters are visualized. The crossed ureter is incised perpendicularly and then longitudinally on its medial aspect. An anterolateral ureterotomy is made on the recipient ureter. A mucosa-to-mucosa anastomosis is completed. Stents are used selectively. Eleven patients with advanced pelvic malignancy underwent this procedure. There was one major complication requiring ureteronephrectomy of the crossed system. Transureteroureterostomy should be considered as a treatment option in patients with unilateral ureteral obstruction.

Phase I Trial of Concomitant Vinorelbine, Paclitaxel, and Pelvic Irradiation in Cervical Carcinoma and Other Advanced Pelvic Malignancies

The aim of this study was to determine the feasibility and toxicity of concomitant vinorelbine, paclitaxel, and pelvic radiation therapy (RT) in patients with advanced cervical cancer and other pelvic malignancies. Eligible patients included those with large or locally advanced cervical cancer. In addition, patients with other advanced gynecologic malignancies were eligible. In part I, vinorelbine was administered as a single agent during pelvic RT at a starting dose of 10 mg/m(2)/week with subsequent cohorts being escalated in 5 mg/m(2)/week increments. In part II, paclitaxel was added to vinorelbine (20 mg/m(2)/week) and pelvic RT at a starting dose of 20 mg/m(2)/week. Thirty-three women with pelvic malignancies (22 cervix, 6 vagina, 3 endometrium, 2 vulva) were enrolled. Twenty-seven received vinorelbine and 6 received both paclitaxel and vinorelbine in combination with pelvic RT. Escalating vinorelbine doses to 25 mg/m(2)/week were well tolerated, with the primary toxicity being hematologic. RT was delayed in only 1 patient due to acute hematologic toxicity. In contrast, the combination of paclitaxel, vinorelbine, and pelvic RT was not well tolerated. Five of 6 patients (83%) experienced grade > or = 2 leukopenia, with 2 patients missing > 1 cycle of chemotherapy. Moreover, RT was delayed for 1 week in 2 of 6 patients (33%). Concomitant pelvic RT and vinorelbine with doses to 25 mg/m(2)/week is well tolerated. The addition of paclitaxel to this combination is associated with significant hematologic toxicity and is thus not a feasible approach.

Percutaneous implantation of subcutaneous prosthetic ureters: long-term outcome.

We have used an extra-anatomic subcutaneous alloplastic ureteral replacement initially to bypass ureteral obstruction secondary to advanced pelvic malignancies in patients with a short life expectancy. Following the encouraging preliminary results, our list of indications has broadened to include complex benign ureteral strictures. We herein report the long-term outcome. A series of 35 subcutaneous prosthetic ureters were implanted percutaneously in 27 patients (19 unilateral and 8 bilateral) to bypass extrinsic ureteral obstructions. The nature of obstruction was neoplastic in 22 patients and benign in 5. A composite prosthesis, consisting of two coaxial tubes--internal pure smooth silicone covered by coiled e-PTFE--has been designed to serve as the ureteral replacement. This tube is inserted percutaneously into the renal pelvis, tunnelled subcutaneously, and introduced through a small suprapubic incision in the bladder. All patients were followed to date or until death from tumor. The mean follow-up was 6.3 months for the deceased patients and 47 months for the surviving ones, the longest follow-up being 84 months. No operative or immediate postoperative deaths were observed. Initial difficulty in placing the prosthesis was encountered in 5 of the 27 patients (19%). Secondary parietal complications occurred in 8.5% of cases (3/35). The prosthetic ureter had to be removed in one patient because of skin erosion. Return to a standard percutaneous nephrostomy was needed in two patients because of local tumor progression with bladder fistulae. Five patients are alive with the prosthesis in place and a follow-up as long as 84 months without encrustation, infection, obstruction, or skin problems and with normally functioning kidneys. The subcutaneous urinary diversion using a silicone-PTFE prosthesis is an efficient and minimally invasive way to bypass malignant or complex benign obstructions of the ureters that otherwise would necessitate permanent nephrostomy drainage.

Development and evolution of pelvic exenteration: historical notes.

Fifty years after the development of pelvic exenteration, the operation remains a gold standard in the surgical management of advanced pelvic malignancy. The operation has evolved through several predictable phases including technical improvements, lowered morbidity and mortality, and improved patient selection. Despite progress in supportive peri-operative care, pelvic exenteration is a major undertaking that should be performed in centers with proven interest and expertise in the field. We trace the early developments of the operation, the period of maturation, and the current place of this procedure in the armamentarium of the oncologic surgeon.

A pharmacokinetic model and the clinical pharmacology of cis-platinum, 5-fluorouracil and mitomycin-C in isolated pelvic perfusion.

An isolated pelvic perfusion technique using multiple agents was used both in patients with unresectable recurrent pelvic neoplasms and as a preoperative therapy for advanced pelvic malignancy. The technique consisted of vascular occlusion via transfemoral balloon catheters, circulation and drug infusion using standard hemodialysis technology, and a 45-min isolation period. Blood and urine samples were analyzed for the levels of cis-platinum (17 patients, 21 courses of therapy, 50-100 mg/m2, infusion 0-10 min), 5-fluorouracil (12 patients, 14 courses, 1500 mg/m2, infusion 1/3 dose 0-1 min, 2/3 dose 1-20 min) and mitomycin-C (11 patients, 14 courses, 10-20 mg/m2, infusion 10-20 min). An empirical, four-compartment pharmacokinetic model was developed to establish drug distribution curves for the pelvic and systemic circulations and to yield valid estimates of the pharmacokinetic parameters. Pelvic isolation of drug was demonstrated by the pelvic-systemic drug exposure ratios of 6.0:1 for cis-platinum, 8.4:1 for 5-fluorouracil and 9.0:1 for mitomycin-C. Isolation at the L3-4 interspace resulted in minor urine drug elimination during isolation (cis-platinum 7.2% of drug, 5-fluorouracil 2.4% and mitomycin-C 2.5%). Because drug infusion was limited to the first 20 min of isolation, drug levels at the end of the isolation period were reduced to the extent that no extracorporeal drug removal mechanism was needed. These pharmacokinetic results indicate that this isolation technique has the potential to provide increased therapeutic indices and is a suitable system for evaluating fast-acting highly toxic experimental drugs to human pelvic cancers which are poorly responsive to conventional clinical protocols.

Primary myocutaneous flap closure following resection of locally advanced pelvic malignancies.

Perineal wounds, created at the time of extended resection for locally advanced malignancy and following chemoradiation, are at risk of serious complications. To determine whether immediate myocutaneous flap closure prevents complications, 57 patients treated with multimodality therapy and proctectomy (35 perineal wounds) or sacrectomy (22 posterior wounds) were studied. Patients were categorized according to whether they underwent primary skin and pelvic closure (group 1; ,n = 20); primary skin and omental pelvic closure (group 2; n = 24); or immediate myocutaneous flap closure (group 3; n = 13). Groups were similar with respect to age and sex; however, group 1 had more primary tumours and required less radical surgery and chemoirradiation than groups 2 and 3. Groups 1 and 2 experienced more complications overall (eight of 20, nine of 24 and three of 13 patients in groups 1, 2 and 3 respectively), more acute wound complications (seven of 20, nine of 24 and two of 13), delayed wound healing (three of 20, six of 24 and one of 13) and more reoperations for perineal wound problems (five of 20, seven of 24 and zero of 13). Patients in group 2 had a significantly longer hospital stay than those in group 1. Flap closure (group 3) did not increase the length of stay. The routine use of primary flap closure reduced overall wound complications (eight of 31 versus ten of 26 patients) and length of hospitalization (13 versus 17 days). Complete wound healing was achieved in all patients; however, immediate myocutaneous flap closure reduced the need for readmission and reoperation.

Phase I Trial of Concomitant Chemoradiotherapy for Cervical Cancer and Other Advanced Pelvic Malignancies

Purpose. The aim of this study was to determine the feasibility and toxicity of concomitant hydroxyurea (HU) and escalating doses of 5-fluorouracil (5-FU) in locally advanced cervical cancer and other pelvic malignancies undergoing radiation therapy (RT). Methods. Treatment consisted of 5-FU, HU, and pelvic RT delivered in an alternate-week fashion. 5-FU was administered as a continuous intravenous infusion at a starting dose of 600 mg/m2/day and was escalated to 1000 mg/m2/day in cohorts of three patients. The HU dose was 500 mg twice daily. Chemoradiotherapy was administered on a 5-day cycle. Following a 9-day rest, the cycle was repeated until the completion of the pelvic RT. Results. Twenty-one patients (18 cervix, 1 bladder, 1 vagina, 1 ovary) were enrolled. 5-FU escalation to 1000 mg/m2/day was well tolerated. No patients developed grade 3-4 hematologic toxicity. Grade 2 leukopenia was noted in 3 patients (14.3%). Grade 3 mucositis, diarrhea, and dermatitis occurred in 10, 10, and 5% of patients, respectively. None of the 99 treatment cycles were delayed secondary to acute toxicity. The overall response rate in the 18 cervical cancer patients was 89% (78% complete, 11% partial). Conclusions. Concomitant continuous infusion 5-FU, twice daily HU, and pelvic RT delivered in an alternate-week fashion is well tolerated. Further study is necessary to evaluate the therapeutic efficacy of this regimen in patients with advanced cervical and other pelvic malignancies.

Metallic ureteric stents: early experience.

To report our experience with metallic self-expanding stents in the palliative care of patients with ureteric obstruction caused by advanced pelvic malignancy. Seven patients (five men and two women, mean age 72.8 years, range 58-88) with ureteric obstruction caused by advanced pelvic malignancy were evaluated. Self-expanding metallic Memotherm stents (Angiomed, Karlsruhe, Germany) were deployed using an antegrade approach in all patients. Patients were followed for a mean (range) of 9 (4-13) months to assess renal function and survival. All seven patients had good palliation; their quality of life was improved and symptom such as loin pain were ameliorated. Renal function was preserved; the mean serum creatinine level before and after stenting was 636 and 263 mumol/L, respectively). The mean duration of stent patency was 9 months. Of the five patients who subsequently died, only two had recurrent renal failure, presumably caused by stent occlusion. The use of metallic stents in the palliative care of ureteric obstruction caused by advanced pelvic malignancy is a safe and effective treatment.

Intraarterial Therapy of Locally Advanced Pelvic Malignancies

Locally advanced pelvic malignancies are typically managed by radiation and chemotherapy with modest results, and high rates of local and nodal failure. Regional chemotherapy offers the opportunity for downstaging these tumors to the point of resectability and possibly improving nodal control. Long-term survival benefit remains to be demonstrated.