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- Publisher
- de Gruyter
- Copyright
- Copyright © 2011 by the
- ISSN
- 1224-3450
- eISSN
- 1224-3450
- DOI
- 10.2478/v10206-011-0015-6
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- See Article on Publisher Site
Abstract
Total pelvic exenteration (TPE) is a radical and aggressive procedure performed in the local advanced pelvic cancer started from any pelvic organ. The experience of 213 TPE performed for local invasive cancer and centro-pelvic recurrences with initial malignancy at the cervix (125 cases), rectum (48 cases), vagina (11 cases), endometer (11 cases), ovary (9 cases), urinary bladder (3 cases), vulva (2 cases), retroperitoneum (2 cases), prostate (1 case) and myometrium (1 case), in 173 females and 40 males with age range 21-78 years, are analysed. The procedures were performed for advanced pelvic cancer in 71 cases (33.34%) and also for invasive centro-pelvic recurrences in 142 cases (66.66%). In 78 cases, TPE was extended laterally. 24 were composite resections. In 125 patients reconstructive procedures were added. All patients survived to surgery but 17 postoperative deaths (7.98%) were recorded. Complications occurred in 45.53% of cases, 97 from 213 patients had one or more than one complication with an average of 1.5 per patient. 52 among these patients (24.41%) requiring operative treatment. The average survival was 49.07 months, the median survival of 55 months and the estimated survival at 11 and 78 months was 66%, respectively 50%. The procedure is indicated in the absence of pelvic wall invasion and secondary distant dissemination and lengthens significantly the life span and increase the quality of life. Key words: total pelvic exenteration, radical resection, cervical cancer, rectal cancer, vaginal cancer, endometrial cancer, vesical cancer, urinary diversion, pelvi-perineal Introduction Many pelvic cancers may evolve with massive local invasion and remain confined to the pelvis, without distance dissemination. This feature is seen in approx. 10% of the cancers that start in the pelvic region, being refered to as locally advanced pelvic cancer (1-8). Locally advanced pelvic cancer include pelvic particular forms of cancer, with a marked local aggressiveness, in the sense of a massive invasion locally, but at the same time, in the absence of distance dissemination, the pelvic region being (clear or apparent) the only location of the neoplasia. This particular development is common for the cancers of all the pelvic and pelvic - perineal organs, so that whatever origin and histological nature the neoplasia may have, the emergence and development of a massive invasive tumor can be noticed, removing the boundaries between organs (the tumor invading a part or all neighboring structures and organs), in the absence of distance metastasis. This particular development can not be assessed in time, but is often long enough to allow therapeutic intervention (1, 2, 9-13). The term locally Address for correspondence: G. Mitulescu, MD, Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Fundeni Street no 258, 022328, Bucharest, Romania, e-mail: gmitulescu@gmail.com Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 G. Mitulescu, G. Gluck, C. Stîngu advanced pelvic cancer refers not only to the cancers of the pelvic organs developing "de novo" with massive invasion locally (or are diagnosed only at this stage) but also to the local-invasive recurrences of these cancers, the pelvic region (clear or apparent) being the only location of the neoplasia. These two forms of pelvic cancers share a marked local aggressiveness, being confined and limited to the pelvic cavity, in the absence of distance metastasis. Consequently, a similar evolution of these tumors (originating in various pelvic organs and having completely different histology) can be noticed. Although this particular type of evolution can be seen in other parts of the body, local aggressive development of pelvic tumors may be linked to: - Vascularization, a decisive factor in tumor growth, is extremely well represented in the pelvis. - Connective subperitoneal tissue, abundant in the pelvis, can be an easy way of tumor progression. - External communication, present in all pelvic organs that are in this way potentially infected; the increased pelvic immune activity may explain the delayed metastasis (1-3, 5-7, 9, 10, 14-20). In the case of massive local invasion tumors, irradiation, even in high doses, is not effective or can not be applied to patients who have already received the entire dose of irradiation; on the other hand, the response of these tumors to chemotherapy is extremely modest. Under these circumstances, surgery remains the only viable option that can be applied with curative intent (if the neoplastic tissue is completely removed). The extreme aggressiveness of these tumors demands an aggressive surgical approach, therefore the necessity of removal of some parts or even of all the pelvic organs, (with intent of removing the neoplastic tissue without residual tumor). Many of these tumors can be removed with radical intent. When dealing with locally advanced pelvic cancer, following certain therapeutic principles is required. = Tumors wich invades the neighboring organs should be resected ,,en bloc" in order to obtain negative section margins, which leads to a survival rate similar to the one of patients with noninvasive tumors (1;2). = The section margins will be circumferential, the three-dimensional resection of the tumor leading to the resection of free tumor nodules, common in this type of local invasive tumors. Even if the tumors adhere to neighboring organs apparently without invading them, the resection must be an aggressive one, the possibility of microscopic invasion in these adhesions being responsible in these cases for the high rate of local recurrences (15; 16, 23, 24). = The tumors will be handled with care in order to avoid the contamination of the operative field. = If digestive or urinary obstruction is encountered, serial operations are preferred, digestive or urinary diversion being the first in the series followed by radical resection (25). = It is important to distinguish between pelvic and perineal recurrences of rectal tumors. Isolated perineal recurrences may be removed through perineal surgery, but these patients rarely heal, radical resection being achieved only through abdominoperineal surgery (2628). = The lateral extension of dissection, beyond the hypogastric vessels plan is a viable surgical option for apparently non-operable tumors due to pelvic parietal invasion, with no bone invasion (1, 3, 13-15, 24, 29). Sometimes the limited bone invasion allows negative section margins to be obtained, the surgical specimen containing portions of the sacrum, coccyx, ischium, pubic symphysis pubis or pubic branches (16, 27, 30-34). = Vaginal or urinary or pelviperineal reconstructions are recommended in all cases where the patient's condition allows extended operation, to fill the pelvic dead space resulting from the dissection and to minimize the mutilating consequences of the process (35-45). = Pelvic lymphadenectomy is required, especially if it hasn't been previouslly performed (25, 46-52). = Residual microscopic disease risk requires postoperative adjuvant chemotherapy (53, 54). Unresectable locally advanced pelvic tumors require palliative radiochemotherapy. = As locally advanced pelvic tumors cause extreme suffering (pain, bleeding, sepsis, etc. unresectable tumors can sometimes be surgically removed operated palliatively Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 (22, 46, 47, 55-58). Better results might be obtained in the future through minimally invasive surgery, new radiation techniques (including intraoperative radiation), the application of hyperthermia and better selection of cases through the study of immunohistochemical receptors, angiogenesis factors, apoptosis factors, parameters that can later on explain the particular development of these tumors (6, 39, 59-63). (Fig. 1, 2, 3). As presented above, the most appropriate method to achieve a good result for locally advanced pelvic cancer is through major surgery, total pelvic exenteration (TPE), the subject of this study. Described as the most aggressive and radical surgical pelvic aproach for locally advanced pelvic cancer (64), this surgical procedure entitles the resection of all pelvic organs and structures, including bladder, prostate and seminal glands, the lower portion of the ureters, vagina, uterus and annexes, rectum and anus, together with all adjacent lymphatic tissue, with permanent colostomy and urinary diversion. TPE is indicated for massive invasive pelvic tumors with a real chance of cure, (complete tumoral resection with no residual disease). Absolute contraindications of the method include visceral and peritoneal metastases, or massive invasion of the pelvic bone (22, 25, 47, 53, 64, 65). Materials and methods This paper is based on a personal experience of 213 cases of TPE, ie 173 women and 40 men with an average age of 56 years (21-78 years), operated in the Centre of General Surgery and Liver Transplant of Fundeni Clinical Institute between 2000 and 2011, accounting for pelvic cancers with massive invasion and their local recurrencies, originating in the cervix (125 cases - 58.69%), rectum (48 cases 22.53%), vagina (11 cases 5.17%), endometrium (11 cases - 5.17%), ovary (9 cases - 4.22%), urinary bladder (3 cases - 1.40%), vulva (2 cases - 0.94%), retroperitoneal (2 cases 0.94%), prostate (1 case - 0.46%) and myometrium (1 case - 0.46%). Surgery was performed for advanced pelvic cancers ,,de novo" - in 71 cases (33.34%) and also for invasive centropelvine recurrences in 142 cases (66.66%). Of the 71 de novo cases, 35 were cervical cancers (49.29%), 19 rectal cancers Figure 1 - Massive locally invasive recurrence of rectal cancer Figure 2 - The same case after total pelvic exenteration Figure 3 - Final aspect of the intervention after complex reconstructive procedures Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 G. Mitulescu, G. Gluck, C. Stîngu (26.76%), 6 vaginal cancers (35.29%), 5 after endometrial cancers (7.04 %), 2 bladder cancers (2.81%), 2 retroperitoneal tumors (2.81%), an ovarian cancer (1.40%) and one prostate cancer (1.40%); of the 142 recurrences, 90 cases were recurrences of cervical cancer (63.38%), 29 of rectum cancer (20.42%), 8 of ovarian cancer (5.63%), 6 of endometrial cancer (4.22%), 5 of vaginal cancer (3.52%), 2 of vulvar cancer (1.40%), one of bladder cancer (0.40%) and one of myometrium cancer (0.40%). We did not include in this study the unresectable tumors, those with extrapelvic dissemination, or the ones in which the surgical resection did not include all the pelvic organs. Due to the massive pelvic invasion, all patients develop common symptoms regardless of cancer origin. Patients usually presented with pelvic pain, bleeding or hematuria (193/213 - 90.61% of patients); in some cases invasion of adjacent organs led to complex fistulas (recto-vaginal, bowel-tobladder, vesicovaginal), or fistulas between tumor and perineal region with local consecutive chronic suppuration (in 11% of cases). Sometimes, the tumor is more than obvious ( in cases of extreme neglection). The first sign of disease was in other cases the incidental finding of the recurrence through radiology exams (13 cases), of hydronephrosis (6 cases) or the finding of abnormal cytology at a routine check on a already operated patient (1 case). Sometimes, patients have presented with signs of urinary retention or chronic intestinal obstruction. We encountered situations in which the extent of tumoral invasion could be detected only during surgery. The physical examination of patients who received high doses of radiation may be irrelevant, and bleeding and pain may be attributed to radiotherapy. Consequently, the cancer / recurrence histological confirmation through analysis of a specimen obtained by biopsy appears to be essential. All patients underwent CT and / or thoraco abdominopelvic MRI exam, in order to assess tumor size and topography and potential areas of possible secondary dissemination (Fig. 4 a, b). In order to assess local invasion and the functionality of several organs we used cystoscopy, rectocolonoscopy, urography etc., and for the diagnosis of metastases bone scan and tumor marker levels. Given the scale of intervention and the relatively mutilating consequences of the surgical Figure 4 - Locally advanced pelvic cancer (a computer tomography, b nuclear magnetic resonance examination) procedure, there is a number of assessments that need to be performed: comorbid conditions, patient's desire to live, the patient's family's ability of caring and postoperative social insertion. The diagnosis was based on the histological confirmation of the cancer, in the context of no pelvic wall invasion and no extrapelvic dissemination. To limit the resection, all patients underwent radiochemotherapy preoperatively; the time frame between radiochemotherapy and surgery (5-6 weeks at its best), was extended to a few years in the case of 2 patients, the symptoms' disappearance after radiochemotherapy leading them to believe they were healed. In the case of urinary or intestinal obstruction, urinary diversion (percutaneous nephrostomy 33 cases 15.49% ) or fecal diversion (4 cases 1. 87%) were performed before radical surgery. Sometimes, intraoperative exploration led to surgical abstention; the massive locally tumoral invasion required an extensive surgical procedure, sometimes more extenisve even than the Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 TPE. For a frail and malnourished patient, with advanced cancer, the surgical stress can be umbearable, even lethal. For this surgical procedure the patient has been placed in the lithotomy position and appropriate vascular access was assured. The input of an experienced urologic and plastic surgeon was necessary throughout the procedure. Intraoperative exploration included biopsying any suspect areas, examined extemporaneously, since the goal was to obtain negative section margins. In some surgical centers, intraoperative radiotherapy accessibility allows resection with uncertain margins, but obvious positive section margins gives an extremely unfavorable prognosis. The surgical procedure has two resection stages: supralevatory exenteration (Fig. 5) and infralevatory exenteration (Fig. 6), performed by a single surgical team. The final steps of the surgery are urinary and fecal diversion (Fig. 7) and in some cases the reconstructive part (performed by the urologic and plastic surgeon). Results Our study includes a total of 213 patients, operated by the author in the Center of General Surgery and Liver Transplantation of Fundeni Clinical Institute during 2000-2011. All patients underwent TPE, of which some required additional surgical procedures. Patients which underwent anterior pelvic exenteration or posterior pelvic exenteration and the ones whose pelvic organs have been preserved were not included. The purpose of this procedure was mainly curative, but in 24 cases (11.26%) the surgery was performed in order to palliate the symptoms; nevertheless, the result of 37 interventions was of a palliative nature, (in 9 cases there was residual tissue on the pelvic wall or metastatic lymph nodes invading the great vessels, and in 4 cases the microscopic invasion of the margins was discovered. The absolute indication of the intervention was the presence of pelvic neoplasia with local massive invasion, with no definite pelvic bone invasion and no distance dissemination (no "extrapelvic disease"). The relative contraindications of the method are retroperitoneal lymph nodes disemination, small bowel invasion, and the presence of hydroureter / hydronephrosis (22, 25, 53, 6669). In our series, however, we encountered Figure 5 - Supralevatory exenteration Figure 6 - Infralevatory exenteration Figure 7 - Urinary and faecal diversion frequently the latter situation. Of the 213 patients, 83 had lymph nodes metastases (38.96%), 51 bowel or sigmoid invasion (23.94%) Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 G. Mitulescu, G. Gluck, C. Stîngu Table 1 - The surgery Table 2 - Complementary procedures Medium duration Blood loss 6 hours (3 13 hours) ~ 1200 ml (500 5500 ml) Transfusion 174 /213 ~ 1250 ml (0 4000 ml) Intraoperative mortality 0 Postoperative hospitalization 16 days (8 45 days) and 131 hidroureter and/or hydronephrosis (61.50%), which required complementary operative procedures. In the case of urinary or intestinal obstruction certain procedures were performed, such as percutaneous nefrostomy (33 cases - 15.49%), ureterostomy previous to the radical surgery and colostomy (4 cases - 1.87%). The average duration of surgery was of 6 hours (3 to 13 hours). The loss of blood was of approximately 1200 ml (500 to 5500), 174 of the 213 patients requiring transfusion. There were no cases of intraoperative mortality. Postoperative mortality was 7.98% (17 deaths). The average duration of hospitalization was 16 days (Table 1). In many cases the neoplasic extension required several additional procedures, which increased the aggressiveness of the surgery (Table 2). Therefore, this surgical procedure is indicated in the absence of important comorbidities for the patient to survive the process: laterally endopelvic extension (78 cases), partial resection of the sacrum (5 cases), pubic resections (2 cases) coccyx resection (18 cases), resection of the obturator nerve (28 cases - 5 bilateral), bowel resection (37 cases), sigmoid colectomy (15 cases), right hemicolectomy (26 cases), complex procedure for ovarian cancer (3 cases), liver metastasectomy (4 cases), nephrectomy (9 cases), deliberate ureteral ligation (27 cases of which two bilateral), lombo-aortic lymphadenectomy (48 cases), cholecystectomy (8 cases). Pelvic lymphadenectomy accompanied all TPE cases, if not previously performed (Fig. 8 a, b.). In the absence of pelvic bone invasion, pelvic wall invasion does not contraindicate the resection. Lateral extension of the exenteration is consequently proven to be viable and was performed in 78 of the cases (36.61%), unilateral side extension for 55 Side extended pelvic exenteration Partial sacral resection Partial pubic resection Coccyx resection Obturator nerve resection Segmental enterrectomies Sigmoidectomies Right hemicolectomies Liver metastasectomies Nephrectomies Deliberate ureteral ligation with kidney abandoning Lomboaortic lymphadenectomy Plas de contenie perineal Rezecie segmentar ven iliac extern cases cases cases cases cases cases cases cases cases cases 27 cases 48 cases 8 cazuri 1 caz Figure 8 a, b - The pelvic lymphadenectomy of the cases unilateral and bilateral side extension in 23 of the cases (Fig. 9 a, b, c.). Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 Figure 9 - The endopelvic extension of the exenteration (a the dissection plan, b - external iliac vein resection and the replacement with a Dacron prosthesis, c the pelvic plexus roots exposed after dissection) Figure 10 - The composite exenteration (a sacral resection, b - horizontal pubic branch resection, c - resection of coccyx) Pelvic bone invasion is a major contraindication of TPE. However, in selected cases, limited bone invasion may be removed by composite TPE (TPE with an associated bone resection). We have performed sacrum partial resection (5 cases), coccyx resection (18 cases) and the resection of the horizontal pubic branch (2 cases) (Fig. 10 a, b, c.). Extensive pelvic cancers are known to produce some very unpleasant symptoms such as pain, digestive and urinary obstructions, fistulas and suppuration, bleeding, local consequences of uncontrolled tumor growth. Therefore, a significant palliation of these symptoms associated with pelvic cancer could determine a substantial improvement in quality of life in selected cases. Of the 213 TPEs, 37 (17.37%) were performed with palliative intent - 24 of them were deliberately palliative (known residual disease, minimal metastatic disease) and 13 of them were a result of the failure in curative procedures despite preoperative data or of the microscopic residual neoplastic tissue. Fecal diversion does not show particular aspects, but in the case of urinary diversion things are more complicated, generating a large number of procedures, continent or not. There are several options for urinary diversion chosen depending on the extention of the procedure, accessibility of the right colon and the terminal ileum and the patient's ability to take care of a continent stoma. Most cases - 164 (76.99%) resulted in simple ureterostomy due to its simplicity of performance; 125 cases resulted in double barrel ureterostomy; 4 cases resulted in "U trans U" uretrostomy and 35 cases in unilateral ureterostomy, the latter being associated with 9 nephrectomies and 27 deliberate ureteral ligation (of which 2 were bilaterally performed). In a small number of cases, the BRICKER procedure (25 cases 11.75%) or the INDIANA procedure (23 cases 10.79%) were performed (Table 3, Fig. 11). In 125 cases (58.68%), pelvic-perineal and vaginal reconstruction were performed, in order to coat the exposed surfaces of the exenterated pelvis, to remove pelvic dead space, to fix the parietal defects in women, to build a neovagina meant to reduce the consequences of the rather mutilating process. Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 G. Mitulescu, G. Gluck, C. Stîngu Table 3 - Urinary diversion Direct cutaneous ureterostomy non-continent 164 cases (74%) - simple bilateral 125 cases - simple unilateral 35 cases - 9 nephrectomies - 27 ureteral ligation - "U trans U" 4 cases Cutaneous ureterostomy mediated through ileal non-continent conduct BRICKER type 25 cases (11,75 %) Cutaneous ureterostomy mediated through colic non-continent conduct 1 case (0,47%) Continent reservoir ureterostomy INDIANA type 23 cases (10,79 %) Figure 12 - Pedicled great omental flap In the beginning of our series, we used perineal contention with mesh replacement (according to a personally developed procedure), in 8 of the cases (3.75%); later on, however, we abandoned this procedure because of its complications (3 perineal eviscerations, 3 late entero perineal fistulae) and we only used reconstruction with pedicled organic flaps (great omentum) in 72 of the cases (Fig. 12), musculo-cutaneous flaps of the gracilis in 9 of the cases, right abdominal flaps in 53 of the cases (Fig. 13 a, b.) and composite flaps (of the gracilis, gluteal and right abdominal muscles) in 15 of the cases (Fig. 14). The vaginal reconstruction is meant to reduce the mutilating consequences of the procedure and also to fix the remaining parietal defect (Fig. 15 a, b). We performed 29 reconstructions, 3 of which with a musculocutaneous gracilis flap and 26 with a right abdominal muscle flap.The reconstructive procedures are summarized in table 4. The histopathological exam confirmed the cancer in 210 of the 213 patients (98.59%), 3 of them (1.41%) presenting inflammatory lesions, septic and destructive processes that did not allow another therapeutic approach. All the tumors were of stage T4, with confirmed neoplastic invasion in all the removed structures (Fig. 16). Ro resection was confirmed in 156 of the 210 cases (74.28%), the rest being either R1 resections - 25 cases (11.91%) or R2 with macroscopic residual tissue 29 cases (13.81%), the intention being palliative. Histopathologically, the encountered cancers were of the most commonly types for those organs. All patients survived the surgical procedure, but Figure 11 - Continent ureterostomy mediated through an ileocolic reservoir INDIANA type Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 Figure 13 - Right abdominal muscle flap (a) and musculo-cutaneous flap (b) Table 4 - Reconstructive procedures · Perineal · Pelvi-perineal · Vaginal Perineal mesh retaining Right abdominal muscle flap Gracilis muscle flap Omental flap Complex reconstructive procedures Inferior gluteal muscle flap Vaginal reconstruction gracilis muscle flap Vaginal reconstruction right abdominal muscle flap 8 cases (11 %) 7 cases (9,5 %) 8 cases (11 %) 30 cases (41 %) 5 cases (7%) 2 cases 2 cases (3%) 5 cases (7%) Figure 14 - Pelvi-perineal reconstruction using multiple musculocutaneous flaps in the postoperative period 17 deaths occurred, with a postoperative mortality of 7.98%. The rate of complications in our series was of 45.53%, 97 of the cases presenting one or more complications, with an average of 1.5 per case; 52 of the cases (24.41%) required one or more surgical reinterventions. Complications were a result of the TPE and also of the urinary diversions and the reconstructive procedures. No significant differences were observed for primary tumors versus recurrences or complications attributable to radiotherapy (Table 5). The 17 deaths occurred were due to peritonitis, myocardial infarction, bronchopneumonia, and massive pulmonary embolism. 196 of the 213 patients survived the procedure (92.02%). 24 patients died in the first six months after the surgery (11.26%); other 16 patients died in the six following months (7.51%). All the 37 palliative intent surgeries are included in these 40 deaths. 121 patients (56.80%) are currently alive, the highest survival being of 11 years (the first total pelvic exenteration to be formed). The standard deviation and the 95% confidence interval were calculated in order to statistically analyse the probable survival curve. The life-table analysis was used for the statistical analysis of survival rates, and the result was represented under the form of the KAPLAN MEIER curve. The figure 17. analyses the survival of Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 G. Mitulescu, G. Gluck, C. Stîngu Figure 15 - Total vaginal reconstruction using the right abdominal muscle - postoperative immediat aspect (a) and after 1 year (b) Table 5 - Complications Early complications Bleeding - 25 Intestinal obstruction 8 Peritonitis 6 Pelvic abscess 4 Ileo-ileal necrosis 1 Ileal reservoir necrosis 1 Ureterostomy necrosis 1 Prolonged intestinal ileus 2 Pyelonephritis 6 Pyonephrosis 1 Flap necrosis 3 Renal failure 3 Intestinal obstruction 2 Enteroperineal fistula 3 Perineal abscess 2 Metabolic disorders 18 Metabolic disorders 4 Pneumopathy 6 Deep vein thrombosis 8 Pulmonary embolism 2 Pelvic evisceration 3 Abdominal wound suppuration 9 Perineal wound suppuration 8 MSOF 3 Myocardial infarction 1 Postoperative depression 7 Ileo-colic anastomosis fistula 1 Intestinal perforation 1 Late complications Hydronephrosis 3 Pyonephrosis 3 Pyelonephritis 3 Localized peritonitis 4 Flap necrosis - 4 Figure 16 - Surgical specimen of total pelvic exenteration Figure 17 - The survival analysis Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 Figure 18 - The compared survival Figure 19 - The survival rates of various pelvic cancer types the operated group on a time frame raging form 0 to 78 months. The average survival was of 49.07 months, SD = 4.81, 95% CI = [39.14, 58.5], and the median was of 55 months. The gross rate of survival of the operated group is of 68.49%, the 78 months survival rate is of 50%. The survival of a group of patients with locally advanced pelvic cancers was studied in collaboration with the Oncology Institute of Bucharest (Dr. Dragos Mitulescu); these patients did not undergo surgery (pelvic bone invasion, major comorbidities or refusal of the surgery), but they underwent chemotherapy, and 18% of them additional radiotherapy. This group was under obesrvation for a period of 11 months, with a 0 gross survival rate. In this group the average survival rate was of 5.18 months, SD = 0.36, CI95% = [4.47, 5.90], and a 4 months median. The survival differences are statistically significant (p = 0.000001), way under the statistically significant threshold (Fig. 18). One can see that the confidence interval of mean survival times do not intersect (log-rank test). The similar data found by comparing various pelvic cancer types survival, shows once again the similar evolution and prognosis of advanced pelvic cancers, regardless of theirs origin (Fig.19). Discussion Pelvic advanced cancers, regardless of the originating organ (uterus, rectum, vagina, vulva, bladder, etc.), are generally treated using a multimodal therapy including surgical resection, radiotherapy, chemotherapy and immunotherapy, the sequence and association depending on the stage of evolution. Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 The locally advanced pelvic cancer form, is found either as a late detected locally advanced primary neoplasia, or as a recurrence of a pelvic organ cancer that occurred some time after initial therapy. These two types of cancer share a marked local aggressiveness, whith the removal of the boundaries between the pelvic organs; the tumors develop by partially or totally invading the neighboring structures and organs (fasciae, ligaments, viscerae), however many of these tumors remaining confined and limited to the pelvic cavity, without distance dissemination. This can appear regardless of tumor histology and the pelvic organ of origin; such an evolution can not yet fully be explained (1, 2, 6, 7, 9 , 14, 23-25, 47, 53, 64, 66, 68, 70, 71). The heterogeneous nature of the pelvic organs' cells leads to difficulties in clarifying the evolution of local invasive tumors with no distant metastases. The exact circumstances leading to this aggressive local development in the absence of distant metastases can not be precisely specified. Even though this happens in other parts of the body too, certain particularities of the pelvis, which orient the tumors in their evolution can be identified: · the vascularization - the main factor in tumoral growth - is extremely well represented in the pelvis; · the connective subperitoneal tissue (also well represented) - may be a relatively rapid factor of local development; · the influence of the environment it is possible, for certain organs communicating with the outside, often infected, to have a more intense immune activity than the other G. Mitulescu, G. Gluck, C. Stîngu more "isolated" internal organs. This certain particularity of the local evolution for some of the tumors which origin in the pelvis, may lead to an interesting research perspective on various changes responsible for this type of transformation and malignant progression. Therapeutically speaking though, it is obviously important to be well aware of this possible evolution, as the therapeutical approach for the extremely aggressive tumors, even in the absence of distance metastases, should therefore be extremely aggressive, even mutilating, though justified and necessary as its is a curative one, even if in entitles a partial or total resection of certain or even all pelvic organs, so that the tumoral tissue to be removed entirely. Massive invasive tumors (even in the absence of distant metastases) respond poorly to radiotherapy and chemotherapy and no study up to the present was able to demonstrate that these treatment options can influence the patient's life expectancy in the absence of complete resection of tumoral tissue (the only chance of healing) (72-82). The treatment of pelvic cancers with distant metastases can only be palliative, based on radiotherapy and chemotherapy; in these cases surgery is palliative too, meant to fix certain life threatening complications (bleeding, intestinal obstruction) or to increase the patient's quality of life. The first TPE was reported by BRUNSCHWIG in 1948 as a particularly radical procedure applied in case of recurrence of advanced cervical cancer (64). Since then, several changes have improved the surgical procedure, especially in what concerns the pelvi-perineal and vaginal reconstruction procedures, the urinary continent reconstruction procedures, and the sphincter savinv procedures; the intensive care techniques have also been improved, the TPE being presently seen as the only healinh chance in these cases. Nowadays the operative mortality ranges between 3% and 5% and the postoperative morbidity between 30% and 44%, acceptable and reasonable figures given the scale of the intervention and that the 5-year survival rate of patients who passed the surgical procedure ranges between 30% and 62% (3, 11, 12, 20, 83-90). Any patient who meets all the required criteria that demonstrate the possibility of complete resection may be therefore subjected to this surgical procedure. Absolute contraindications include visceral and peritoneal metastases ("the extrapelvic disease") and the invasion of the pelvic bone wall, and the relative ones include retroperitoneal lymph node disemination, small bowel invasion and the presence of hydroureter - hydronephrosis. The diagnosis is based on the biopsy evaluation, the only method able to confirm 100% sure the presence of cancer; the histology of the tumor seems to have no importance in determining the particular type of evolution (the local aggressiveness with no distant metastases). Other criteria which need to be taken into account when dealing with total pelvic exenteration: · The first and most important condition is that the patient does not have important comorbidities, given the magnitude of the surgery and the possibility of a significant loss of blood and fluids. · The psycho-social assessment is crucial; the patient must have a stable and strong personality, a great will to live and adequate social and family support to adapt to the particular postoperative conditions. · The patient must be fully informed not only in what concerns the diagnosis and radical nature of the surgical procedure, but also about the possible intra-and postoperative complications, and especially about the consequences of the procedure (somatic, functional, psychological and social). TPE results in significant pelvi-perineal defects which, particularly after preoperative radiotherapy, can cause severe difficulties in the healing process and may lead to outstanding complications (the simply denude pelvic areas and the dead pelvic space resulted after the resection predipose to suppuration, intestinal prolapse, fistulae, intestinal obstructions) (36, 37, 40, 41, 43, 45, 91-112). The TPE involves the removal of urinary and anal sphincters resulting in the need for definitive diversions, and in women the removal of external genitalia which problems of psychological, family, social and sexual nature. All these require for a psychologist, an anesthesiologist, a radiotherapeut, a chemotherapeut, an urology surgeon and a plastic surgeon to join the surgical team (10, 38, 39, 91, 91, 92, 113, 114) . Currently a number of therapeutic options Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 have been proposed: = In order to reduce the mutilating consequences of the procedure a series of sphincter saving procedures should be performed, and mainly coloanal tank anastomosis and neobladders (39, 40, 43, 93, 115-132). The opponents of this procedure believe that, on one hand, the sphincter preservation amplifies the surgical aggression by adding a series of specific complications and increasing the postoperative morbidity and mortality, at the same time making it harder to diagnose and treat a possible recurrence (which can occur nomatter how radical the surgery may have been). The sectioning of pelvic and hypogastric nerves, together with abdominal pain, nausea, diarrhea, involuntary loss of feces and urine, are all factors that decrase the patient's quality of life. We consider that "sphincter saving" TPE are no longer total ones, and consequently those patients are no longer part of the statistics. These type of TPE has been performed with good results in most cases so we disagree with the opponents of the method. = The additional reconstructive procedures significantly reduce morbidity, and the vaginal reconstruction reduces the mutilating consequences of TPEs. The total pelvic exenteration also results in large pelvi-perineal region defects, especially in patients who underwent preoperative radiotherapy ( radiotherapy alters the vascularization of the tissues, wich together with the particualr aspect of each area, result in outstanding difficulties in the healing process and may lead to serious complications (92). Such a defect varies in dimensions, is three dimensional and transfixiant and it creates a communication between the abdominal cavity and the outside. Even when the perineal skin reserves allow a direct suture, the three-dimensional and transfixiant nature exposes the area to serious complications among which: the persistence of the pelvic dead space which predisposes to infection, the intestinal prolapse, fistulae and intestinal obstruction. The defect caused by TPE heals extremely slowly (133-137). Local mobility, difficult hygiene, the frequent replacement of bandages, along with a gradual decrease in patient compliance are factors which lead to a late healing and to the augmentation of morbidity. The peripheric contraction of the wound is reduced and the local infectious processes maintain the vicious circle. By the removal of external female genitalia, the TPE raises serious sexual, psychological, family and social issues (138-143). For these reasons, a plastic surgeon needs to join the surgical team together with the urology surgeon, the anesthesiologist, the radiotherapeut, the chemotherapeut, which emphasize once more the complex and multidisciplinary character of this therapeutical approach to advanced pelvic cancer. = On the other hand, we tried to extend the indications of this surgical procedure. The TPE can be lateral extended in the case of pelvic wall invasion (but with no bone invasion), - particularly the infrailiac pelvic wall invasion - , the invaded area being resected en bloc with the endopelvic fascia and the other structures of the pelvic wall (muscles, iliac vessels) (10, 14-16, 144-146). In our series, wew performed a number of 78 side extended TPEs. The composite TPE is a viable option for apparently unresectable tumors due to pelvic wall bone invasion, meaning the resection of the pelvic tumor en bloc with the invaded pelvic bone area (10, 32 - 34, 147); in our series, we performed this type of TPE in 24 cases. = The symptoms of extended pelvic cancers are extremely unpleasant, such as pain, fistulae and suppuration, urinary and intestinal obstruction, etc.., therefore, a significant palliation of these symptoms could determine a substantial improvement in the quality of life (52). The therapeutic value of palliative TPE remains a subject of controversy. Although post-palliative TPE mortality is not higher than postradical TPE mortality (60), morbidity is significantly higher, ranging between 13% and 77%, 1.5 to 2.3 complications per case, with a reintervention rate ranging between 65% and 75% of the cases (39, 59, 60, 148). On the other hand, palliative TPE determines a significant relief of symptoms, in 88% of cases after BROPHY -1994 (149), in 70% by YEUNG -1993 (150) and in 90% after WANEBO -1987 (151153). Most authors agree that because of the remaining macroscopic tumor tissue the disease will progress inexorably and, although on a short-term a relief of symptoms can be noticed (for 3 to 4 months), the patient is likely to die before a significant improvement in the quality of life is achieved, not to mention the risk of losing the patients because of the significant morbidity of a surgical procedure performed on very poor biological subjects (11, 14, 25, 27, 29). None of the 37 patients on which we performed palliative TPE survive more Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 G. Mitulescu, G. Gluck, C. Stîngu than 6 to 12 months, probably as much as they would have lived with simple urinary and fecal diversions. = As a therapeutic approach of pelvic bone invasive cancer with no metastases the most mutilating ever described surgery was proposed: the hemicorporectomy or the translumbar amputation, a procedure which consists in the entire removal of the pelvis and of both legs, vital functions bneing maintained in the upper torso. Eventhough 44 of such surgeries have been performed, its high mutilating character and spectrum of outstanding complications are reasons for which most surgeons find the hemicorporectomy beyond reason (154). It remains as an option for patients with an extremely high desire of living and in a very good physical condition. TPE is an extremely aggressive procedure, associated with a mortality of up to 5% and with a significant morbidity despite of continuous improvement of the surgical techniques, anesthesia and intensive care. At least one complication can be found in most patients, of which approx. 40-50% major ones, requiring specific diagnostic and therapeutical procedures (79, 155-169). This happens because of the magnitude of the surgical trauma, because of the age, of a significant blood and fluid loss, because of the inability to accurately monitorize the fluid input/output after the cutting of the ureters. Postoperative mortality seems to follow a downward trend, due to experience (the 30 days rate of mortality of BRICKER series decreases from 13.4% to 1.8% in a period of 15 years (170), the SYMMONDS series rate of mortality decreases of 13% to 3% after 20 years (171), KRAYBILL (172) reporting similar data). Postoperative morbidity, however, continues to be high, ranging between 13 and 77% of cases (11;70), YEUNG from 1.5 to 2.3% complications per patient (173), 65 up to 75% requiring reintervention (174, 175). There are four main sources for the complications: bleeding, urinary diversion, the simply denude areas and the dead pelvic space (2); other possible complications are: sepsis, anastomotic dehiscences (digestive anastomosis or ureteral implantation), intestinal obstructions, pyelonephritis, renal failure, deep vein thrombosis and pulmonary embolism, replacement flaps necrosis, etc. (2, 11, 70). The pelvic located sepsis may appear because of the aggressiveness of the surgery, the duration of the intervention, the pelvic dead space and the pelvi-perineal preexistent septic processes. The pelvi-perineal reconstruction procedures may minimize the dead space but also generate a specific rate of complications (176, 177). Pulmonary embolism occurred in 1.5% of the cases, despite specific prophylaxis. Some of the possible complications are intra-abdominal collections or digestive anastomosis dehiscence or uretero-intestinal anastomosis dehiscence. SHINGLETON (178) reported a mortality of 40%, associated with anastomosis dehiscence, 93% of patients receiving high doses of preoperatively radiotherapy. In RODRIGUES-BIAZ series, 67% of the preoperatively irradiated patients developed anastomosis dehiscence, and only 26% of the nonirradiated ones (179). LOPEZ finds in his series a 75% morbidity for the irradiated group, and a 13% morbidity in the nonirradiated group (180 - 182). Most of the authors (including our study) do not describe these differences (LAW (183) WANEBO (184) BOEY (185), etc.).. The type of urinary diversion is crucial for the rate of urinary complications, the continent diversion being linked to the lowest rate of complications (EHRLICH (186), PENALVER (187), etc..) compared with the direct ureterostomy or the ileal conduct mediated ureterostomy (CHEN (188), ROBERTS (189), etc.). In our series we did not find significant differences in the rate of complications between primary pelvic cancers and pelvic recurrences. The reintervention rate ranges in the international literature between 29% and -50% of cases (80, 190196). The reinterventions are often extremely difficult and increase the postoperative morbidity; sometimes they lead to the death of the patient, especially the ones for enteral fistulae and intestinal obstructions (a mortality of 40% and 50% (ROBERTS (197), PLUKKER (198), SYMMONDS (199), etc.)..) The pelvic lymphadenectomy associated to the TPE increases the complications rate up to 75% of cases (THORTON (200), EHRLICH (201), RODRIGUEZ (202). Data on the palliative TPE show a much higher rate of complications (FINLAYSON (203) HAFNER (204), YEUNG (205), etc.). The five year survival rate varies between 23% and 61% in the international literature (BOEY (206), LOPEZ (207), LINDSEY (208), LIU (209) SHIROUZU (111), etc..) - regarding primary pelvic tumors. In the case of the pelvic recurrences, the prognosis is more reserved, only 1 of LAW's 9 patients being alive after 5 years (210); YEUNG obtained a long-term survival rate for Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011 only 2 of the 43 patients of his series with EPT for recurrences of rectal cancer (211). Negative prognostic factors are considered by most authors: · The tumors larger than 3 cm. (Husain) (212), · The pelvic wall invasion, · The positive section margins · Lymph nodes metastases (BOEY (213), LOPEZ (214) SHIROUZU (215), etc.) · The appearance of the pelvic recurrence in less than one year after the initial surgery (BROPHY (216), YEUNG (217), etc.). The following factors influence in our opinion the results of this surgical procedure: a rigorous case selection (the endopelvic invasion, the absence of distant metastases and judicious analysis of comorbidities), performing the surgical procedure in specialized medical units and assembling a large highly trained therapeutical team (general surgeons, anesthesiologists, intensive therapists, urology surgeons, plastic surgeons, radiotherapeuts, chemoterapeuts, radiologists, anatomopathologists, psychologists, endocrinologists, sexologists, etc.. Conclusions Despite its aggressive nature, the TPE is fully justified for treating locally advanced pelvic cancers and pelvic recurrences, being the only therapeutic method with curative intent in these cases. The similar evolution of these tumors so different regarding their origin and histology, demands for all the locally advanced pelvic cancers the same therapeutic sanction: Total Pelvic Exenteration. The absence of extrapelvic metastases and the negative section margins justifie the use of this surgical procedure. The total pelvic exenteration can significantly increase the life expectancy and improve the quality of life for these patients. But in the end the patient is the one who gets to decide whether he will undergo the surgery or not, as stated by the intervention promoter BRUNSCHWIG: "... because of the advanced stage of disease, one can not predict whether many or none of these patients will survive for very long periods of time ... on the other hand, for those who do survive, in this moment when I'm writing these lines no one could express their feelings, no one can tell if they would have preferred to not be subjected to the surgery". Reference List 1. Gertsch P, Preitner J, Pettavel J, Mosimann R. [Total pelvic exenteration for invasive tumors of the pelvis]. Helv Chir Acta 1984 April;51(1):75-8. Mattingly RF. 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Shingleton HM, Soong SJ, Gelder MS, Hatch KD, Baker VV, Austin JM, Jr. Clinical and histopathologic factors predicting recurrence and survival after pelvic exenteration for cancer of the cervix. Obstet Gynecol 1989 June;73(6):1027-34. 179. Rodriguwz-Bigas MA, Petrelli NJ. Pelvic exenteration and its modifications. Am J Surg 1996 February;171(2):293-8. 180. Lopez MJ, Standiford SB, Skibba JL. Total pelvic exenteration. A 50-year experience at the Ellis Fischel Cancer Center. Arch Surg 1994 April;129(4):390-5. 181. Lopez MJ, Standiford SB, Skibba JL. Total pelvic exenteration. A 50-year experience at the Ellis Fischel Cancer Center. Arch Surg 1994 April;129(4):390-5. 182. Rodriguwz-Bigas MA, Petrelli NJ. Pelvic exenteration and its modifications. Am J Surg 1996 February;171(2):293-8. 183. Law WL, Chu KW, Choi HK. Total pelvic exenteration for locally advanced rectal cancer. J Am Coll Surg 2000 January; 190(1):78-83. 184. Wanebo HJ, Gaker DL, Whitehill R, Morgan RF, Constable WC. 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Lindsey WF, Wood DK, Briele HA, Greager JA, Walker MJ, Bork J, Das Gupta TK. Pelvic Exenteration. J Surg Oncol 1985 December;30(4):231-4. 209. Liu SY, Wang YN, Zhu WQ, Gu WL, Fu H. Total pelvic exenteration for locally advanced rectal carcinoma. Dis Colon Rectum 1994 February;37(2):172-4. 210. Law WL, Chu KW, Choi HK. Total pelvic exenteration for locally advanced rectal cancer. J Am Coll Surg 2000 January;190(1):78-83. 211. Yeung RS, Moffat FL, Falk RE. Pelvic Exenteration for Recurrent and Extensive Primary Colorectal Adenocarcinoma. Cancer 1993 September 15;72(6):1853-8. 212. Amreen Husain, Nelson Teng. Pelvic Exenteration. 2-2-2006. Ref Type: Internet Communication 213. Boey J, Wong J, Ong GB. Pelvic Exenteration for Locally Advanced Colorectal Carcinoma. Ann Surg 1982 April;195(4): 513-8. 214. Lopez MJ, Standiford SB, Skibba JL. Total pelvic exenteration. A 50-year experience at the Ellis Fischel Cancer Center. Arch Surg 1994 April;129(4):390-5. 215. Shirouzu K, Isomoto H, Kakegawa T. Total pelvic exenteration for locally advanced colorectal carcinoma. Br J Surg 1996 January;83(1):32-5. 216. Brophy PF, Hoffman JP, Eisenberg BL. The Role ofPalliative Pelvic Exenteration. Am J Surg 1994 April;167(4):386-90. 217. Yeung RS, Moffat FL, Falk RE. Pelvic Exenteration for Recurrent and Extensive Primary Colorectal Adenocarcinoma. Cancer 1993 September 15;72(6):1853-8. Annals of Fundeni Hospital, volume 16, no 3 - 4, 2011
Journal
Annals of Fundeni Hospital – de Gruyter
Published: Dec 1, 2011