Nonirradiated Patient Research Articles

Surgical Approaches to the Irradiated Breast

The use of radiation therapy for treatment of breast cancer has steadily increased since the 1990s. Plastic surgeons must be prepared to reconstruct patients with prior lumpectomy and radiation now needing salvage mastectomy, as well as the growing number of patients who will go on to need post mastectomy radiation therapy. Operating in the irradiated field presents unique challenges, including but not limited to intra-operative difficulties such as friable vessels when performing autologous-based reconstruction and higher rates of post-operative complications when performing implant-based reconstruction. Reconstructed outcomes are often inferior to the non-irradiated patient and as such the plastic surgeon should be prepared to perform further revision as necessary. This chapter will review indications for radiation therapy, both autologous- and implant-based approaches to reconstructing the irradiated breast and how to manage post-operative complications. This review contains 3 figures, 5 tables, and 75 references. Keywords: radiation, breast irradiation, breast reconstruction, radiation therapy, autologous reconstruction, implant-based reconstruction, revisionary breast surgery, complications

Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia.

Background/objectiveThe number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children’s irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors.DesignWe compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI.Subjects/methodsBody fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture.ResultsPatients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation.ConclusionsThese results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.

AUTHOR REPLY

Thank you for the insightful feedback on our study evaluating exchange of the artificial urinary sphincter (AUS) pressure regulating balloon. We agree it would be beneficial to know more of the details regarding the nature of incontinence (recurrent vs persistent) and the etiologies of the prior AUS explants, which was not obtained in 64% of the cohort. Of note, however, there was no significant difference in erosion rates, perhaps the most morbid outcome, between those with a prior AUS implant/explant and those who underwent pressure regulating balloon exchange with a virgin AUS. Further, it is important to emphasize that this procedure is beneficial in a very select cohort, ideally the nonirradiated patient with pure stress incontinence lacking urethral atrophy. Despite the efficacy demonstrated by our study, there is certainly a need for multi-institutional, prospective studies evaluating this management option for post AUS incontinence.

Height Deficit and Impairment of the GH/IGF-1 Axis in Patients Treated for Acute Lymphoblastic Leukemia during Childhood

Background: Endocrine complications after acute lymphoblastic leukemia (ALL) are common. Methods: Final height, GH/IGF-1 axis, and body mass index were analyzed after 13.7 (7.0–20.7) years from diagnosis in 34 boys aged <12 years at diagnosis and 41 girls <10 years at diagnosis. A modified German BFM-83 ALL protocol included (n = 42) or did not include (n = 33) prophylactic cranial irradiation. In 27 patients, GH after insulin tolerance test, IGF-1, cortisol, free T₄ and estradiol/testosterone were determined. Results: Final height was significantly reduced (mean Z-score for height between final height and diagnosis, ΔHAZ = –0.61, p = 0.0001). At that point, 3 patients were obese (4%) and 17 were overweight (22.7%). Patients aged ≤4 years at diagnosis and those irradiated had a greater loss in final height (p = 0.001 and p = 0.008, respectively). Abnormalities in GH/IGF-1 axis were observed in 4 patients: 3 had a GH peak <6 ng/ml and 1 had a serum IGF-1 concentration <25 ng/ml. Growth deficit was significantly higher in patients with hormonal deficiency (p = 0.006). Conclusions: Treatment of ALL during childhood is associated with final height deficit. Young age at diagnosis and radiotherapy were the major risk factors. GH/IGF-1 deficiency was found particularly in irradiated patients, even though it was detected in 1 non-irradiated patient.

Cognitive performance after postoperative pituitary radiotherapy: a dosimetric study of the hippocampus and the prefrontal cortex

The hippocampus and prefrontal cortex (PFC) are important for memory and executive functioning and are known to be sensitive to radiotherapy (RT). Radiation dosimetry relates radiation exposure to specific brain areas. The effects of various pituitary RT techniques were studied by relating detailed dosimetry of the hippocampus and PFC to cognitive performance. In this cross-sectional design, 75 non-functioning pituitary macroadenoma (NFA) patients (61±10 years) participated and were divided into irradiated (RT+, n=30) and non-irradiated (RT-, n=45) groups. The RT+ group (who all received 25 fractions of 1.8 Gy; total dose: 45 Gy) consisted of three RT technique groups: three-field technique, n=10; four-field technique, n=15; and five-field technique, n=5. Memory and executive functioning were assessed by standardized neuropsychological tests. A reconstruction of the dose distributions for the three RT techniques was made. The RT doses on 30, 50, and 70% of the volume of the left and right hippocampus and PFC were calculated. Cognitive test performance was not different between the four groups, despite differences in radiation doses applied to the hippocampi and PFC. Age at RT, time since RT, and the use of thyroid hormone varied significantly between the groups; however, they were not related to cognitive performance. This study showed that there were no significant differences on cognitive performance between the three-, four-, and five-field RT groups and the non-irradiated patient group. A dose-response relationship could not be established, even with a radiation dose that was higher on most of the volume of the hippocampus and PFC in case of a four-field RT technique compared with the three- and five-field RT techniques.

Free Vastus Lateralis Myocutaneous (VLMC) Flap for Reconstruction of Radionecrotic Defect of the Head and Neck

Radionecrosis is a common complication in head and neck cancer patients who received post-operative radiotherapy. It is a difficult problem not only poor head and neck appearance and care but also the risk of vessels rupture and mortality. Skin grafts, local skin, or mucosal flaps that might be perfectly adequate in a non-irradiated patient are unlikely to resolve the problem in a wound that has been previously irradiated or is to undergo adjuvant radiotherapy. From Oct. 2001 to Sep. 2002, eleven patients suffered from radionecrosis after post-operative radiotherapy were included. We used free vastus lateralis myocutaneous flaps in the huge radionecrotic defects of head and neck and got a good result. Two patients with post-operative wound infection healed after debridement and wound dressing. VLMC flap not only can provide enough skin territory to cover the huge wound and defect, but also has the ability to resist wound infection. We commend VLMC flap to reconstruct the radionecrotic defect of head and neck.

Practical guidelines for the reconstruction of the mandible and maxilla

With the wide range of treatment options now available, surgeons are challenged to select the optimal method, material, and timing for a particular reconstruction. Four areas of the maxillofacial complex frequently require reconstruction: the mandible, maxilla, orbit, and zygoma. Part I of this clinic will cover reconstruction of the mandible and maxilla while Part II will cover the orbit and zygoma. Mandibular defects can be divided into marginal defects, continuity defects, and continuity defects that include the mandibular condyle. Treatment varies among these 3 types of defects and also depends a great deal on the quantity and quality of the surrounding soft tissue. Mandibular defects with well-vascularized surrounding soft tissue of good volume can be treated by a variety of techniques using free autogenous bone grafts. When the soft tissue is deficient in quantity and/or quality, it must be improved or replaced before free autogenous bone grafting or free vascularized flaps may be used. The choice of reconstructive system is based on the experience of the surgeon and on the specific characteristics of the defect and the overall health of the patient. Our preferred technique in the nonirradiated patient with healthy surrounding soft tissue is a combination of a reconstruction plate and block corticocancellous graft from the posterior ilium. These grafts have demonstrated excellent retention over time and are compatible with osseointegrated implants. Maxillary defects can be divided into those defects that have loss of hard and soft tissue and those with loss of hard tissue only. Defects with loss of hard tissue only are less difficult to treat and are frequently treated by placement of free autogenous bone grafts, in many cases with subsequent or simultaneous implant placement. For the hemimaxillectomy defect in which there is loss of both hard and soft tissue, 3 general approaches can be used. The first is use of the traditional prosthetic obturator. A second is use of a pedicled flap such as the temporalis muscle flap, which separates the oral cavity from the nasal cavity and maxillary sinus region. A third would be use of free vascularized tissue transfer of soft tissue or soft tissue and bone. Although the obturator approach may be difficult for younger patients to accept, it has the advantage of avoiding another donor site and may give the most stable and predictable results long term. References Macintosh RB: Current spectrum of costochondral and dermal grafting, in Bell WH (ed): Modern Practice of Orthognathic and Reconstructive Surgery. Philadelphia, PA, Saunders, 1992, p 873 Keller EE: Mandibular discontinuity reconstruction with composite grafts: Free autogenous iliac bone, titanium mesh trays and titanium endosseous implants. Oral Maxillofac Surg Clin North Am 3:877, 1991 Bach DE, Burgess LPA, Zislis T, et al: Cranial, iliac and demineralized freeze-dried bone grafts of the mandible in dogs. Arch Otolaryngol Head Neck Surg 117:390, 1991

Cost-effectiveness of preoperative radiotherapy in rectal cancer: results from the Swedish Rectal Cancer Trial

Purpose: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short-term regimen of high-dose fractionated preoperative radiotherapy (5 × 5 Gy) reduced the local recurrence rates and improved overall survival. This has had an impact on the primary treatment of rectal cancer. The current study investigated the cost-effectiveness of the new combined approach. Methods and Materials: After an 8-year follow-up, in-hospital and outpatient costs related to the treatment of rectal cancer and its complications were analyzed for 98 randomly allocated patients who participated in the SRCT from a single Swedish health care region. The costs were then related to the clinical data from the SRCT regarding complications, local and distant recurrences, and survival. Results: The total cost for a nonirradiated patient was US$30,080 compared with US$35,268 for an irradiated patient. The surgery-alone group had increased costs related to local recurrences, and the radiotherapy group had increased costs for irradiation and complications. With a survival benefit of 21 months (retrieved from the SRCT), the cost for a saved year was US$3654. Sensitivity analyses for different rates of local recurrences, the costs related to complications and less marked survival benefit showed that this figure could vary up to US$15,228. Conclusion: The cost for a life-year saved in these data was US$3654. This figure could reach US$15,228 in the most pessimistic setting of the sensitivity tests, a cost still comparable with other well-accepted medical interventions.

Radiation effects on breast reconstruction with the deep inferior epigastric perforator flap.

Immediate breast reconstruction has important advantages over delayed reconstruction, including a shorter operative time and decreased psychological distress for the patient. However, the authors' experiences with the deep inferior epigastric perforator flap demonstrate variable aesthetic outcomes among patients who undergo radiation postoperatively. To establish an association between radiation and poor postoperative results, a matched-pairs analysis was conducted. Thirty irradiated patients were paired with 30 nonirradiated patients, according to age and body mass index. For each group, the incidence of fat necrosis, fibrosis/shrinkage, and flap contracture was recorded. In addition, an aesthetic evaluation was conducted to compare before-and-after images of 10 irradiated patients with those of 10 nonirradiated patients from similar time periods. The images were randomized and blindly evaluated by a panel of eight judges. A five-point scale was used to evaluate symmetry, aesthetic proportion, and the appearance of the superior pole. Statistical analysis demonstrated a significant difference in the score changes for irradiated and nonirradiated patients, according to all three criteria. Nonirradiated patient scores increased by one-half point, and irradiated patient scores decreased by one-half point. In addition, the incidences of fat necrosis, fibrosis, and flap contracture were all significantly higher among the irradiated group. These results suggest that when possible, reconstruction should be delayed until after radiation therapy is complete. Persons who smoke or are obese may be at particular risk for complications following radiation therapy.

Breast cancer: chest wall recurrences.

Irradiation is indicated for patients undergoing mastectomy as surgical management for breast cancer treatment when clinical or pathologic tumor and nodal features predict risk of local/regional recurrence. Such features include: tumor size >/= 5 cm, inadequate surgical margins; skin, facial, or skeletal muscle invasion; dermal lymphatic invasion; poorly differentiated tumor histology; four or more lymph nodes positive; gross extracapsular tumor nodal extension into soft tissues; and matted lymph nodes or enlarged lymph nodes > 2 cm. Patients who were treated with irradiation after mastectomy can develop local/regional recurrences despite such adjuvant therapy. General management for chest wall and nodal recurrences is structured on the extent and volume of local/regional disease, the absence of distant metastases, the general health of the patient, and the extent of prior local/regional therapies, especially irradiation. Management of local/regional recurrence in the setting of no prior irradiation includes tumor debulking by systemic or surgical treatment followed by comprehensive chest wall and regional lymphatic irradiation. Doses are selected by tissue tolerances and volume of remaining disease. The management strategy for the patient with a history of irradiation parallels the nonirradiated patient with respect to systemic and surgical therapies to debulk the tumor to maximal response or no gross clinical disease. Radiation field design is determined by prior therapies. Doses to these fields are adjusted to normal tissue tolerance. Irradiation is given with a sensitizer such as hyperthermia or 5-fluorouracil chemotherapy. Use of radiation sensitizers can allow for a more meaningful biologic tumor effect when normal tissue tolerances prohibit delivery of standard tumor doses. Hyperthermia has been used effectively to promote complete tumor responses with use of irradiation in re-treatment cases.

Why change a good thing? Revisiting the fleur-de-lis reconstruction of the breast.

Although the latissimus flap is known for its simplicity and reliability, use of the fleur-de-lis pattern was plagued by undesirable T-shaped donor sites and small breast volumes in thin patients. We report a modified technique for optimal shaping of the standard latissimus with the successful application of a modified fleur-de-lis pattern. Because a "wet" tumescent infiltration was utilized and large amounts of subcutaneous fat were harvested, these changes permitted application to a wide variety of patients, with generous breast volumes reducing the size of the implant placed and resulting in excellent donor-site scars. This is a retrospective cohort study of 53 delayed or immediate reconstructions performed consecutively by the principal author (M.E.A.) on 48 patients at a university-based, urban hospital. Each case was analyzed between April of 1995 and February of 1999, with a follow-up from 2.5 to 44 months. All patients underwent injection of tumescent solution into the subcutaneous plane and harvest of large amounts of subcutaneous fat with the neurologically intact latissimus muscle. The last 25 reconstructions utilized the modified fleur-de-lis skin pattern, an inferiorly based vertical limb and replacement of skin deficiency in both axes. Of 11 perioperatively irradiated patients, none required skin grafting, whereas 6 percent of all native mastectomy flaps were grafted. There was one instance of minor distal tip flap necrosis in a nonirradiated patient. No implants became infected or were extruded. Donor sites were without wound complications and unveiled a 16 percent overall seroma rate.Through selective addition of harvested tissue, this modified technique, particularly the fleur-de-lis pattern, permits improved volume and projection in the inferior pole. The T-shaped donor-site closure is not only acceptable, but is also desirable, with reduced wound tension and minimization of dog-ear formation. With a relative paucity of complications, this conceptually ideal modification is technically simple and aesthetically comparable to our transverse rectus abdominis muscle flap results.

Malignant transformation in a young adult with recurrent laryngeal papillomatosis

The term “papilloma” was first described by Mackenzie in 1880 when he described papillomas in the larynx of a child and used the term “Juvenile laryngeal papillomatosis”; he also claimed that it was the most benign tumour of the larynx [1]. Human Papilloma Virus (HPV) types 6 and 11 have been associated with recurrent respiratory papillomatosis (RRP). In view of the recurrent nature of this condition majority of patients require multiple surgical procedures for tumour removal and maintenance of airway [2, 3]. Malignant transformation of RRP is uncommon, however squamous cell carcinoma (SCC) can arise in RRP but is uncommon in the absence of aggravating factors such as tobacco smoking, irradiation and exposure to chemical agents. Genetic mutation of p53 in association with integration of HPV-11 is seen in histologically malignant lesions. This association may promote a progressive genetic instability that can lead to the development and clonal expansion of malignant lesions in RRP [3]. We report a rare case of a 28 year old JCO, non-smoker, non-irradiated patient who underwent malignant transformation of benign recurrent papillomatosis during LASER treatment. He was treated with widefield laryngectomy with primary tracheo-oesophageal puncture (TEP) and insertion of PROVOX -2 voice prosthesis for voice restoration.

Recurrent Stage I Endometrial Adenocarcinoma in the Nonirradiated Patient: Preliminary Results of Surgical "Staging"

Recurrent endometrial carcinoma, even when clinically confined to the vagina or pelvis, is associated with poor survival. Pelvic radiotherapy for patients with localized recurrences who have not been previously irradiated has not been highly effective. Our hypothesis was that local salvage therapy fails because a significant number of patients have occult, subclinical distant metastases at the time of relapse. In order to accurately assess disease status at the time of the recurrence, we prospectively evaluated eight patients with recurrent disease limited to the vagina/pelvis by physical examination, routine laboratory tests, and radiologic imaging. All patients underwent a "staging" procedure which included laparotomy, selective pelvic/periaortic lymphadenectomy, peritoneal biopsies, and washings. Three (37.5%) of eight patients had upper abdominal disease found at laparotomy (95% confidence interval 0.11 to 0.71). Presence of subclinical metastases was associated with larger tumor size (⩾ 2 cm) and elevated serum CA 125 antigen levels. Treatment was modified in three patients according to the results of surgical staging. One patient was treated with chemotherapy while two patients received whole-abdominal radiation in addition to pelvic fields. Seven of eight patients are alive 21 to 61 months following salvage therapy. Three (43%) of seven patients treated with radiotherapy suffered nonneoplastic bowel obstruction requiring laparotomy at 3, 6, and 15 weeks following completion of radiation therapy. Since 37.5% of patients with recurrent endometrial carcinoma clinically confined to the pelvis had occult upper abdominal disease, surgical reassessment may be warranted, especially in those with elevated serum CA 125 levels or large tumors. Our limited sample size precludes any definitive conclusions regarding our data. Further research will determine the frequency of subclinical metastases and the value of serum CA 125 levels in assessing disease status.

Squamous cell carcinoma of the lung in a nonsmoking, nonirradiated patient with juvenile laryngotracheal papillomatosis: Evidence of human papillomavirus-11 DNA in both carcinoma and papillomas : Guillou L, Sahli R, Chaubert P, Monnier P, Cuttat J-F, Costa J. Institut Universitaire de Pathologie, 25, rue du Bugnon, 1011 Lausanne. Am J Surg Pathol 1991;15:891–8

Squamous cell carcinoma of the lung in a nonsmoking, nonirradiated patient with juvenile laryngotracheal papillomatosis: Evidence of human papillomavirus-11 DNA in both carcinoma and papillomas : Guillou L, Sahli R, Chaubert P, Monnier P, Cuttat J-F, Costa J. Institut Universitaire de Pathologie, 25, rue du Bugnon, 1011 Lausanne. Am J Surg Pathol 1991;15:891–8

Squamous cell carcinoma of the lung in a nonsmoking, nonirradiated patient with juvenile laryngotracheal papillomatosis. Evidence of human papillomavirus-11 DNA in both carcinoma and papillomas.

Malignant transformation of laryngeal juvenile papillomatosis most often occurs in patients with previous radiation therapy or smoking histories. We report the case of a 35-year-old, nonsmoking, nonirradiated man who developed squamous cell carcinoma of the lung with a 33-year history of laryngotracheal juvenile papillomatosis. Postmortem examination showed pulmonary cavitating papillomatosis and chest wall, vertebrae, and peribronchial lymph node involvement by tumor. Molecular studies (Southern blot, polymerase chain reaction) showed extrachromosomal human papillomavirus-11 (HPV11) DNA in both carcinoma and two laryngotracheal squamous cell papillomas, including one excised 20 years previously. Our observation is analogous to the previously reported cases of spontaneous (not related to irradiation or smoking) malignant transformation of juvenile laryngotracheal papillomatosis. Although HPV11 viral infection likely played a role in the malignant transformation, other less likely factors, such as drugs given for treatment and radiography performed throughout the illness, should be considered. Repeated pulmonary infections and the host immune response are additional considerations.

Mandibulotomy in the irradiated patient.

Though the "mandibular swing," as an approach to certain upper aerodigestive tract malignancies, has been gaining popularity in recent years, there has been little reported as to the feasibility of this procedure in subjects who have received radical preoperative radiotherapy. We have recently reported the results of 23 such patients, and we now present an update. The results presented are of a retrospective analysis of 44 patients, 50% of whom received radical preoperative radiotherapy to fields including the osteotomy site. As in the previous study, there were no statistically significant differences between the complication rates in the irradiated and nonirradiated patient populations. All the patients were orally rehabilitated.

Current status of genitourinary fistula

From 1970-1985, 303 women with genitourinary fistulas were seen at the Mayo Clinic. The fistula formed after treatment for benign conditions in 74% of the patients and malignant conditions in 14%; in 12%, we were unable to establish the nature of the condition. Gynecologic surgery was responsible for 82% of the fistulas, obstetric procedures for 8%, various forms of irradiation for 6%, and trauma or fulguration for 4%. In the nonirradiated patient, the ideal time for operative repair was eight to 12 weeks after fistula formation or failed repair. With ureterovaginal fistulas, the patient's general condition and the degree of obstruction of the ureter influenced the time and method of repair. We used a vaginal approach for urethral fistulas and an abdominal one for ureteral repairs. Because of difficulty with adequate exposure and the proximity of the ureter, an abdominal approach was used in 20% of the patients with vesicovaginal fistulas; the remaining 80% were approached vaginally, regardless of size, number, or history of previous repairs. Ninety-two percent of the urethrovaginal fistulas were corrected on the first attempt; the four failures were managed successfully at the second attempt. Ninety-eight percent of the vesicovaginal fistulas were corrected on the first attempt when approached vaginally, and all were managed successfully when approached abdominally, regardless of the number, size, or previous operative attempts.

A Comparative Study of Perioperative Complications with Kock Pouch Urinary Diversion in Highly Irradiated Versus Nonirradiated Patients

To define the nature and risk of complications associated with Kock pouch urinary diversion after high dose radiation (more than 4,500 rad), we analyzed the clinical course of 44 irradiated patients and a comparable group of 42 selected retrospectively from the nonirradiated patient cohort. Of the 42 patients in the irradiated group 18 had received 4,500 to 5,700 rad and 24 had received 6,000 to 8,700 rad. With standard statistical methods we found no difference between the irradiated and control groups when compared for age, sex ratio, followup interval, surgical procedure, operative time or estimated blood loss. There were 2 operative mortalities in the irradiated and 1 in the control groups.In the immediate postoperative period there was no difference between the irradiated and control groups when compared for hospital stay, incidence of urine leak or fascial dehiscence. The irradiated group had 8 urine leaks (20 per cent) and 3 patients (7.5 per cent) required surgical repair. The control group had 5 urine leaks and 1 patient (2.3 per cent) required repair. Diarrhea severe enough to require further hospitalization or medication was significantly more frequent in the irradiated group (18 versus 2 per cent) but the postoperative stay was not significantly different (13 versus 11 days). We conclude that Kock pouch urinary diversion may be performed safely in highly irradiated patients.