Incidence Of Recurrent Disease Research Articles

Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity.

Anti-cancer effects of cyclooxygenase (COX)-2 inhibitors have been reported, but not fully investigated in skin and oral diseases. 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for treating those patients with skin and oral lesions is a highly sophisticated procedure, but the incidence of disease recurrence after treatment is rather significant. To confirm that COX-2 could be a molecular target in adjunctive therapy to ALA-based PDT, we investigated (i) COX-2 expression in various skin and oral diseases, and (ii) the inhibitory effects on cellular growth of COX-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on human oral squamous cell carcinoma (SCC) cell lines. A total of 129 biopsy samples from the skin and oral mucosal lesions were tested immunohistochemically for COX-2 expression. Then the in vitro effects of nimesulide, ALA-based PDT, and their combination were determined on two SCC cell lines, HSC-2 and HSC-4. Three different methods (MTT assay, double-staining for annexin V and propidium iodide, caspase-3/CPP32 fluorometric protease assay) were applied for evaluation of their inhibitory effects on these two cell lines. Among the skin diseases, a considerable number of COX-2 high expressers were found in actinic keratosis (15 of 25, 60%), Bowen's disease (13 of 17, 76%) and extramammary Paget's disease (15 of 15, 100%). In contrast, only one of 33 (3%) basal cell carcinoma tumours was a COX-2 high expresser. Among the oral mucosal biopsies, the proportion of COX-2 high expressers increased gradually from hyperplasia (one of six, 17%) through mild dysplasia (five of eight, 63%) and moderate dysplasia (20 of 23, 87%) to severe dysplasia (two of two, 100%). Nimesulide had an inhibitory effect in vitro on HSC-2 (proven to be a COX-2 high expresser), but not on HSC-4 (a COX-2 non-expresser). While ALA-based PDT showed an inhibitory effect on both HSC-2 and HSC-4, most importantly the combination of nimesulide and ALA-based PDT demonstrated a significant synergistic effect on the cellular growth inhibition of only HSC-2, but not of HSC-4. Our study strongly suggests that COX-2 can be one of the molecular targets in treating various skin and oral diseases. The results from our in vitro experiments also prompt us to develop a new protocol with a combination of COX-2 selective inhibitor and ALA-based PDT for more effective treatment of those diseases.

Reconstrução tridimensional da face nos tumores avançados com invasão da fossa craniana anterior

OBJETIVO: Analisar as indicações cirúrgicas e o seguimento pós operatório, ressaltando as complicações e efetividade da abordagem multidisciplinar, para os tumores avançados da base do crânio. MÉTODO: Análise retrospectiva de 46 prontuários de pacientes submetidos à ressecção de tumores invadindo a fossa craniana anterior e reconstruídos com retalhos microcirúrgicos, operados entre março de 1990 e julho de 2002. Todos os pacientes foram operados pelo núcleo de cirurgia de base do crânio do INCA. RESULTADOS: As estruturas mais envolvidas na ressecção foram por ordem: a órbita (76,5%), seio maxilar (76,5%), seio esfenoidal (63,8%), paredes da cavidade nasal (59,5%) e palato (42,5%). A dura-máter estava acometida em 32,6% dos casos. A reconstrução microcirúrgica utilizando os retalhos do músculo reto abdominal foi empregada em 93,5 % dos casos. A taxa de sucesso dos transplantes livres foi de 97,8%. As complicações ocorreram em 58,6% dos pacientes e as mais freqüentes foram: infecções locais (21,7%), fístulas liquóricas (15,2%), meningite (6,5%) e hematoma (6,5%). CONCLUSÕES: A reconstrução com técnica microcirúrgica permite que se realizem ressecções alargadas destes tumores com limites seguros e índices de complicações aceitáveis, permitindo a estes pacientes uma melhoria da qualidade de vida e da sobrevida, com baixo índice de recidiva.

Cryosurgery—a putative approach to molecular-based optimization

Cryosurgery must be performed in a manner that produces a predictable response in an appropriate volume of tissue. In present-day clinical practice, that goal is not always achieved. Concerns with cryosurgical techniques in cancer therapy focus in part on the incidence of recurrent disease in the treated site, which is commonly ∼20–40% in metastatic liver tumors, and prostate cancers. Whether the cause of this failure is disease-based or technique related, cryosurgery for cancer commonly needs the support of adjunctive therapy in the form of anti-cancer drugs or radiotherapy to increase the rate of cell death in the peripheral zone of the therapeutic lesion where cell survival is in balance for several days post-treatment. Recent evidence has identified a third mechanism of cell death associated with cryosurgery. This mechanism, apoptosis or gene regulated cell death, is additive with both the direct ice-related cell damage that occurs during the operative freeze–thaw intervals and coagulative necrosis that occurs over days post-treatment. In this manuscript we discuss, through a combination of literature review and new data, the combined roles of these distinct modes of cell death in a prostate and colorectal cancer. Data are presented suggesting that sub-freezing temperatures, when sequentially applied with low dose chemotherapy, may provide improved cancer cell death in the freeze zone periphery. Since the mechanism of action of most common chemotherapeutic agents is to initiate apoptosis in cancer cells, the observation that sub-freezing exposures yields a similar effect provides a possible route toward molecular-based procedural optimization to improve therapeutic outcome.

Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence.

The goal of the current study was to assess the effect of pregnancy on the subsequent risk of recurrence after treatment for breast carcinoma, adjusting for established prognostic factors. Between 1974 and 1998, 383 patients age < or =35 years were treated for breast carcinoma with adjuvant chemotherapy at The University of Texas M. D. Anderson Cancer Center (Houston, TX). The median follow-up period was 13 years. Of these, 13 patients were excluded from analysis, as no history was available regarding pregnancy; 240 (65%) were >30 years old; 47 (13%) had at least 1 pregnancy after therapy; 32 had full-term pregnancies; 10 had spontaneous or elective abortions; 4 had miscarriages; and 1 had a premature delivery. Estrogen receptor (ER) status, lymph node involvement, and disease stage were evaluated as potential risk factors for recurrence. Information on ER status was unavailable for 123 (33%) patients. Patients who experienced a pregnancy tended to have earlier-stage disease (Stage I/II: 80% vs. 73%), fewer positive lymph nodes (<4: 87% vs. 52%), more ER negativity (68% vs. 58%), and younger age (<30 years: 57% vs. 32%) than patients who did not. The incidence of disease recurrence was 23% for women who experienced a pregnancy and 54% for women who did not. The hazard ratio (using the multivariate Cox proportional hazards model) for disease recurrence in patients with posttreatment pregnancy was 0.71 (P=0.4). In the current study population, pregnancy was not associated with an increased risk of disease recurrence or poorer survival in patients previously treated for breast carcinoma.

Can selective retroperitoneal lymphadenectomy be better than unilateral retroperitoneal lymphadenectomy?

To propose a new modality of retroperitoneal lymphadenectomy as a complementary treatment for patients with high risk, stage I nonseminomatous testicular tumor. We studied 76 patients with stage I nonseminomatous testis tumor (T1-T4, NX, M0) treated by orchiectomy and retroperitoneal lymphadenectomy. Among them, 33 patients underwent unilateral retroperitoneal lymphadenectomy (URL) and 43 selective retroperitoneal lymphadenectomy (SRL). URL consisted in removing the lymph nodes located around the great vessel homolateral to the tumor (aorta or vena cava and iliac vessels), and anterior and posterior to the contralateral great vessel (aorta or vena cava). SRL was performed removing the lymph nodes located anterior and between the great vessels (aorta or vena cava) and laterally to the homolateral great vessel, extending the distal dissection until the level of inferior mesenteric artery. In these groups of patients, the incidence of disease recurrence, disease-free survival index, and frequency of post-operative aspermia were assessed. Mean post-operative follow-up time was 96 months. In the SRL group there was only 5% of aspermia versus 79% in the URL group (p < 0.0001). Tumor recurrence was observed in only 5 of the 76 patients and was not related to the surgical technique. The disease-free survival rate after the mean follow-up of 96 months was similar in both groups, being 94% in the SRL group and 93% in the URL group. The selective retroperitoneal lymphadenectomy constitutes an effective technique with a lower morbidity than unilateral lymphadenectomy, representing an excellent option for the management of patients with high-risk, stage I nonseminomatous testis tumor.

Prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder in Taiwan

Objectives. To develop a prognostic-factors-based predictive model for invasive urothelial carcinoma of the urinary bladder derived from statistical comparison of clinical characteristics. Methods. The medical records for patients with invasive urinary bladder urothelial carcinoma were reviewed. Clinical data for age, sex, serum lactate dehydrogenase, creatinine, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin and hemoglobin levels, white blood cell and platelet counts, positive urine cytology, Eastern Cooperative Oncology Group performance status score, tumor size, histologic grading, T stage, presence of lymph node metastases, squamous differentiation, hydronephrosis, prostatic involvement, Charlson comorbidity index, surgical procedures, and adjuvant chemotherapy status were recorded. Univariate and multivariate analyses were performed to test independent factors for prediction of survival and disease recurrence. Results. After univariate and multivariate analyses, six independent prognostic factors were found: T stage, grading, prostatic involvement, Eastern Cooperative Oncology Group performance status score, and pretreatment serum creatinine and albumin levels. A scoring system was developed on the basis the relative risk associated with the proposed prognostic factors and patients were stratified into three groups according to their scores, with statistically significant prognostic differences revealed for each of the between-group comparisons. Independent factors affecting recurrence-free survival and best predicted disease recurrence were pretreatment serum creatinine, T stage, and surgical procedure. Conclusions. This prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder may help clinicians predict outcome and select the most appropriate therapeutic modalities. The incidence of recurrent disease is significantly higher for patients with poor renal function before treatment or advanced T stage and those undergoing transurethral tumor resection instead of radical cystectomy.

Transcanal atticoaditotomy and transcortical mastoidectomy for cholesteatoma: the Farrior-Olaizola technique revisited.

Conservative mastoid surgery in the management of middle ear cholesteatoma has been a subject of controversy for decades. Proponents of the combined-approach tympanoplasty for cholesteatoma do not entirely support the conservative approach in children, especially in the hands of an inexperienced surgeon. We describe here our experience with a modified technique of conservative mastoid surgery involving an atticoaditotomy and a separate simple mastoidectomy with lateral attic wall reconstruction (modified Farrior technique) that can be relatively safely used in the majority of cases of chronic squamous otitis media, even in children. This was a prospective analysis of the therapeutic effects and benefits of the technique used in 103 cases of cholesteatoma at Staffordshire General Hospital from 1991 to 1997. The follow-up was between 3 and 9 years. The study group consisted of 55 male patients and 48 female patients, including 28 children less than 16 years of age. The age ranges were 9 to 61 years in male patients and 10 to 48 years in female patients. After an audiological assessment, all patients underwent the described mastoid procedure, and some of them required revision surgery, mostly for a second look or for ossiculoplasty. The chief outcome measures used were complete eradication of disease, incidence of disease recurrence, and restoration of hearing. The steps of the procedure, its pros and cons, and the results of the series are presented. Also discussed is an overview of the literature pertaining to intact-canal wall mastoid surgery. Of the 103 patients, only 3 had a recurrence of disease, and 9 patients showed no hearing improvement. We conclude that this modified technique has several advantages over the previously described mastoidectomy procedures. It is a relatively simple and effective technique that can be performed even in children.

Chronic axillary hidradenitis — the efficacy of wide excision and flap coverage

A number of different modalities of surgical treatment for axillary hidradenitis suppurativa have been suggested. This study compares three different methods of surgical excision. Fifty-nine patients (94 axillae) were treated over a 14-year period. There were 42 females and 17 males with an average age of 32 years (range 16-65 years). Twenty-six axillae had excision of only the diseased skin and recurrent disease occurred in seven. However, in 39 axillae that were treated by excision of all the hair bearing skin, only three developed recurrent disease, which is a significant reduction in the incidence of recurrent disease (P = 0.04, Fischer's exact test). Twenty-nine axillae were treated by wide local excision (2 cm beyond the hair bearing skin) and no recurrence occurred. However, there was no statistical difference (P = 0.18, Fischer's exact test) in disease recurrence between excision of all the hair bearing skin and wide local excision. This study suggests that excision of all the hair bearing skin is the preferred method of surgical treatment. Flap coverage was an effective method to achieve wound closure after adequate excision and can be achieved by random fasciocutaneous flaps for small or medium sized defects and parascapular flaps for large defects.

Vascular endothelial growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric carcinoma.

Recently many studies have demonstrated that the degree of tumor angiogenesis is related to the aggressiveness of the tumor and clinical outcome. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. In this study, the authors investigated the prognostic significance of VEGF expression in patients with early gastric carcinoma together with p53 gene abnormality and tumor cell proliferation. One hundred ninety-five endoscopically biopsied specimens obtained preoperatively from patients with early gastric carcinoma were studied immunohistochemically. According to conventional clinicopathologic factors, submucosal invasion, lymph node metastases, and tumor size were associated significantly with the incidence of disease recurrence. According to conventional biologic factors, VEGF expression was observed more frequently in patients with disease recurrence compared with those without disease recurrence whereas neither p53 abnormality nor tumor cell proliferation were correlated with prognosis. Moreover, multivariate analysis indicated that VEGF expression (as well as submucosal invasion and lymph node metastases) is an independent predictor of disease recurrence. The results of the current study show that VEGF expression may be a useful prognostic factor for patients with early gastric carcinoma.

Pediatric Functional Endoscopic Sinus Surgery

Based on experience with functional endoscopic sinus surgery in over 200 children, we suggest that technical considerations modify the approach in the pediatric patient. We present details of our surgical approach with emphasis on modifying the uncinectomy. We believe our modifications reduce the incidence of recurrent disease.

The influence of native nephrectomy on the incidence of recurrent disease following renal transplantation for primary glomerulonephritis.

Factors influencing the incidence of recurrent glomerulonephritis following renal transplantation are poorly understood. Bilateral pretransplant native nephrectomy has been advocated to reduce the likelihood of recurrence after renal transplant. However, there is significant morbidity of native nephrectomy in the uremic population. Therefore, we sought to determine the effect of pretransplant native nephrectomy on the incidence of recurrent primary glomerulonephritis and the attendant risk of graft failure due to recurrent disease. Three hundred sixty-four consecutive cadaveric (n = 214), living-related (n = 137), and living-unrelated (n = 13) renal transplants were performed in 319 patients with a diagnosis of primary glomerulonephritis. Specific diagnoses included were focal segmental glomerulosclerosis (FSGS), rapidly progressive glomerulonephritis/idiopathic crescentic glomerulonephritis (RPGN/ICG), IgA nephropathy (IgA), mesangioproliferative glomerulonephritis, type I and II (MPG), anti-glomerular basement membrane nephritis (anti-GBM), and membranous glomerulonephritis (MGN). Rates of recurrence and graft loss were compared between patients treated with bilateral native nephrectomy (n = 61) and those who were not (n = 303). Bilateral nephrectomy did not prevent or delay the onset of recurrent glomerulonephritis in the renal allograft. In fact, there was a significantly increased five- and ten-year risk of recurrence in patients undergoing pretransplant nephrectomy vs. no nephrectomy (25.2% and 42% vs. 13.9% and 19.4%, P < 0.02, respectively). The increased rate of recurrence was evident in the CAD/LUD recipients, but not in recipients of LRD transplants. Of the specific diseases, FSGS and MGN recurred more commonly (20.2% and 20.3%, respectively). A detrimental effect of pretransplant nephrectomy on recurrence rates and incidence of graft loss due to recurrent disease independent of other variables could be demonstrated only for FSGS patients. Based on these findings, we no longer recommend native nephrectomy in the prospective renal transplant recipient at high risk for developing recurrent glomerulonephritis.

Flow cytometric DNA analysis on renal cell carcinoma--a study of 116 cases on fresh surgical specimens

DNA ploidy was investigated using flow cytometry on fresh surgical specimens from 116 cases with renal cell carcinoma. DNA diploid tumor was observed in 39 cases (33.6%) and aneuploid in 77 cases (66.4%). DNA aneuploid group was further classified into 3 subgroups by DNA index (D.I.); near-diploid group (D.I.: 0.8-1.2, 21.6%), near-tetraploid group (D.I.: 1.8-2.2, 12.9%) and other aneuploid group (31.9%). DNA ploidy pattern correlated with clinical stages and histological grading, indicating significantly a higher incidence of DNA diploid in cases in stage I and grade 1. DNA clonal heterogeneity was observed in 48.1%, and homogeneously diploid was in 28.6% of 77 cases who were analyzed more than 2 specimens. Incidences of DNA heterogeneity and homogeneous diploid correlated with the number of analyzed specimens and our results showed that more than 4 specimens were necessary to diagnose the DNA ploidy patterns. The near-tetraploid group was shown to have an extremely poor prognosis compared with the diploid group and the other aneuploid group. There were no significant difference between the diploid group and the aneuploid group in terms of the early prognosis, however, the incidence of disease recurrence was significantly higher in the aneuploid group. Our results demonstrated that DNA ploidy was an useful prognostic factor in the evaluation of patients with renal cell carcinoma.

A comparison of wound healing after epithelial resection by ultrasonic surgical aspiration and ablation by the carbon dioxide laser

The ultrasonic surgical aspirator (USA) offers unique surgical options in the treatment of vulvar intraepithelial diseases. Clinical observations have shown results that equal those achieved with the use of the carbon dioxide laser with regard to patient satisfaction and incidence of recurrent disease. The purpose of this study was to compare the USA to the carbon dioxide laser in the laboratory with respect to ease of use, adequacy of epithelial removal, amount of tissue damage, and timing of wound healing. The backs of ten Hartley guinea pigs were marked with eight 1-cm 2 patches placed 2 cm apart. Each instrument was used to ablate or resect the area within four patches on each animal's back to the level of the middermis (0.5–1.0 mm). At time intervals from 0 hr to 28 days, the eight 1-cm patches were removed and evaluated histologically. The USA was easier to control and maintain within the 1-cm 2 patch than the laser was. On histologic evaluation, the USA demonstrated less adjacent epithelial damage. The peak inflammatory response, depth of collagen denaturation, reepithelialization, and healing at 28 days were similar in both groups. The study indicates that the ultrasonic surgical aspirator is effective in epithelial removal and allows rapid wound healing with minimal scarring.

Role of thyroid stimulating hormone suppression in the management of thyroid cancer

Well-differentiated thyroid cancers (papillary, follicular, and some Hurthle cell tumors) contain membrane receptors for TSH. Responsiveness of these tumors to TSH stimuli is documented by increased radioactive iodine uptake, secretion of thyroglobulin, increase in thyroid size, and potential progression to an anaplastic type. Although TSH suppression has a variable effect on the growth of existing tumors and the incidence of recurrent disease, there is a sound rationale for long-term TSH suppression in all patients with differentiated tumors of the thyroid. The ultrasensitive TSH test permits ready monitoring of the adequacy of thyroxine dosage. The cost is minimal (approximately $.10/day) and the risks are negligible if one assumes the avoidance of hyperthyroxinemia.

Recurrence of Disease Following Renal Transplantation

The diagnosis of recurrent renal disease after transplantation is dependent on an accurate and complete diagnosis of the initial cause of renal failure and a similar determination of the cause of graft failure. To be classified as recurrent, the disease in the renal graft must be identical to that seen in the native kidneys. Recurrence of disease accounts for less than 2% of all graft failures, but the overall incidence of recurrent disease is probably 5 to 10 times more common. The most frequent cause of recurrent disease is glomerulonephritis, which was first recognized to recur soon after renal transplantation was introduced. It was then recognized that a variety of metabolic disorders would recur, but it has taken 25 years of experience for a clear picture to emerge of recurrence in most conditions. No initial cause of renal failure poses a contraindication to at least one attempt at transplantation, although with Fabry's disease and oxalosis, a special assessment of the risks for the individual recipient is warranted. In some patients, experience has shown the need for a delay in the commitment to transplantation (eg, in those with anti-glomerular basement membrane [GBM] antibody glomerulonephritis or Henoch Schonlein purpura), the need for the choice of a particular immunosuppressive regimen (eg, in hemolytic uremic syndrome [HUS]), the need for avoidance of primary nonfunction (eg, in oxalosis), and the desirability of avoiding live kidney donation (eg, in heterozygote donors in Fabry's disease, high-risk recipients with focal glomerulosclerosis, and in recipients with HUS). Probably all types of glomerulonephritis recur, but with great variation in frequency and severity. In some forms of glomerulonephritis, recurrence may be frequent and definite on histopathological criteria but may only have a minor clinical expression (eg, dense deposit disease, anti-GBM antibody glomerulonephritis, IgA nephropathy), but in others, recurrence is less predictable yet it is clearly associated with premature graft failure (eg, focal glomerulosclerosis, membranous nephropathy). A common theme emerging is that where the initial glomerulonephritis is aggressive and causes kidney failure over a short time, recurrence is more likely, and when present, it will lead to graft failure with an increased frequency. Clinical manifestations, the frequency of recurrence, and the prognosis of the graft are now identified for most conditions. Unexpected observations have included the rarity of recurrent systemic lupus erythematosus (SLE), the immediate return of heavy proteinuria in focal glomerulosclerosis, and the predictable return of dense deposit disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Cone biopsy of the cervix: does surgical technique influence cytological follow-up?

A 10-year experience of cone biopsy of the cervix was reviewed to determine whether the surgical method used delayed the diagnosis of recurrent disease. Although there is a trend to selective ablation of cervical intraepithelial neoplasia, cone biopsy is a necessary adjunct to the colposcopist and remains the technique used by many gynaecologists. Two surgical techniques were compared; 1) Sturmdorf sutures, where the denuded cervical stump was covered by squamous epithelium 2) Interrupted vertical sutures, where the cervical epithelium was not covered. There was a 15% incidence of recurrent disease which was related to the completeness of initial excision and the age of the patient. The surgical technique employed did not influence the future cytological follow-up nor delay the diagnosis of recurrent disease.

Radiotherapy in the treatment of carcinoma of the vocal cords: results of a 10-year experience.

A 10-year period of treatment at the Department of Radiotherapy of the Royal Prince Alfred Hospital was analysed retrospectively to assess the efficacy of "radical" irradiation in patients with early glottic cancer (Stages I and II). From June, 1964, to June, 1974, 120 patients were treated primarily with radiotherapy, which was followed by salvage laryngectomy for those with locally recurrent disease. Patient follow-up ranged from 0.5 to 12 years (mean, 6.2 years). The incidence of disease recurrence after radiotherapy was 13.7% for patients with Stage-I disease and 13.6% for patients with Stage-II disease. The five-year actuarial probability of local tumour control was 85% for patients with Stage-I disease. Ninety-one patients (77.8%) remain alive and well without disease recurrence, with an actuarial five-year survival probability for patients with stage-I disease of 93.8%. "Radical" irradiation for early glottic cancer can result in excellent survival rates with a small probability of local recurrence and few complications.

Anterior resection for adenocarcinoma: Lahey clinic experience from 1963 through 1969

The results of anterior resection for adenocarcinoma of the rectum and rectosigmoid are reported with respect to survival rates and complications. Anastomotic recurrence is related to low lying, ulcerated, and less well differentiated tumors that have penetrated the bowel wall. The incidence of recurrent disease at the anastomosis increases with decreases in the margin of resection. Distal margins of at least 6 cm offer significant protection from recurrence. This study shows that anastomotic septic and fistulous complications are related to advanced age, diabetes, anemia, atherosclerotic disease, construction of the anastomosis below the peritoneal reflection, perforated bowel, obstructed bowel, and the use of drains. The determination of those factors that correlate with the development of anastomotic complications can be accomplished with pre- and intraoperative examinations. The role of these factors in operative decision-making and patient management is emphasized.