Surgical Treatment Of Recurrence Research Articles

Recurrent laryngeal papillomatosis: multimodal therapeutic strategies. Literature review and multicentre retrospective study.

Recurrent respiratory papillomatosis (RRP) is a benign, rare disease caused by Human Papilloma Virus (HPV) that can be divided into juvenile and adult forms. The course of the disease is variable, but is usually more aggressive in the juvenile form. The standard surgical treatment is represented by CO2 laser resection, although photoangiolytic lasers represent a valid alternative. Adjuvant therapies have been proposed for disease control in case of frequent surgical resections or spreading into the lower airways. In recent years, the development of immunotherapy led to the use of bevacizumab either intratumorally or intravenously, but the most promising therapeutic development is represented by HPV vaccination. This paper aims to present a narrative review of the literature and the experience of three different University Centres in the treatment of RRP. A retrospective analysis of the clinical charts of all patients affected by laryngeal papillomatosis and treated in three different University Centres between 2002 and 2022 was performed. The following parameters were collected: sex, age at first evaluation, sites of larynx involved, HPV type, type of first surgical treatment, presence and number of recurrences, surgical treatment of recurrences, adjuvant therapies, side effects and status at last follow-up. Seventy-eight patients were available for evaluation. Of these, 88% had adult onset RRP (Ao-RRP) and 12% juvenile onset RRP (Jo-RRP). The glottis was the most frequently involved subsite; all patients were submitted to surgical resection with CO2 laser under general anaesthesia. Recurrences appeared in 79% of the patients, the patients who did not recur were all adults. The mean number of recurrences was 9 (range 1-110). Recurrences were more frequent in children (M = 20; range 2-110) than adults (M = 5; range 1-21). Thirty-two (52%) of the 62 patients who recurred were re-treated with CO2 laser under general anaesthesia, while office-based treatment with a photoangiolytic laser was preferred in the remaining 30 (48%) patients. Adjuvant treatments were applied in 26 patients. The analysis of the course of the disease showed that in the 9 patients with Jo-RRP, 6 (67%) were free of lesions at the last follow-up, while the other 3 (33%) had papillomas. Of the 69 patients with Ao-RRP, 53 (77%) were alive and free of disease at the last visit, 14 (21%) were alive with disease, 1 (1%) was lost at follow-up and 1 (1%) died for other disease. Severe side effects were not observed except for 2 patients, who developed posterior glottic stenosis. Our results confirmed the literature review. RRP is a potentially aggressive disease, especially in juvenile onset. Surgical resection is still first-line treatment, but in case of multiple recurrences the use of adjuvant therapies must be taken into consideration.

Surgical treatment of patients with lymph node involvement in recurrent ovarian cancer: immediate and long-term results

Objective: analysis of the immediate and long-term results of surgical treatment of patients with lymph node (Ln) involvement in recurrent ovarian cancer (OC), as well as the search for prognostic factors for progression-free survival (PfS) and overall survival (OS).Materials and methods. The retrospective analysis included patients under the age of 75 who underwent surgery for recurrence of OC with Ln involvement at n.n. Blokhin national medical Research Center of Oncology in the period from 2005 to 2020. All patients had previously received combined treatment due to a primary diagnosis of OC. Exclusion criteria: the presence of concomitant pathology in the decompensation phase, primary multiple malignant tumors and recurrences of non-epithelial ovarian tumors. The analysis of the main operational characteristics, the frequency of postoperative complications according to Clavien–Dindo within 30 days after surgery, PfS, OS, as well as parameters affecting the long-term results of treatment were performed.Results. The study included 123 patients: a cohort of isolated lesions of the Ln (n = 65) and a group of combined recurrence in the Ln and other anatomical locations (n = 58). The frequency of complete cytoreduction was significantly higher in the group of patients with isolated recurrence in the Ln: 86.62 % versus 53.4 % in patients with combined relapse, p <0.0001. The median duration of the operation was also significantly higher in patients with combined recurrence: 245 min versus 180 min in a cohort of patients with isolated recurrence in the Ln, p <0.0001. Postoperative complications of grade III B were more often observed in the group of combined recurrence: 6.8 % versus 1.5 % in the group of isolated recurrence in the Ln, p = 0.148. none of the patients in the group of isolated recurrence in the Ln had postoperative mortality, while in the group of combined recurrence 2 (3.4 %) patients died after surgery from developed complications. In patients with isolated recurrence in the Ln and combined recurrence of OC, the median PfS was significantly higher when complete cytoreduction was achieved: 31.0 months and 18.0 months versus 10.0 months and 9.0 months with incomplete repeated cytoreduction, p <0.0001. In patients with isolated recurrence in the Ln and combined recurrence of OC, the median OS was identically significantly higher when complete repeated cytoreduction was achieved: 97.0 months and 60.0 months versus 34.0 months and 27.0 months with incomplete cytoreduction, p <0.0001.Conclusion. Surgical treatment of recurrence of OC is justified only if it is possible to achieve complete cytoreduction and platinum-sensitive type of recurrence of OC. Low grade tumor, platinum-sensitive type of recurrence, absence of marker recurrence of OC, isolated recurrence in Ln, complete repeated cytoreduction and lymphodissection were identified as predictors of PfS in multivariate analysis. The following factors had an independent favorable effect on OS in multivariate analysis: low tumor grade, platinum-sensitive type of recurrence, satisfactory overall status on the ECOg scale (0–1 points) at the time of detection of relapse, isolated recurrence in the Ln and complete repeated cytoreduction.

The therapeutic significance of the novel photodynamic material TPE-IQ-2O in tumors.

Combination therapies based on photodynamic therapy (PDT) have received much attention in various cancers due to their strong therapeutic effects. Here, we aimed to explore the safety and effectiveness of a new mitochondria-targeting photodynamic material, TPE-IQ-2O, in combination therapies (combined with surgery or immunotherapy). The safety and effectiveness of TPE-IQ-2O PDT were verified with cytotoxicity evaluation in vitro and a zebrafish xenograft model in vivo, respectively. The effectiveness of TPE-IQ-2O PDT combined with surgery or immune checkpoint inhibitors (ICIs) was verified in tumor-bearing mice. Small animal in vivo imaging, immunohistochemistry, and flow cytometry were used to determine the underlying mechanism. TPE-IQ-2O PDT can not only reduce tumor recurrence in surgical treatment but also effectively improve the response to ICIs in immunotherapy without obvious toxicity. It was also found to ameliorate the immunosuppressive tumor microenvironment and promote the antitumor immunity induced by ICIs by increasing CD8+ tumor-infiltrating lymphocyte accumulation. Thus, TPE-IQ-2O PDT is a safe and effective antitumor therapy that can be combined with surgery or immunotherapy.

Benefits of re-do surgery for recurrent intracranial meningiomas

Meningiomas are the most common intracranial extra-axial tumor. While the literature is abundant on the therapeutic management of meningioma recurrence after the initial surgery, the natural history of repeated recurrences is poorly described, as well as and their respective management. A partly retrospective, partly prospective review was conducted in a Norwegian cohort of 1469 consecutive cases of meningioma surgically treated, totaling 11 414 patient-years of follow-up. 114 recurrences (7.7%) were treated surgically with a risk a surgical retreatment of 1% per patient-year of follow-up. 36 patients were operated on 3 times or more. The time-to-retreatment (TTR) decreased significantly and steadily between surgeries, from 4.3 ± 4 years after the first surgery to 2.4 ± 2.9 years after the third surgery. The primary driver for recurrence was the WHO grade (OR 7.13 [4.40;11.55], p < 0.001 for the first recurrence and OR 4.13 [1.49;12.15], p 0.008 for the second), the second predictive factor being a skull base location (OR 2.76 [1.95;3.99] p < 0.001 and OR 0.24 [0.09;0.65], p0.006 respectively). The rates of postoperative hematomas and infections were not influenced by the number of surgeries, whereas the rate of postoperative neurological worsening increased from 3.9% to 16.6% and 13.9%, respectively, after the first, second, and third surgeries. We observed that the TTR decreased significantly between surgeries in patients requiring repeated resections, indicating that surgical treatment of recurrences does not reset the clock but is indeed a “race against time”. This should be considered when assessing the benefit-to-risk ratio of patients undergoing repeated surgeries for a recurrent meningioma.

Salvage lymphadenectomy for isolated cervical lymph node recurrence after curative resection of thoracic esophageal squamous cell carcinoma.

Patients with thoracic esophageal squamous cell carcinoma (ESCC) often display recurrence in the cervical lymph nodes after surgery. The optimal treatment strategy for these patients has not been established. We retrospectively reviewed patients who underwent salvage lymphadenectomy plus adjuvant radiotherapy/chemotherapy for recurrence limited to the cervical lymph nodes to explore whether salvage treatment could provide an opportunity for curing these patients and to observe the prognostic factors for the patients after salvage treatment. All patients with ESCC who underwent esophagectomy with lymphadenectomy and who were diagnosed with a relapse in the cervical nodes between 2007 to 2014. All cases received salvage lymphadenectomy plus adjuvant radiotherapy/chemotherapy. Their clinical characteristics and outcomes were analysed. A total of 66 patients were diagnosed with recurrence in the cervical nodes after esophagectomy. Among these patients, 21 (31.8%) relapsed 6 months after esophagectomy and 45 (68.2%) recurrences were found 6 months later. Solitary cervical node recurrence was found in 31 (47.0%) patients while 35 (53.0%) cases showed multiple node relapse. Fifty-four (81.8%) patients underwent radical resection while 12 (18.2%) received reduction surgery. The univariate survival analysis showed that patients with solitary cervical node relapse had a better prognosis than patients with multiple node relapse (P=0.001). Patients who were diagnosed with a recurrence in 6 months after esophagectomy had worse outcomes than patients who relapsed 6 months later (P=0.007). Patients who underwent radical salvage lymphadenectomy had better survival than patients who underwent reduction dissection (P=0.004). The number of positive nodes at esophagectomy (3 or more/2 or less) and surgical treatment for recurrence (reduction/radical surgery) were found to have independent prognostic values by multivariate analysis, whereas the other two factors were not statistically significant. Salvage cervical lymphadenectomy plus adjuvant radiotherapy/chemotherapy is an effective and safe treatment for ESCC patients who develop cervical lymph node recurrence after curative esophagectomy. A lower primary N stage and radical resection of recurrent nodes were found to have independent prognostic values for these patients.

Oncological outcome of surgical management in patients with recurrent uterine cancer-a multicenter retrospective cohort study-CEEGOG EX01 Trial.

To assess the survival of patients who have received an operation for recurrent cervical and endometrial cancer and to determine prognostic variables for improved oncologic outcome. A retrospective multicenter analysis of the medical records of 518 patients with cervical (N = 288) or endometrial cancer (N = 230) who underwent surgery for disease recurrence and who had completed at least 1 year of follow-up. The median survival reached 57 months for patients with cervical cancer and 113 months for patients with endometrial cancer after surgical treatment of recurrence (p = 0.036). Histological sub-type had a significant impact on overall survival, with the best outcome in endometrial endometrioid cancer (121 months), followed by cervical squamous cell carcinoma, cervical adenocarcinoma, or other types of endometrial cancer (81 vs 35 vs 35 months; p <0.001). The site of recurrence did not significantly influence survival in cervical or in endometrial cancer. Cancer stage at first diagnosis, tumor grade, lymph node status at recurrence, progression-free interval after first diagnosis, and free resection margins were associated with improved overall survival on univariate analysis. On multivariate analysis, the stage at first diagnosis and resection margins were significant independent predictive parameters of an improved oncologic outcome. Long-term survival can be achieved via secondary cytoreductive surgery in selected patients with recurrent cervical and endometrial cancer. An excellent outcome is possible even if the recurrence site is located in the lymph nodes. The possibility of achieving complete resection should be the main criterion for patient selection.

Stage-related outcome for thymic epithelial tumours

BackgroundThymic epithelial tumours (TETs) are characterized by a wide variety of biological behaviors. Radical resection and stage are strong prognostic factors. Aim of this study is to review our Single Center Experience.MethodsOne hundred and seventy-seven patients observed in the period from January 2000 to December 2016 were included in the study. Data regarding clinicopathologic features, treatment, and survival were collected. Stage-related clinical standpoints and therapeutic options were also evaluated.ResultsNon-surgical treatment was primarily performed in 15 (8.47%), unresectable disease was intraoperatively found in 12 cases (7.4%). The analysis of 150 patients undergoing curative surgery revealed 70 stage I TET (46.66%), 49 stage II (32.66%), 19 stage III (12.66%), 6 stage IVa (4%) and 6 stage IVb (4%) at the first hospital admission. Histology identified 12 A thymoma (8%), 38 AB (25.33%), 24 B1 (16%), 50 B2 (33.33%), 19 B3 (12.66%) and 7 carcinomas (4.66%). The mean follow up time was 84.14 months (sd = 61.68 months). Disease relapse occurred in 13 patients (8.78%) at a mean period of 78.85 months (sd = 60.87 months) after surgery. Exitus due to thymoma happened in 6 cases (4.05%) after a mean survival of 56.02 months (sd = 25.17 months). The 5-year overall survival rate was 0.94 (95%CI 0.88–0.97) and the 5-year disease-free survival rate was 0.90 (95%CI 0.83–0.94). The 5-year overall survival rates were 96.1% (95% CI, 89.9–98.5%) for the early stages and 87.4% (95% CI, 65.6–95.8%) for the advanced stages (p = 0.670). The 5-year disease-free survival rates resulted being 98.8% (95% CI, 92.3–99.8%) for the early stages and 59.8% (95% CI, 37.8–76.2%) for the advanced stages (p < 0.001).ConclusionsAdvanced stage TETs are characterized by higher mortality and recurrence rates. Although technically demanding, surgery, as part of multimodality therapy, could prolong survival. Iterative surgical treatment of recurrences is a viable option for selected patients.Trial registrationThe study was approved by the Institutional Review Board of Perugia and Terni University Hospitals [Code T1003] and was retrospectively registered.

The clinical outcome of recurrent sacral chordoma with further surgical treatment.

Case series.To analyze the clinical results and related factors of further surgical treatment for recurrent sacral chordomas.Chordomas are rare primary malignant tumors with a high recurrence rate. The treatment of recurrent tumors is difficult and controversial. Contamination by previous operations and disturbed local anatomical structures may increase the risk of reoperation. Most previous studies have focused on the primary tumor; there are very few reports on the clinical diagnosis, treatment, and prognosis of recurrent sacral chordomas.Thirty-four patients with recurrent sacral chordomas from 1979 to 2014 were included in this study. The patients comprised 25 men and 9 women with an average age of 50.7 (24–75) years. The average time until recurrence was 19.4 (4–51) months postoperatively, and 85.3% of the recurrent tumors were located in bone. The patients had an average of 1.2 (1–3) recurrences before further operations were performed in our hospital. The mean maximum tumor diameter was 8.1 (4.6–12.0) cm. Thirty-one patients underwent further tumor resection in our hospital. The postoperative recurrence, metastasis, and survival results were followed and analyzed.The mean follow-up after surgical treatment of recurrence was 49.6 (12–144) months. Nine patients (37.5%) developed recurrence again after an average of 26.7 months. The 3-year and 5-year recurrence-free survival rate was 69.4% and 63.1%, respectively. Multivariate analysis showed that the tumor level within the sacrum (P = .001) and the surgical margin (P = .001) were significant recurrence-related factors. Four patients (16.7%) developed lung metastasis. Eighteen patients were alive at last follow-up. The 5-year and 10-year survival rate after surgical treatment of recurrence was 67.3% and 53.9%, respectively.Most recurrent tumors are located in bone, and a safe osteotomy margin is important. The surgical margin is the only controllable factor of further tumor recurrence. Some patients with recurrence achieve long survival and obtain a clinical benefit from repeated operations if complete resection is achieved.

A randomised controlled trial to assess the cost-effectiveness of intensive versus no scheduled follow-up in patients who have undergone resection for colorectal cancer with curative intent.

Intensive follow-up after surgery for colorectal cancer is common practice but lacks a firm evidence base. To assess whether or not augmenting symptomatic follow-up in primary care with two intensive methods of follow-up [monitoring of blood carcinoembryonic antigen (CEA) levels and scheduled imaging] is effective and cost-effective in detecting the recurrence of colorectal cancer treatable surgically with curative intent. Randomised controlled open-label trial. Participants were randomly assigned to one of four groups: (1) minimum follow-up (n = 301), (2) CEA testing only (n = 300), (3) computerised tomography (CT) only (n = 299) or (4) CEA testing and CT (n = 302). Blood CEA was measured every 3 months for 2 years and then every 6 months for 3 years; CT scans of the chest, abdomen and pelvis were performed every 6 months for 2 years and then annually for 3 years. Those in the minimum and CEA testing-only arms had a single CT scan at 12-18 months. The groups were minimised on adjuvant chemotherapy, gender and age group (three strata). Thirty-nine NHS hospitals in England with access to high-volume services offering surgical treatment of metastatic recurrence. A total of 1202 participants who had undergone curative treatment for Dukes' stage A to C colorectal cancer with no residual disease. Adjuvant treatment was completed if indicated. There was no evidence of metastatic disease on axial imaging and the post-operative blood CEA level was ≤ 10 µg/l. Primary outcome Surgical treatment of recurrence with curative intent. Secondary outcomes Time to detection of recurrence, survival after treatment of recurrence, overall survival and quality-adjusted life-years (QALYs) gained. Detection of recurrence During 5 years of scheduled follow-up, cancer recurrence was detected in 203 (16.9%) participants. The proportion of participants with recurrence surgically treated with curative intent was 6.3% (76/1202), with little difference according to Dukes' staging (stage A, 5.1%; stage B, 7.4%; stage C, 5.6%; p = 0.56). The proportion was two to three times higher in each of the three more intensive arms (7.5% overall) than in the minimum follow-up arm (2.7%) (difference 4.8%; p = 0.003). Surgical treatment of recurrence with curative intent was 2.7% (8/301) in the minimum follow-up group, 6.3% (19/300) in the CEA testing group, 9.4% (28/299) in the CT group and 7.0% (21/302) in the CEA testing and CT group. Surgical treatment of recurrence with curative intent was two to three times higher in each of the three more intensive follow-up groups than in the minimum follow-up group; adjusted odds ratios (ORs) compared with minimum follow-up were as follows: CEA testing group, OR 2.40, 95% confidence interval (CI) 1.02 to 5.65; CT group, OR 3.69, 95% CI 1.63 to 8.38; and CEA testing and CT group, OR 2.78, 95% CI 1.19 to 6.49. Survival A Kaplan-Meier survival analysis confirmed no significant difference between arms (log-rank p = 0.45). The baseline-adjusted Cox proportional hazards ratio comparing the minimum and intensive arms was 0.87 (95% CI 0.67 to 1.15). These CIs suggest a maximum survival benefit from intensive follow-up of 3.8%. Cost-effectiveness The incremental cost per patient treated surgically with curative intent compared with minimum follow-up was £40,131 with CEA testing, £43,392 with CT and £85,151 with CEA testing and CT. The lack of differential impact on survival resulted in little difference in QALYs saved between arms. The additional cost per QALY gained of moving from minimum follow-up to CEA testing was £25,951 and for CT was £246,107. When compared with minimum follow-up, combined CEA testing and CT was more costly and generated fewer QALYs, resulting in a negative incremental cost-effectiveness ratio (-£208,347) and a dominated policy. Although this is the largest trial undertaken at the time of writing, it has insufficient power to assess whether or not the improvement in detecting treatable recurrence achieved by intensive follow-up leads to a reduction in overall mortality. Rigorous staging to detect residual disease is important before embarking on follow-up. The benefit of intensive follow-up in detecting surgically treatable recurrence is independent of stage. The survival benefit from intensive follow-up is unlikely to exceed 4% in absolute terms and harm cannot be absolutely excluded. A longer time horizon is required to ascertain whether or not intensive follow-up is an efficient use of scarce health-care resources. Translational analyses are under way, utilising tumour tissue collected from Follow-up After Colorectal Surgery trial participants, with the aim of identifying potentially prognostic biomarkers that may guide follow-up in the future. Current Controlled Trials ISRCTN41458548. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 32. See the NIHR Journals Library website for further project information.

Chronic pancreatitis and pancreatic cancer demonstrate active epithelial-mesenchymal transition, regulated by the feedback loop between miR-217 and SIRT1

RESULTS: 191 of 1202 patients experienced recurrence during the mean follow-up period of 4.4 years. Surgical treatment of recurrence with curative intent was about 3x higher in each of the three more intensive follow-up arms compared with the minimum follow-up arm (absolute difference 4.3-5.7%; overall p1⁄40.019). There was no benefit to performing both CEA and CT. Pulmonary recurrence was most frequently associated with rectal tumours and multi-site recurrence most commonly from right-colonic cancers. Whilst the benefit of follow-up was not stage dependent, rectal tumours benefited the most (proportion of participants followed-up with treatable recurrence detected: rectum 8.9%, left colon 5.4%, right colon 3.1% p1⁄40.003). Median survival following recurrence was 2.28 years and was influenced by stage (log rank p1⁄40.004) and site of primary (log rank p1⁄40.008).

Prognostic and predictive role of epidermal growth factor receptor mutation in recurrent pulmonary adenocarcinoma after curative resection.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment prolongs the progression-free survival of patients with advanced non-small-cell lung cancer harbouring EGFR mutations. This study aimed to evaluate the prognostic factors influencing survival after recurrence, and the effectiveness of EGFR-TKIs in patients with recurrent pulmonary adenocarcinoma after curative resection. EGFR mutations were prospectively evaluated in 594 patients who underwent curative surgical resection for pulmonary adenocarcinoma. Among them, 138 patients who had postoperative recurrent disease were enrolled in the study. Potential prognostic factors for post-recurrence survival (PRS) were evaluated, and predictive factors of responsiveness to EGFR-TKIs were also analysed. Among the 138 patients who had postoperative recurrent disease, EGFR mutations were identified in 73 (52.9%) patients. In multivariable analysis, never-smoking status [hazard ratio (HR), 0.522; P = 0.012], adjuvant radiotherapy (HR, 1.995; P = 0.016), disease-free interval of less than 1 year from initial resection to recurrence (HR, 2.382; P = 0.001), surgical treatment for recurrence (HR, 0.346; P = 0.002) and EGFR mutation (HR, 0.552; P = 0.013) were independent prognostic factors for PRS. Among patients treated with EGFR-TKI, EGFR mutation status was the only predictor of response to EGFR-TKI (P < 0.001), and patients with EGFR mutation showed better PRS (3- and 5-year survival rates after recurrence, 68.8 and 41.1%, respectively) than those without EGFR mutations (3- and 5-year survival rates after recurrence, 39.1 and 15.7%, respectively; P = 0.017). Our study demonstrated that EGFR mutation is an independent prognostic factor for PRS. Considering that EGFR mutations were the only independent predictors for response to EGFR-TKIs, selecting patients for EGFR-TKI therapy according to EGFR mutation status may lead to a better prognosis in patients with recurrent pulmonary adenocarcinoma.

Effect of 3 to 5 Years of Scheduled CEA and CT Follow-up to Detect Recurrence of Colorectal Cancer

Intensive follow-up after surgery for colorectal cancer is common practice but is based on limited evidence. To assess the effect of scheduled blood measurement of carcinoembryonic antigen (CEA) and computed tomography (CT) as follow-up to detect recurrent colorectal cancer treatable with curative intent. Randomized clinical trial in 39 National Health Service hospitals in the United Kingdom; 1202 eligible participants were recruited between January 2003 and August 2009 who had undergone curative surgery for primary colorectal cancer, including adjuvant treatment if indicated, with no evidence of residual disease on investigation. Participants were randomly assigned to 1 of 4 groups: CEA only (n = 300), CT only (n = 299), CEA+CT (n = 302), or minimum follow-up (n = 301). Blood CEA was measured every 3 months for 2 years, then every 6 months for 3 years; CT scans of the chest, abdomen, and pelvis were performed every 6 months for 2 years, then annually for 3 years; and the minimum follow-up group received follow-up if symptoms occurred. The primary outcome was surgical treatment of recurrence with curative intent; secondary outcomes were mortality (total and colorectal cancer), time to detection of recurrence, and survival after treatment of recurrence with curative intent. After a mean 4.4 (SD, 0.8) years of observation, cancer recurrence was detected in 199 participants (16.6%; 95% CI, 14.5%-18.7%) overall; 71 of 1202 participants (5.9%; 95% CI, 4.6%-7.2%) were treated for recurrence with curative intent, with little difference according to Dukes staging (stage A, 5.1% [13/254]; stage B, 6.1% [34/553]; stage C, 6.2% [22/354]). Surgical treatment of recurrence with curative intent was 2.3% (7/301) in the minimum follow-up group, 6.7% (20/300) in the CEA group, 8% (24/299) in the CT group, and 6.6% (20/302) in the CEA+CT group. Compared with minimum follow-up, the absolute difference in the percentage of patients treated with curative intent in the CEA group was 4.4% (95% CI, 1.0%-7.9%; adjusted odds ratio [OR], 3.00; 95% CI, 1.23-7.33), in the CT group was 5.7% (95% CI, 2.2%-9.5%; adjusted OR, 3.63; 95% CI, 1.51-8.69), and in the CEA+CT group was 4.3% (95% CI, 1.0%-7.9%; adjusted OR, 3.10; 95% CI, 1.10-8.71). The number of deaths was not significantly different in the combined intensive monitoring groups (CEA, CT, and CEA+CT; 18.2% [164/901]) vs the minimum follow-up group (15.9% [48/301]; difference, 2.3%; 95% CI, -2.6% to 7.1%). Among patients who had undergone curative surgery for primary colorectal cancer, intensive imaging or CEA screening each provided an increased rate of surgical treatment of recurrence with curative intent compared with minimal follow-up; there was no advantage in combining CEA and CT. If there is a survival advantage to any strategy, it is likely to be small. isrctn.org Identifier: 41458548.

Surgical Treatment and Prevention of Recurrence of Urethral Calculi Associated with Hairballs after Urethroplasty

Objectives: To evaluate technical aspects and outcome of preventing urethrocutaneous fistula and calculi recurrence in surgical treatment of urethral calculi associated with hairballs after urethroplasty. Patients and Methods: Sixteen patients who had urethral calculi associated with hairballs after urethroplasty underwent urethrolithotomy and trimming and epilation of the neourethra. While operating, we made a staggered incision of the skin and urethra, carefully su-tured the urethral incision, and covered it by well-vascularized tissue. A tube-in-tube stent method was performed on the latter 12 patients for better drainage of the exudates that accumulated in the urethra. Results: All calculi were successfully removed. Surgical site infection occurred in the last one of the former 4 patients and resulted in an urethrocutaneous fistula. There were no other complications. All patients were followed up for 2-7 years; no urethral stenosis or recurrence of calculi was observed, and remarkable reduction of urethral hair was obtained. Conclusions: Urethrolithotomy and trimming and epilation of the neourethra seem to be appropriate treatments for urethral calculi associated with hairballs after urethroplasty. Full attention should be paid to fistula prevention.

Resection of Adrenocortical Carcinoma Liver Metastasis: Is it Justified?

Adrenocortical carcinoma (ACC) liver metastases (LM) represent a therapeutic challenge, and it is unclear whether resection is justified. This study assesses long-term outcome and prognostic factors after liver resection for metastatic ACC. Patients who underwent resection of ACC LM were identified from institutional databases. Recurrence, survival, and tumor characteristics, including β-catenin and TP53 status based on immunohistochemistry and sequencing, were reviewed. The prognostic value of variables was assessed with log-rank test for univariate analysis and Cox proportional hazard models for multivariate analysis. From 1978 to 2009, 28 patients (20 females; median age, 45 years), including 11 with synchronous metastasis and 3 with extrahepatic metastasis, underwent resection for ACC LM (major hepatectomy in 61%). Postoperative mortality was nil and morbidity 55%. On pathological examination, tumors were multiple in 68%, with a median size of 43 mm, and resections were R0, 1, and 2 in 59%, 33%, and 7%, respectively. All 28 patients developed recurrent disease, which was treated surgically in 11, including repeat hepatectomy in 4. Of the 15 patients with adequate tissue for analysis, β-catenin immunostaining was positive in 7, with 4 corresponding CTNNB1 mutations associated with decreased survival; p53 staining was positive in 5 (4 with corresponding TP53 mutations). The median disease-free and overall survival after hepatectomy was 7 and 31.5 months, respectively, with a 5-year survival of 39%. In multivariate analysis, nonfunctional tumor and surgical treatment of recurrence were independent predictors of good outcome. In selected patients with ACC LM, resection is associated with long-term survival and is, therefore, justified but rarely curative.

Accuracy of endoanal ultrasound in the follow-up assessment for squamous cell carcinoma of the anal canal treated with radiochemotherapy

Radiochemotherapy has largely replaced surgery in the treatment for squamous cell cancer of the anal canal. Transanal ultrasonography is well documented as an important investigation method in the management of anal carcinoma. This study aimed to evaluate the accuracy of endoanal ultrasound in the study of the postradiation findings and to distinguish between postradiation fibrosis, residual tumor, and local recurrence. The study enrolled 16 consecutive patients with biopsy-proven squamous carcinoma of the anal canal between 2003 and 2006. All the patients underwent a pretreatment and at least four posttreatment endosonographies, according to the follow-up period. All the patients were treated with the same radiochemotherapy protocol. Nine patients had stage uT2 disease; none had uT3 disease; and seven had uT4 disease. There was no evidence of residual tumor in the T2 group after treatment. In the T4 patients after treatment, ultrasound demonstrated tumor regression or abnormalities considered to be radiation-induced changes rather than residual diseases. Only for three patients was a posttreatment biopsy performed to evaluate recurrence (two uT2 and one uT4). Surgical treatment of recurrence was performed for two uT4 patients. Endoanal ultrasound is a safe and effective method for evaluating and following anal cancer before and after treatment. Experience and evaluation during the period of the ultrasonographic abnormalities could give a clear idea concerning the evolution of the anal tumors treated with radiochemotherapy.

Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis.

Very little is known about the natural history, effects of therapy, and survival after recurrence of hepatocellular carcinoma (HCC) after liver transplantation. All adult patients undergoing liver transplant from September 19, 1988, until September 19, 2002, were reviewed. Only patients with histologically proven HCC in the explant who subsequently developed recurrence were included in further analysis. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics and laboratory values, technique of transplant (whole cadaver, split, or living donor), and tumor characteristics were analyzed. The time to, location of, and any medical or surgical treatment of recurrences also were considered. Of the 311 patients with HCC in the explant, 57 (18.3%) eventually were diagnosed with recurrent tumor after transplant. Median time to recurrence was 12.3. Five-year survival was significantly lower for patients with recurrence (22%) than for patients without recurrence (64%)(P < 0.0001). Multivariate analysis demonstrated that the size and differentiation of the original tumor, as well as the presence of bone recurrence, were independently associated with survival from transplant in patients with recurrence. When survival from the time of recurrence was analyzed, multivariate analysis showed that the absence of bone metastases, recurrence more than 12 months from transplant, and surgical treatment of the recurrence were independently associated with significantly longer survival. In conclusion, recurrence of HCC significantly shortens survival after transplant. Nonetheless, some patients with recurrence can be expected to live for a considerable period of time. Recurrent disease should be treated surgically when possible, because surgery is independently associated with longer survival.

3499 Therapeutic ercp in the setting of long limb surgical bypass: improved success and outcome of therapeutic procedures.

INTRODUCTION: We reported initial ERCP experience in 18 long-limb surgical bypasses (Gastrointest Endosc 1998;47: 62-7). Only 6 had intact papillas and only 3 required sphincterotomy (ES). We report additional experience. PATIENTS & METHODS: From 4/93-8/99, 47 pts (male 18, female 29, age 24-80) were referred for consideration of therapeutic ERCP with long-limb surgical bypasses: 8 with gastric bypass; 16 with Whipple's, 11 with hepatojejunostomy; and 12 with post-gastrectomy Roux-en-Ys. Indications: pain (n=26), jaundice (n=17), recurrent or chronic pancreatitis (n=11), suspected CD stones (n=7), and anastomotic bleeding (n=1). An enteroscope was used in 13, a pediatric colonoscope in 17 and a duodenoscope in 17. RESULTS: The papilla or pancreaticobiliary anastomosis was reached in 41 of 47 (87%). The overtube was used with 5 and only in the setting of an intact stomach. 6 failures were due to inability to pass into the afferent limb. 2 failures were due to inability to locate the PD anastomoses. 20 patients had intact papillas (12 with Roux-en-Ys, 8 with gastric bypass). Cannulation failed in 4 of these 20 (20%) due to an inability to align the long front viewing instruments. 7 pts with intact papillas needed ES; 3 methods were used: (1) Following guidewire and temporary stent placement, a stent guided needle-knife ES was used when alignment could be achieved (n=4); (2) A wire-guided B-II type sphinctertome was used (n=1). (3) One patient failing guidewire placement underwent successful needle knife ES only. The final patient required a combined procedure with PTC guidewire placement followed by B-II type ES at a second ERCP. Among the 35 cannulated patients, successful Rx followed in 34: stents in 16 (10 biliary plastic stents, 2 PD stents, 4 Wallstents); biliary dilatation in 6; stone extraction 3; tissue sampling 3; pancreatic dilatation 1; duodenal dilatation 1. In 1 patient, coagulation of a visible vessel required surgical treatment for recurrence. No post-ERCP pancreatitis, bleeding, or perforation was noted. CONCLUSION: Although technically difficult, successful therapeutic ERCP is generally possible with long limb surgical bypasses with a high success rate and a low complication rate. The intact papilla greatly exacerbates these difficulties and occasionally requires percutaneous wire placement for assistance. The development of a colonoscope length, oblique-viewing enteroscope with an elevator should greatly enhance therapeutic ERCP in these patients.

Oral Cancer - Results of Treatment in the Copenhagen University Hospital

During the period 1992-96, 304 patients with malignant tumours of the oral cavity were treated in Copenhagen University Hospital. The female:male ratio was 1:2. Age ranged between 20 and 96 years, median 61 years. Ninety-five percent of the tumours were squamous cell carcinomas. Twenty-two percent were in stage I, 21% were in stage II, 21% were in stage III and 36% were in stage IV. Sixty percent of the patients underwent primary surgical resection, combined with reconstructive procedures if necessary. In 39% of all cases, surgery was followed by radiotherapy, while 21% of the patients, mainly stage I and II patients, were only treated surgically. Radiotherapy alone was received by 36% of the patients, mainly stage III and IV. Four percent of the patients received no treatment due to advanced disease or general poor condition. The overall recurrence rate was 42%, ranging from 23% in stage I to 61% in stage IV. Thirty-eight percent of these patients were treated for recurrence, almost exclusively by surgery. The survival rate 1 year after treatment of recurrence was 90%, 60% and 50% for patients in stage I, II and III respectively, while only 1 of 16 patients in stage IV was alive after 1 year. Three-year crude survival for the whole material was 42%, ranging from 58% in stage I to 18% in stage IV. This is an improvement of 12% compared with a similar group of patients treated in our departments in the period 1978-82, when the primary treatment of choice was external irradiation. The survival rate was, as expected, closely related to T- and N-stage at time of diagnosis. In conclusion, we recommend primary surgery followed by irradiation therapy for patients in stages II, III and IV. Surgical treatment of recurrence in patients who were formerly treated by irradiation therapy should be reserved for patients in good general condition and in a low TNM stage, stage IV patients will only benefit from salvage surgery in a few exceptional cases.

Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation.

Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

The Italian registry for adrenal cortical carcinoma: Analysis of a multiinstitutional series of 129 patients

Adrenal cortical carcinoma is an uncommon tumor with a poor prognosis. The low incidence of this tumor makes it difficult to achieve reliable data on clinical manifestations, natural history, and the impact of therapies. The purpose of this study was to evaluate such aspects in a large series. A retrospective series of 129 cases (55 men and 74 women, mean age of 49 years) was collected from 18 surgical institutions. At the time of diagnosis 45.7% of patients had endocrine symptoms. One hundred twenty-four patients underwent surgery, which was considered curative in 91 cases and palliative in 33. Sixty-three patients had local disease, 48 had regional disease, and 43 had distant metastases. This study confirmed a higher incidence in the 40- to 50-year-old population with a female prevalence; hormonal hyperincretion was more common in women, but it was not caused by advanced disease. The overall 5-year survival rate was 35%. Tumor stage and curative resection affected prognosis significantly. The influence of gender, side, age, and hormonal function has not been confirmed. Adjuvant therapies were ineffective in prolonging survival. Reoperated patients experienced better survival (mean, 41.5 months) than nonreoperated cases (mean, 15.6 months). The poor prognosis of adrenal cortical carcinoma may be improved by early diagnosis and complete resection. Radical surgery is the sole effective therapy, particularly in early stages. Surgical treatment of recurrence seems to improve survival and should be attempted systematically. Adjuvant therapies obtained contrasting results, and their role should be evaluated in prospective multicentric trials.