Endonasal and Transoral Approaches to the Craniovertebral Junction: A Quantitative Anatomical Study.

BACKGROUND: The endoscopic endonasal approach has recently been added to the surgical armamentarium to access the anterior craniovertebral junction (CVJ). Comparative analyses with the transoral approach are scarce. The aim of this study was to provide a quantitative anatomical analysis of both approaches. METHODS: In four specimens the endoscopic endonasal approach (before and after sphenoidectomy) and the transoral approach (without and with a soft palate split) were performed. ApproachViewer-part of GTx-UHN (Guided Therapeutics software, developed at University Health Network, Toronto, ON, Canada)-was used to quantify and visualize the working volume, as well as the exposed area, of each surgical approach. Different modalities (crossing and non-crossing) were used to quantify the exposure of the deep surface, providing an indirect quantitative value of the 'surgical freedom'. The lowest point exposed by the endonasal approaches was compared with that predicted by preoperative radiological lines. Non-parametric Welch analysis of variance (ANOVA) was used for statistical analyses. RESULTS: The working volume was significantly larger and the distance to the target was shorter with the transoral approaches than with the endonasal approaches. Clival exposure was better with the endonasal approaches than with the non-crossing transoral approach without a soft palate split; areas below C1 were better exposed with the transoral routes. The nasoaxial line best predicted surgical exposure with the endonasal approaches. CONCLUSION: Endoscopic endonasal and transoral approaches to the anterior CVJ provide optimal exposure of different areas that overlap at the level of C1 when no anatomical anomalies are present. A split of the soft palate is not necessary during the transoral approach if it is combined with an endoscopic endonasal approach.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

BACKGROUND: Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. METHODS: Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. RESULTS: Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). CONCLUSIONS: Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018;124:2948-55. © 2018 American Cancer Society.

Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multicenter international pooled validation study.

PURPOSE: There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions. PATIENTS AND METHODS: We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions. RESULTS: In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I (2) statistic = 0). CONCLUSION: Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.

Endoscopic transnasal odontoidectomy using ultrasonic bone curette: Technical case report.

A 65-year-old woman, a case of cranio-vertebral junction anomaly, presented with a sudden onset of quadriparesis, dysphagia, and breathing difficulty and required emergency surgery. She underwent image-guided endoscopic transnasal odontoidectomy followed by occipito-cervical decompression and stabilization. She recovered well, with immediate improvement of respiratory function. Burning paresthesias disappeared and the upper limbs function normalized.

Depth of invasion alone as an indication for postoperative radiotherapy in small oral squamous cell carcinomas: An International Collaborative Study.

BACKGROUND: We aimed to investigate whether depth of invasion (DOI) should be an independent indication for postoperative radiotherapy (PORT) in small oral squamous cell carcinomas (SCC). METHODS: Retrospective analysis of DOI (<5, 5 to <10, ≥10 mm) and disease-specific survival (DSS) in a multi-institutional international cohort of 1409 patients with oral SCC ≤4 cm in size treated between 1990-2011. RESULTS: In patients without other adverse factors (nodal metastases; close [<5 mm] or involved margins), there was no association between DOI and DSS, with an excellent prognosis irrespective of depth. In the absence of PORT, the 5-year disease-specific mortality was 10% with DOI ≥10 mm, 8% with DOI 5-10 mm, and 6% with DOI <5 mm (P = .169), yielding an absolute risk difference of only 4%. CONCLUSION: The deterioration in prognosis with increasing DOI largely reflects an association with other adverse features. In the absence of these, depth alone should not be an indication for PORT outside a clinical trial.

Complications and donor site morbidity of 3-layer reconstruction with iliotibial tract of the anterior skull base: Retrospective analysis of 186 patients.

BACKGROUND: Anterior skull base reconstruction after resection of sinonasal cancers may be challenging when pedicled flaps are unavailable. The purpose of the present study was to analyze the complication rate and donor site morbidity of 3-layer reconstruction with the iliotibial tract (ITT). METHODS: We retrospectively reviewed all anterior skull base reconstructions with ITT performed from 2007 to 2015. Donor site morbidity was investigated by a dedicated questionnaire. Factors impacting on cerebrospinal fluid (CSF) leak were assessed using the Fisher's exact test. RESULTS: One hundred eighty-six patients were included. The overall complication rate was 9.7%. A CSF leak occurred in 11 patients (5.8%). Twenty patients (10.8%) and 130 patients (69.9%) underwent previous or adjuvant radiotherapy, respectively. Neither radio(chemo)therapy nor age impacted the risk of CSF leak. Six patients (3.2%) experienced complications at the donor site. The questionnaire demonstrated minimal functional and aesthetic morbidity. CONCLUSION: Three-layer reconstruction with the ITT is a safe procedure with acceptable complication rate and donor site morbidity.

Multicentric prospective study on the prevalence of sublevel IIb metastases in head and neck cancer.

OBJECTIVE: To evaluate the prevalence of sublevel IIB lymph node (LN) metastases for head and neck primary tumors in a large cohort of patients. DESIGN: Prospective study. SETTING: One referral university hospital and 2 national institutes of oncology. PATIENTS: Between 2003 and 2005, 297 patients (male to female ratio, 3.5:1; mean age, 58.8 years [range, 18-89 years]) affected by head and neck cancer were treated by surgery on the primary tumor and/or the neck. Primary site distribution included the following: oral cavity in 111 patients, larynx in 92, oropharynx in 32, thyroid gland in 22, skin of the lateral face or scalp in 16, hypopharynx in 11, unknown primary in 7, and parotid gland in 6. Sublevel IIB was evaluated for the number of LNs and pathologic N (pN) status. INTERVENTIONS: All patients underwent unilateral or bilateral neck dissection (ND) with therapeutic or elective intent according to the primary site and clinical T (cT) and clinical N (cN) status. Sublevel IIB was selectively dissected at the beginning of ND, labeled, and processed independently. MAIN OUTCOME MEASURES: The distribution of metastases among the different levels was analyzed. The influence of several factors (institution in which the surgical procedure was performed, sex of the patient, site of primary, histotype, pathologic T [pT] status, cN status, lower level involved in the neck together with sublevel IIB, association with sublevel IIA metastasis, ipsilateral number of involved levels, and previous surgical treatment limited on the primary site) on the prevalence of sublevel IIB metastasis was statistically evaluated by the Pearson chi(2) test or Fisher exact test. RESULTS: A total of 443 NDs were performed (unilateral in 151 patients and bilateral in 146). Among the patients, the tumors were staged cN0/pN0 in 27%, cN+/pN+ in 50%, cN+/pN0 in 7%, and cN0/pN+ in 16%. The mean number of LNs collected at sublevel IIB was 5.4 (range, 0-24). The overall prevalence of sublevel IIB metastases was 5.6% (26 neck sides). Tumor histologic type in the sublevel IIB+ population was squamous cell carcinoma in 80%, papillary carcinoma in 8%, melanoma in 8%, and adenocarcinoma in 4%. The chi(2) test showed a significantly higher risk for LN metastases at sublevel IIB in patients affected by parotid gland primary tumors (33%), tumors of the skin or scalp (25%), unknown primary tumors (14%), and cancers of the oral cavity (10%) (P = .02) and in those clinically staged as cN+ (P < .001). CONCLUSIONS: Sublevel IIB dissection is strongly recommended for all patients with cN+ tumors and in those affected by tumor of the parotid gland, skin, and scalp scheduled for elective ND. Patients affected by laryngeal cancer scheduled for elective ND can be considered the ideal candidates for preservation of sublevel IIB. However, whether this policy could be associated with a better functional outcome remains to be demonstrated by prospective studies on a large series of patients.

Two-Dimensional High Definition Versus Three-Dimensional Endoscopy in Endonasal Skull Base Surgery: A Comparative Preclinical Study.

BACKGROUND AND OBJECTIVE: Three-dimensional (3D) endoscopy has been recently introduced in endonasal skull base surgery. Only a relatively limited number of studies have compared it to 2-dimensional, high definition technology. The objective was to compare, in a preclinical setting for endonasal endoscopic surgery, the surgical maneuverability of 2-dimensional, high definition and 3D endoscopy. METHODS: A group of 68 volunteers, novice and experienced surgeons, were asked to perform 2 tasks, namely simulating grasping and dissection surgical maneuvers, in a model of the nasal cavities. Time to complete the tasks was recorded. A questionnaire to investigate subjective feelings during tasks was filled by each participant. In 25 subjects, the surgeons' movements were continuously tracked by a magnetic-based neuronavigator coupled with dedicated software (ApproachViewer, part of GTx-UHN) and the recorded trajectories were analyzed by comparing jitter, sum of square differences, and funnel index. RESULTS: Total execution time was significantly lower with 3D technology (P < 0.05) in beginners and experts. Questionnaires showed that beginners preferred 3D endoscopy more frequently than experts. A minority (14%) of beginners experienced discomfort with 3D endoscopy. Analysis of jitter showed a trend toward increased effectiveness of surgical maneuvers with 3D endoscopy. Sum of square differences and funnel index analyses documented better values with 3D endoscopy in experts. CONCLUSIONS: In a preclinical setting for endonasal skull base surgery, 3D technology appears to confer an advantage in terms of time of execution and precision of surgical maneuvers.

Sinonasal mucosal melanoma: A 12-year experience of 58 cases.

BACKGROUND: Sinonasal mucosal melanoma is a rare malignancy with poor prognosis. METHODS: Patients with sinonasal malignant melanoma who underwent surgery by different approaches were included in this study. Overall survival (OS) and event-free survival were calculated, and statistically significant variables by univariate analysis were entered in a multivariate Cox regression model. RESULTS: Pathological staging was pT3, pT4a, and pT4b in 30 cases (51.7%), 17 cases (29.3%), and 11 cases (19.0%). At 3 and 5 years, OS was 43.5% and 29% and event-free survival was 23.6% and 12.4%, respectively. At univariate analysis, OS was significantly influenced by male sex, advanced pT classification, positive margins, and surgical approach; event-free survival was affected by positive margins. At multivariate analysis, the risk of death was independently associated with male sex (hazard ratio [HR] = 2.27; p = .04) and positive margins (HR = 2.32; p = .03). CONCLUSION: Male sex and positive margins were negative prognostic factors. Endoscopic resection did not show an increased risk of death compared with more extensive surgical approaches. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1737-E1745, 2016.

Comparison of the American Joint Committee on Cancer N1 versus N2a nodal categories for predicting survival and recurrence in patients with oral cancer: Time to acknowledge an arbitrary distinction and modify the system.

BACKGROUND: We hypothesized that pathological N1 (pN1) and N2a (pN2a) nodal disease portend a similar prognosis in patients with oral cancer. METHODS: An international multicenter study of 739 oral squamous cell carcinoma (SCC) patients with pN1 or pN2a stage disease was conducted. Multivariable analyses were performed using Cox proportional hazard models to compare locoregional failure, disease-specific survival (DSS), and overall survival (OS). Institutional heterogeneity was assessed using 2-stage random effects meta-analysis techniques. RESULTS: Univariate analysis revealed no difference in locoregional failure (p = .184), DSS (p = .761), or OS (p = .475). Similar results were obtained in adjusted multivariable models and no evidence of institutional heterogeneity was demonstrated. CONCLUSION: The prognosis of pN2a and pN1 disease is similar in oral SCC suggesting these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy. However, these results may reflect more aggressive treatment of N2a disease; hence, we caution against using these data to deintensify treatment.

Endoscopic endonasal surgery for malignancies of the anterior cranial base.

OBJECTIVE: Data from several centers worldwide have demonstrated that transnasal endoscopic surgery performed with or without a transcranial approach is capable of achieving radical resection of selected sinonasal malignancies. We report our experience with endoscopic management of sinonasal cancers, with emphasis on naso-ethmoidal malignancies encroaching on the anterior skull base. METHODS: Major series reporting results concerning the endoscopic endonasal approach with or without craniectomy for treatment of sinonasal and anterior skull base cancers were reviewed. Preoperative work-up, indications and exclusion criteria, surgical techniques, postoperative management, and adjuvant therapy are reported. RESULTS: In the 2 largest series analyzed, the most common malignancies were adenocarcinoma (28%), olfactory neuroblastoma (14.5%), and squamous cell carcinoma (13.5%). The 5-year disease-specific survival rate ranged from 81.9%-87%, with no major differences in the mean follow-up time (34.1 months vs. 37 months). CONCLUSIONS: Endoscopic endonasal resection performed with or without a transcranial approach, when properly planned and in expert hands, has an accepted role with precise indications in the surgeon's armamentarium for the treatment of sinonasal and skull base malignancies.

Oncocytic carcinoma of the nasolacrimal duct treated by transnasal endoscopic resection.

BACKGROUND: Malignancies of the nasolacrimal apparatus are rare lesions that usually originate from the lacrimal sac. To the best of our knowledge, this is the first case of a primary oncocytic carcinoma of the nasolacrimal duct reported in the literature. METHODS: A 43-year-old woman presented with a 3-month history of right epiphora. At nasal endoscopy, an exophytic lesion occupying the right inferior meatus was visible. Imaging studies showed an expansile lesion involving the nasolacrimal duct and the inferior meatus, but not invading the orbit or adjacent soft tissues. A biopsy was suggestive for an oncocytic lesion. RESULTS: A radical resection was obtained through an endoscopic extended medial maxillectomy with a definitive diagnosis of oncocytic carcinoma. Forty-two months after surgery there was no evidence of disease. CONCLUSIONS: In selected malignant lesions of the nasolacrimal duct not involving the adjacent soft tissues or lacrimal sac, an exclusive endoscopic approach can be considered.

Ruptured aneurysm in sphenoid sinus: which is the best treatment?

Internal carotid artery (ICA) aneurysms involving the sphenoid sinus are uncommon, and their optimal treatment remains debated. We report the case of a patient presenting with recurrent epistaxis due to a bleeding cavernous ICA aneurysm. We suggest a combined endovascular and endoscopic approach when ICA occlusion may not be performed.

Intracerebral bullet removal through an endoscopic transnasal craniectomy.

BACKGROUND: In the past decade, the endoscopic transnasal technique has been broadly applied as a feasible and less invasive approach to the skull base. The adaptability of the endoscopic technique allows a case-specific approach in order to minimize both endonasal and cranio-cerebral manipulation; therefore it can be also used in patients complaining exceptional skull base lesions and in weak patients. The objective of this paper is to present the first case of intracerebral bullet removal using a pure endoscopic transnasal route through a custom made unilateral craniectomy. CASE DESCRIPTION: A 59-year-old patient was admitted to the emergency department after a gunshot injury to the head, thorax, abdomen, and pelvis. Admission Glasgow Coma Scale was 7. Brain computed tomography (CT) scan highlighted a right occipital hole defect due to perforative impact, intracerebral dislocations of bone fragments, right intracerebral and subdural hematoma, and midline shift to the left side; the bullet was localized in the right frontal lobe and its tip was in contact with the ethmoid roof. The patient underwent emergency decompressive craniectomy and evacuation of the subdural hematoma and abdominal explorative laparotomy, ileum resection, and gastrorrhaphy. After 1 month, the patient underwent endoscopic transnasal removal of the bullet and skull base reconstruction due to cerebrospinal fluid infection. The postoperative course was uneventful and he has done well in follow-up with no evidence of cerebrospinal fluid leak and preservation of olfaction. CONCLUSION: The adaptability of the endoscopic transnasal technique offers patients complaining exceptional skull base lesions a case-specific strategy minimizing morbidity and postoperative stay.

Endoscopy-assisted iliotibial tract harvesting for skull base reconstruction: feasibility on a cadaveric model.

During the last years, multiple methods and a wide set of materials for skull base reconstruction have been described. In our experience, the ideal graft for duraplasty is the iliotibial tract due to its favorable characteristics in terms of thickness, pliability, and strength. In this report, we show the iliotibial tract-harvesting technique under endoscopic guidance with a minimally invasive approach using a cadaveric model. Two longitudinal incisions of 1 cm each were made at 4 cm down a line drawn between the anterior-superior iliac spine and the lateral margin of patella at the extremities of the middle third of the thigh. By using a set of instruments for endoscopic face-lifting, the graft was easily set up and harvested. The endoscopic approach is associated with less visible scars, but longer operative time in comparison with open traditional procedure. The pros and cons in terms of morbidity need to be evaluated by further studies on actual cases.

Ethmoid adenocarcinoma--from craniofacial to endoscopic resections: a single-institution experience over 25 years.

OBJECTIVES: To identify factors that influence hospitalization time, complications, and prognosis of patients with ethmoid adenocarcinoma treated with different surgical techniques. DESIGN: Single-institution retrospective review. SETTING: Academic tertiary care center. PATIENTS: Sixty-seven patients with ethmoid adenocarcinoma treated from January 1985 to August 2009 were retrospectively evaluated. Surgical treatment included endoscopic resection (n = 12), endoscopic resection with transnasal craniectomy (n = 17), cranioendoscopic resection (n = 9), external approaches limited to the ethmoid (n = 11), and craniofacial resection (n = 18). MAIN OUTCOME MEASURES: A Cox model was adopted to relate time to death to previous treatment, pT category, grade, and surgical technique. The impact of the same variables on hospitalization time and risk of complications was assessed by linear regression and logistic regression, respectively. RESULTS: The risk of complications increased for pT4a-b lesions (P = .02) and craniofacial resection (P = .01). Hospitalization time increased by 6.3 days for cranioendoscopic resection (P = .03) and by 11.7 days for craniofacial resection (P < .001). Three- and 5-year overall survivals were 68.0% (standard error = 5.8%) and 48.4% (standard error = 6.9%). Three-year survival was 76.62% and 51.81% for previously untreated and treated patients, respectively, and it was 92.98% and 33.33% in patients treated with endoscopic techniques and craniofacial resection, respectively. Multivariate analysis showed that previous treatment (hazard ratio of death = 3.9, P = .01) and craniofacial resection (HR = 5.16, P = .05) were mainly associated with survival. CONCLUSIONS: Endoscopic techniques, in properly selected patients, were associated with a favorable oncologic outcome and a statistically significant reduction in both complication rate and hospitalization time. This study supports the role of endoscopic techniques in surgical treatment of ethmoid adenocarcinoma.

Endoscopic transnasal craniectomy in the management of selected sinonasal malignancies.

BACKGROUND: Because of a better understanding of the anatomy from an endoscopic perspective, the acquisition of surgical experience, and concomitant technological advances, endoscopic resection of the anterior skull base (ASB) and overlying dura has now become a reality, opening new possibilities in the management of sinonasal malignancies. Here, the authors review a series of 62 patients, the largest reported to date, who underwent endoscopic transnasal craniectomy (ETC) and endoscopic dural repair for the management of selected sinonasal malignancies. Special emphasis is placed on the surgical technique, technical tricks, choice of materials for endoscopic dural repair, postoperative management, and complications. METHODS: From 2004, 62 patients underwent ETC at two referral hospitals, which extended anteroposteriorly from the frontal sinus to planum sphenoidale and laterolaterally from the nasal septum to the lamina papyracea (unilateral resection, n = 28; 45%) or from papyracea to papyracea (bilateral resection, n = 34; 55%). Duraplasty with a three-layer technique was performed using the iliotibial tract and fat tissue. RESULTS: The most frequent histotypes were adenocarcinoma (58%) and olfactory neuroblastoma (22%). Forty-five (73%) patients were previously untreated. The incidence of early (T1-2, Kadish A-B) and advanced (T3-4, Kadish C) tumors was similar. The complication rate was 15%, mostly cerebrospinal fluid leaks (13%). Its prevalence did not correlate with patient age, medical comorbidities, previous treatment, presence of ASB involvement, or whether ETC was mono- or bilateral, but tended to correlate with advanced tumor stage, dural involvement, and the period of treatment. After a mean follow-up of 17.5 months (range, 1-54 months), 58 (94%) patients had no evidence of disease. CONCLUSION: In correctly selected patients with sinonasal tumors involving the ASB, ETC offers a less invasive alternative than resection by an open approach with an acceptable morbidity.

Endoscopic surgery for juvenile angiofibroma: a critical review of indications after 46 cases.

BACKGROUND: At present, transnasal endoscopic surgery is considered a viable option in the management of small-intermediate size juvenile angiofibromas (JAs). The authors critically review their 14-year experience in the management of this lesion to refine selection criteria for an endoscopic approach. METHODS: From January 1994 to May 2008, 46 patients were treated by a pure endoscopic resection after vascular embolization (87%). The lesions were classified according to Andrews (Andrews JC, et al., The surgical management of extensive nasopharyngeal angiofibromas with the infratemporal fossa approach, Laryngoscope 99:429-437, 1989) and Onerci (Onerci M, et al. Juvenile nasopharyngeal angiofibroma: A revised staging system, Rhinology 44:39-45, 2006) staging systems. All patients were followed by regular endoscopic and magnetic resonance imaging (MRI) examinations. RESULTS: Lesions were classified as follows: stage I, n = 5; stage II, n = 24; stage IIIa, n = 14; stage IIIb, n = 3 according to Andrews classification system; stage 1, n = 9; stage II, n = 12; stage III, n = 26 according to Onerci's system. Unilateral blood supply was detected in 39 (85%) cases. Feeding vessels from the internal carotid artery (ICA) were also reported in 14 (30%) patients. Intraoperative blood loss ranged from 250 to 1300 mL (mean, 580 mL). In four (8.7%) cases, suspicious residual disease was detected by MRI. In one patient, a 1-cm persistent lesion was endoscopically removed because septoplasty was required and a slight increase in size was noticed. The other three lesions, all located in the root of the pterygoid plate, are nearly stable in size and are currently under MRI follow-up. CONCLUSION: The improvement of surgical instrumentation and the experience acquired during a 14-year period have contributed to expanding the indications for endoscopic surgery in the management of JAs. Even stage III lesions may be successfully managed, unless the ICA is encased or if it provides an extensive blood supply. An external approach may be required when critical structures such as the ICA, cavernous sinus, or optic nerve are involved by lesions that are persistent after previous treatment; such a situation may prevent safe and radical dissection with a pure endoscopic approach. Better understanding of the factors influencing the growth of residual lesions is needed to differentiate those requiring re-treatment from those which can be simply observed.