[Possibilities of transanal endoscopic microsurgery: the experience of 202 operations].

Transanal endoscopic microsurgery (TEM/TEO) is a standard treatment for rectal adenomas but can also be used for selected malignant tumors. Rectal adenomas, selected adenocarcinomas and carcinoids were chosen for operations. Preoperative work-up included: digital rectal examination, rectoscopy with biopsy, colonoscopy, EUS, pelvic CT (MRI). Two hundred and two patients [mean age of 62.4 ± 10.3 (33-86)] had TEO. The mean size ± SD of tumors was 3.2 ± 1.4 cm (0.6-8.0). Mean distance from anal verge and dental line was 7.1 ± 2.4 cm (2.5-14.0) and 4.6 ± 2.6 cm (0.5-12.0), respectively. Preoperative biopsy revealed: adenoma--156/202 (77.2%), adenocarcinoma--39/202 (19.3%) and carcinoid--7/202 (3.5%). The median operating time was 40 (20-180) min. Tumor-free margins were obtained in 200/202 (99%) operative specimens, 2/202 (1.0%) cases tumors were fragmented. Morbidity was 7/202 (3.5%). Pathological investigation revealed: adenoma in 109/202 (54.0%) cases, adenocarcinoma stage Tis, T1, T2 and T3 in 86/202 (42.5%), carcinoid in 5/202 (2.5%), neurilemoma in 1/202 (0.5%), neurofibroma in 1/202 (0.5%). One hundred and two patients had follow-up (95%). Median follow-up at 20 (1-41) months; 3/192 patients with adenocarcinoma, 1/192 patient with adenoma and 1/192 patient with carcinoid had local recurrence. Thus, transanal endoscopic microsurgery for rectal adenomas and selected malignant tumors is associated with low morbidity and low recurrents rates.

Factors affecting carbon dioxide laser treatment for oral precancer: a patient cohort study.

BACKGROUND: Although the benefits of CO(2) laser surgery in oral precancer management have been evaluated, little consideration has been given to the factors which may influence treatment outcome, especially amongst patients developing recurrence or malignant transformation. STUDY DESIGN: Seventy eight patients (51 males, 27 females; mean age 57.8 years) undergoing CO(2) laser excision of single, new dysplastic oral precancer lesions (OPLs) were followed up for a minimum of 2 years and the influence of clinico-pathological parameters, socio-demographic factors and the presence or absence of residual dysplasia in excision margins upon clinical outcome were examined. RESULTS: Seventy three percent of patients were smokers and 78% consumed alcohol regularly. The majority of lesions were leukoplakias arising in the floor of mouth and ventro-lateral tongue and moderate or severe dysplasia accounted for 86% of histopathological diagnoses. Patient follow up ranged from 24 to 119 months (mean 58 months). Sixty four percent of patients were disease free at most recent clinical follow up, whilst 32% developed local recurrent dysplasia or new site dysplasia with 4% developing oral squamous cell carcinoma (but at sites distinct from their initial OPL). Excision margins were clear in 55% of cases, but 19% showed mild, 21% moderate and 5% severe dysplasia on histopathological examination. No statistically significant associations were seen between patients' age, gender, lesion appearance, site of origin, histopathological grading, presence of dysplasia in resection margins, or alcohol consumption and clinical outcome. Smokers, however, were at significantly higher risk of dysplasia recurrence compared to ex-smokers or non-smokers (P = 0.04). CONCLUSIONS: In the absence of agreed treatment protocols for OPLs, we recommend CO(2) laser surgery as an effective treatment modality offering precise lesion excision, full histopathological assessment, minimal post-operative morbidity and a 64% disease free clinical outcome. Regular patient follow up is encouraged due to the persistence of field cancerisation effects.

The efficacy of collagen membrane as a biodegradable wound dressing material for surgical defects of oral mucosa: a prospective study.

PURPOSE: The aims and objectives of this study were to evaluate the efficacy of collagen membrane as a biodegradable wound dressing material for surgical defects of the oral mucosa. MATERIALS AND METHODS: Sixty healthy adult patients were included in the study. Purified bovine reconstituted collagen with a dimension of 10 x 10 cm and 0.6 mm thickness was used. This study was confined to secondary defects of the oral mucosa, which occur after excision of premalignant lesions and other conditions, such as benign lesions, reactive proliferations, and incisional biopsy wounds. Only those lesions that were sufficiently large and could not be closed primarily were included in the study. RESULTS: The results were evaluated on the day of surgery and in the postoperative period. The usefulness of collagen membrane as an intraoral temporary wound dressing material to promote hemostasis, relieve pain, induce granulation, and assist in rapid epithelialization at the wound site and prevent infection, contracture, scarring, donor-site morbidity, and rejection of graft was evaluated; and finally, the efficacy of collagen membrane was tested by use of chi(2) test and P less than .001, which is a statistically and clinically significant value. CONCLUSION: In this study of short duration and small sample, the nature of collagen membrane was observed and was found to be a very suitable alternative to other graft materials mentioned for the repair of defects in the mucous membrane of the oral cavity. Therefore, when used judiciously in a controlled clinical situation, collagen membrane is biologically acceptable to the oral mucosa and is, from the clinical point of view, an excellent wound graft material.

Endoscopic laryngo-pharyngeal surgery for elderly patients.

OBJECTIVE: Due to the rising number of elderly patients and advances in endoscopic devices, early laryngeal and pharyngeal cancers are increasingly found in elderly patients. In these cases, minimally invasive endoscopic larygo-pharyngeal surgery (ELPS) may be indicated. However, the safety and efficacy of ELPS in elderly populations has not been established. The purpose of this study was to investigate the safety, outcomes and feasibility of ELPS in very elderly patients. METHODS: Between February 2010 and April 2016, 29 pharyngeal cancerous or pre-cancerous lesions in 19 patients aged 75 years or older were treated with ELPS. Twenty-six resections were performed in total, and the patients' clinical courses were reviewed. RESULTS: Sixteen patients had multiple comorbidities and moderate to severe comorbidities were observed in 17 patients. The average surgical time and hospitalization period was 54.3min and 18.8 days, respectively. On average, oral intake began 4.4days after the procedure, and all patients eventually received nourishment by mouth; no percutaneous endoscopic gastrostomy dependency was observed. Complications included post-operative bleeding and aspiration pneumonia in two cases each, and all complications were safely managed. The 3-year overall survival rate was 90.2% and the 3-year disease-specific survival rate was 100%. CONCLUSION: ELPS was safely performed in elderly patients, suggesting that it is a feasible treatment option for pharyngeal lesions in very elderly patients.

[Benign "mixed" odontogenic tumors]. / Benigne "gemischte" odontogene Tumoren.

Benign "mixed"odontogenic tumors consist of an epithelial and ectomesenchymal tumor component, distinguishing them from pure epithelial and pure ectomesenchymal odontogenic tumors. In addition, they may have the ability to produce dentin, enamel or cementum. Therefore, they can sometimes already be differentiated radiologically from epithelial odontogenic tumors. Some of the mixed odontogenic lesions are regarded as true tumors (ameloblastic fibroma, odontoameloblastoma, dentinogenic ghost cell tumor), while others are assumed to represent hamartomatous lesions (complex and compound odontoma, probably also ameloblastic fibrodentinoma and ameloblastic fibroodontoma). Preceded by keratocystic odontogenic tumor, complex and compound odontomas are the second most common odontogenic tumors, while other members of the "mixed" odontogenic tumor group are far less frequently diagnosed. Odontoameloblastoma and dentinogenic ghost cell tumors are locally aggressive lesions that require total resection. All other lesions of this group are treated by local excision. Since ameloblastic fibrosarcoma may evolve from ameloblastic fibroma, patients with ameloblastic fibroma should remain in long-term follow-up.

Oral human papillomavirus lesion identified using VELscope instrumentation: case report.

The role of oral human papillomavirus (HPV) in the incidence of oral carcinoma has increased among traditional non-risk patients under the age 40. This case study describes how a squamous papilloma (attributed to the HPV) was discovered using the VELscope oral screening device. Photographs of the lesion that might help dentists to identify these areas, using both white light and fluorescence visualization with VELscope, are included.

Surgical Management of Oral Cancer.

Today, most head and neck cancer subsites, such as the larynx, hypopharynx, nasopharynx, and oropharynx, are treated with radiation therapy with or without chemotherapy as a primary treatment modality. Surgery is reserved for the salvage of recurrent tumors that occur within the head and neck in the absence of distant (ie, lung, liver) metastasis. However, unlike all other head and neck subsites, oral cancer should ideally be managed with primary surgery with the possibility of adjuvant radiation therapy with or without chemotherapy depending on the presence of certain high-risk pathologic features.

Effect of Polyglycolic Acid Mesh for Prevention of Pancreatic Fistula Following Distal Pancreatectomy: A Randomized Clinical Trial.

Importance: The rate of postoperative pancreatic fistula (POPF) after distal pancreatectomy ranges from 13% to 64%. To prevent POPF, polyglycolic acid (PGA) mesh was introduced, but its effect has been evaluated only in small numbers of patients and retrospective studies. Objective: To evaluate the efficacy of PGA mesh in preventing POPF after distal pancreatectomy. Design, Setting, and Participants: Prospective randomized clinical, single-blind (participant), parallel-group trial at 5 centers between November 2011 and April 2014. The pancreatic parenchyma was divided using a stapling device; no patient was given prophylactic octreotide. Perioperative and clinical outcomes were compared including POPF, which was graded according to the criteria of the International Study Group For Pancreatic Fistulas. A total of 97 patients aged 20 to 85 years with curable benign, premalignant, or malignant disease of the pancreatic body or tail were enrolled (44 in the PGA group and 53 in the control group). Interventions: Patients in the PGA group underwent transection of the pancreas and application of fibrin glue followed by wrapping the PGA mesh around the remnant pancreatic stump. Main Outcomes and Measures: The primary end point of this study was the development of a clinically relevant POPF (grade B or C by the International Study Group grading system). The secondary end point was the evaluation of risk factors for POPF. Results: The study therefore evaluated a total of 97 patients, 44 in the PGA group and 53 in the control group. Thirty-nine patients were women and 58 patients were men. There were no differences in mean (SD) age (59.9 [12.0] years vs 54.5 [14.1] years, P = .05), male to female ratio (1.0:1.3 vs 1.0:1.7, P = .59), malignancy (40.9% vs 32.1%, P = .37), mean (SD) pancreatic duct diameter (1.92 [0.75] mm vs 1.94 [0.95] mm, P = .47), soft pancreatic texture (90.9% vs 83.0%, P = .17), and mean (SD) thickness of the transection margin (16.9 [5.4] mm vs 16.4 [4.9] mm, P = .63) between the PGA and control groups. The rate of clinically relevant POPF (grade B or C) was significantly lower in the PGA group than in the control group (11.4% vs 28.3%, P = .04). Conclusions and Relevance: Wrapping of the cut surface of the pancreas with PGA mesh is associated with a significantly reduced rate of clinically relevant POPF. Trial Registration: clinicaltrials.gov Identifier: NCT01550406.

Clinical evaluations of complete autologous fibrin glue, produced by the CryoSeal® FS system, and polyglycolic acid sheets as wound coverings after oral surgery.

The CryoSeal® FS System has been recently introduced as an automated device for the production of complete fibrin glue from autologous plasma, rather than from pool allogenic or cattle blood, to prevent viral infection and allergic reaction. We evaluated the effectiveness of complete autologous fibrin glue and polyglycolic acid (PGA) sheet wound coverings in mucosa defect oral surgery. Postoperative pain, scar contracture, ingestion, tongue dyskinesia, and postoperative bleeding were evaluated in 12 patients who underwent oral (including the tongue) mucosa excision, and received a PGA sheet and an autologous fibrin glue covering. They were compared with 12 patients who received a PGA sheet and commercial allogenic fibrin glue. All cases in the complete autologous fibrin glue group demonstrated good wound healing without complications such as local infection or incomplete cure. All evaluated clinical measures in this group were similar or superior to the commercial allogenic fibrin glue group. Coagulation and adhesion quality achieved with this method was comparable to that with a PGA sheet and commercial fibrin glue. Covering oral surgery wounds with complete autologous fibrin glue produced by an automated device was convenient, safe, and reduced the risk of viral infection and allergic reaction associated with conventional techniques.

Primary intraosseous carcinoma and odontogenic cyst. Three new cases and review of the literature.

INTRODUCTION: The Odontogenic Primary Intraosseous Carcinoma (PIOC) are a rare group of malignant tumours with strict clinic and anatomy pathological diagnosis criteria. The different classification suggested for these tumours and the small amount of cases described in literature makes it hard to know exactly how many of the cases published until now are real. MATERIAL AND METHODS: We present three new cases of PIOC originated from a previous cystic lesion that where treated in our Hospital. Two of them in the posterior jaw region where is more frequent, and the third in the upper jaw. We explain the procedure we used in each case and the aesthetic-functional reconstruction used witches are two fibula osteomyocutaneous free flaps and a bone graft of iliac crest and further placing of implants. The classification, the clinical and radiological diagnosis, the treatment and its survival are discussed. RESULTS: In all three cases we were able to see in the anatomy pathological study an epithelial, exclusively without surrounding oral mucosa affectation or tissues near the lesion as well as the lack of tumorous pathology in other parts of the body. One of the patients died because of premature massive cervical recidiva while the other two patients are currently free form illness, for ten years one of them and fifteen months the other. CONCLUSIONS: The anatomy pathological study of all of the lesions of cystic characteristics at jaw level is very important because of the risk of coexisting with carcinomatous cells. The treatment of these tumours consists in practising aggressive surgery and, in some cases, radio and/or chemotherapy post intervention.

Relative Frequency of Oral Malignancies and Oral Precancer in the Biopsy Service of Jazan Province, 2009-2014.

BACKGROUND: The objective of this study was to report the types and relative frequency of oral malignancies and precancer in the Jazan region of Saudi Arabia during the period 2009-2014. MATERIALS AND METHODS: Pathology reports were retrieved from the archives of Histopathology Department, King Fahd hospital in Jazan. Demographic data on tobacco habits, clinical presentation and histologic grading of oral precancer and cancer cases were transcribed from the files. RESULTS: 303 (42.7%) oral pre-malignant and malignant cases were found out of 714 oral biopsy lesions. A pathology diagnosis of squamous cell carcinoma (85.1%) was most frequent, followed by premalignant lesions/epithelial dysplasia (8.6%), verrucous carcinoma (3.3%) and malignancy of other histological types (3%) such as ameloblastic carcinoma, salivary gland malignancy and sarcomas. Oral squamous cell carcinoma was predominant in females with a male to female ratio of 1:1.9. Patient age ranged from 22 to 100 years with a mean of 65±13.9. Almost 44.6% of oral cancer had occurred after 65 years of age. Only 16.3% cases were reported in patients younger than 50 years, predominantly females. The majority of female patients had the habit of using shammah with a long duration of usage for more than 45 years. Bucco- alveolar mucosa (52.3%) was the common site of involvement followed by tongue/ floor of the mouth (47.7%) and clinically presented mostly as ulceration/swelling clinically. Moderately differentiated tumours (53.9%) were common followed by well differentiated (32.2%) and poorly differentiated tumours (5.8%). The prevalence of oral verrucous carcinoma (3.3%) was comparatively low with an equal distribution in both males and females. Both bucco-alveolar mucosa and tongue were predominantly affected. Oral precancer/epithelial dysplasia (8.6%) was common in females with a shammah habit. Bucco-alveolar mucosa was commonly involved and clinically presented mostly as white/red patches. Most cases were mild followed by moderate and severe dysplasia. Tumours of other histological types (3%) include 1 ameloblastic carcinoma, 3 malignant salivary gland tumours and 5 sarcomas. CONCLUSIONS: In this study, it was found that oral cancers reported in the pathology service to be a common occurrence. This study reconfirms previous reports of the high burden of oral cancer in this population This indicates that conventional preventive programs focused on oral cancer are in need of revision. In addition, further research into identifying new risk factors and molecular markers for oral cancer are needed for screening high risk individuals.

Transoral carbon dioxide laser ablation for cancer, tumors, and other diseases.

A carbon dioxide laser was used on 71 patients for the removal of oral cavity or oropharyngeal cancers, premalignant lesions, benign tumors, or elongated soft palates. Evaluation of patient morbidity, speech, and swallowing, as well as survival data, suggests that the use of this modality for treatment of these conditions is highly successful, with excellent preservation of oral and pharyngeal function and minimal patient morbidity. Deep excisions of tumors that could lead to restricted motion of the tongue and/or jaw tended to have an adverse effect on both speech and swallowing. Immediate reconstruction should be considered, especially for defects created by excision of large tumors in the anterior oral cavity or in the lateral oropharyngeal wall cancers. Multimodality cancer therapy should be considered for large oral cavity and oropharyngeal cancers that have been treated by carbon dioxide laser excision.

The use of processed allograft dermal matrix for intraoral resurfacing: an alternative to split-thickness skin grafts.

BACKGROUND: The standard reconstruction of significant mucosal defects in head and neck surgery has been split-thickness skin grafting (STSG). OBJECTIVE: To examine the use of a commercially available acellular dermal matrix as an alternative to STSG to reduce the scarring and contracture inherent to meshed split-thickness autografting and avoid the additional donor site morbidity. PATIENTS AND METHODS: Twenty-nine patients with full-thickness defects of the oral cavity were included in this retrospective chart review. Candidate patients had their operative procedure performed at a tertiary care center during a 24-month period. Allograft dermal matrix, an acellular tissue-processed biomaterial, was applied to these intraoral defects. The defects were reconstructed with an acellular dermal graft matrix in the same technical fashion as with an autologous skin graft. Patients were evaluated for rate of "take," functional return time to reepithelialization, average surface area of graft, associated pain and discomfort, evidence of restrictive graft contracture, patient diagnosis, and graft location within the oral cavity. Any evidence of incomplete graft reepithelialization was considered grounds for graft failure, either complete or incomplete. Epithelialization and contracture were assessed during outpatient clinical examinations. Patient complaints with regard to discomfort at the graft bed were considered evidence of pain. RESULTS: Graft locations included 9 in the tongue (32%), 5 in the maxillary oral vestibule (17%), 4 in the mandible (14%), 4 in the floor of mouth (14%), 3 in the hard and/or soft palate (10%), 3 in the tonsil (10%), and 1 in the lip (3%). The overall rate of take was 90% with complete epithelialization noted on clinical evaluation within 4 weeks. Patients were followed up for an average of 8.6 months. The average grafted surface area was 25 cm2. Pain or discomfort was noted in 3 patients (12%). One patient (4%) was noted to have clinical evidence of graft contracture. CONCLUSIONS: Allograft dermal matrix was successful as a substitute to autologous STSG for resurfacing of intraoral defects. Allograft dermal matrix may be considered a useful reconstructive option for patients with oral mucosal defects.

Bilateral small radial forearm flaps for the reconstruction of buccal mucosa after surgical release of submucosal fibrosis: a new, reliable approach.

Oral submucous fibrosis is a collagen disorder affecting the submucosal layer and often severely limiting mouth opening. Previous surgical treatments have been disappointing. This article introduces a new surgical approach: reconstructing the bilateral buccal mucosa with two small radial forearm flaps. The surgical method includes the complete surgical release of fibrotic buccal mucosa and, if necessary, a bilateral coronoidectomy and temporalis muscle myotomy. From 1997 to 1999, 15 patients with moderate-to-severe trismus received reconstructive surgery, for a total of 30 small radial forearm flaps after surgical release. The flap size was between 1.5 x 5 and 2.5 x 7 cm. All donor sites were directly closed, and all flaps survived completely, except for one with partial necrosis. Six flaps required minor revisions because of size redundancy. Two patients developed buccal cancer in the area of reconstruction. At an average of 12 months' follow-up, the inter-incisal distance averaged 33 mm, an increase of 17 mm compared with the preoperative value. The donor-site morbidity was minimal, except in one heavy smoker who developed dry gangrene of his fingertips. The use of two small free forearm flaps for buccal mucosa reconstruction allows more radical release of fibrotic tissue. Coronoidectomy and temporal muscle myotomy further contribute to the effect of trismus release. The combined effects of this approach have consistently given good results. An aggressive approach toward surgical treatment of this precancerous lesion also facilitates the detection of cancer at an early stage.

Treatment of verrucous hyperplasia and verrucous carcinoma by shave excision and simple cryosurgery.

Wide excision and skin or mucosa grafting has been the primary form of therapy for verrucous hyperplasia and verrucous carcinoma. But those with wide involvement often make the procedures complicated. A simple management, shave excision followed by simple cryosurgery, is presented. The treatment modality described is simple, and less traumatic. It can be performed under local anaesthesia, and requires no hospitalization. It has been easily used to treat 26 lesions in 20 patients with satisfactory results.

Intraoral grafting of an ex vivo produced oral mucosa equivalent: a preliminary report.

The objective of this study was to assess the efficacy of the use of an ex vivo produced oral mucosa equivalent (EVPOME) for intraoral grafting procedures. Autogenous keratinocytes were harvested from a punch biopsy 4 weeks prior to surgery, placed in a serum-free culture system and seeded onto a human cadaveric dermal equivalent, AlloDerm. Thirty patients with either a premalignant or cancerous lesion were triaged into two groups, depending on the stage of disease: Group 1: EVPOME or Group 2: AlloDerm, control without an epithelial layer. Clinically, EVPOME grafts were easy to handle and showed excellent compliance on grafting. Both, EVPOME and AlloDerm grafts, showed a 100% take rate. At 6 days post-grafting, the EVPOME clinically showed changes indicating vascular ingrowth and had cytologic evidence of the persistence of grafted cultured keratinocytes on the surface. The EVPOME grafts had enhanced maturation of the underlying submucosal layer associated with rapid epithelial coverage when compared to the AlloDerm grafts at biopsies taken at 28 days post-grafting. In summary, EVPOME appears to be an acceptable oral mucosal substitute for human intraoral grafting procedures and results in a more favorable wound healing response than AlloDerm alone.

Interventional laser surgery: an effective surgical and diagnostic tool in oral precancer management.

Invasive oral squamous cell carcinomas (OSCCs) are often preceded by precancerous lesions, the management of which remains controversial, polarized between active surgical excision to try to prevent malignant change or more conservative, medical or observational techniques. In order to determine the efficacy of interventional CO2 laser surgery in oral precancer management, the records of 57 consecutive laser-treated patients presenting over a 4-year period, with histologically confirmed dysplastic lesions, were reviewed. Leukoplakias were the commonest clinical lesions (69%), whilst the floor of the mouth was the most frequent anatomical site (42%). Laser surgery successfully excised 55 precancerous lesions, 11 of which exhibited more severe dysplasia or neoplasia compared with initial biopsy. Postoperative scarring and morbidity were minimal. After surgery, patients were followed for between 1 and 44 months (mean 18 months). Of these patients, 76% remained disease-free, whilst 24% developed new dysplastic lesions at distinct or multiple sites, often exhibiting increased dysplasia. Of the patients experiencing recurrence, 7% developed OSCC, whilst a further 3.5% presented with other aerodigestive tract cancers. Neither initial lesion appearance nor histological diagnosis predicted clinical behaviour. Interventional laser surgery is thus advised, in contradistinction to conservative management of oral precancers, to facilitate efficacious, low-morbidity treatment and to establish definitive histological diagnosis. As a consequence of field change carcinogenesis, regular follow up of treated precancer patients is mandatory for effective tertiary prevention.

Oral submucous fibrosis: a new concept in surgical management. Report of 100 cases.

Oral submucous fibrosis (OSF) is a collagen disorder commonly seen in the Indian subcontinent. A series of 100 patients is presented. All lesions were biopsied. The condition was staged into four categories. Very early and early cases were treated by local injection of triamicinolone acetonide, while advanced cases were treated by surgical intervention. A new surgical technique of a palatal island flap based on the greater palatine artery in combination with temporalis myotomoy and bilateral coronoidectomy was used in 35 cases. A follow-up ranging from 6 months to 31/2 year showed good results.

Salivary gland duct involvement in oral epithelial dysplasia and squamous cell carcinoma.

The clinical implications and prognostic significance of oral dysplastic or cancerous epithelium involving salivary gland ducts have not been previously investigated. Screened routine tissue sections of 1216 cases of oral epithelial dysplasias and squamous cell carcinomas revealed 26 examples (2.14%) that exhibited unequivocal ductal involvement. Ductal involvement was more likely to occur in floor of mouth lesions and in lesions exhibiting severe dysplasia or carcinoma in situ. Clinical follow-up on 23 cases showed that the recurrence rate of the preinvasive lesions that exhibited ductal involvement was equal to that of the squamous cell carcinomas. The depth of ductal dysplasia did not correlate with recurrence rate. These results suggest that the involvement of salivary gland ducts by oral epithelial dysplasias and carcinomas in situ is an uncommon but significant finding. Surgical stripping or ablation of such lesions should extend at least 3 mm below the surface to ensure eradication of these reservoirs of dysplastic cells.