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Background Postoperative complications are an independent predictor of poor survival across several tumors. However, there is limited literature on the association between postoperative morbidity and long-term survival following total laryngectomy (TL) for cancer. Methods We conducted a retrospective review of all TL patients at a single institution from 2008 to 2013. Demographic and clinical data were collected and analyzed, including postsurgical outcomes, which were classified using the Clavien-Dindo system. Multivariable Cox regression analyses were performed to identify factors associated with overall survival (OS) and disease-free survival (DFS). Results A total of 362 patients were identified. The mean age was 64 years, and the majority of patients were male (81%). The median follow-up interval was 21 months. Fifty-seven percent of patients had received preoperative radiation, and 40% had received preoperative chemotherapy. Fifty-seven percent of patients underwent salvage TL, and 60% underwent advanced reconstruction (45% free flap and 15% pedicled flap). A total of 136 patients (37.6%) developed postoperative complications, 92 (25.4%) of which were major. Multivariable modeling demonstrated that postoperative complications independently predicted shorter OS (hazard ratio [HR], 1.50; 95% CI, 1.16-1.96; P = .002) and DFS (HR, 1.36; 95% CI, 1.05-1.76; P = .021). Other independent negative predictors of OS and DFS included positive lymph node status, preoperative chemotherapy, comorbidity grade, and delayed adjuvant therapy. Severity of complication and reason for TL (salvage vs primary) were not shown to be predictive of OS or DFS. Conclusion Postoperative complications are associated with worse long-term OS and DFS relative to uncomplicated cases. Patient optimization and timely management of postoperative complications may play a critical role in long-term survival.

BACKGROUND: The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) is the universal framework for toxicity reporting in oncology trials. The objective of this study was to develop a CTCAE-compatible modified barium swallow (MBS) grade for the purpose of grading pharyngeal dysphagia as a toxicity endpoint in cooperative-group organ-preservation trials for head and neck cancer (HNC). It was hypothesized that a 5-point, CTCAE-compatible MBS grade (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]) based on the interaction of pharyngeal residue and laryngeal penetration/aspiration ratings would be feasible and psychometrically sound. METHODS: A modified Delphi exercise was conducted for content validation, expert consensus, and operationalization of DIGEST criteria. Two blinded raters scored 100 MBSs conducted before or after surgical or nonsurgical organ preservation. Intrarater and interrater reliability was tested with weighted kappa values. Criterion validity against oropharyngeal swallow efficiency (OPSE), the Modified Barium Swallow Impairment Profile (MBSImP (TM)(c)), the MD Anderson Dysphagia Inventory (MDADI), and the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) was assessed with a 1-way analysis of variance and post hoc pairwise comparisons between DIGEST grades. RESULTS: Intrarater reliability was excellent (weighted kappa=0.82-0.84) with substantial to almost perfect agreement between raters (weighted kappa=0.67-0.81). DIGEST significantly discriminated levels of pharyngeal pathophysiology (MBSImP TM VC : r=0.77; P

BACKGROUND To evaluate long-term disease control, survival, and functional outcomes after surgical and nonsurgical initial treatment for T4 larynx cancer.

BACKGROUND: Cervical cancer is common in the elderly. The authors examined the patterns of care, treatment, and outcomes of elderly women with cervical cancer. METHODS: Women with cervical cancer diagnosed between 1988 and 2005 and registered in the Surveillance, Epidemiology, and End Results database were analyzed. Patients were stratified by age

Despite the diagnostic value of lymphadenectomy for early-stage cervical cancer, its therapeutic role is unknown. We examined the therapeutic potential of extensive lymphadenectomy in women with early-stage cervical cancer.Women with stage IA2-IIA cervical cancer who underwent radical hysterectomy with lymphadenectomy in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients were stratified according to the number of nodes removed. The effect of the extent of lymphadenectomy on overall and cancer-specific survival was examined using multivariable Cox proportional hazards models. Separate analyses were performed for node positive and node negative patients.Among 5522 women, 893 (16%) had10 nodes, 2030 (37%) had 11-20, 1487 (27%) had 21-30 nodes, and 1112 (20%) had30 nodes removed. Black women, those65 years of age and those diagnosed later in the study, were less likely to have 10 or more nodes removed (P.05 for all). Among women with positive lymph nodes, a more extensive lymphadenectomy had no effect on survival (HR = 0.75; 95% CI, 0.47-1.22). For women with negative lymph nodes, a more extensive lymphadenectomy was associated with improved survival. Compared with node negative patients with less than 10 nodes removed, patients with 21-30 nodes removed were 24% (HR = 0.76; 95% CI, 0.53-1.09) less likely to die, whereas those with30 nodes removed were 37% (HR = 0.64; 95% CI, 0.43-0.96) less likely to die from their tumors.Node negative, early-stage cervical cancer patients who undergo a more extensive lymphadenectomy have an improved survival.

BACKGROUND: The objective of this study was to identify measurable parameters that provide quality data for assessing how well cancer care adheres to accepted treatment guidelines and is delivered to any given patient with oral tongue cancer. METHODS: A retrospective chart review included 116 patients treated for T1-T2/N0-N1 squamous cell carcinoma (SCC) of the oral tongue between 1998 and 2003. A set of quality measures considered critical for outcome included: 1) accurate TNM staging at presentation, 2) documentation of margin status, 3) appropriate referral for adjuvant radiation therapy, and 4) neck dissection for depth of invasion >4 mm. In addition, 26 clinical endpoints involving pretreatment assessment, staging, treatment, surveillance, and symptom control were analyzed. RESULTS: Patients comprised 73 men and 43 women (median age, 57 years). Forty-one (35.3%) patients presented with stage I disease, 61 (52.6%) with stage II, and 14 (12.1%) with stage III. The overall 5-year survival rate for all patients was 68.6%. There was a 90.5% compliance with TNM staging at presentation, 99.1% for documentation of margin status, 98.2% for adequate referral to radiation therapy, and 88.7% for appropriate neck dissection based on depth of invasion. Compliance with clinical endpoints was variable and ranged from 100% for endpoints related to radiation therapy to

BACKGROUND. The current study was conducted to determine the effect of goserelin and bicalutamide on progression-free survival (PFS) in patients with epithelial ovarian cancer who were in second or greater complete disease remission. METHODS. Patients received bicalutamide at a dose of 50 mg orally daily and goserelin at a dose of 3.6 mg subcutaneously every 4 weeks. CA 125 was obtained monthly, with computed tomography performed every 3 months. Correlative studies included serum luteinizing hormone, follicle-stimulating hormone, vascular endothelial growth factor, free testosterone, and androstenedione and the germline polymorphisms CYP19A1 and androgen receptor. RESULTS. Between October of 2000 and October of 2002, 35 patients were enrolled. Three patients (9%) received therapy at the time of first disease remission and were removed from the study, and 1 patient (3%) was removed for liver function test abnormalities. The most frequent toxicities were grade 1 alkaline phosphatase (54%), fatigue (57%), and hot flashes (42%) based on the National Cancer Institute common toxicity scale, version 2.0. The PFS for patients receiving protocol therapy in second disease remission (21 patients) was 11.4 months (95% confidence interval [95% CI], 10.2–12.6 months). The PFS for patients receiving protocol therapy in third or fourth disease remission (11 patients) was 11.9 months (95% CI, 10.8–14.1 months). The percentage of patients remaining in second disease remission at given times are: 100% at 3 months, 100% at 6 months, 72% at 9 months, 47% at 12 months, 28% at 15 months, 22% at 18 months, 19% at 21 months, and 13% at 24 months. There were no associations noted between androgen receptor repeat number, genotype, allelotype, or haplotypes and PFS. CONCLUSIONS. The use of goserelin and bicalutamide did not appear to prolong PFS in patients with epithelial ovarian cancer in second or greater complete disease remission. The number of patients in disease remission at given time points may serve as a clinical trial endpoint for future studies of consolidation therapy. Cancer 2007. © 2007 American Cancer Society.

BACKGROUND In previous studies in the high risk population of Linxian, China, the majority of foci of high grade (moderate and severe) squamous dysplasia (HGD) and invasive squamous carcinoma (CA) of the esophagus were associated with endoscopically visible lesions that could be targeted for biopsy, but some foci of HGD were missed by routine endoscopic examination. This study examined whether spraying the mucosa with Lugol's iodine solution, which stains normal epithelium brown but leaves dysplasia and carcinoma unstained, could improve endoscopic detection and delineation of these lesions. METHODS Two hundred twenty-five Linxian adults with balloon cytologic evidence of dysplasia or carcinoma underwent endoscopy. All visible lesions were described and photographed before and after staining with 1.2% Lugol's iodine solution. Biopsies were taken from all lesions visible before staining, from all unstained lesions (USLs) after applying the stain, and from representative control areas of stained mucosa. RESULTS Two hundred fifty-three USLs and 255 control sites were biopsied. No complications occurred. Ninety-four biopsy sites contained HGD and 20 contained CA. Before staining, the sensitivity of visible lesions for identifying HGD or CA was 62%, and the specificity was 79%. After staining, the sensitivity of USLs for identifying HGD or CA was 96%, and the specificity was 63%. Eighty-eight percent of the HGD and CA lesions were larger or more clearly defined after staining. The diagnostic lesions in 17 of 31 patients with moderate dysplasia (55%), 8 of 35 patients with severe dysplasia (23%), and none of the 19 patients with invasive carcinoma (0%) were identified only after staining. CONCLUSIONS Mucosal iodine staining improved endoscopic detection and delineation of HGD and CA in these patients. This simple technique is highly sensitive for identifying these precursor and invasive squamous lesions, and it should be used whenever optimal visualization of squamous mucosal abnormalities is required. Cancer 1998;83:220-231. © 1998 American Cancer Society.

BACKGROUND This case-referent study was conducted to elucidate the role of selected exogenous agents in the etiology of head and neck cancer. The factors studied were tobacco smoking, alcohol intake, the use of moist oral snuff, dietary factors, occupational exposures, and oral hygiene. In this first report, the authors discuss the impact of tobacco smoking, the use of oral snuff, and alcohol consumption. METHODS The study base was approximately 2 million person-years at risk and consisted of Swedish males age 40-79 years living in 2 geographic regions during the years 1988-1990. A total of 605 cases were identified in the base, and 756 controls were selected by stratified random sampling from population registries covering the base. RESULTS Among those who were tobacco smokers at the time of the study, the relative risk of head and neck cancer was 6.5% (95% confidence interval, 4.4-9.5%). After cessation of smoking, the risk gradually declined, and no excess risk was found after 20 years. The relative risk associated with alcohol consumption of 50 grams or more per day versus less than 10 grams per day was 5.5% (95% confidence interval, 3.1-9.6%). An almost multiplicative effect was found for tobacco smoking and alcohol consumption. CONCLUSIONS Tobacco smoking and alcohol intake had a strong interactive effect on the risk of squamous cell carcinoma of the head and neck. Moderate alcohol intake (10-19 grams per day) had little or no effect among nonsmokers. No increased risk was found for the use of Swedish oral snuff. Cancer 1998;82:1367-75. © 1998 American Cancer Society.

BACKGROUND In view of the many studies of early stage colorectal carcinoma from Japan, it is essential to know whether the criteria for the histologic diagnosis of colorectal carcinoma are similar in Japan and Western countries. METHODS Eight expert pathologists from Japan (4), North America (2), and Europe (2) individually reviewed microscope slides of 20 colorectal lesions from Japanese patients who had undergone endoscopic mucosal resection or surgery because early stage carcinoma and/or adenoma was suspected. The pathologists indicated the pathologic findings on which they based each diagnosis. RESULTS For 11 slides that showed adenoma according to the Western pathologists with low grade dysplasia according to at least half of them, the Japanese diagnosed definite carcinoma with or without adenoma in 4 cases and adenoma in 5, and in 2 cases they were equally divided between a diagnosis of adenoma and carcinoma. For five slides showing adenoma with high grade dysplasia according to the Western pathologists, the Japanese diagnosed definite carcinoma with adenoma in three cases and adenoma in one, and in one case they were equally divided between a diagnosis of adenoma and carcinoma. For one case in which the Western pathologists were equally divided between a diagnosis of carcinoma and adenoma with high grade dysplasia, all the Japanese pathologists diagnosed definite carcinoma with or without adenoma. Three slides showed definite carcinoma with or without adenoma, according to both the Western and the Japanese pathologists. The presence of invasion was the most important diagnostic criterion of colorectal carcinoma for the Western pathologists, whereas for the Japanese the nuclear features and glandular structures were more important. CONCLUSIONS In Japan, colorectal carcinoma is diagnosed on the basis of nuclear and structural criteria, even in cases considered by Western pathologists to be noninvasive lesions with low grade dysplasia. This diagnostic practice may contribute to the relatively high incidence of early stage colorectal carcinoma reported in Japan as compared with Western countries. Cancer 1998;82:60-69. © 1998 American Cancer Society.

Background Linxian, China, has some of the highest rates of esophageal cancer in the world. Previous authors have proposed that esophagitis, atrophy, and dysplasia may be precursor lesions of esophageal cancer in such high risk populations. Methods To examine the relationship between squamous esophageal histology and subsequent esophageal cancer in Linxian, the authors prospectively followed 682 participants of a 1987 endoscopic survey for 3.5 years and compared their initial biopsy diagnoses with the occurrence of squamous cell carcinoma during this follow-up period. Results Squamous cell carcinoma of the esophagus was identified in 52 (7.6%) of the participants during the follow-up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for squamous cell carcinoma incidence by initial histologic diagnoses were as follows: normal, 1.0 (reference); basal cell hyperplasia, 2.1 (0.4-9.8); mild dysplasia, 2.2 (0.7-7.5); moderate dysplasia, 15.8 (5.9-42.2); severe dysplasia, 72.6 (29.8-176.9); dysplasia not otherwise specified, 22.9 (6.7-78.0); and carcinoma in situ, 62.5 (24.1-161.9). Conclusion In this study, moderate dysplasia, severe dysplasia, and carcinoma in situ were the only histologic lesions associated with a significantly increased risk of developing squamous cell carcinoma of the esophagus within 3.5 years after endoscopy. Increasing grades of dysplasia were associated with increasing risk, but severe dysplasia were associated with increasing risk, but severe dysplasia and carcinoma in situ had similar degrees of risk, findings that suggest a continuous spectrum of esophageal intraepithelial neoplasia, without morphologically distinguishable dysplasia and in situ carcinoma. A longer follow-up will be necessary to fully evaluate the less severe diagnostic categories, which may take more than 3.5 years to affect the occurrence of squamous cell carcinoma in this high risk population.

Background. Linxian, China, has one of the highest rates of esophageal cancer in the world. Other authors have described high prevalences of histologic esophagitis, atrophy, and dysplasia in Linxian and have suggested that these findings may represent precancerous lesions in this population. In 1987, a new endoscopic survey allowed the authors to make an independent study of esophageal histology in Linxian. Methods. There were 1567 satisfactory squamous esophageal biopsies available from 754 patients. These biopsies were classified as normal, atrophy, acanthosis, esophagitis, squamous dysplasia, or squamous cancer. Results. Classified by their worst diagnosis, 56.5% of the 754 patients had normal mucosa, 0.0% atrophy, 11.5% acanthosis, 4.6% esophagitis, 22.7% squamous dysplasia, and 4.6% squamous cancer. Conclusions. The results show a different distribution of esophageal squamous diagnoses than has been reported previously from this population. The authors believe that the major reason for this discrepancy was differences in histologic criteria. In this survey, seemingly small differences in criteria could cause large differences in apparent disease prevalence; this was especially true for esophagitis. By the criteria used in this study, histologic esophagitis and atrophy are uncommon findings in Linxian, raising questions about their significance as precursor lesions of esophageal cancer in this population.

Cervical cancer is common in the elderly. The authors examined the patterns of care, treatment, and outcomes of elderly women with cervical cancer.Women with cervical cancer diagnosed between 1988 and 2005 and registered in the Surveillance, Epidemiology, and End Results database were analyzed. Patients were stratified by age:50, 50 to 59, 60 to 69, 70 to 79, and ≥80 years. Multivariate logistic regression models were constructed to examine treatment; cancer-specific survival was examined using Cox proportional hazards models.A total of 28,902 women were identified, including 2543 women 70 to 79 years old and 1364 ≥80 years. For women with early stage (IB1-IIA) tumors, primary surgery was performed in 82.0% of women50 years old compared with 54.5% of those 70 to 79 years old and 33.2% of those ≥80 years old (P.0001). For women treated surgically, lymphadenectomy was performed in 66.8% of women50 years old versus 9.1% of patients ≥80 years old (P.0001). Compared with patients50 years old, those80 years old were less likely to undergo radical hysterectomy (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.07-0.14) and lymphadenectomy (OR, 0.11; 95% CI, 0.08-0.16) and to receive adjuvant radiation therapy (OR, 0.06; 95% CI, 0.01-0.35). Among women with stage IIB-IVA disease, use of brachytherapy declined with age (P.0001). For women with stage IB1-IIA tumors, the hazard ratio for death from cancer was 1.35 (95% CI, 1.16-1.58) for women 70 to 79 years old and 2.08 (95% CI, 1.72-2.48) for those ≥80 years old compared with younger women.Elderly women with cervical cancer are less likely to undergo surgery, receive adjuvant radiation, and receive brachytherapy. After adjusting for treatment disparities, cancer-specific mortality is higher in older women.

BACKGROUND: Pharyngoesophageal defects traditionally have been reconstructed using a jejunal or radial forearm flap. In 2002, the authors began using the anterolateral thigh flap for pharyngoesophageal reconstruction, and it has become our preferred method. The purpose of this study was to analyze the clinical and functional outcomes achieved using this technique. METHODS: The medical records of 91 male and 23 female patients who underwent pharyngoesophageal reconstruction using an anterolateral thigh flap were retrospectively reviewed. Outcomes analyzed included length of hospital and intensive care unit stay, fistula and anastomotic stricture formation and other complications, swallowing and tracheoesophageal speech function, and survival. Most patients had primary (27%) or recurrent (42%) squamous cell carcinoma. Before reconstruction, 71% of patients had undergone surgery, radiotherapy, or both. There were 67 circumferential and 47 near-circumferential defects. RESULTS: Mean intensive care unit stay was 1.9 ± 2.2 days, and mean hospital stay was 9.0 ± 4.7 days. Two patients experienced total flap loss, and 1 patient had partial flap necrosis. Pharyngocutaneous fistulas and strictures occurred in 9% and 6% of patients, respectively. Ninety-one percent of patients tolerated an oral diet without the need for tube feeding. Tracheoesophageal puncture was performed for speech rehabilitation in 51 patients. Eight-one percent of patients with a secondary tracheoesophageal puncture achieved fluent speech versus 41% of patients with a primary tracheoesophageal puncture. CONCLUSIONS: This series demonstrates that excellent clinical and functional outcomes, with minimal donor site morbidity and quick recovery, are possible with pharyngoesophageal reconstruction using an anterolateral thigh flap. Cancer 2010. © 2010 American Cancer Society.

BACKGROUND: The objective of this study was to comprehensively review overall survival, functional outcomes, and prognostic factors in patients who underwent salvage surgery for locally recurrent squamous cell carcinoma of the oropharynx (SCCOP) after initial radiotherapy. METHODS: The authors retrospectively reviewed 1681 consecutive patients who completed definitive therapy for primary SCCOP and identified 168 patients with locally recurrent SCCOP who underwent salvage surgery (41 patients), reirradiation or brachytherapy (18 patients), palliative chemotherapy (70 patients), or supportive care (39 patients). RESULTS: Twenty-six of 39 patients (67%) developed a second recurrence after salvage surgery. The 3-year overall survival rate for patients who underwent salvage surgery or received reirradiation, palliative chemotherapy, or supportive care were 48.7%, 31.6%, 3.7%, and 5.1%, respectively. For patients who underwent salvage surgery, older age (P = .03), the absence of a disease-free interval (P < .01), and advanced recurrent tumor stage (P = .07) were associated with lower overall survival. Patients with recurrent neck disease (P = .01) and positive surgical margins (P = .04) had higher rates of recurrence after salvage surgery. Postoperative complications occurred in 19 patients (46%), and there were no perioperative deaths. Functionally, 71% of patients demonstrated ≥80% speech intelligibility, 68% were able to tolerate some oral intake, and 87% who required a tracheotomy subsequently were decannulated. CONCLUSIONS: Age, disease-free interval, recurrent tumor stage, recurrent neck disease, and surgical margin status influenced overall survival or recurrence rate after salvage surgery for recurrent SCCOP. Although most patients had good functional outcomes, only a select group of patients with recurrent SCCOP achieved long-term survival after salvage surgery. Cancer 2009. © 2009 American Cancer Society.

BACKGROUND. Radical trachelectomy is a surgical procedure intended to preserve fertility in patients with early-stage cervical carcinoma in which the cervix is amputated in continuity with the parametrium and upper vagina, thereby sparing the uterus and adnexa. Follow-up is performed with periodic cytology specimens. The objective of the current study was to analyze the cytologic findings after this novel procedure. METHODS. Isthmic and vaginal Papanicolaou-stained ThinPrep cytology specimens taken from patients after radical vaginal and abdominal trachelectomy were reviewed. The specimens were also analyzed for the presence of benign endocervical cells, lower uterine segment glandular cells, endometrial stromal cells, and endometrial cells. The findings were correlated with the original diagnosis and follow-up, which included subsequent cytology specimens and biopsies. RESULTS. Cytology specimens (n = 223) from 44 patients were included in this study. An endometrial component was identified in 131 of the cases (59%). Twenty-eight cases were diagnosed as abnormal in the original cytology examination. Twenty of these cases and 5 additional cases that were diagnosed cytologically as benign had subsequent biopsies. The biopsies confirmed the presence of a lesion in only 4 of 25 biopsies (3 low-grade squamous intraepithelial lesions and 1 adenosquamous carcinoma). All cases diagnosed as atypical glandular cells represented tubal metaplasia, lower uterine segment glandular cells, or endometrial stromal cells. CONCLUSIONS. Cytology specimens after trachelectomy frequently contain glandular cells from the lower uterine segment epithelium or endometrial stromal cells, which can lead to a misdiagnosis of atypical glandular cells of undetermined significance. Tubal metaplasia is also a potential pitfall in these specimens. Pathologists and gynecologic oncologists should be aware of the potential pitfalls in the surveillance of smears after trachelectomy. Cancer (Cancer Cytopathol) 2008. © 2007 American Cancer Society.

John C. Lewin, M.D. Ijust arrived back in California after 17 years in Hawaii. There, I had the opportunity to play a number of different roles in my career: President and CEO, California Medical Associapublic health leader; family practice physician; CEO of a hospital tion. system; and developer and implementer of a health insurance plan for the uninsured. Throughout these career stops, I have been a primary physician and have maintained contact with patients. I have ‘‘rubber hitting the road’’ experience in patient care. At the patient care level, I believe California has a system that really has not attended well to health status improvement and the issues dealing with chronic disease, cancer, heart disease, etc. California has been oriented around acute, emergent, and episodic intervention.

BACKGROUND Large discrepancies have been found between Western and Japanese pathologists in the diagnosis of adenoma/dysplasia versus carcinoma for gastric and colorectal glandular lesions. It is important to determine whether similar differences exist in the diagnosis of esophageal squamous lesions. METHODS Eleven expert gastrointestinal pathologists from Japan, North America, and Europe individually reviewed a set of microscopic slides containing 21 sections of biopsies and corresponding endoscopic mucosal resection specimens from Japanese patients with superficial esophageal squamous neoplastic lesions. The pathologists indicated the pathologic findings on which they based each diagnosis. RESULTS Invasion was the most important diagnostic criterion of carcinoma for the Western pathologists whereas nuclear and structural features were more important for the Japanese pathologists. For two sections showing low grade dysplasia according to most Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in one case and definite carcinoma in the other. For nine sections with high grade dysplasia according to the Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in two cases and definite carcinoma in seven cases. For six sections with suspected carcinoma according to most Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in one case and definite carcinoma in five cases. Four sections showed definite carcinoma according to both the Western and Japanese pathologists. Thus, there was agreement among the Western and Japanese pathologists for only 5 of the 21 sections (kappa value, 0.04). However, when high grade dysplasia, noninvasive carcinoma, and suspected carcinoma were grouped together, the agreement was excellent (19 of the 21 sections; kappa value, 0.75). CONCLUSIONS In Japan, esophageal squamous cell carcinoma is diagnosed mainly based on nuclear criteria, even in cases judged to be noninvasive low grade dysplasia in the West. This difference in diagnostic practice may contribute to the relatively high incidence rate and good prognosis of superficial esophageal carcinoma in Japan. To improve the comparability of research data, the authors recommend that high grade dysplasia, noninvasive carcinoma, and suspected carci- noma be grouped together into one category of “noninvasive high grade neoplasia.” [See editorial on pages 969-70, this issue.] Cancer 2000;88:996–1006. © 2000 American Cancer Society.

In previous studies in the high risk population of Linxian, China, the majority of foci of high grade (moderate and severe) squamous dysplasia (HGD) and invasive squamous carcinoma (CA) of the esophagus were associated with endoscopically visible lesions that could be targeted for biopsy, but some foci of HGD were missed by routine endoscopic examination. This study examined whether spraying the mucosa with Lugol's iodine solution, which stains normal epithelium brown but leaves dysplasia and carcinoma unstained, could improve endoscopic detection and delineation of these lesions.Two hundred twenty-five Linxian adults with balloon cytologic evidence of dysplasia or carcinoma underwent endoscopy. All visible lesions were described and photographed before and after staining with 1.2% Lugol's iodine solution. Biopsies were taken from all lesions visible before staining, from all unstained lesions (USLs) after applying the stain, and from representative control areas of stained mucosa.Two hundred fifty-three USLs and 255 control sites were biopsied. No complications occurred. Ninety-four biopsy sites contained HGD and 20 contained CA. Before staining, the sensitivity of visible lesions for identifying HGD or CA was 62%, and the specificity was 79%. After staining, the sensitivity of USLs for identifying HGD or CA was 96%, and the specificity was 63%. Eighty-eight percent of the HGD and CA lesions were larger or more clearly defined after staining. The diagnostic lesions in 17 of 31 patients with moderate dysplasia (55%), 8 of 35 patients with severe dysplasia (23%), and none of the 19 patients with invasive carcinoma (0%) were identified only after staining.Mucosal iodine staining improved endoscopic detection and delineation of HGD and CA in these patients. This simple technique is highly sensitive for identifying these precursor and invasive squamous lesions, and it should be used whenever optimal visualization of squamous mucosal abnormalities is required.

In view of the many studies of early stage colorectal carcinoma from Japan, it is essential to know whether the criteria for the histologic diagnosis of colorectal carcinoma are similar in Japan and Western countries.Eight expert pathologists from Japan (4), North America (2), and Europe (2) individually reviewed microscope slides of 20 colorectal lesions from Japanese patients who had undergone endoscopic mucosal resection or surgery because early stage carcinoma and/or adenoma was suspected. The pathologists indicated the pathologic findings on which they based each diagnosis.For 11 slides that showed adenoma according to the Western pathologists with low grade dysplasia according to at least half of them, the Japanese diagnosed definite carcinoma with or without adenoma in 4 cases and adenoma in 5, and in 2 cases they were equally divided between a diagnosis of adenoma and carcinoma. For five slides showing adenoma with high grade dysplasia according to the Western pathologists, the Japanese diagnosed definite carcinoma with adenoma in three cases and adenoma in one, and in one case they were equally divided between a diagnosis of adenoma and carcinoma. For one case in which the Western pathologists were equally divided between a diagnosis of carcinoma and adenoma with high grade dysplasia, all the Japanese pathologists diagnosed definite carcinoma with or without adenoma. Three slides showed definite carcinoma with or without adenoma, according to both the Western and the Japanese pathologists. The presence of invasion was the most important diagnostic criterion of colorectal carcinoma for the Western pathologists, whereas for the Japanese the nuclear features and glandular structures were more important.In Japan, colorectal carcinoma is diagnosed on the basis of nuclear and structural criteria, even in cases considered by Western pathologists to be noninvasive lesions with low grade dysplasia. This diagnostic practice may contribute to the relatively high incidence of early stage colorectal carcinoma reported in Japan as compared with Western countries.

The authors had previously reported preliminary results of a treatment regimen of concurrent hyperfractionated radiation therapy and chemotherapy in patients with locally advanced head and neck carcinoma that demonstrated both feasibility and high local control. In an attempt to reduce acute mucosal and hematologic toxicity, granulocyte-colony stimulating factor (G-CSF) was added during the second phase of this study.Seventy patients (53 with Stage IV and 17 with Stage III disease) were entered between May 1988 and June 1995 into a Phase I/II trial of concurrent radiation therapy (74.4 gray (Gy) total dose; 1.20 Gy twice daily), 5-fluorouracil (1000 mg/m2/24 hours for 72 hours), and cisplatin (50 mg/m2) for 3 cycles with the addition of mitomycin C (8 mg/m2) in Cycle 2. G-CSF was added after the initial entry of 34 patients.At a median follow-up of 41 months (range, 12-80 months), 44 patients were alive with a projected median overall survival of 54 months. Grade 3/4 mucositis, observed in 65% of patients, was equally prevalent and prolonged in both G-CSF-treated (+) and G-CSF-naive (-) patients. Grade 3/4 leukopenia was present in 45% and 36% of G-CSF- and G-CSF+ patients, respectively. The 3-year locoregional control and cause specific survival rates were 68% and 75%, respectively.This regimen was feasible and effective but caused severe mucositis. No benefit was derived from the addition of G-CSF. This regimen deserves further modification to reduce acute mucositis toxicity yet maintain the high locoregional control rate.

Linxian, China, has some of the highest rates of esophageal cancer in the world. Previous authors have proposed that esophagitis, atrophy, and dysplasia may be precursor lesions of esophageal cancer in such high risk populations.To examine the relationship between squamous esophageal histology and subsequent esophageal cancer in Linxian, the authors prospectively followed 682 participants of a 1987 endoscopic survey for 3.5 years and compared their initial biopsy diagnoses with the occurrence of squamous cell carcinoma during this follow-up period.Squamous cell carcinoma of the esophagus was identified in 52 (7.6%) of the participants during the follow-up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for squamous cell carcinoma incidence by initial histologic diagnoses were as follows: normal, 1.0 (reference); basal cell hyperplasia, 2.1 (0.4-9.8); mild dysplasia, 2.2 (0.7-7.5); moderate dysplasia, 15.8 (5.9-42.2); severe dysplasia, 72.6 (29.8-176.9); dysplasia not otherwise specified, 22.9 (6.7-78.0); and carcinoma in situ, 62.5 (24.1-161.9).In this study, moderate dysplasia, severe dysplasia, and carcinoma in situ were the only histologic lesions associated with a significantly increased risk of developing squamous cell carcinoma of the esophagus within 3.5 years after endoscopy. Increasing grades of dysplasia were associated with increasing risk, but severe dysplasia were associated with increasing risk, but severe dysplasia and carcinoma in situ had similar degrees of risk, findings that suggest a continuous spectrum of esophageal intraepithelial neoplasia, without morphologically distinguishable dysplasia and in situ carcinoma. A longer follow-up will be necessary to fully evaluate the less severe diagnostic categories, which may take more than 3.5 years to affect the occurrence of squamous cell carcinoma in this high risk population.

Linxian, China, has one of the highest rates of esophageal cancer in the world. Other authors have described high prevalences of histologic esophagitis, atrophy, and dysplasia in Linxian and have suggested that these findings may represent precancerous lesions in this population. In 1987, a new endoscopic survey allowed the authors to make an independent study of esophageal histology in Linxian.There were 1567 satisfactory squamous esophageal biopsies available from 754 patients. These biopsies were classified as normal, atrophy, acanthosis, esophagitis, squamous dysplasia, or squamous cancer.Classified by their worst diagnosis, 56.5% of the 754 patients had normal mucosa, 0.0% atrophy, 11.5% acanthosis, 4.6% esophagitis, 22.7% squamous dysplasia, and 4.6% squamous cancer.The results show a different distribution of esophageal squamous diagnoses than has been reported previously from this population. The authors believe that the major reason for this discrepancy was differences in histologic criteria. In this survey, seemingly small differences in criteria could cause large differences in apparent disease prevalence; this was especially true for esophagitis. By the criteria used in this study, histologic esophagitis and atrophy are uncommon findings in Linxian, raising questions about their significance as precursor lesions of esophageal cancer in this population.