The prognostic value of tumor budding in patients who had surgery for rectal cancer with and without neoadjuvant therapy.

BACKGROUND: The aim of this study was to investigate the prognostic value of tumor budding (TB) in rectal cancer patients. TB in the specimens of patients who received neoadjuvant chemoradiotherapy was specifically analyzed. METHODS: This study was conducted on rectal cancer patients treated at Dokuz Eylul University Hospital, Turkey, between January 2000 and June 2010. Prospectively recorded clinicopathological data and the oncological outcomes of patients who received neoadjuvant chemoradiotherapy (CRT) (n = 117) and also patients who did not receive it (n = 113) were analyzed. TB was defined as an isolated single cancer cell or a cluster of cells composed of less than 5 cells of a "budding focus". Budding intensity was scored as follows: none (0), mild (1-5 buds), moderate (6-10 buds), and severe (> 10 buds). Two tumor budding intesity groups were created, TB-1 (none, few) and TB-2 (moderate, severe) for statistical analysis. RESULTS: The median follow-up time was 40.12 ± 27.5 months. The 5-year overall and disease-free survival (DFS) rates were 66% and 62%, respectively. Multivariate analysis of overall survival in all patients showed that TB intensity (HR 2.64; 95% CI 1.46-4.77) and radial margin status (HR 2.16; 95% CI 1.18-3.96) were independent predictors of decreased overall survival. In patients who received CRT, TB (HR 4.87; 95% CI 2.10-11.28) and distant metastasis (HR 4.31; 95% CI 1.81-10.22) were predictive of survival while in patients who did not receive CRT, TB (HR 4.28; 95% CI 1.60-11.49), distant metastasis (HR 2.33; 95% CI 1.19-4.60), radial margin status (HR 2.53; 95% CI 1.09-5.91), and venous invasion (HR 4.48; 95% CI 2.14-9.39) were significantly independent predictors of survival. In multivariate analysis of all patients decreased DFS was correlated with lymph node involvement (HR 2.78; 95% CI 1.60-4.87), venous invasion (HR 1.76; 95% CI 1.00-3.09), and with radial margin status (HR 2.31; 95% CI 1.27-4.22). In multivariate analysis in the CRT group, decreased DFS was significantly associated with lymph node involvement (HR 4.39; 95% CI 1.70-11.33) and radial margin status (HR 2.56; 95% CI 1.12-5.90) while only lymph node involvement (HR 2.33; 95% CI 1.16-4.66) was a significant predictor of decreased DFS in patients who did not receive CRT. CONCLUSIONS: TB has prognostic value as important as lymph node involvement and radial margin status and it may be a helpful prognostic indicator even after CRT. TB should be included in the TNM classification and may be used in planning adjuvant therapy.

Submandibular gland invasion and feasibility of gland-sparing neck dissection in oral cavity carcinoma.

OBJECTIVE: This study investigated the incidence and routes of submandibular gland involvement in oral cavity carcinoma to determine the feasibility of submandibular gland sparing neck dissection. METHODS: The records of 155 patients diagnosed with oral cavity squamous cell carcinoma, with a total of 183 neck specimens, including those involving level I, were reviewed retrospectively. RESULTS: Submandibular gland involvement, via direct invasion from the anatomical proximity of T4a tumours, was evident in two patients. The floor of mouth location, either primarily or as an extension of the primary tumour, was the only risk factor for submandibular gland involvement in oral cavity carcinoma (p = 0.042). Tumour location, clinical and pathological tumour (T) and nodal (N) stages, and radiological suspicion of mandible invasion, were not found to be statistically relevant (p > 0.05). CONCLUSION: The results suggest the feasibility of preserving the submandibular gland in early stage oral cavity carcinoma unless the tumour is located in, or extends to, the floor of mouth.

The prognostic impact of the log odds of positive lymph nodes in colon cancer.

AIM: This study aimed to investigate the prognostic impact of the log odds of positive lymph nodes (LODDS) in colon cancer. METHOD: Four hundred and forty patients with colon cancer were divided into three each groups according to their lymph node ratio (LNR) and LODDS. Survival analysis was performed. RESULTS: The 5-year overall survival (OS) rate was 70.2%. In univariate analysis age, pT and pN stage, tumour grade, lymphatic, venous and perineural invasion, surgical margin clearance, LNR and LODDS were significantly associated with OS. In multivariate analysis age, surgical margins, perineural invasion and LODDS were found to be independent prognostic factors. In subgroup analysis of patients with an inadequate number of examined lymph nodes (NELN) (n = 76) and node-negative patients (n = 210), LODDS retained its prognostic value, whereas the impact of LNR was not statistically significant (P = 0.063). The overall survival rates of node-negative patients in the LODDS groups 0, 1 and 2 were 81%, 74.2% and 50%, respectively (P = 0.020). LNR and LODDS classifications were both significantly associated with survival in Stage III colon cancer, but only LODDS was an independent prognostic factor. CONCLUSION: Conventional TNM staging for nodes (pN) and LNR status cannot reliably classify node-negative patients into homogeneous groups. LODDS provides more valuable information than LNR independently of the NELN.

Patterns of cervical lymph node metastases in oral tongue squamous cell carcinoma: implications for elective and therapeutic neck dissection.

OBJECTIVES: To determine the patterns of lymph node metastases in oral tongue carcinomas, and examine the implications for elective and therapeutic neck dissection. METHOD: The study entailed a retrospective analysis of 67 patients with previously untreated oral tongue squamous cell carcinoma who had undergone simultaneous glossectomy and neck dissection. RESULTS: Of the 40 clinically node-negative patients, 7 patients had metastatic lymph nodes on pathological examination. No occult metastasis was found at level IV. Of the 27 clinically node-positive patients, the incidence rate of level IV metastasis was 11.1 per cent (3 out of 27 patients). No 'skip metastases' were found at level IV. Level IV metastases were significantly related to clinically staged nodes categorised as over 2a (p = 0.03) and metastasis to level III (p = 0.01). CONCLUSION: Routine inclusion of level IV in elective neck dissection is not necessary for clinically node-negative patients with oral tongue squamous cell carcinoma. Furthermore, extended supraomohyoid neck dissection with adjuvant radiotherapy can be sufficient in the treatment of selected patients with clinically node-positive necks.

Role of gelatinases (matrix metalloproteinases 2 and 9), vascular endothelial growth factor and endostatin on clinicopathological behaviour of rectal cancer.

AIM: The aim of this study was to evaluate the role of matrix metalloproteinases (MMPs), their tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] and activators [membrane-type MMPs (MT1-MMPs)], vascular endothelial growth factor (VEGF) and endostatin on clinicopathological variables and prognosis in patients with rectal cancer. METHOD: Paired samples of tumour tissue and normal tissue were obtained from patients with rectal cancer who underwent curative surgery (n = 34). Gelatin zymography for MMP-2 and MMP-9, an activity assay for MT1-MMP and enzyme-linked immunoassays for TIMP-2, VEGF and endostatin were performed using extracts from the paired tissue samples. RESULTS: Active MMP-9 showed statistically significant relationships with metastatic disease and perineural invasion (P = 0.002 and P = 0.042). A significant relationship was observed between the levels of tumoral pro-MMP-2 and pro-MMP-9 and the presence of lymph node metastasis (P = 0.012 and P = 0.021, respectively). Tumoral TIMP-2 levels showed a significant relationship with tumour recurrence (P = 0.011). A significant relationship was also observed between tumour VEGF levels and the presence of perineural invasion (P = 0.044), and VEGF levels were correlated with the size of the tumour (P = 0.009, r = 0.454). CONCLUSION: These results might contribute to further investigation of a possible prognostic significance in rectal cancer.

Prevalence of primary Sjogren's syndrome in Turkey: a population-based epidemiological study.

OBJECTIVES: The aim of this study was to determine the prevalence of primary Sjogren's syndrome (pSS) in a general Turkish population according to the latest proposed American-European Consensus Group (AECG) criteria and European-1 (EU-1) criteria. METHODS: The study was conducted in two districts of Izmir and involved 2835 subjects 20 years of age and older. In the first stage, face-to-face interviews were performed at the registered households. In the second stage, subjects reporting symptoms of both dry eye and dry mouth were invited to the hospital for a full examination, which included Schirmer-1, sialometry and serologic tests. In the third stage, a minor salivary gland biopsy was performed as required. RESULTS: A total of 2887 subjects were contacted and a complete interview was obtained for 2835 (1551 female, 1284 male) subjects. A total of 159 subjects (126 female, 33 male) confirmed oral and ocular dryness, and 86 of these patients (54.1%) underwent a detailed clinical examination in the hospital. pSS was diagnosed in 10 patients (nine females) according to the EU-1 criteria, and in six patients (six females) according to the AECG criteria. We found a minimum crude prevalence of 0.21% [95% confidence interval (CI): 0.03-0.29] in the sample population and an age-sex adjusted prevalence of 0.16% (95% CI: 0.06-0.35), according to AECG criteria. According to EU-1 criteria, these prevalence rates were found to be 0.35% (95% CI: 0.10-0.45) and 0.28% (95% CI: 0.13-0.51) respectively. CONCLUSION: The pSS prevalence rates found in the Turkish population in this study were lower than the estimated prevalence rate in a general population.

Hyperuricemia influences chronic cyclosporine nephropathy.

BACKGROUND: The observation that long-standing hyperuricemia is associated with chronic tubulointerstitial disease, afferent arteriolopathy, intrarenal vasoconstriction, and increased vascular resistance raises the hypothesis that hyperuricemia might contribute to chronic cyclosporine (CsA) nephropathy. The aim of the present study was to investigate the effect of hyperuricemia on chronic CsA nephropathy. METHODS: Patients who were treated with CsA-based immunsuppressive regimens and underwent a renal biopsy were enrolled in this case-control study. We retrospectively obtained posttransplant baseline serum creatinine, uric acid (UA), mean serum UA, and creatinine values 3 months prior to biopsy. CsA trough levels, mean blood pressure, diuretic and antihypertensive treatment were recorded. Biopsy specimens showing CsA nephropathy (n = 34) were revaluated by a pathologist to score CsA nephropathy according to recent quantitative criteria for calcineurin inhibitor arteriolopathy as proposed by M.J. Mihatsch. RESULTS: As compared with the non-CsA nephropathy group, recipient and donor ages, donor origin and cold ischemia times were similar for the CsA nephropathy group (P > .05). Mean CsA doses, CsA trough (C(0)), and C(2) levels were not different between the groups (P > .05). Systolic and diastolic blood pressure, glomerular filtration rate, diuretic usage, and antihypertensive treatment were also similar in CsA nephropathy and non-CsA nephropathy groups (P > .05). Mean serum UA level within 3 months prior to biopsy in the CsA nephropathy and non-CsA nephropathy groups were 7.5 +/- 1.4 mg/dL versus 5.7 +/- 1.4 mg/dL, respectively (P < .001). CONCLUSION: Hyperuricemia seems to exacerbate CsA-induced nephropathy.

Vascular endothelial growth factor expression and vascularity in renal allograft biopsies.

BACKGROUND: Vascular endothelial growth factor (VEGF) expression influences tubular repair and promotes angiogenesis. The aim of the present study was to determine the relation of VEGF expression and cortical vascularity with renal pathological changes and clinical parameters in allograft biopsies. MATERIALS AND METHODS: Sections from 50 renal allograft biopsies were evaluated by streptavidine-biotin immunohistochemistry by primary antibodies against VEGF and CD34. Cortical tubulointersititial (TI) VEGF expression was scored by light microscopic examination considering intensity and density. Glomerular expression was scored as 0: no staining; 1: faint staining in less than 50% of glomeruli; 2: moderate to strong staining in more than 50% of glomeruli. We determined the number of vessels per cortical high power field (Nves) highlighted by CD34 staining. The clinical and pathological features were retrieved from patient files. RESULTS: Nves was decreased with interstitial fibrosis (IF): 56.3 +/- 3.7; 53.3 +/- 9.8, 46.6 +/- 10.5, 36.75 +/- 1.89 for cases with no IF to mild, moderate, and severe forms, respectively (P << .000). There was increased TI VEGF expression: 1.86 +/- 2.12, 5.8 +/- 3.1, 5.85 +/- 4.4, 10.25 +/- 2.06, respectively (P = .004). The NVes values were not different for cases with high and low to negative VEGF expression scores. There was a negative correlation between Nves values and creatinine at the time of biopsy and time from transplantation to biopsy (r = -.325, P = .024 and r = -.294, P = .038, respectively). Nves and VEGF scores were not different when acute rejection scores or cyclosporine toxicity were considered (P > .05), while Nves were significantly different for chronic allograft nephropathy scores (P = .05). CONCLUSIONS: Chronic renal changes seemed to be associated with decreased cortical vascularity in renal allografts, while the TI VEGF expression was increased. In contrast Nves was not increased with VEGF expression in this series. It seems that along with VEGF, other factors are required for protection against vascular reduction. The aging of the allograft is also a negative influence on cortical vascularity.

Successful therapy with rituximab of refractory acute humoral renal transplant rejection: a case report.

Acute humoral rejection (AHR) is generally less responsive to conventional anti-rejection treatment with consequent allograft losses. Therapeutic options include antilymphocyte antibody (ATG), intravenous immunglobulin (IVIG), plasmapheresis, or immunoadsorption with protein A together with intensification of immunsuppression with a tacrolimus/mycophenolate mofetil combination. This report describes a transplant recipient who responded to rituximab therapy as treatment for steroid-, ATG-, IVIG-, and plasmapheresis-resistant AHR.

Quantitative digital histochemistry with methenamine silver staining in renal allograft biopsies excluding pure chronic allograft nephropathy cases.

Deterioration of renal function is correlated with irreversible damage in chronic diseases. Recently we described a digital quantitative histochemistry method, relying on periodic acid methenamine silver (PAMS) staining to determine the chronic renal lesions. This index was strongly correlated with progressive deterioration of renal function in grafts with chronic allograft nephropathy (CAN). Herein the method has been applied to a cohort of renal allografts which were biopsied for various reasons, we sought to highlight its value to quantify chronic graft damage. Forty-four renal allograft biopsies from 37 patients with elevated serum creatinine values (SCr) underwent light microscopic image analysis (Mediscope, Dokuz Eylül University, Clinical Engineering Department, Izmir, Turkey) of the PAMS-stained area percentage (SAP). SCr was recorded at four intervals to overcome acute effects: the under SCr value before (SCr1) and after a biopsy within 3 months (SCr3), SCr at the time of the biopsy (SCr2), and the latest value (SCr4). The PAMS-SAP scores were strongly associated with increased interstitial fibrosis and tubular atrophy Banff scores (Kruskal-Wallis test, P = .006 and P = .003, respectively). There was a moderate positive correlation between PAMS and SCr3 (Pearson correlation test, P = .04, r = .312), and a strong positive correlation between time from transplantation to biopsy (Pearson correlation test, P << .000, r = .532). The present results show that PAMS-SAP seems to be of value to quantify renal scarring in allograft biopsies, reflecting four compartments. The strong correlation with time is noteworthy especially as a probable reflection of aging of the renal allograft.

Renal medullary changes in renal allograft recipients with raised serum creatinine.

OBJECTIVE: To test the hypothesis that the renal medulla may reflect rejection related changes and thus have a predictive value in the assessment of acute renal allograft rejection or chronic graft damage. METHODS: 75 post-transplant biopsies from 57 patients were scored according to the Banff 1997 scheme. The biopsies with adequate cortical and medullary tissue (n = 23) were selected and medullary tissues were reviewed for rejection related lesions except intimal arteritis. Chronic damage was determined by image analysis depending on periodic acid-methenamine silver (PAMS)-Masson trichrome (MT) staining. Medullary and cortical changes were compared. RESULTS: Interstitial inflammation and tubulitis were more frequent and severe in the cortex (p<0.001). Medullary tubulitis was associated with intimal arteritis (p = 0.003, r = 0.598). Medullary interstitial inflammation (n = 8) and tubulitis (n = 4) were associated with cortical borderline changes (n = 5) or allograft rejection (n = 3). The sensitivity, specificity, and positive and negative predictive values of medullary inflammatory changes in predicting cortical allograft rejection were 43%, 69%, 37%, and 73%, respectively. A significant association was observed between medullary MT-SAP and cortical PAMS-SAP values (p = 0.02, R(2) = 0.23). CONCLUSIONS: Acute rejection related lesions are more common and severe in the cortex, and the renal medulla does not sufficiently reflect cortical rejection. The positive and negative predictive values of medullary changes for allograft rejection are low, and medullary inflammation is not a reliable indicator of allograft rejection. Increased medullary fibrosis is correlated with chronic cortical damage.

What is the risk of pyelonephritis due to desmopressin in rats with cystitis?

The risk of pyelonephritis in children with asymptomatic cystitis or bacteriuria, using desmopressin for primary nonpoliuric nocturnal enuresis, is not known. The aim of this study was to study whether there is a risk of pyelonephritis in rats with cystitis using desmopressin. Wistar rats (n = 28) were divided into four groups of cystitis (groups I-IV). DDAVP (2 microg daily) and saline (0.5 ml daily) were injected intramuscularly for 7 days in groups II and IV and groups I and III, respectively. The urinalysis, urine culture, and 24-h urinary volume (UV(24)) were assessed for all rats on days 1, 3, 5, and 7. In groups III and IV these studies were also performed on days 14, 21, and 28. Serum creatinine was determined on day 7 in all rats and on day 28 in groups III and IV. Groups I and II and groups III and IV were killed at the end of days 7 and 28, respectively. Kidneys and urinary bladders were graded subjectively for inflammation and fibrosis. Inflammation and fibrosis scores in kidney and bladder tissues were not different between DDAVP or saline-injected rats in cystitis groups at weeks 1 and 4. No fibrosis was found in any of the urinary bladders on histological examination. Ascendant pyelonephritis was detected in each of the four rats in DDAVP-administered and saline-administered cystitis groups. The histopathologic scores of the renal tissue with pyelonephritis showed no correlation with the daily urine volume, the positive test results for urine leukocyte esterase with dipstick test, the urine culture results for E. coli based on colony-forming unit per milliliter, or serum creatinine levels in cystitis groups. It was found that the administration of DDAVP to cystitis groups did not increase the risk of ascendant pyelonephritis.

Desmoplasia measured by computer assisted image analysis: an independent prognostic marker in colorectal carcinoma.

AIMS: The assessment of desmoplasia by traditional semiquantitative methods does not provide reliable prognostic data. The aim of this study was to quantify desmoplasia by computerised image analysis in primary colorectal carcinomas and to investigate its ability to predict overall survival. METHODS: In total, 112 colorectal adenocarcinomas, with a median follow up of 66 months, were studied. The representative tumour sections were stained by the van Gieson method, which stains collagen rich stroma red. For quantitative histochemical measurement, digital images were analysed by a computerised image analysis program to calculate the percentage of red stained tissue area. The percentage of desmoplasia (PD) was related to conventional clinicopathological prognostic factors and overall survival. RESULTS: The mean (SD) PD was 4.85 (3.37). PD was found to be significantly associated with lymph vessel and venous invasion. By Kaplan-Meier analysis, PD was associated with survival-patients with PD > 4 had a shorter survival than those with PD

Prognostic significance of EGF receptor expression in early glottic cancer.

OBJECTIVE: A positive relationship between epidermal growth factor receptor (EGFR) expression and radioresistance has been shown both in vitro and in vivo. In a group of 31 patients with early glottic cancer treated with definitive radiotherapy, the relationship of EGFR expression with patient and tumor related parameters were analyzed and the prognostic effect of EGFR expression on local control (LC) was assessed. MATERIAL AND METHOD: Between 1991 and 2001, 114 patients with early glottic (Tis-T2N0M0) squamous cell carcinoma were treated with radiotherapy at our institution. Among these, 31 patients whose pretreatment pathology specimens were available for immunohistochemical analysis formed the study population. Median age was 64 (46-77). Anterior commissure involvement was evident in 12 (38.7%) patients. Distribution according to T stage was as follows: Tis 6 (19.3%), T1 22 (71%), and T2 3 (9.7%). Histopathological grades of the 25 T1-2 tumors were 10/25 (40%) grade 1, 9/25 (36%) grade 2 and 6/25 (24%) grade 3. Our radiotherapy regimen was 66-70 Gy in 33-35 fractions over 6.5-7 weeks. The median follow-up period was 45 months (range, 5-116). Following immunohistochemical staining, quantitative immunohistochemistry (IHC) was performed by image analysis software and stained tumoral area percentage (STAP) was identified. The cut-off value was < or =5% versus >5%. The relationship of EGFR expression with patient (age) and tumor related (T stage, histopathological grade, and anterior commissure involvement) parameters was evaluated using chi-square test. Prognostic significance of EGFR expression, age, T stage, histopathological grade, and anterior commissure involvement on LC was assessed using log-rank test. RESULTS: No difference was found in EGFR content distribution in relation to age, T stage, histopathological grade, and anterior commissure involvement. In the univariate analysis including age (< or =60 versus >60), T stage (Tis and T1 versus T2), histopathological grade (grade 1 and 2 versus grade 3), anterior commissure involvement (present versus absent), and EGFR expression (high versus low), only T stage and EGFR expression were found to be significant prognostic factors affecting LC (P = 0.0006 and P = 0.03, respectively). CONCLUSION: The results of this series support that EGFR expression is an unfavorable prognostic factor in early glottic carcinomas. For this reason EGFR IHC may be considered for selecting patients for more aggressive therapies (radiotherapy with different fractionation schemes or surgery) or enrollment into trials targeting EGFR signaling pathways.

Sialometaplasia arising in the ectopic salivary gland ductal inclusions of multiple intraparotid lymph nodes.

Sialometaplasia, squamous metaplasia of salivary gland lobules, is a benign condition occasionally presenting with lesions clinically simulating malignancy. "Necrotising sialometaplasia", recognised by lobular infarction, necrosis, and simultaneous squamous metaplasia of ducts and acini is a well known condition. There are only a few reports of the "proliferative type of sialometaplasia", which is recognised by a more mature morphology of larger and more irregular metaplastic nests, lacking necrosis. This report describes a unique case of "proliferative sialometaplasia of multiple intraparotid lymph nodes" occurring in a 55 year old woman, presenting with multiple parotid lumps. This interesting case points to the importance of intraparotid lymph nodes as sites for multiple lesions of the parotid region.

Tubular CD44 expression in renal allograft biopsies.

CD44 is a type I transmembrane glycoprotein serving as a cell adhesion receptor, whose main ligand is hyaluronic acid, but also may interact with collagen, laminin, fibronectin, and osteopontin. This marker is involved in cell migration, homing, activation, metastasis, and inflammation. Tubular CD44 expression has been shown to correlate with scarring in renal diseases, but there is little data on allograft biopsies. This deficiency is important since experimental studies have shown that blockade of the CD44-hyaluronic acid interaction may prolong allograft survival. In an attempt to clarify the role of tubular CD44 expression in renal allografts, CD44 expression was determined immunohistochemically in 37 allograft and 10 implantation biopsies, as the percentage of tubules expressing this marker. For implantation biopsies the mean tubular CD44 expression was 6% +/- 14%; for allograft biopsies, 13% +/- 20% (P =.17, Mann-Whitney U). By the Spearman correlation test, CD44 expression did not correlate with Banff scores, but was moderately correlated with serum creatinine values at the time of biopsy (P =.017, r =.4). These findings suggest an important role of tubular CD44 expression in renal allografts. It appears to be induced by more than one pathway, resulting in a pattern of expression that correlated with renal function. However larger series are required before recommending the routine use of this marker.

Methenamine silver staining quantitative digital histochemistry in chronic allograft nephropathy.

Renal function and final outcome of renal allografts have been correlated with irreversible damage. This study describes a quantitative histochemical method relying on periodic acid methenamine silver (PAMS) staining of all renal compartments. Among 60 renal allograft biopsies from 43 patients, 15 biopsies showing pure chronic allograft nephropathy were selected to determine PAMS-stained area percentage (SAP), using image analysis with quantitative histochemistry. Of the 15 cases, 9 (60%) were grade I and 6 (40%) were grade II chronic allograft nephropathy (CAN). The mean serum creatinine (sCr) value was 1.86 +/- 0.47 for allograft biopsies. The mean (+/-SD) SAP for the implantation biopsies was 10.58 +/- 1.87%, and for allograft biopsies 25.26 +/- 9.67 (P <<.000). The serum creatinine (sCr) values for grade I versus II CAN were 1.63 +/- 0.24 versus 2.20 +/- 0.54 mg/dL, respectively (P=.019), and SAP values were 18.97 +/- 0.24 versus 34.7 +/- 5.89 (P=.003). There was a strong positive correlation between sCr values and SAP (P=.005; r=0.64). These findings show the PAMS approach to be a useful alternative method for reflecting damage in more than one compartment of the renal tissue. Also, the method can discriminated implantation and allograft biopsies as well as grade I and II CAN cases. The series is small for a multivariate analysis of the value of SAP measurements in PAMS-stained sections as a prognosticator, but the data support its use.