Diffusion-weighted imaging for predicting tumor consistency and extent of resection in patients with pituitary adenoma

This study aimed to investigate the role of diffusion-weighted imaging (DWI) in predicting tumor consistency, extent of surgical resection, and recurrence in pituitary adenoma (PA). We reviewed a prospectively collected database of surgically treated PA between March 2016 and October 2017. Predictors for extent of resection and recurrence/progression were assessed with logistic and Cox regression analysis. Of the 183 patients, the tumor consistency was found soft in 107 (58.5%) patients, intermediate in 41 (22.4%) patients, and hard in 35 (19.1%) patients. The mean of ADC ratio was 0.92 ± 0.22 for hard tumor, 1.03 ± 0.22 for intermediate tumor, and 1.41 ± 0.62 for soft tumor (P < 0.001). The mean collagen content was 25.86% ± 15.00% for hard tumor, 16.05% ± 9.90% for intermediate tumor, and 5.00% ± 6.00% for soft tumor (P < 0.001). Spearman analysis showed a significant correlation between ADC ratio and collagen content (ρ = ? 0.367; P < 0.001). Gross-total resection (GTR) was obtained in 68.3% of patients, and multivariable logistic regression analysis showed that ADC ratio (OR, 12.135; 95% CI, 4.001–36.804; P < 0.001), giant PA (OR, 0.233; 95% CI, 0.105–0.520; P < 0.001), and invasion (OR, 0.459; 95% CI, 0.220–0.960; P = 0.039) were significantly predictive of GTR. Twenty-seven (14.8%) patients suffered recurrence/progression in the mean follow-up of 35.14 months. Invasion (HR, 2.728; 95% CI, 1.262–5.899; P = 0.011) was identified as independent predictors of recurrence/progression. ADC ratio of DWI could be used for preoperative assessment of tumor consistency, tumor collagen content, and extent of surgical resection, which might be useful in preoperative planning for patients with PA.

     

Location of Rectal Cancer Within the Circumference of the Rectum Does Not Influence Lymph Node Status

Background Patients with rectal cancer are treated in multimodal concepts on the basis of their tumor stage. In the context of local excision, it is of major importance to assess the risk of lymph node metastases in patients with T1 or T2 tumors. To identify patients with an increased risk of lymph node metastases, the influence of the location of the tumor within the rectum (anterior, posterior, lateral) and of other variables on lymph node status was investigated. Methods All consecutive patients undergoing low anterior resection or abdominoperineal resection for primary rectal cancer between October 2001 and September 2003 were included. A multivariate analysis was performed focussing on tumor location and other variables as potential predictive factors for lymph node metastases. Results Of 148 included patients, 135 (91%) had an anterior and 13 (9%) an abdominoperineal resection. All patients routinely underwent total mesorectal excision. A statistically significant correlation with positive lymph node status was found for patients with lymphatic invasion (P < .0001), higher T stage (P < .0001), presence of distant metastases (M1) (P = .0003), and circular growth of the tumor (P = .003), but not for tumor location. Multivariate analysis confirmed that patients without lymphatic invasion (odds ratio, .1; 95% confidence interval, .02–.48; P = .006) and with a low T stage (odds ratio, .07; 95% confidence interval, .002–.9; P = .004) have a significantly lower risk for positive lymph nodes. Conclusions Location of rectal cancer (anterior, posterior, lateral) is not a good predictor for lymph node metastases.     

Cell Cycle Proteins Predict Recurrence in Stage II and III Colon Cancer

Purpose

To investigate the prognostic value of multiple cell cycle-associated proteins in a large series of stage II and III colon cancers.

Methods

From formalin-fixed, paraffin-embedded tumor samples of 386 patients with stage II and III colon cancer, DNA was isolated and tissue microarrays were constructed. Tissue microarray slides were immunohistochemically stained for p21, p27, p53, epidermal growth factor receptor, Her2/Neu, β-catenin, cyclin D1, Ki-67, thymidylate synthase, and Aurora kinase A (AURKA). Polymerase chain reaction–based microsatellite instability analysis was performed to allow for stratification of protein expression by microsatellite instability status.

Results

Overall, low p21, high p53, low cyclin D1, and high AURKA expression were significantly associated with recurrence (P = 0.01, P < 0.01, P = 0.04, and P < 0.01, respectively). In stage II patients who did not receive adjuvant chemotherapy (n = 190), significantly more recurrences were observed in case of low-p21 and high-p53-expressing tumors (P < 0.01 and P = 0.03, respectively). In stage III patients who did not receive chemotherapy, high p53 expression was associated with recurrence (P = 0.02), and in patients who received chemotherapy, high AURKA expression was associated with relapse (P < 0.01). In patients with microsatellite stable tumors, high levels of p53 and AURKA were associated with recurrence (P = 0.01 and P < 0.01, respectively). Multivariate analysis showed p21 (odds ratio 1.6, 95% confidence interval 0.9–2.8) and AURKA (odds ratio 2.7, 95% confidence interval 1.3–5.6) to be independently associated with disease recurrence.

Conclusions

p21, p53, cyclin D1, and AURKA could possibly be used as prognostic markers to identify colon cancer patients with high risk of disease recurrence.

     

Prognostic Factors Affecting Survival and Recurrence of Patients with pT1 and pT2 Colorectal Cancer

Background Data on the prognostic factors of survival and recurrence in patients with colorectal cancers confined to the bowel wall (T1 and T2) are limited. The aim of the present study was to determine factors that might predict the survival and recurrence of patients who had T1 and T2 colorectal cancers. Patients and Methods All patients with T1 or T2 colorectal cancers who underwent resection in the Department of Surgery, University of Hong Kong Medical Centre, from 1996 to 2004 were included. Analysis was made from the prospectively collected database. Predictive factors for lymph node metastasis and prognostic factors were analyzed. Results A total of 265 patients (144 men) with the median age of 71 years (range: 33–93 years) were included. Seventy-two patients had T1 cancers (rectal cancer n = 44; colon cancer n = 28; p = 0.89) and 193 patients suffered from T2 cancer (rectal n = 120; colon cancer n = 73). The overall incidence of lymph node metastasis was 12.7% (5.6% for T1 cancer and 14.5% for T2 cancer; p = 0.021). The presence of lymphovascular permeation was the only independent factor associated with a higher incidence of lymph node metastasis on multivariate analysis (odds ratio: 1.48, 95% CI: 1.44–13.47, p = 0.009). There were no significant differences in disease-free 5-year survival (T1 = 84.6%; T2 = 81.1%) and 5-year cancer-specific survival in patients with T1 and T2 tumors (T1 = 90.2%; T2 = 90.6%). Patients with lymph node metastasis had a significantly shorter disease-free 5-year survival (p < 0.001) and 5-year cancer-specific survival (p = 0.002) when compared with those having a negative lymph node status. Cox proportional hazards model analysis showed that lymph node status was the only significant independent factor predicting cancer-specific survival (hazard ratio: 3.52, 95% CI: 1.60–7.71, p = 0.002) and disease-free survival (hazard ratio: 3.42, 95% CI: 1.75–6.69, p < 0.001). Conclusions Presence of lymphovascular permeation would have a significant higher chance of lymph node metastasis. Positive lymph node status was predictive of poorer survival in patients with T1 or T2 colorectal cancers. For those cancers with positive lymphovascular permeation, radical surgery is recommended.     

Recommendation for Subclass Evaluation of TNM stage IVA Papillary Thyroid Carcinomas: T4aN1b Patients Are at Risk for Recurrence and Survival

Background Although all tumor, node, metastasis system (TNM) stage IVA papillary thyroid carcinomas (PTCs) do not seem to behave equivalently as a result of various tumor and node stages, to our knowledge, subclass evaluation has never been attempted. Methods We reviewed 119 stage IVA PTC patients who underwent initial thyroidectomy with modified neck dissection as curative surgery at our institution (33 male patients, 86 female patients; age 61.6 years; follow-up 87.7 months). These patients were divided into groups A (T1–3N1b; n = 79), B (T4aN0–1a; n = 9), and C (T4aN1b; n = 31). Outcomes were compared between the groups. Results The rates of recurrence (P < .05) and disease mortality (P < .001) were 13.9% and 1.3%, 0% and 0%, and 35.5% and 19.4% in groups A, B, and C, respectively. The 10-year disease-free survival (DFS) and disease-specific survival (DSS) were 73.4% and 97.9%, 100% and 100%, and 54.9% and 69.7% in groups A, B, and C, respectively. DFS and DSS curves differed significantly between group A + B and group C (P < .005 and P < .0005, respectively). The relative risks of DFS and DSS in group C were 2.8-fold and 14.9-fold, respectively, compared with group A (P < .05), and 3.2-fold and 17.5-fold compared with group A + B (P < .01). Thus, outcomes were worse in group C. In multivariate analysis, esophageal invasion and lymphadenopathy were independent risk factors for both DFS and DSS in stage IVA PTC patients. Conclusions Outcomes in stage IVA are not equivalent, and patients with T4aN1b are at greater risk for worse prognosis. Therefore, we recommend subclass evaluation for TNM stage IVA PTCs.     

Ki-67 is an independent indicator in non–muscle invasive bladder cancer (NMIBC); Combination of EORTC risk scores and Ki-67 expression could improve the risk stratification of NMIBC

ObjectiveTo prove the predicting role of Ki-67 expression and to demonstrate that the combination of European Organization for Research and Treatment of Cancer (EORTC) risk scores and Ki-67 staining status could improve the risk stratification in a large series of patients with non–muscle invasive bladder cancer (NMIBC).Material and methodsFrom October 2002 to July 2010, in our cohort, 332 patients who were treated with transurethral resection of the bladder tumor were diagnosed with NMIBC by histopathologic analysis. Two experienced uropathologists rereviewed the slides. The EORTC risk scores for recurrence and progression were determined. Ki-67 expression was evaluated using immunohistochemical studies and scored for intensity and area of staining. We correlated Ki-67 expression scores with clinical and pathologic variables. We evaluated the prognosis role of EORTC risk scores, Ki-67 staining, and their combination on tumor recurrence-free survival and progression-free survival (PFS) by univariate analysis, multivariate analysis, and Kaplan-Meier survival curves.ResultsWith a median follow-up of 47 (range, 2–124) months, 119 patients (35.8%) had tumor recurrence and 40 patients (12%) had tumor progression. Ki-67 positivity (Ki-67>25%) was reported in 108 tumors (32.5%), and it was significantly associated with high EORTC risk scores for both tumor recurrence and progression. In univariate analysis, multifocality, tumor size, tumor stage, tumor grade, and Ki-67 staining correlated with recurrence-free survival, whereas tumor size, tumor stage, tumor grade, concomitant CIS, and Ki-67 staining correlated with PFS. In multivariable analysis, Ki-67 expression was an independent risk factor for predicting tumor recurrence (hazard ratio, 2.14; P<0.0001) and progression (hazard ratio: 2.97, P = 0.004). Kaplan-Meier curves showed that combining EORTC risk scores and Ki-67 staining led to more accurate prediction for tumor recurrence and progression (log-rank test; P<0.0001).ConclusionsKi-67 positivity is prognostic for predicting tumor recurrence and progression. Combination of EORTC risk scores with Ki-67 expression could improve the risk stratification for both recurrence and progression in NMIBC.     

The Impact of Postoperative Complications on Long-Term Outcomes Following Curative Resection for Colorectal Cancer

Background This study aimed to investigate the impact of postoperative complications on long-term survival and disease recurrence in patients who underwent curative resection for colorectal cancer. Method Patients who underwent radical resection for colorectal cancer with curative intent from January 1996 to December 2004 were included. Operative mortality and morbidity were documented prospectively. Factors that might affect long-term outcome were analyzed with multivariate analysis. Results Curative resection was performed in 1657 patients (943 men), and the median age was 70 years (range: 24–94 years). The 30-day mortality was 2.4%, and the complication rate was 27.3%. Age over 70 years (P < .001, odds ratio: 2.06, 95% CI: 1.63–2.61), male gender (P = .001, odds ratio: 1.49, 95% CI: 1.19–1.88), emergency operation (P < .001, odds ratio: 3.14, 95% CI: 2.26–4.35) and rectal cancer (P < .001, odds ratio: 1.41, 95% CI: 1.25–1.61) were associated with a significantly higher complication rate. With exclusion of patients who died within 30 days, the median follow-up of the surviving patients was 45.3 months. The 5-year overall survival was 64.9%, and the overall recurrence rate was 29.1%. The presence of postoperative complications was an independent factor associated with a worse overall survival (P = .023, hazard ratio: 1.26; 95% CI: 1.03–1.52) and a higher overall recurrence rate (P = .04, hazard ratio: 1.26; 95% CI: 1.01–1.57). Conclusion The presence of postoperative complication not only affects the short-term results of resection of colorectal cancer, but the long-term oncologic outcomes are also adversely affected. Long-term outcomes can be improved with efforts to reduce postoperative complications.     

h-prune Is an Independent Prognostic Marker for Survival in Esophageal Squamous Cell Carcinoma

Background  The human homologue of Drosophila prune (PRUNE, which encodes h-prune) protein interacts with glycogen synthase kinase 3 and promotes cell motility. The aim of our study was to investigate the impact of immunohistochemically detected h-prune expression on the survival of patients with esophageal squamous cell carcinoma (ESCC). Methods  Immunohistochemical staining of h-prune was performed for 205 surgically resected specimens of ESCC. Results  In total, 43 (21%) of 205 ESCC cases were positive for h-prune. h-prune-positive ESCC cases showed a more-advanced T stage (P < 0.0001), N stage (P < 0.0001), and tumor stage (P < 0.0001) than h-prune-negative ESCC cases. In the group of 116 stage II and III ESCC cases, recurrence of ESCC was frequently found in h-prune-positive cases. In patients with lung recurrence, the tumors were more likely to be h-prune positive than h-prune negative. Univariate analysis revealed that T stage (P < 0.0001), N stage (P < 0.0001), tumor stage (P < 0.0001), and h-prune staining (P < 0.0001) were significant prognostic factors for survival. Multivariate analysis indicated that N stage (P = 0.0182) and h-prune staining (P < 0.0001) were independent predictors for survival. Conclusions  These results indicate that immunostaining of h-prune is useful to identify patients at high risk for recurrence or poor prognosis associated with ESCC.     

Type 2 diabetes mellitus predicts worse outcomes in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor

ObjectivesThe aim of this multicenter study was to investigate the prognostic role of type 2 diabetes mellitus (T2DM) comorbidity in a large multi-institutional cohort of patients with primary T1HG/G3 non–muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB).Materials and methodsA total of 1,172 patients with primary T1 HG/G3 who had NMIBC on re-TURB and who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance were included. Endpoints were recurrence-free survival and progression-free survival.ResultsA total of 231 (19.7%) of patients had T2DM prior to TURB. Five-year recurrence-free survival estimates were 12.5% in patients with T2DM compared to 36% in patients without T2DM, P < 0.0001. Five-year PFS estimates were 60.5% in patients with T2DM compared to 70.2% in patients without T2DM, P = 0.003. T2DM was independently associated with disease recurrence (hazard ratio = 1.41; 95% confidence interval = 1.20–1.66, P < 0.001) and progression (hazard ratio = 1.27; 95% confidence interval = 0.99–1.63, P < 0.001), after adjusting for other known predictive factors such as tumor size, multifocality, T1G3 on re-TURB, body mass index, lymphovascular invasion, and neutrophil-to-lymphocytes ratio.ConclusionsGiven the potential implications for management, prospective validation of this finding along with translational studies designed to investigate the underlying biology of such an association are warranted.     

Recurrence of hepatocellular carcinoma after liver transplantation

Outcome after liver transplantation (OLT) clearly depends on recurrence of hepatocellular carcinoma (HCC). After recurrence, patient outcome will depend on the time and site of appearance. The aim of this study was to analyze the therapeutic implications of tumor recurrence behavior. From October 1988 to December 2005, 685 patients received OLT, including 202 due to HCC (32%). We analyzed 28 recurrences (15.2%) among 184 patients who survived at least 3 months (minimum follow-up 1 year). According to the time of recurrence, we divided the patients into early recurrence (ER < 12 months; n = 9; 32.1%) and late recurrence (LR > 12 months n = 19; 67.9%). Actuarial survivals at 1, 5, and 10 years were 82%, 65%, and 50% and disease-free survival, 80%, 58%, and 46%, respectively. Risk factors for recurrence were: vascular invasion (P < .01), bad differentiation (P < .01), and previous hepatectomy (P < .05). After OLT, ER presented at: 5.7 ± 2.3 months (range 3-10) vs 33.5 ± 24.3 months (range 12-103) for LR P < .001). Survival postrecurrence (SPR) was shorter: 3.1 ± 2.4 (range 1-8) months vs 16.4 ± 14.2 (range 1-5) months (P < .001). Treatment was offered to one ER (11%) and to eight LR (47.1%; P < .05), achieving in these cases longer SPR: 20.1 ± 14 vs 6.9 ± 9 months (P < .05).The most common sites of recurrence were liver (n = 7), lung (n = 7), bone (n = 5), adrenal gland (n = 2), peritoneum (n = 2), lymph node (n = 2), skin (n = 2) or cerebral (n = 1). Early recurrences showed short survivals; no treatment could be offered to these patients. Liver recurrence appeared early. In contrast, most lung recurrences appeared later with the possibility of treatment and longer SPR. Bone recurrence appeared later, usually associated with other locations. Treatment was paliative and prognosis was worse. Skin and lymph node recurrences can be treated curatively with prolonged survival. In conclusion, HCC recurrence was difficult to treat curatively and was only prevented by employing restricted criteria.     

An Analysis of Resection vs Transplantation for Early Hepatocellular Carcinoma: Defining the Optimal Therapy at a Single Institution

Background The reported survival after liver transplantation (OLT) for early hepatocellular carcinoma (HCC) is superior to the results of liver resection (LR), but few analyses have considered long waiting times and patient drop-offs due to tumor progression. Methods From 1995–2005, 347 patients with HCC were evaluated at our institution and underwent either LR (n = 174) or placed on the OLT waiting list (n = 173). Patients who only underwent ablation were not included. After eliminating patients with 1) incidental tumors after OLT, 2) tumors outside of Milan criteria, 3) preoperative vascular invasion prior to LR and 4) Child-Pugh Class C cirrhosis prior to OLT, 261 patients (LR = 121; OLT = 140) were included in this analysis. Results Median follow-up time was 35 months. Median waiting time for OLT was 7.7 months; during this time, 30 patients were taken off the waiting list. Overall survival (OS) from time of listing or LR was not different between the two groups; 1, 3, and 5 year OS after LR was 89%, 75%, and 56% compared with 90%, 70%, and 64% for OLT (P = .84). Only patients who waited <4 months for OLT (n = 67) had better survival than those who underwent LR (P = .05). Patients who waited longer that four months for OLT had a 2.5× higher risk of death in a Cox multivariate model [odds ratio (OR) 2.5; 95% confidence interval (CI): 1.3–5; P = .007]. Conclusion Unless waiting time is short (<4 months), the survival of patients with early HCC is similar between LR and LT. Presented at the 2006 Seventh International Hepato-Pancreato-Biliary Association, Edinburgh, Scotland, September 3–7, 2006.     

Loss of p27<Superscript>(Kip1) </Superscript>CDKI is a predictor of poor recurrence-free and cancer-specific survival in patients with renal cancer

The importance of cyclin-dependent kinase inhibitors (CDKI) in benign and malignant urological diseases is a subject of intense ongoing investigation. The goal of the current study was to analyze the expression of p27^(Kip1) CDKI in benign and malignant renal cells and assess their possible association with different clinical parameters. Expression of p27^(Kip1) was evaluated and compared in 24 normal human kidneys and in 52 renal cell carcinoma (RCC) tissue samples. Intensity of the expression was compared between the groups and association was analyzed with cancer clinical parameters. The expression of the marker was significantly higher in normal than in RCC samples (P = 0.0045). Intensity of p27^(Kip1) expression in RCC was negatively correlated with tumor size (Rho = −0.438, P = 0.0051) and associated with pathological stage and grade (P = 0.0488 and < 0.0001, respectively). The patients with symptomatic disease had significantly less marker expression than incidentally discovered tumors (P = 0.0301). Loss of p27^(Kip1) expression, pathological stage, grade and tumor size were the risk-factors for disease recurrence (P = 0.0072, 0.0011, 0.0467 and < 0.0001, respectively) and patient survival (P = 0.0021, 0.0106, 0.0151 and 0.0021, respectively). With Cox multivariate analysis loss of p27^(Kip1) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. Expression of p27^(Kip1) is significantly decreased in RCC as compared with normal kidney tissue. Intensity of the expression is associated with clinical parameters: tumor size, stage, grade and disease presentation. Loss of p27^(Kip1) expression is a risk-factor for disease recurrence and the strongest predictor of cancer-specific survival.     

Clinical impact of lymphadenectomy extent in resectable gastric cancer of advanced stage

Background Advanced, but potentially still curable gastric cancer (stages IIIA, IIIB, or stage IV M0) is associated with very high recurrence rates after gastrectomy. The value of an extended lymph node dissection (ELND) remains unclear in this setting. Methods A resected gastric cancer data set was created through structured queries to the SEER 1973–2000 database. Relationships between the number of lymph nodes (LNs) examined and survival outcomes were analyzed for the stage subgroups characterized by the N categories N2 or N3, and transmural tumor extension (T categories T2b or T3). Results The study group encompassed 1,377 patients, including T2b/3N2 (n = 1,076) and T2b/3N3 stage subgroups (n = 301). Total LN count (or number of negative LNs examined; P < 0.0001), number of positive LNs (P < 0.0001), age (P < 0.0001), primary site (P = 0.0002), T category (P = 0.0271), race (P = 0.0301) and gender (P = 0.0261) were independent prognostic survival predictors. A cut point analysis yielded the ability to detect significant survival differences for LN numbers up to 30 (N2) or up to 40 (N3), always in favor of the higher number of LNs examined. Best long-term survival outcomes were observed with negative LN counts of more than 15 (N2) or more than 20 (N3). Conclusions Even in transmural or serosa-positive gastric cancer with advanced nodal involvement, more extensive LN dissection and analysis influences survival. Stage-based survival prediction depends on total LN number and number of negative LNs. The mechanism remains uncertain, but is not limited to stage migration. ELND during potentially curative gastrectomy is recommended even for advanced gastric cancer.     

Prognosis of Perihilar Cholangiocarcinoma: Hilar Bile Duct Cancer versus Intrahepatic Cholangiocarcinoma Involving the Hepatic Hilus

Background Clinically hepatobiliary resection is indicated for both hilar bile duct cancer (BDC) and intrahepatic cholangiocarcinoma involving the hepatic hilus (CCC). The aim of this study was to compare the long-term outcome of BDC and CCC. Methods Between 1990 and 2004, we surgically treated 158 consecutive patients with perihilar cholangiocarcinoma. The clinicopathological data on all of the patients were analyzed retrospectively. Results The overall 3-year survival rate, 5-year survival rate, and median survival time for BDC patients were 48.4%, 38.4 %, and 33.7 months, respectively, and 35.8%, 24.5 %, and 22.7 months, respectively, in CCC patients (P = .033). On multivariate analysis, three independent factors were related to longer survival in BDC patients: achieved in curative resection with cancer free margin (R0) (P = .024, odds ratio 1.862), well differentiated or papillary adenocarcinoma (P = .011, odds ratio 2.135), and absence of lymph node metastasis (P < .001, odds ratio 3.314). Five factors were related to longer survival in CCC patients: absence of intrahepatic daughter nodules (P < .001, odds ratio 2.318), CEA level ≤2.9 ng/mL (P = .005, odds ratio 2.606), no red blood cell transfusion requirement (P = .016, odds ratio 2.614), absence or slight degree of lymphatic system invasion (P < .001, odds ratio 4.577), and negative margin of the proximal bile duct (P = .003, odds ratio 7.398). Conclusions BDC and CCC appear to have different prognoses after hepatobiliary resection. Therefore, differentiating between these two categories must impact the prediction of postoperative survival in patients with perihilar cholangiocarcinoma. T. Sano is currently with: Hepato-Biliary and Pancreatic Surgery Division, Aichi Cancer Center Hospital, Nagoya, Japan.     

Laparoscopic Adrenalectomy for Isolated Adrenal Metastasis

Background Use of laparoscopy for isolated adrenal metastases is controversial. The aims of this study were to characterize patients with isolated adrenal metastases; compare operative characteristics of the laparoscopic adrenalectomy (LA) versus open adrenalectomy (OA) approach; and compare long-term oncological and surgical outcomes. Methods Our adrenal resection database (1995–2006) identified 63 OA and 31 LA cases done for isolated adrenal metastases. Subset analysis was performed for all patients from isolated lung metastases (n = 39) and for all tumors smaller than 4.5 cm (n = 49). Results Overall, local recurrence was 17%, median survival 30 months and 5-year estimated survival 31%. The only independent predictor of survival for all (n = 94) was adrenal tumor size less than 4.5 cm (P = 0.01). When comparing LA with OA, no differences in local recurrence, margin status, disease-free interval or overall survival were observed for the entire group, or for patients with metastases only from lung cancer (n = 39) or for those with tumors smaller than 4.5 cm (n = 49). LA provided significantly shorter operative time (175 vs 208 min, P = 0.04), lower estimated blood loss (EBL) (106 vs 749 cc, P < 0.0001), shorter length of hospital stay (2.8 vs 8.0 days, P < 0.0001) and fewer total complications (P < 0.0001). Conclusions LA is equivalent to OA in terms of margin status, local recurrence, disease-free interval and overall survival. LA for metastatic adrenal lesions is safe, with equivalent long-term oncological outcomes providing the additional benefits of a minimally invasive technique. LA can be recommended as an appropriate initial approach for isolated adrenal metastases.     

Management of malignant T1 colorectal cancer polyps: results from a 10-year prospective observational study

Aim

The recurrence risk associated with residual malignant cells (bowel wall/regional nodes) following T1 colorectal cancer (CRC) polypectomy must be weighed against operative morbidity. Our aim was to describe the management and outcomes of a large prospective cohort of T1 CRCs.

Method

All T1 CRCs diagnosed between March 2007 and March 2017 at the Glasgow Royal Infirmary were included. Patients were grouped by polypectomy, rectal local excision and formal resection status. χ² testing, multivariate binary logistic and Cox regression were performed.

Results

Of 236 patients, 90 (38.1%) underwent polypectomy only, six (2.6%) polypectomy and then rectal excision, 57 (24.2%) polypectomy and then resection, 14 (5.9%) rectal excision only and 69 (29.2%) primary resection. Polypectomy only correlated with male sex (P = 0.028), older age (P < 0.001), distal CRCs (P < 0.001) and pedunculated polyps (P < 0.001); primary resection with larger polyps (P < 0.001); polypectomy then resection with piecemeal excision (P = 0.002) and involved polypectomy margin (P < 0.001). Poor differentiation (OR 7.860, 95% CI 1.117–55.328; P = 0.038) independently predicted lymph node involvement. Submucosal venous invasion (hazard ratio [HR] 10.154, 95% CI 2.087–49.396; P = 0.004) and mucinous subtype (HR 7.779, 95% CI 1.566–38.625; P = 0.012) independently predicted recurrence. Submucosal venous invasion (HR 5.792, 95% CI 1.056–31.754; P = 0.043) predicted CRC-specific survival. Although 64.4% of polypectomy-only patients had margin involvement/other risk factors, none developed recurrence. Of 94 with polypectomy margin involvement, five (5.3%) had confirmed residual tumour. Overall, lymph node metastases (7.1%), recurrence (4.2%) and cancer-specific mortality (3.0%) were rare. Cancer-specific 5-year survival was high: polypectomy only (100%), polypectomy and then resection (98.2%), primary resection (100%).

Conclusion

Surveillance may be safe for more T1 CRC polyp patients. Multidisciplinary team discussion and informed patient choice are critical.     

Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression

Objectives. To evaluate microstaging by means of quantifying the depth of invasion of the subepithelial connective tissue in pT1 transitional cell carcinoma (TCC) of the bladder for its additional prognostic value with respect to disease recurrence and progression.Methods. We reviewed the pathologic findings of a consecutive series of 124 patients with pT1 tumors entered in a prospective randomized multicenter trial comparing mitomycin C and bacillus Calmette-Guérin treatment, with at least 3 years of follow-up and clinical outcome hidden from reviewers. The depth of invasion was established by identifying submucosal tumor invasion up to, in, or beyond the muscularis mucosae or vascular plexus and classified as pT1a, pT1b, or pT1c, respectively. In addition to tumor grade, the presence of carcinoma in situ (CIS) near the primary tumor or in biopsy specimens taken from abnormal looking mucosa was taken into account. The risks of recurrence and progression were calculated using Kaplan-Meier curves and modeled with proportional hazard models.Results. pT1 subclassification was possible in more than 90% of the specimens. The 3-year risk of recurrence was not different in any of the subgroups. By contrast, the Kaplan-Meier 3-year risk for progression was 6%, 33%, and 55% for pT1a, pT1b (hazard ratio [HR] 5.51), and pT1c (HR 12.35) tumors, respectively (log-rank test P < 0.001). The Kaplan-Meier 3-year risk of progression was 9% versus 39% (HR 5.62) for the absence or presence of CIS in the tumor (P = 0.001) and 8% versus 49% (HR 6.72) for CIS in biopsy specimens (P < 0.001). Tumor grade had no statistically significant prognostic value with respect to progression, nor had tumor volume or multifocality. The combination of the parameters (pT1c and CIS) increased the risk of progression by a factor of 27 (P < 0.0001) compared with the absence of pT1c and CIS.Conclusions. These data show that the extent of lamina propria invasion (pT1a, pT1b, pT1c) is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder. With the combination of this pT1 subclassification and the presence of CIS subgroups, distinct risks of progression can be identified that may give additional information for follow-up and treatment policies.     

Evaluation of p21WAF1/CIP1 and cyclin D1 expression in the progression of superficial bladder cancer

Immunoreactivity of p21^WAF1/CIP1 and cyclin D₁ proteins was assessed in a cohort of 207 patients with superficial (pTa-pT₁) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21^WAF1/CIP1 positive (≥5% of cells positive) and cyclin D₁ positive (≥10% of cells positive), respectively. The p21^WAF1/CIP1 expression was related to cyclin D₁ immunolabelling (P < 0.001) but not to the other variables studied. The expression of cyclin D₁ was inversely associated with T category (P=0.001), WHO grade (P=0.006), MIB-1 score (P=0.014), p53 expression (P=0.001), and bcl-2 (P=0.011) immunoreactivity. In univariate analysis, T category (P=0.0001), WHO grade (P < 0.0001), MIB-1 score (P < 0.0001), bcl-2 (P=0.0092), p53 (P=0.0016) and p21^WAF1/CIP1 (P=0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D₁ was without any prognostic significance (P=0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P=0.03), whereas tumor grade (P=0.002) and cyclin D₁ expression (P=0.04) were independent predictors of tumor recurrence. Only the WHO grade (P=0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21^WAF1/CIP1 and cyclin D₁ immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease. Received: 13 September 1999 / 22 March 2000     

p53 expression in patients with advanced urothelial cancer of the urinary bladder

Study Type – Prognosis (inception cohort)
Level of Evidence 1b

OBJECTIVE

To test whether assessing p53 expression could improve the ability to predict disease recurrence and disease‐specific survival in a multi‐institutional cohort of patients with advanced urothelial carcinoma of the urinary bladder (UCB).

PATIENTS AND METHODS

The study comprised 692 patients with pT3–4 N0 or pTany N+ UCB treated with radical cystectomy and lymphadenectomy. The predictive accuracy (PA) was quantified using the 200 bootstrap‐corrected concordance index. The base model comprised age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of lymph nodes positive, concomitant carcinoma in situ, and adjuvant chemotherapy.

RESULTS

p53 expression was altered in 341 (49.3%) patients. In multivariable analyses, p53 expression was independently associated with disease recurrence (hazard ratio, 1.66; P < 0.001) and cancer‐specific mortality (hazard ratio 1.65, P < 0.001). Overall, adding p53 did not significantly improve the PA of the base model (recurrence +0.7%, P = 0.085, and cancer‐specific mortality +1.2%, P = 0.050). In the subgroups of pT3N0 (280) and pT4N0 (83) patients, p53 slightly improved the PA of the base model by a statistically significant degree (recurrence +1.7% and +3.6%, respectively; cancer‐specific mortality +1.9% and +3.5%, respectively; all P < 0.001). In 329 patients with pTany N+ disease p53 status did not improve the PA of the base model.

CONCLUSION

While assessing p53 expression has limited utility in patients with lymph node‐positive UCB, it marginally improves prognostication in patients with advanced non‐metastatic UCB. Integration of p53 into a panel of biomarkers might be necessary to capture a more accurate picture of the biological potential of advanced UCB.     

Subepithelial growth patterns in urothelial carcinoma—frequency and prognostic significance

PurposeMost urothelial carcinomas are exophytic, but some tumors exhibit subepithelial components, either in the form of endophytic growth pattern (EGP) or as von Brunn's nests involvement (VBNI). The purpose of this study was to investigate the frequency, inter-relations and clinical significance of these forms of subepithelial neoplasia in urothelial carcinoma.Patients and methodsBetween June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of bladder tumors in our institution, including 478, 157, and 112 patients with stage Ta, T1, and ≥T2 disease, respectively. Isolated or concomitant Tis were present in 137 (18%) patients. Median postoperative follow-up period was 53 months.ResultsEGP was found in 86 cases (11.3%) and VBNI in 30 (3.9%) patients. Both forms of subepithelial growth were significantly more common in higher stage and grade tumors and were associated with each other. Multivariate analysis showed that EGP is an independent prognostic factor of stage progression (HR 4.6, P < 0.0001) and disease specific mortality (HR 2.6, P = 0.001) but not of tumor recurrence (HR 1.2, P = 0.51). VBNI was found an independent prognostic factor of tumor progression (HR 5.1, P < 0.0001), but neither of tumor recurrence nor disease specific mortality.ConclusionsSubepithelial growth is not an uncommon in bladder cancer. It is more frequent in high-grade and high-stage tumors. The findings of this study suggest that subepithelial growth carries a higher risk for stage progression (EGP and VBNI) and mortality (EGP), but not tumor recurrence.