Multi-Institutional Analysis of Localized Renal Cell Carcinoma that Demonstrates the Impact of Diabetic Status on Prognosis After Nephrectomy

Background

The purpose of our study was to determine whether preoperative diabetes mellitus (DM) can predict the prognosis of localized clear-cell renal cell carcinoma (RCC).

Methods

At five institutes, 2,597 patients with pT1 and pT2 clear-cell RCC were enrolled. Univariate and multivariable analyses were performed to determine factors that associated with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). To identify the effect of DM on survival after recurrence, a subgroup of 127 patients who had recurrences was analyzed.

Results

In total, 357 patients had DM. Compared with patients without DM, these patients were older, more likely to be male, and had a higher body mass index, lower GFR, and higher incidence of hypertension. Kaplan–Meier curves showed that patients with DM had a significantly worse rate of RFS, CSS, and OS than patients without DM (log-rank test, all P < 0.05). Multivariate analysis revealed that DM was an independent prognostic factor in terms of RFS, CSS, and OS. In the subgroup analysis of 127 patients with recurrence, DM was associated with a lower survival rate after the initial recurrence.

Conclusions

DM appeared to be an important determinant of prognosis in clear-cell localized RCC, especially in patients experiencing recurrence.     

Clinical Nodal Stage is a Significant Predictor of Outcome in Patients with Oral Cavity Squamous Cell Carcinoma and Pathologically Negative Neck Metastases: Results of the International Consortium for Outcome Research

Background

We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN?).

Methods

A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990–2011) had pN? disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan–Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis.

Results

A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN?. The 5-year OS and DSS of cN? patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates.

Conclusions

Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN? nodes.     

The impact of immunohistochemical expression of nitric oxide synthases on clinical and pathological features of renal cell carcinoma

Purpose

To evaluate the immunohistochemical expression of nitric oxide synthase (NOS) types 1, 2, and 3 in intratumoral and non-neoplastic samples of renal cell carcinoma (RCC) and correlate it with the clinical and pathological features of this malignancy.

Methods

We analyzed 110 patients with RCC underwent radical nephrectomy (RN) or partial nephrectomy (PN) by streptavidin–biotin peroxidase method, tissue microarray, and digital microscopy. As endpoints, NOS expression was correlated with pathological features, overall survival (OS), and cancer-specific survival (CSS).

Results

Non-neoplastic samples had higher NOS3 and lower NOS 2 levels than RCC tissues. Greater expression of all NOS isoforms was associated with larger tumors. High NOS1 expression correlated with microscopic venous invasion (MVI) (p = 0.046) and lymph node metastases (p = 0.007). High NOS2 expression was linked to MVI, more RN performed, and male gender (p = 0.035, p = 0.003, and p =  0.027, respectively). High NOS3 expression correlated with lymph node metastases (p = 0.039), microlymphatic invasion (p = 0.029), invasion of the renal pelvis and ureter (p = 0.004), RN (p = 0.003), and shorter OS (58.1 vs. 79.4 % respectively, p = 0.033) by univariate analysis. DFS was not influenced by any NOS isoform. By multivariate analysis, the risk factors for death were TNM stages III and IV (hazard ratio [HR] = 4.5), high Fuhrman’s grade (HR = 2.9), Karnofsky performance status ≤80 (HR = 2.5), progression (HR = 5.5), and recurrence (HR = 6.3). Stage III disease was an independent risk factor for recurrence (HR = 9.5).

Conclusions

High NOS expression in RCC is associated with a poor prognosis and larger tumors. NOS3 influences OS by univariate analysis.     

Prognostic value of alpha-methyl CoA racemase (AMACR) expression in renal cell carcinoma

Purpose

Alpha-methyl CoA racemase (AMACR) is used as an immunohistochemical marker for renal cell carcinoma (RCC) subtyping to distinguish papillary (pap) RCC. Expression of AMACR in other renal tumor subtypes is inhomogeneous, and the clinical and prognostic value of AMACR is unknown. The aim of this study was to asses AMACR protein expression in different RCC subtypes and to investigate its prognostic significance.

Methods

Protein expression of AMACR was analyzed in 1,088 renal tumor samples, among them 809 clear cell RCC and 151 papRCC, by immunohistochemistry using tissue microarry (TMA) technique. Results were correlated with clinicopathological data and to follow-up data [overall (OS)/cancer-specific survival (CSS)].

Results

Frequency of AMACR expression was significantly higher in papRCC compared to other tumor subtypes (83% vs. 15–35%, p < 0.0001). Presence of AMACR did not correlate with stage or nodal metastases in papRCC. In a dichotomized scoring (negative vs. positive expression), an inverse correlation between higher grade (p = 0.03) and presence of distant metastasis (p = 0.014) was observed in papRCC. AMACR expression correlated with the presence of nodal metastasis in ccRCC (p = 0.02). Both in ccRCC and in papRCC, OS and CSS did not correlate with the AMACR expression status.

Conclusions

The high expression in papRCC confirms AMACR to be a marker for subtype differentiation in RCC, while a missing expression in this subtype seems to be associated with negative pathological features. However, in contrast to other tumor entities, AMACR expression seems to have a limited prognostic impact in renal carcinoma, especially with regard to survival.     

Minimally invasive liver surgery for metastases from colorectal cancer: oncologic outcome and prognostic factors

Background

Few reports exist on long-term survival after minimally invasive liver surgery (MILS) for colorectal liver metastases (CRLM). No data are available assessing prognostic factors in the era of current modern treatment strategies.

Methods

Between October 2002 and December 2008, 274 consecutive patients were analyzed on an intention-to-treat basis. Open liver surgery (OLS) was performed in 193 patients for a total of 437 metastases, and MILS was performed in 81 patients for 176 metastases. Systemic chemotherapy was administered preoperatively in 173 and postoperatively in 174 patients. The impact of 23 potential prognostic factors on disease-free (DFS) and overall survival (OS) was evaluated using univariable and multivariable Cox regression models.

Results

Postoperative complications were observed in 54 patients after OLS and in 11 after MILS (p = 0.016). The median postoperative length of hospital stay was 9 days after OLS and 5 days after MILS (p < 0.0001). For the entire patient population, the 5 year DFS and OS rates were 29.9 and 59.5%, respectively. No differences in survival between patients treated with MILS and OLS were observed (p = 0.63). In univariable analyses, the number of liver metastases and the overall Fong’s clinical risk score (CRS) were the only two variables that predicted DFS (p ≤ 0.0035) and OS (p ≤ 0.0005). In multivariable analyses, the total CRS was the only independent predictor of both DFS (p = 0.0002) and OS (p = 0.002).

Conclusion

The long-term oncologic outcome of surgically treated patients with CRLM is determined by the Fong’s CRS. Although MILS does not influence long-term survival, it has a beneficial impact on the immediate postoperative clinical outcome.     

Does preoperative platelet count and thrombocytosis play a prognostic role in patients undergoing nephrectomy for renal cell carcinoma? Results of a comprehensive retrospective series

Purpose

To evaluate the still controversially discussed prognostic role of preoperative platelet level (PPL) and thrombocytosis (TC) in patients who undergo surgery for renal cell carcinoma (RCC) based on the largest patient series reported to date.

Methods

A total of 3,139 patients, who underwent radical or nephron-sparing nephrectomy at four centres, were subdivided based on a threshold for preoperative platelets of 400 × 10⁹ cells/L. Univariate and multivariable Cox regression analyses were applied to determine the prognostic influence of PPL and TC on cancer-specific survival (CSS) for patients with localized and metastatic disease at presentation.

Results

Group 1 (PPL ≤ 400/nl) and Group 2 (PPL > 400/nl) included 2,862 (91 %) and 277 patients (9 %), respectively. With a median follow-up (FU) of 69.5 months (IQR: 35–105), CSS of all patients after 5 years was 84.6 % in Group 1 versus 53.4 % in Group 2 (p < 0.001). At multivariable analysis, TC (HR:1.337; p = 0.007) and continuous PPL (HR:1.001; p = 0.002) independently predicted a decreased survival. However, integration of these parameters into multivariable models for the entire study group and for patients with localized tumours did only result in marginal improvement of the model quality (0.66 and 1.04 %, respectively). Interestingly, neither TC (p = 0.257) nor PPL (p = 0.132) significantly influenced survival in M1 patients.

Conclusions

Preoperative TC turned out an independent predictor for decreased CSS in patients undergoing surgery for localized RCC. However, significant improvement of multivariable models comprising standard clinical and pathological parameters by the inclusion of TC is not achieved. In metastatic disease, TC did not reveal an independent influence on CSS.     

Ablation for Hepatocellular Carcinoma: Validating the 3-cm Breakpoint

Background

Although many previous studies on local ablation outcomes for hepatocellular carcinoma (HCC) have dichotomized tumor size with a 3-cm cutoff to determine prognostic significance, a growing number of reports describe excellent outcomes for larger tumors. To address the logic of this 3-cm cutoff beyond small single-center experiences, we stratified patients by 1-cm tumor size intervals and hypothesized that disease-specific survival (DSS) would not vary significantly between adjacent groups.

Methods

Patients treated with local ablation for T1 HCC (≤8 cm) were identified from the surveillance, epidemiology, and end results database (2004–2008). Log-rank tests and multivariable Cox proportional hazards models were used to compare DSS curves of adjacent study groups.

Results

There were 1,083 patients included in the study (26 % female, median age: 62 years). The 3-year DSS was significantly lower in patients with 3- to 4-cm tumors compared to 2- to 3-cm tumors (58 vs. 72 %, p = 0.002). In adjusted models, DSS did not vary significantly between any size intervals up to 3 cm. Patients with 3- to 4-cm tumors, however, had a poorer prognosis compared with patients with 2- to 3-cm tumors (hazard ratio: 1.6, 95 % confidence interval: 1.18–2.18, p = 0.002). DSS also fell when tumor size increased from 5–6 to 6–7 cm (53 vs. 21 %, 0.006).

Conclusions

This study emphasizes the 3-cm size, and possibly the 6-cm size, as informative predictive thresholds when ablating HCC, because variability of DSS occurred specifically at these tumor sizes. Future research in this field should either adopt a 3-cm breakpoint or provide evidence for alternative thresholds.     

Does Histologic Type Correlate to Outcome after Pelvic Exenteration for Cervical and Vaginal Cancer?

Background

Adenocarcinoma (AC) of the cervix comprises 15–20 % of all cervical carcinomas, and data regarding the prognostic value of histologic type after pelvic exenteration (PE) are lacking. Our aim was to analyze the prognostic value of histologic type in overall survival (OS) and disease-specific survival (DSS) after PE and correlate it to clinical and pathologic variables.

Methods

We reviewed a series of 77 individuals who underwent PE for cervical or vaginal cancer from January 1980 to December 2010.

Results

Mean age was 54.5 years. Fifty-three patients (68.9 %) had cervical and 24 (31.1 %) vaginal cancer. Fifty-six (72.7 %) were squamous cell carcinoma (SCC) and 21 (27.3 %) ACs. We performed 42 (54.5 %) total, 18 anterior, 8 posterior, and 9 lateral extended PE. Median tumor size was 5 cm. Surgical margins were negative in 91.7 % of cases. Median operative time, length of hospital stay, and blood transfusion volume were, respectively, 420 (range 180–720) mins, 13.5 (range 4–79) days, and 900 (range 300–3900) ml. Median follow-up was 13.7 (range 1.09–114.3) months. SCC statistically correlated with presence of perineural invasion (p = 0.004). Five-year OS and DSS were, respectively, 24.4 and 37.1 %. SCC (p = 0.003) and grade 3 (p = 0.001) negatively affected OS in univariate analysis. SCC (p = 0.006), grade 3 (p = 0.003), perineural invasion (p = 0.03), lymph node metastasis (p = 0.02), and positive margins (p = 0.04) negatively affected DSS in univariate analysis. SCC and grade 3 retained the higher risk of death (OS and DSS) in multivariate analysis.

Conclusions

AC histology in cervical and vaginal cancer is associated with better outcome after PE compared to SCC.     

Differences in histopathological evaluation of standard lymph node dissections result in differences in nodal count but not in survival

Objective

To analyse whether the reported differences in nodal yield at pelvic lymph node dissection (PLND) for bladder cancer, between two hospitals, are reflected in the survival rates.

Patients and methods

We assessed follow-up data of all 174 patients (mean age: 62.7, median follow-up: 3 years) who underwent PLND between 1 January 2007 and 31 December 2009 at two different hospitals. PLND was performed according to a standardized template by the same urologists for comparable bladder cancer patients. Mean number of reported lymph nodes was 16 at hospital A versus 28 at hospital B. We compared the overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) between both cohorts and performed a multivariate analysis.

Results

The cumulative probability for 2-year OS, DSS and RFS for hospital A are 61, 64 and 54 %, versus 58, 58 and 53 % for hospital B, respectively. Kaplan–Meier survival curves did not reveal statistically significant differences between both groups (OS: p log-rank = 0.75, DSS: p log-rank = 0.56, and RFS: p log-rank = 0.80). Also after adjustment for pT stage and neoadjuvant chemotherapy, survival was not significantly different between hospital A and hospital B.

Conclusion

Despite differences in lymph node yield in PLND specimens, this study reveals no significant differences in survival outcomes between both hospitals. Standardized histopathological methods should be agreed upon by pathologists before integrating nodal yield and subsequent lymph node density as indicators of the quality of surgery and as prognostic factors.     

Metaplastic Breast Cancer: To Radiate or Not to Radiate?

Background

The role of radiation therapy (RT) is unclear for metaplastic breast cancer (MBC). We hypothesized that RT would improve overall survival (OS) and disease-specific survival (DSS).

Materials and Methods

We used the Surveillance, Epidemiology, and End Results (SEER) database to identify MBC patients diagnosed from1988 to 2006. Univariate analyses of patient, tumor, and treatment-specific factors on OS and DSS were performed using the Kaplan–Meier method and differences among survival curves assessed via log rank. Variables assessed included patient age, race/ethnicity, histologic subtype, tumor grade, T stage, N stage, M stage, hormone receptor status, surgery type, and use of RT. Cox proportional hazards models used all univariate covariates. Risks of mortality were reported as hazard ratios (HR) with 95% confidence intervals (95% CI); significance was set at P ≤ 0.05.

Results

Among 1501 patients, RT was given to 580 (38.6%). Ten-year OS and DSS were 53.2, and 68.3%, respectively. In the overall analysis, RT provided an OS (HR 0.64; 95% CI, 0.51–0.82; P < 0.001) and DSS (HR 0.74; CI, 0.56–0.96; P < 0.03) benefit. When patients were stratified according to type of surgery, RT provided an OS but not a DSS benefit to lumpectomy (HR 0.51; CI, 0.32–0.79, P < 0.01) and mastectomy patients (HR 0.67; CI, 0.49–0.90; P < 0.01).

Conclusions

Our findings support the use of RT for patients with MBC following lumpectomy or mastectomy. These retrospective findings should be confirmed in a prospective clinical trial.     

Tumor Response Ratio Predicts Overall Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods.

Methods

Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I–III breast cancer who had NAC and pretreatment imaging at City of Hope (1997–2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0–0.4 (strong partial response, SPR), TRR > 0.4–1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan–Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders.

Results

There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016).

Conclusions

TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.     

REG1A Expression Status Suggests Chemosensitivity Among Advanced Thoracic Esophageal Squamous Cell Carcinoma Patients Treated with Esophagectomy Followed by Adjuvant Chemotherapy

Background

Regenerating gene 1A (REG1A) plays an important role in tissue regeneration and in cell proliferation in the mucous membrane of the gastrointestinal tract. We previously reported that the positive expression status of REG1A was predictive of chemoradiosensitivity in patients treated with preoperative chemoradiotherapy before esophagectomy or with definitive chemoradiotherapy. To further confirm the utility of REG1A as a chemosensitivity marker, we carried out an additional retrospective clinical study aimed at determining whether REG1A is a reliable chemosensitivity marker in patients treated with esophagectomy followed by adjuvant chemotherapy.

Method

A total of 177 patients with T2–4 thoracic esophageal squamous cell carcinoma received curative surgery without preoperative treatment at Akita University Hospital between 2001 and 2011. A tissue microarray was constructed, and REG1A expression status was analyzed immunohistochemically. We then statistically analyzed the relationships between REG1A expression status and 5-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS).

Results

In the adjuvant group (n = 105), REG1A-positive patients showed significantly better prognoses than REG1A-negative patients. (5-year OS, p = .0022; DSS, p = .0004; and DFS, p = .0040). However, there were no significant differences between REG1A-positive and REG1A-negative patients in the surgery group (n = 72). Univariate and multivariate analyses showed REG1A expression status to be a significant prognostic factor affecting 5-year DSS, comparable to lymph node metastatic status.

Conclusion

The present study suggests REG1A expression status has the potential to be a highly reliable and clinically useful chemosensitivity marker in patients treated with advanced thoracic esophageal squamous cell carcinoma. REG1A expression status will provide a good indication of treatment strategy and enable more individualized treatment for patients.     

The effect of intra- and postoperative allogenic blood transfusion on patients’ survival undergoing radical cystectomy for urothelial carcinoma of the bladder

Purpose

Radical cystectomy (RC) can be associated with significant blood loss. Allogenic blood transfusion (ABT) may alter disease outcome because of a theoretical immunomodulatory effect. We evaluated the effects of ABT on overall survival (OS) and progression-free survival (PFS) of patients undergoing RC for urothelial carcinoma of the bladder (UCB).

Materials and methods

This is a retrospective single-center study of 350 consecutive patients of a university health center with a median follow-up of 70.1 month. All patients underwent RC and pelvic lymph node dissection. The effect of ABT on OS and PFS was analyzed using univariable and multivariable Cox proportional hazards models.

Results

The overall ABT rate was 63 % (n = 219), with intraoperative blood transfusion and postoperative blood transfusion being performed in 183 patients (52 %) and 99 patients (28 %), respectively. Preoperative anemia was detected in 156 patients (45 %) with median estimated blood loss of 800 ml (IQR: 500–1,200). ABT was associated with significant decrease of OS and PFS in multivariable analyses (p < 0.001), whereas patients’ prognosis worsened the more packed red blood cells (PRBC) were transfused (p < 0.001). The study is limited in part due to its retrospective design.

Conclusions

We found that ABT and the number of PRBC transfused are associated with poor prognosis for UCB patients undergoing RC, whereas preoperative anemia had no influence on survival. This emphasizes the importance of surgeon’s awareness for a strict indication for ABT. A prospective study will be necessary to evaluate the independent risks associated with ABT during surgical treatments.     

Female gender is associated with higher risk of disease recurrence in patients with primary T1 high-grade urothelial carcinoma of the bladder

Purpose

An increasing body of evidence suggests gender differences in the presentation and prognosis of bladder cancer. We aimed to assess the impact of gender on outcomes in patients with primary T1 high-grade (HG) urothelial carcinoma of the bladder (UCB).

Methods

We retrospectively analysed the data from 916 patients with primary T1HG UCB from 7 tertiary care centres. Patients were treated with transurethral resection of the bladder with or without intravesical instillation therapy (IVT). Univariable and multivariable Cox regression analyses assessed the effect of gender on outcomes.

Results

Within a median follow-up of 42.8 months, 365 (39.8 %) patients experienced disease recurrence, 104 (11.4 %) progression, 59 (6.4 %) cancer-specific mortality and 190 (20.7 %) mortality of any cause. Overall, 634 (69.2 %) patients received IVT of which 234 (25.5 %) received BCG therapy. Female gender (n = 190, 20.7 %) was associated with higher risk of disease recurrence (HR:1.359;1.071–1.724, p = 0.012) in all patients and in a subgroup of patients treated with BCG therapy (HR:1.717;1.101–2.677, p = 0.017). There was no difference between genders with regard to disease progression, cancer-specific mortality and any-cause mortality. In multivariable analyses that adjusted for the effects of concomitant carcinoma in situ (CIS), tumour size, number of tumours, and IVT, gender remained an independent predictor for disease recurrence (p = 0.026) when analysed in all patients, but not in the subgroup of BCG treated patients (p = 0.093).

Conclusions

In patients with T1HG UCB, female gender is associated with higher risk of disease recurrence, but not with disease progression. This gender disparity may be due to differences in care and/or biology of UCB.     

The prognostic value of cyclin D1 in renal cell carcinoma

Introduction

Renal cell carcinoma (RCC) is a family of distinct tumors, and a variety of molecules have been evaluated as prognostic markers for RCC. Cyclin D1, a cell cycle regulator, is overexpressed in several primary tumors.

Objective

To evaluate cyclin D1 expression as a prognostic marker in RCC.

Method

In total, 109 tumor specimens from patients with RCC were obtained from 2005 to 2010 at Hospital das Clínicas—Ribeirão Preto School of Medicine—USP, Brazil, and submitted to immunohistochemical analysis along with seven normal kidney tissue samples.

Results

All of the normal kidney samples lacked cyclin D1 immunohistochemical staining. In addition, there was lower protein expression in the papillary and chromophobe RCC samples. Patients with cyclin D1^low tumors (≤30 % positive cells) showed worse clinical outcome (p = 0.03), lower survival without metastasis and/or death by RCC (p = 0.03), high nuclear grade (p = 0.001), larger tumor size (p = 0.01), presence of symptoms at diagnosis (p = 0.04), necrosis (p = 0.004) and sarcomatoid morphology (p = 0.04). After multivariate analysis, cyclin D1 was not an independent significant factor for worse outcome; however, it improved the accuracy of the adopted prognostic system. The analysis performed for clear cell RCC alone showed similar statistical significance to that of the total cases.

Conclusions

Cyclin D1 protein was overexpressed in RCC. The types of RCC appear to exhibit different immunohistochemical staining patterns for cyclin D1; high protein expression was related to good clinical outcome and to most known favorable prognostic factors. Further investigations are necessary to reveal which mechanisms lead to cyclin D1 accumulation in neoplastic cells.     

Survival following laparoscopic and open colorectal surgery

Background

Laparoscopic colorectal surgery is known to provide increased benefits to patients during the postoperative recovery period. Initial scepticism over the oncological adequacy of resection has been dismissed by a number of major randomized trials. Emerging evidence indicates that laparoscopic surgery may provide a potential survival benefit in colorectal cancer.

Methods

Patients undergoing elective laparoscopic or open resection for colorectal cancer between October 2003 and December 2010 were analyzed. Data were collated and a database compiled. Survival analysis was calculated by using the Kaplan–Meier method.

Results

A total of 665 resections were performed with 457 laparoscopically and 208 open. The median length of stay was 4 days following laparoscopic resection and 7 days following open (p < 0.0005). There was no significant difference between the two groups apart from gender (p = 0.03), ASA (p = 0.03), and the number of patients with extranodal metastatic disease (p = 0.01). The 5-year overall survival (OS) in the completed laparoscopic group was 75.8 versus 72.5 % in the open group (p = 0.12). The 5-year OS in patients who were converted was 52 %. The 5-year OS for nonmetastatic disease in the completed laparoscopic group was significantly greater at 79.4 versus 74 % in the open group (p = 0.03). There was no difference between the groups in OS for rectal cancer (p = 0.66), but there was an OS advantage for laparoscopically resected colon cancer (p = 0.02).

Conclusions

Laparoscopic resection for nonmetastatic colon cancer may provide an overall survival advantage.     

Local Immune Response Predicts Survival in Patients with Thick (T4) Melanomas

Background

Tumor infiltrating lymphocytes (TIL) and histological regression in primary melanoma are generally considered indicators of the local immune response but their roles as prognostic factors have been variably reported. We examined the prognostic role of these variables in patients with high risk (T4) primary melanomas in a large series of patients with long-term follow-up.

Methods

From a prospectively maintained cohort of patients diagnosed between 1971 and 2004, 161 patients were retrospectively identified with primary thick melanomas (>4 mm), no clinical evidence of regional nodal disease (RND) at diagnosis and complete histopathologic data. Univariate and multivariate Cox regression models were performed to identify clinical and histopathologic predictors of disease-specific survival (DSS) and to identify subgroups with differential survival.

Results

Factors significantly associated with decreased DSS by univariate analysis included male gender, age ≥ 60 years, axial anatomic location, presence of ulceration, RND, absence of TIL, and presence of regression. In the final multivariate model, TIL and regression, as interacting variables, and RND status remained significantly associated with DSS. In the presence of TIL, concomitant regression was associated with significantly worse survival (p ≤ 0.0001). In the absence of TIL, there was no effect of regression on survival (p = 0.324).

Conclusions

Primary TIL and regression status and RND status are independently associated with melanoma-specific survival in patients with T4 melanomas; presence of TIL in the primary melanoma with concomitant radial growth phase regression is associated with a poor prognosis and may reflect an ineffective local regional immune response.     

Surgical Cytoreduction and Survival in Appendiceal Cancer Peritoneal Carcinomatosis: An Evaluation of 46 Consecutive Patients

Background

Surgical cytoreduction and intraperitoneal chemotherapy is increasingly accepted as an effective treatment modality for mucinous appendiceal neoplasm. For the majority of patients with low-grade histology, outcomes have been encouraging. The survival of patients with neoplasms of malignant character is protracted and this study was designed to evaluate the effectiveness of this surgical strategy on outcomes.

Methods

Forty-six consecutive patients with mucinous and nonmucinous appendiceal cancer with peritoneal dissemination were studied. Clinicopathological and treatment related factors were obtained from a prospective database. The study’s end points of disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.

Results

The median DFS and OS after cytoreduction were 20.5 and 56.4 months respectively. Five-year overall survival rate was 45%. Five independent factors associated with DFS and OS were identified through a multivariate analysis: age (DFS p = 0.001, OS p = 0.002), completeness of cytoreduction (DFS p = 0.001, OS p = 0.003), previous chemotherapy treatment (DFS p = 0.021), CA 199 levels (DFS p = 0.013), and tumor grade (OS p = 0.005).

Conclusions

Cytoreductive surgery and intraperitoneal chemotherapy may achieve long-term survival in appendiceal malignancies with peritoneal dissemination for which the predictors of outcomes identified through this study may tailor the disease management to commit patients early toward this successful surgical strategy.     

SNAI1 Protein Expression is an Independent Negative Prognosticator in Muscle-Invasive Bladder Cancer

Background

The prognosis of muscle-invasive bladder cancer is poor. Molecular prognosticators have gained increasing attention for individualized therapeutic options because they can identify patients with different prognoses.

Methods

Tissue microarrays of formalin-fixed and paraffin-embedded tumor samples from 206 bladder cancer patients treated with cystectomy and chemotherapy were studied for SNAI1 protein expression by immunohistochemistry. SNAI1 expression was evaluated using an immunoreactive score (IRS). For statistical analysis, the patients were separated into two groups: those with tumor specimens negative for SNAI1 expression (IRS = 0), and the other positive for SNAI1 expression (IRS ≥1).

Results

Tumor samples from 42 patients showed negative SNAI1 expression, whereas the nuclei of tumor cells from 164 patients showed detectable nuclear staining of SNAI1. A Kaplan–Meier analysis of the bladder cancer patients with negative SNAI1 expression showed significantly reduced disease-specific survival (DSS) and progression-free survival (PFS) compared to the patients with positive expression (p = 0.010 and 0.013). A multivariate Cox regression analysis (adjusted for gender, age, tumor stage, tumor grade, lymph node metastasis, chemotherapy, and histologic subtype) again showed a significant correlation between patients lacking SNAI1 expression and DSS (p = 0.005; relative risk 2.31; 95 % confidence interval 1.28–4.17) or PFS (p = 0.004; relative risk 2.20; 95 % confidence interval 1.29–3.78) compared to patients with positive SNAI1 staining.

Conclusions

Loss of SNAI1 protein expression is an independent prognosticator for PFS and DSS in bladder cancer patients treated by radical cystectomy and adjuvant chemotherapy. Its prognostic value for neoadjuvant or adjuvant chemotherapy must be evaluated in further prospective randomized controlled trials.     

Overweight Patients Achieve Ideal Body Weight Following Curative Gastrectomy Resulting in Better Long-Term Prognosis

Background

The relationship between body mass index (BMI) and long-term outcome in gastric cancer patients following radical gastrectomy continues to be debated. We investigated the association between BMI, clinicopathological features, and prognosis in Chinese gastric carcinoma patients.

Methods

A retrospective consecutive cohort study was performed on 1,296 patients who underwent gastrectomy with curative intent at the Tianjin Cancer Institute Hospital between 1999 and 2004. The clinicopathological characteristics, overall 5-year survival rate (OS), and preoperative and six-month postoperative BMIs of both overweight (BMI ≥25 kg/m²; H-BMI; n?=?364) and non-overweight (BMI <25 kg/m²; N-BMI; n?=?932) patients were compared.

Results

Among these patients, 364 (28.1 %) were overweight. The OS was significantly higher in the H-BMI than N-BMI group (33.2 vs. 24.1 %, respectively; p?<?0.001). Preoperative and six-month postoperative BMIs were 27.1?±?2.0 and 24.8?±?2.0 kg/m², respectively, in the H-BMI group (p?<?0.001), whereas they were 21.7?±?2.2 and 20.7?±?2.2 kg/m², respectively, in the N-BMI group (p?=?0.007). There was significantly better differentiation (p?=?0.034), less distant metastases (p?=?0.006), and a lower metastatic lymph node ratio (p?=?0.014) observed in the H-BMI groups. Multivariate analyses indicated age, BMI, pathological tumor depth, distant metastases, metastatic lymph node ratio, and tumor size as independent prognostic factors.

Conclusions

Our findings suggest that overweight patients were less likely to have tumors with aggressive features and can achieve ideal body weight following curative gastrectomy, possibly resulting in better long-term prognosis