DOK2 as a Marker of Poor Prognosis of Patients with Gastric Adenocarcinoma After Curative Resection

Background

DOK2 is known as the substrate of chmeric p210bcr/abl oncoprotein characterizing chronic myelogenous leukemia with Philadelphia chromosome. Reduced DOK2 expression was recently reported in lung adenocarcinoma, suggesting that this protein acts as a tumor suppressor in solid tumors. The purpose of this study was to determine the significance of DOK2 in gastric cancer.

Methods

The study subjects were 118 patients who underwent curative surgery for gastric cancer, as well as 7 gastric cancer cell lines. The tissues and cell lines were analyzed for DOK2 gene and protein expressions by histopathology and immunohistochemistry, and also using a microsatellite marker for loss of heterozygosity. Correlation of survival with clinicopathological parameters was investigated by univariate and multivariate analyses.

Results

DOK2 expression was confirmed in the normal gastric mucosa. Considerable differences in the gene expression were noted among the gastric cell lines. Positive DOK2 expression was noted in the noncancerous regions of all pathological specimens, whereas 59 (50.0%) specimens of 118 patients were negatively stained in the tumor. Loss of heterozygosity was observed in 54.5% of DOK2(?) cases. DOK2(?) patients were more likely to develop recurrence than DOK2(+) and showed poorer 5-year overall survival (59.1%) than DOK2(+) (76.4%, P = .0403). Multivariate analysis identified pT (hazard ratio [HR] = 2.748, 95% confidence interval [95% CI] = 1.061–8.927, P = .0361), pN (HR = 2.486, 95% CI = 1.264–4.932, P = .0086), and DOK2(?) (HR = 2.343, 95% CI = 1.211–4.727, P = .0112) as significant and independent determinants of poor survival.

Conclusions

Our data suggest the potential usefulness of DOK2 as a marker of poor prognosis in patients with gastric cancer after curative resection.

     

Nuclear Notch3 Expression is Associated with Tumor Recurrence in Patients with Stage II and III Colorectal Cancer

Background

The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.

Methods

The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.

Results

Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).

Conclusions

Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.     

Prognostic Impact of CD133 mRNA Expression in 48 Glioblastoma Patients Treated with Concomitant Radiochemotherapy: A Prospective Patient Cohort at a Single Institution

Background

Cancer stem cells are thought to represent the population of tumorigenic cells responsible for tumor development. The CD133 antigen has been described as a putative stem cell marker in malignant brain tumor that could identify such a tumorigenic population in a subset of glioblastoma. To date, the correlation between CD133 expression in primary glioblastoma and patient prognosis is not clearly established. To address this question we investigated the relationship between CD133 mRNA expression and patient outcome in a glioblastoma patient cohort.

Materials and Methods

The quantitative expression of CD133 stem cell antigen mRNA using real-time QRT-PCR was assessed in a cohort of 48 consecutive primary glioblastoma patients treated by chemoradiation with temozolomide.

Results

On multivariate survival analysis, high CD133 mRNA expression was a significant (P = 0.007) prognostic factor for adverse progression-free and overall survival independent of extent of resection (P = 0.012) and MGMT methylation status (P = 0.002). Patient age was also an independent prognosticator of overall survival (P = 0.037). Furthermore, according to the conjoined expression of CD133 mRNA and MGMT status, the patients were categorized into 3 groups with homogenous prognosis.

Conclusions

These findings constitute conclusive evidence that the measurement of the mRNA expression of CD133 stem cell antigen actually impacts the survival of GBM patients.     

Clinical Significance of Melanoma Antigen-Encoding Gene-1 (MAGE-1) Expression and its Correlation with Poor Prognosis in Differentiated Advanced Gastric Cancer

Background

Melanoma antigen-encoding gene-1 (MAGE-1), a cancer/testis antigen, has been reported to be expressed in various types of cancer. We investigated the clinicopathological features and prognostic significance of MAGE-1 expression in advanced gastric cancer (AGC).

Methods

Immunohistochemical staining for MAGE-1 was performed on surgical specimens obtained from 135 patients with AGC.

Results

Positive expression of MAGE-1 detected in cytoplasm was observed in 44 of 135 cases (32.6%) in primary tumors and 26 of 96 (27.1%) in lymph node metastases. In noncancerous gastric tissues, apparent MAGE-1 expression was not detected. MAGE-1 in primary tumor was correlated with advanced age (P < 0.001), macroscopic infiltrated type (P = 0.035), and presence of vascular invasion (P = 0.027). The 5-year cancer-specific survival rates of AGC patients with positive MAGE-1 expression were significantly lower than those of patients with negative MAGE-1 (positive: 31.6%, negative: 57.6%, P = 0.038). On multivariate analysis, MAGE-1 expression was not an independent prognostic predictor of AGC (P = 0.064). In differentiated AGC patients, MAGE-1 expression was correlated with advanced age (P = 0.003), macroscopic infiltrated type (P = 0.009), and presence of lymph node metastasis (P = 0.033). The cancer-specific survival rates of differentiated AGC patients with positive MAGE-1 were significantly lower than those of patients with negative MAGE-1 (P = 0.003). Positive MAGE-1 expression was an independent prognostic factor of differentiated AGC patients on multivariate analysis (P = 0.031).

Conclusions

These findings suggest that MAGE-1 protein expression can serve as a predictive marker of poor prognosis in differentiated AGC patients.     

Prognostic Significance of CD151 Expression in Esophageal Squamous Cell Carcinoma with Aggressive Cell Proliferation and Invasiveness

Background

CD151 is a member of the tetraspanins and has recently been reported as a promoter of the malignant progression of cancer. The purpose of this study was to clarify the clinicopathological outcome and prognostic significance of the immunohistochemical expression of CD151 in esophageal squamous cell carcinoma (ESCC).

Methods

We evaluated the significance of CD151 expression by immunohistochemistry in 138 surgically resected ESCC and the association of CD151 expression with clinicopathological features.

Results

Seventy-five (51.7%) ESCC showed a positive expression of CD151, which indicated a significant association with tumor depth (P = 0.004), lymph node metastasis (P = 0.002), distant metastasis (P = 0.025), and lymphatic invasion (P = 0.046), as well as the Ki-67 labeling index (P = 0.011). The 5-year survival rate of ESCC patients with CD151-positive expression was significantly lower than with CD151-negative expression (positive, 43.1%; negative, 63.8%; P = 0.003). Multivariate analysis showed that positive CD151 expression was not an independent factor for poor survival (P = 0.096).

Conclusions

CD151 expression is associated with tumor proliferation and invasiveness in ESCC.     

SIRT3 Expression as a Biomarker for Better Prognosis in Gastric Cancer

Background

SIRT3—mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-3—plays an important role in regulating cell metabolism and carcinogenesis. The role of SIRT3 in gastric cancer has not yet been investigated.

Methods

A total of 221 gastric cancer patients who underwent curative surgery were enrolled at the Department of Surgery, Taipei Veterans General Hospital. SIRT3 expression in gastric tissues and tumors were examined in these patients using immunohistochemical staining. Clinicopathologic characteristics and survival were analyzed and compared in gastric cancer patients with or without SIRT3 expression.

Results

The 5-year survival rates of patients with or without SIRT3 expression were 51.2 and 39.1 %, respectively (p = 0.005). The 5-year disease-free survival rates of patients with or without SIRT3 expression were 49.6 and 38.0 %, respectively (p = 0.010). Microscopic features showed that there are more poor cell differentiation (p = 0.001), more diffuse-type Lauren’s histology (p = 0.018), and more scirrhous-type stromal reactions (p = 0.027) in gastric cancer without SIRT expression. Multivariate analysis with overall survival as an endpoint showed that age (p < 0.001), Lauren’s histology (p = 0.007), stromal reaction (p = 0.035), TNM pathologic N category (p < 0.001), and SIRT3 expression (p < 0.001) were significantly correlated with gastric cancer.

Conclusions

Gastric cancer patients with SIRT3 expression have a better prognosis than those without. SIRT3 expression is an independent prognostic marker for overall survival and may act as a tumor suppressor in gastric cancer.     

High Level of Notch1 Protein is Associated with Poor Overall Survival in Colorectal Cancer

Background

Notch1 regulates cell proliferation, development, and apoptosis. Aberrant expression of Notch1 has been discovered in many types of tumors. We examined Notch1 expression in colorectal cancer to assess its role as a prognostic indicator.

Methods

Notch1 protein expression was examined by immunohistochemistry in 223 surgically resected specimens of colorectal cancer and adjacent tissues. The relationship between various clinicopathological features and overall patient survival rate was analyzed. The association of Notch1 expression with the colorectal cancer survival rate was assessed by Kaplan–Meier and Cox proportional-hazards regression.

Results

Significantly high Notch1 expression was found in colorectal cancer cells compared with that of normal colorectal epithelial cells. Notch1 was positively correlated with depth of invasion (P = 0.005), lymph node metastases (P = 0.03), and tumor–node–metastasis (TNM) stage (P < 0.001). Consistently, the overall survival rate was significantly lower for patients with Notch1-positive than those with Notch1-negative tumors. However, no correlation between Notch1 expression and patient age, sex or tumor location was found.

Conclusion

Notch1 might serve as a novel prognostic marker that is independent of, and additive to, the TNM staging system.     

Perineural Invasion as a Major Determinant for the Aggressiveness Associated with Increased Tumor Thickness in T1–2 Oral Tongue and Buccal Squamous Cell Carcinoma

Background

Neck management for cN0 neck remains controversial for T1–2 oral tongue and buccal squamous cell carcinoma (SCC). Increased tumor thickness and perineural invasion (PNI) are two pathologic features that correlated with cervical lymph node (LN) metastasis and poor survival. However, the relationships between these two features remain unclear.

Methods

Detailed histologic reevaluation under hematoxylin and eosin staining was performed in tumors of 212 consecutive patients with T1–2, cN0 oral tongue and buccal SCC. The interrelationships between the impacts of tumor thickness and PNI on cervical LN metastasis and disease-specific survival (DSS) were analyzed.

Results

Increased tumor thickness (>6 mm) correlated with higher LN metastasis and poor 5-year DSS rates in univariate analysis. However, only PNI independently predicted both in multivariate analysis (P = 0.004 and P = 0.039, respectively). When stratified by PNI status, increased tumor thickness did not correlate with higher LN metastasis rate in either PNI-negative or PNI-positive groups (P = 0.337 and P = 0.730). Compared to patients with thin tumors (≤6 mm), patient with thick tumors revealed significantly higher LN metastasis rate (41.9 vs. 16.4 %, P = 0.001) and lower 5-year DSS rate (77.5 vs. 93.7 %, P = 0.006) only at the presence of PNI.

Conclusions

PNI can be a major determinant for higher LN metastasis and poor 5-year DSS rates associated with increased tumor thickness in T1–2 oral tongue and buccal SCC. Careful evaluation of PNI should be mandatory in routine pathologic examination, aside from the measurement of tumor thickness.     

Aggressive Surgical Approach for Patients with T4 Gastric Carcinoma: Promise or Myth?

Background

Surgical outcomes of multiorgan resection (MOR) for T4 gastric carcinoma reported in the literature are widely variable. We herein report a large surgical series of T4 gastric carcinoma.

Methods

One hundred seventy-nine patients with cT4 gastric carcinoma were recruited onto the study. Patient characteristics, surgical strategy and related complications, long-term survival, and prognostic factors of T4 gastric carcinoma were analyzed.

Results

Of 179 cT4 gastric carcinoma, there were 57 cT4 (pT3) with MOR, 91 pT4 with MOR, and 31 cT4 without MOR. pT4 with MOR were more likely to be associated with nodal metastasis, cellular dedifferentiation, and lymphoperineural infiltration compared to those of pT0–3 (P < 0.01 for all). For 91 pT4 with MOR, their surgical mortality and morbidity rates were 4.4 and 28.6%, respectively; their 1-, 3-, and 5-year overall survival rates were 55.2, 22.4, and 12.2%, respectively. The long-term survival of cT4 (pT3) with MOR was superior to pT4 with MOR (P = 0.006) and cT4 without MOR (P = 0.004). There was a striking difference between pT4 with MOR, R0 and pT4 with MOR, and R1 or R2 (P = 0.007). By means of multivariate analysis, lymph node status, liver invasion, and positive surgical margin were independent prognostic factors.

Conclusions

Aggressive surgical management of pT4 gastric carcinoma should be limited to patients without adverse prognostic factors such as advanced nodal involvement and pancreatic invasion.     

Overexpression of microRNA-100 predicts an unfavorable prognosis in renal cell carcinoma

Purpose

Dysregulation of microRNA-100 (miR-100) has been reported to be involved in tumorigenesis and tumor progression of several cancer types. However, its expression patterns in tumors are controversial. The aim of this study was to investigate the expression and clinical significance of miR-100 in renal cell carcinoma (RCC).

Methods

Real-time quantitative PCR was performed to detect the expression levels of miR-100 in 96 paired samples of RCC and adjacent non-cancerous renal tissues. Then, statistical analysis was performed to determine the associations of miR-100 expression with the clinical features and the prognosis of RCCs.

Results

miR-100 expression was significantly higher in RCC tissues compared with adjacent non-cancerous renal tissues (5.3 ± 2.2 vs. 1.9 ± 0.8, P < 0.001). In addition, high miR-100 expression in RCC tissues was significantly associated with advanced tumor T stage (P = 0.005) and grade (P = 0.01), and the presence of metastasis (P = 0.008). Moreover, Kaplan–Meier analysis showed the significant differences in 5-year overall (50.0 vs. 83.3 %, P = 0.006) and tumor-specific survival (58.3 vs. 83.3 %, P = 0.008) for patients with high and low miR-100 expression, respectively. Furthermore, multivariable Cox regression analysis identified high miR-100 expression in RCC tissues as an independent poor prognostic marker of both overall (P = 0.01) and tumor-specific survival (P = 0.02) in patients with RCCs.

Conclusion

Our data offer convincing evidence that miR-100 overexpression strongly associates with advanced tumor progression and unfavorable clinical outcome of patients with RCC. miR-100 expression may be a useful prognostic marker for this disease.     

High Expression of Glucose Transporter 1 on Primary Lesions of Esophageal Squamous Cell Carcinoma is Associated with Hematogenous Recurrence

Purpose

Glucose transporter type 1 (Glut1) plays a crucial role in cancer-specific metabolism to adapt to the rapid growth and tumor microenvironment in diverse malignant tumors. This study examined the clinical, pathological, and prognostic features of Glut1 expression on primary lesions of esophageal squamous cell carcinoma.

Methods

Immunohistochemical staining of Glut1 and CD34 was performed using paraffin-embedded sections of tissues obtained from 145 resectable esophageal squamous cell carcinoma patients without preoperative treatment. Microvessel density was calculated from CD34 staining.

Results

Glut1 positivity was observed in 41 patients (28.2 %) and associated with depth of invasion [odds ratio (OR) 2.984; 95 % confidence interval (CI) 1.208–7.371; P = 0.018] and vascular invasion (OR 2.771; 95 % CI 1.118–6.871; P = 0.028) in multivariate analysis. Glut1 positivity was a significant disadvantage to both relapse-free survival [hazard ratio (HR) 2.021; 95 % CI 1.100–3.712; P = 0.023] and esophageal cancer-specific survival (HR 2.223; 95 % CI 1.121–4.411; P = 0.022) in univariate Cox hazard analysis, but was not independently associated with relapse-free survival or cancer-specific survival in multivariate analysis. The relationship between Glut1 expression and first relapse site was investigated. Glut1 positivity was not associated with lymph node recurrence (HR 1.009; 95 % CI 0.402–2.530; P = 0.985) but was significantly associated with hematogenous recurrence (HR 3.701; 95 % CI 1.655–8.273; P = 0.001) in univariate Cox hazard analysis. Microvessel density was calculated to evaluate angiogenesis, and it was observed that Glut1 positivity was significantly associated with high microvessel density (P < 0.001).

Conclusions

Glut1 expression was associated with hematogenous recurrence. The findings provide evidence of the significance of Glut1 expression as a biomarker.     

Outcomes and Prognostic Factors of Post-irradiation and de novo Sarcomas of the Head and Neck: A Histologically Matched Case-Control Study

Background

This study was designed to compare post-irradiation sarcomas (PIS) and de novo sarcomas (DN) of the head and neck in terms of tumor characteristics, prognostic factors, and survival outcomes.

Methods

All (N = 83) head and neck sarcoma patients treated at National Cancer Centre, Singapore (Feb 2002–May 2011) were included: DN (N = 60; 72 %); PIS (N = 23; 28 %). Clinicopathologic features and outcomes of all patients and histologically matched pairs were compared. Prognostic factors were identified using univariate and multivariate analyses.

Results

Median age, gender, smoking status, and tumor size were not significantly different. Significant differences were seen in histology (most prevalent: PIS–sarcoma-NOS; DN–angiosarcoma) and tumor subsite (most prevalent: PIS–nasal cavity and sinuses; DN–skin). Median latency of PIS development was 16.7 years. PIS patients had shorter overall survival (OS) and disease-specific survival (DSS) compared with DN patients, most clearly seen on histologically matched pair analysis: 2-year OS (PIS: 54 %; DN: 83 %; P = 0.028). Multivariate analyses showed that age >50 years (hazard ratio (HR) = 3.68; P = 0.007), ever-smokers (HR = 2.79; P = 0.017), and larger tumor-size (cm) (HR = 1.12; P = 0.045) were associated with worse OS, and age at >50 years (HR = 2.77; P = 0.04) and ever-smokers (HR = 2.94; P = 0.021) were associated with worse DSS. When treated with curative intent, no significant survival difference was noted between DN and PIS patients.

Conclusions

In our cohort, PIS constituted 28 % of head and neck sarcomas. Poorer prognosis traditionally associated with PIS compared with DN was not seen amongst patients treated with curative intent.     

The impact of tumor size on outcomes in patients with upper urinary tract urothelial carcinoma

Purpose

To investigate the association between tumor size and clinicopathologic factors and outcomes of upper urinary tract urothelial carcinoma (UTUC) in patients treated surgically for UTUC.

Methods

A single-center series of 235 consecutive patients who were treated surgically for UTUC between January 1999 and December 2011 was evaluated. Patients with a history of muscle-invasive urothelial carcinoma of the urinary bladder, those who received neoadjuvant therapies, and those with previous contralateral UTUC were excluded. Bladder-only recurrence, any recurrence, and cancer-specific mortality after surgery were analyzed. Recurrence-free probabilities and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method and Cox regression analyses.

Results

Tumor size was significantly associated with age of the patient (P = 0.001), tumor location (P < 0.0001), tumor multifocality (P = 0.005), higher tumor stage (P < 0.0001), higher tumor grade (P = 0.038), lymphovascular invasion (P = 0.002), and mode of operation (P = 0.001). Tumor size was not associated with bladder-only recurrence (HR 0.91; 95 % CI 0.46–1.80; P = 0.79). The Kaplan–Meier method showed that tumor size >3 cm was significantly associated with worse CSS (P = 0.006, log rank). The 5-year CSS for patients with tumor size ≤3 cm was 70.1 % and for patients with tumor size >3 cm was 56.1 %. Tumor size was not associated with cancer-specific survival in multivariable analysis (HR 1.53; 95 % CI 0.89–2.61; P = 0.12).

Conclusions

Tumor size >3 cm was associated with a lower 5-year CSS at Kaplan–Meier analysis, but was not an independent predictor of CSS, bladder-only recurrence, and any recurrence-free survival at multivariable analysis.     

Palliative Resection for Advanced Gastric and Junctional Adenocarcinoma: Which Patients will Benefit from Surgery?

Background

Whereas palliative chemotherapy offers a median survival of approximately 10 months in advanced gastric and junctional adenocarcinoma (AGJA), the survival impact of primary tumor resection is controversial. Our purpose was to identify which AGJA patients benefit from palliative resection.

Methods

In 3,202 AGJA patients scheduled for surgery in 21 French centers between 1997 and 2010, prognostic factors were identified in palliative group and the impact of each combination of these factors on survival was studied.

Results

Surgery was defined as palliative due to solid organ metastasis (5.6 %), localized (4.6 %) or diffuse (2.3 %) peritoneal carcinomatosis (PC), or incomplete tumoral resection (12.8 %). Median survival of AGJA patients resected with a palliative intent (n = 677) was longer than in nonresected patients (n = 532; 11.9 vs. 8.5 months, P < 0.001). Multivariable analyses identified ASA score III-IV (P < 0.001) as a predictor of postoperative mortality and solid organ metastasis (P = 0.009), localized PC (P = 0.004), diffuse PC (P = 0.046), and signet ring cell histology (SRC; P = 0.02) as predictors of survival. Only ASA I–II patients with incomplete resection without metastasis or PC, one site solid organ metastasis without PC, or localized PC without SRC had a survival benefit after palliative surgery with median survivals from 12.0 to 18.3 months. Nonresected ASA I–II patients with same risk factors had median survivals from 3.5 to 8.8 months (P < 0.05 for each).

Conclusions

In AGJA, patient and tumor-related factors should be used to select candidates for palliative surgery in association with chemotherapy.     

Retrospective Evaluation of the Influence of Postoperative Tumor Marker Status on Survival and Patterns of Recurrence After Surgery for Pancreatic Cancer Based on RECIST Guidelines

Purpose

The purpose of this study was to obtain a comprehensive understanding of the impact of postoperative tumor marker (TM) normalization on survival after pancreatectomy for pancreatic carcinoma. We propose the concept of surgical RECIST based on residual tumor and TM status.

Methods

A total of consecutive patients with pancreatic carcinoma underwent pancreatectomy between August 1, 1989, and August 1, 2008. Pre- and postoperative TM values were available for 194 patients. The relationship between TM status, survival, and other clinical and demographic data was determined with univariate log-rank tests and Cox proportional hazards analysis.

Results

Postoperative TM levels remained elevated in 92 patients (47.4%; partial responders). TM levels normalized in 102 patients (52.6%; complete responders). Lymph node metastases, portal vein resection, absence of retroperitoneal clearance, residual tumor, preoperative high CA19-9, and surgical partial response were associated with decreased survival. Nodal stage (P = 0.0227) and surgical RECIST (P = 0.025) were significant predictors of survival. Partial responders had a significantly lower median survival time (P = 0.0008) and significantly higher frequency of hepatic metastasis (P = 0.0299).

Conclusions

Postresection TM normalization is a strong prognostic factor for pancreatic cancer. The efficacy of pancreatic cancer surgery should be evaluated in the context of both local clearance and serum TM kinetics.     

Absence of hMLH1 or hMSH2 Expression as a Stage-Dependent Prognostic Factor in Sporadic Colorectal Cancers

Background

The predictive role of mismatch repair (MMR) status for survival after sporadic colorectal cancer remains a point of controversy. This study was designed to test the prognostic value of MMR status in sporadic colorectal cancers.

Methods

The study included 318 patients with sporadic colorectal cancer who underwent primary tumor resection. MMR status was determined by the immunohistochemical analysis of hMLH1 and hMSH2 expression.

Results

Thirty-six carcinomas (11.3%) showed abnormal MMR protein expression (22 hMLH1 negative and 14 hMSH2 negative) and were classified as MMR-defective tumors. An MMR defect was strongly associated with a reduced likelihood of lymph node (odds ratio, 0.32; 95% confidence interval [95% CI], 0.13–0.75) or distant organ metastases at diagnosis (odds ratio, 0.07; 95% CI, 0.01–0.62), independent of the clinicopathological features. Overall survival was significantly better in patients with MMR-defective tumors than in those with MMR-intact tumors (P = 0.013). In the subgroup analysis by stage, adjusted for other potential confounding variables, MMR status was not a statistically significant prognostic factor in stage I and II patients, while the MMR defect predicted a significantly better overall survival in stage III and IV patients (adjusted hazard ratio, 0.23; 95% CI, 0.06–0.97; P = 0.045).

Conclusions

At initial diagnosis, metastases were found at lower rates in MMR-defective tumors. MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.     

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Improves Survival of Patients with Peritoneal Carcinomatosis from Gastric Cancer: Final Results of a Phase III Randomized Clinical Trial

Background

This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer.

Methods

Sixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60–90 min. The primary end point was overall survival, and the secondary end points were safety profiles.

Results

Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2–36 (median 15) in the CRS + HIPEC and 3–23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0–1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5–83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8–8.2 months) in CRS and 11.0 months (95% confidence interval 10.0–11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0–1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival.

Conclusions

For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.     

Treatment and Outcome of Patients with Gastric Remnant Cancer After Resection for Peptic Ulcer Disease

Background

To study the pathology, treatment, and outcome of patients with gastric remnant cancer (GRC) after resection for peptic ulcer disease (PUD).

Methods

Review of a prospective gastric cancer database identified patients with GRC after gastrectomy for PUD. Clinicopathologic and treatment-related variables were obtained. Multivariate analysis was performed for factors associated with disease-specific survival (DSS).

Results

From January 1985 to April 2010, 4402 patients with gastric adenocarcinoma were treated at our institution and 105 patients (2.4%) had prior gastrectomy for PUD. Prior resections were most often Billroth II (N = 97, 92%). The median time from initial resection to development of GRC was 32 years (3–60 years), and the majority of tumors were located at the gastrointestinal anastomosis (N = 72, 69%). Median DSS was 1.3 years (0.6–2.1 years). Patients who had resection had a significantly better outcome than patients who did not have resection (median DSS 5 vs 0.35 years, P < .0001). Factors associated with DSS on multivariate analysis included advanced T-stage (HR 16.5 (CI 2.2–123.4), P = .0006) and lymph node metastasis (HR 1.1 (CI 1.0–1.2), P < .0001). Stage-specific survival following R0 resection was similar to patients with conventional gastric cancer.

Conclusions

Patients have a lifetime risk for the development of GRC following resection for PUD. As with conventional gastric cancer, determinants of survival of patients with GRC include advanced T stage and nodal metastasis. Patients with GRC amenable to curative resection exhibit the best DSS and have stage-specific outcomes similar to patients with conventional gastric cancer.