Loss of heterozygosity on chromosome 6q14-q24 is associated with poor outcome in children and adolescents with T-cell lymphoblastic lymphoma.

Deletions of chromosome 6q have been reported in several hematological malignancies, but data are not conclusive regarding their biological and prognostic impact. Therefore, we focused on pediatric patients diagnosed with T-cell lymphoblastic lymphoma (T-LBL) treated uniformly according to the NHL-BFM95 protocol. We used loss-of-heterozygosity (LOH) analysis of 25 microsatellite markers located on chromosome 6q14-q24. Fragment-length analysis was performed on ABI-PRISM3100 Genetic-Analyzer. Eligibility criterion was > or =3 informative markers. Between April 1995 and March 2003, 185 T-LBL patients were treated according to the NHL-BFM95 protocol. Five-year event-free (EFS) and disease-free survival (DFS) were 79+/-3 and 87+/-3% (median follow-up 4.7 [1.2-10.1] years). Sixty-one patients were evaluable for LOH analysis, including 18 out of 23 patients with relapse. EFS and DFS were 67+/-6 and 69+/-6% for these 61 patients. Testing of 853 markers in the 61 patients identified the presence of LOH in 19 patients (31%): 13 of the 18 relapse patients and five of the 41 in complete remission (odds ratio 18.7, 95% confidence interval 4.7-75.3). One LOH-positive patient died from treatment-related toxicity. We conclude that LOH on chromosome 6q14-q24 may have conferred a high risk of relapse on our group of children with T-LBL treated according to the NHL-BFM95 protocol.

Immunoglobulin class-switch recombination occurs in mantle cell lymphomas.

Mantle cell lymphoma (MCL) is an IgM-expressing B cell lymphoma that originates from naive B cells and responds poorly to chemotherapy. We show here that several MCLs harbour isotype-switched subclones. Similar to the situation in normal B cells, in vitro stimulation of MCL cell lines with CD40 ligand (CD40L) and interleukin-4 induced expression of activation-induced cytidine deaminase (AID) and germline transcription at the immunoglobulin heavy chain gene locus. Additionally, the occurrence of switch-circle transcripts and mature IgG transcripts after stimulation indicated ongoing class-switch recombination in mantle cell lymphoma cell lines. Furthermore, stimulation of primary MCL cells in vitro induced expression of class-switched IgG mRNA in the tumour cells. Our data indicate that mantle cell lymphomas have retained the ability to undergo class-switch recombination if appropriate stimuli, such as the CD40 ligand, are provided.

Chemotherapy may be more effective in highly proliferative ovarian carcinomas--a translational research subprotocol of a prospective randomized phase III study (AGO-OVAR 3 protocol).

OBJECTIVE: Proliferative activity (PA) may be an indicator of a neoplasm's malignant potential, and it has been described as a prognostic factor in different malignant tumors. It was our aim to study the prognostic significance of PA defined by Ki-S5 and Ki-S2 immunohistochemical staining in a large homogeneously treated cohort with primary advanced-stage ovarian carcinomas. METHODS: Immunohistochemical detection of PA was performed using monoclonal Ki-S5 and Ki-S2 antibodies and standard immunostaining protocols. Kaplan-Meier survival analysis and Cox regression multivariate analysis were performed. RESULTS: High Ki-S5 PA was associated with a better prognosis. This finding was statistically significant after univariate and multivariate analysis. A similar trend was found in the subgroup of completely debulked patients. No prognostic effect of Ki-S2 PA could be detected in the present study. CONCLUSION: High Ki-S5 PA is an indicator of a more favourable prognosis in patients with advanced ovarian carcinomas. Antiproliferative chemotherapy may be more effective in tumors which are highly proliferative, possibly due to an increased chemosensitivity.

Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma.

Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells. Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6. The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001). Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL. A high MCM6 expression level of more than 75% positive cells was associated with a significantly shorter overall survival time (16 months) compared to MCL with a low MCM6 expression level of less than 25% (no median reached, P<0.0001). Multivariate analysis revealed MCM6 to be an independent predictor of survival that is superior to the international prognostic factor and the Ki-67 index. Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL.

Stable remission after administration of rituximab in a patient with primary hepatic marginal zone B-cell lymphoma.

We describe a case of primary hepatic marginal zone B-cell lymphoma in a 36-year-old Caucasian male with a history of chronic hepatitis B infection. Immunohistochemically, extensive infiltration by a CD20-positive, CD5- negative and CD10-negative lymphoid cell population displaying a follicular arrangement was detected. Molecular analysis of immunoglobulin heavy chain gene rearrangements confirmed the clonal expansion of lymphoma cells. Fourteen months after surgical treatment, the tumour recurred in close proximity to the liver hilus, hampering further surgery. Therefore, we implemented a therapy using the monoclonal anti-CD20-antibody rituximab in a dose of 375 mg/m(2), administered four times once a week. Six, 10, 18, and 26 months later the recurrent lymphoma could no longer be detected as shown by abdominal ultrasonography and CT. This case report demonstrates the difficulties of treating this extremely rare liver disease and shows its response to rituximab therapy.

Sequential application of chemotherapy and monoclonal CD 20 antibody: successful treatment of advanced composite-lymphoma.

We describe successful treatment of a 38-year-old patient with composite lymphoma stage IV(A), who presented with multifocal enlarged lymph nodes. The lymph node histology showed classic morphologic features of Hodgkin's disease, mixed cellularity subtype and follicular B-cell lymphoma. Immunophenotypic analysis showed immunoreactivity for CD20, CD10 and Ki-67 in the malignant small cell population. The areas of Hodgkin's disease demonstrated positive immunoreactivity for CD30 and CD20 in the Hodgkin's cells. Both cell populations were bcl2-oncoprotein positive. Eight courses of dose-escalated BEACOPP were administered. Restaging after chemotherapy showed radiological partial remission, but biopsy confirmed persisting follicular B-cell lymphoma without bone marrow infiltration and no evidence of Hodgkin's disease. He was treated with monoclonal CD 20-antibody (Rituximab) 10 mg/kg weekly for eight consecutive weeks due to marked positivity of CD 20-antigen in follicular lymphoma cells. This treatment was well tolerated and final staging showed complete remission of the composite lymphoma. This patient continues to be in remission 28 months after the end of the treatment. In conclusion, in the very rare case of composite lymphoma a combination of chemotherapy and subsequent immunotherapy might be considered as a promising therapeutic option.

Telomerase activity in B and T lymphocytes of patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate telomerase activity as a marker of lymphocyte proliferation in systemic lupus erythematosus (SLE). METHODS: CD19+, CD4+, and CD8+ lymphocytes were isolated from the peripheral blood of nine patients with SLE and nine healthy controls by means of magnetic bead-coupled antibodies and tested for telomerase activity with the TRAP assay. RESULTS: Telomerase activity was significantly increased in CD19+ B cells from patients with SLE. CD4+ and CD8+ T cells from lupus patients displayed increased mean telomerase activity, although the difference from normal controls did not reach statistical significance. CONCLUSIONS: Increased telomerase activity in the B and the T cell lineage might indicate activation and proliferation of these lymphocytes.

Topoisomerase IIalpha expression in mantle cell lymphoma: a marker of cell proliferation and a prognostic factor for clinical outcome.

Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3-4 years. Treatment usually consists of combination chemotherapy, often including topoisomerase (topo) inhibitors such as doxorubicin, etoposide and mitoxantrone. Topo IIalpha is an enzyme that is needed whenever uncoiling of DNA is necessary during the cell cycle. The enzyme is a marker of cell proliferation. We analyzed the expression of topo IIalpha in relation to Ki-67 and the clinical outcome in patients with MCL. Biopsy specimens from 95 untreated patients enrolled in two multicenter trials (1975-1985) were investigated immunohistochemically with monoclonal antibodies against topo IIalpha (Ki-S4) and Ki-67 (Ki-S5). Patients with low (0-10%) topo IIalpha expression had a median overall survival time of 49.0 months, compared to 17.0 months for patients with high (more than 10%) topo IIalpha expression. The Kaplan-Meier analysis showed a significant difference in the overall survival time related to the percentage of topo IIalpha (P<0.001) and Ki-67 (P<0.001) positive tumor cells. Multivariate Cox regression analysis revealed the expression of topo IIalpha as the most important prognostic factor (P<0.001) in MCL superior to the international prognostic index (IPI), the Ki-67 index and other clinical characteristics.

[Primary renal manifestation in malignant lymphomas and leukemia]. / Primäre renale Manifestation bei malignen Lymphomen und Leukämie.

Primary manifestation of malignant lymphoma and/or leukaemia rarely occurs in the kidney. It can be the cause of a hitherto unexplained acute renal failure or it is incidentally detected as shown in the three cases under report.1.A 68-year-old man was operated on because of a symptomatic tumour in his right kidney. At nephrectomy, a conventional (clear cell) renal cell carcinoma was found simultaneously with an occult mantle cell lymphoma infiltrating the adjacent renal and extrarenal tissue. Clinical follow-up uncovered nodal and bone marrow involvement, so that a primary renal manifestation of mantle cell lymphoma was apparent.2.A 69-year-old man with suspected vertebral metastasis underwent partial renal resection because of a mass in his left kidney. Histologically and immunohistochemically, the renal infiltration was diagnosed as a precursor B-lymphoblastic lymphoma. After chemotherapy and irradiation, leukaemic blood cell counts with 50% lymphoblasts proved a primary renal manifestation of precursor B-lymphoblastic leukaemia/lymphoma.3.A 13-year-old boy presented clinically with renal failure, enlarged kidneys, and normal urinalysis. Renal biopsy showed a diffuse interstitial infiltration with atypical T-lymphoblasts compressing tubules and surrounding preserved glomeruli. Subsequent clinical bone marrow smears presented 60% T-lymphoblasts, so that the final diagnosis of a primary renal manifestation of acute T-lymphoblastic leukaemia of mature thymic cortex type was made. Immediate chemotherapy resulted in total recovery of renal function and bone marrow findings.

Segmental chromosomal aberrations and centrosome amplifications: pathogenetic mechanisms in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma?

Tumor cell metaphases of classical Hodgkin's lymphoma (cHL) characteristically display highly rearranged karyotypes with chromosome numbers in the hyperploid range and marked intraclonal variability. The causes of this cytogenetic pattern remain largely unknown. An unusual type of chromosomal abnormality coined as segmental chromosomal aberration (SCA) has been recurrently observed in HL cell lines and was suggested to be associated with ribosomal DNA (rDNA) rearrangements. Moreover, centrosome abnormalities provoking deficient chromosome segregation have been reported in many solid tumors and also in cHL cell lines. Whether SCA, rDNA rearrangements or centrosome abnormalities also occur in primary cHL is not yet known. Thus, we performed extensive molecular cytogenetic and immunohistological studies in two cHL cases. Both cases presented SCA associated with genomic gains of the REL and JAK2 loci, respectively. The SCA involving JAK2 was associated with rDNA rearrangements. The absolute centrosome size of HRS cells in both cases was significantly larger than in non-HRS cells, but the relative centrosome size of HRS cells corrected for nuclear size was in the same range as that of the non-neoplastic cells. These findings demonstrate that the various mechanisms associated with chromosomal instability warrant a more detailed characterization in cHL.

DNA damage transiently increases TRF2 mRNA expression and telomerase activity.

Telomerase activity transiently increases when HL60 cells are treated with the topoisomerase II inhibitor etoposide. A quantitative assessment revealed that telomerase is activated by etoposide treatment in a number of cell lines and that the increase is reversible after withdrawal of etoposide from the cell culture. Telomerase activation correlated with the occurrence of DNA damage but not with cell cycle arrest. We did not detect any transcriptional upregulation of hTERT mRNA, suggesting a post-transcriptional mechanism of telomerase activation. Furthermore, the mRNA expression of the telomere binding protein TRF2 was upregulated early and reversibly after etoposide treatment. TRF1 mRNA expression levels were unchanged after DNA damage, but increased when the cells accumulated in the G2/M phase. The data show that the telosome reacts after DNA damage by upregulating telomerase activity and TRF2 expression in malignant cells. It has previously been shown that overexpression of TRF2 can repress senescence signals arising from critically shortened telomeres. We show here that TRF2 is upregulated by undirected DNA damage that also affects the telomeric DNA. These data suggest that upregulation of telomerase activity and TRF2 expression might act as antiapoptotic mechanisms in the DNA-damage response of malignant cells.

Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomere-binding protein expression but uncoupled from proliferation.

Telomere maintenance is a prerequisite for immortalisation, and in most malignant cells is carried out by telomerase, an enzyme that synthesis new telomeric repeats on the chromosome ends. In normal or reactive tissues with a high regenerative capacity, telomerase is regulated according to the telomere loss that occurs during proliferation. To evaluate the interaction of proliferation and telomerase activity in malignant lymphomas, we quantified telomerase expression in different non-Hodgkin lymphomas in comparison to normal or reactive lymph nodes. Surprisingly, the activity levels were the same in most of the lymphomas analysed as compared to reactive lymph nodes. Significantly higher activity was detected only in Burkitt's lymphoma. Telomerase activity correlated well with hTERT and c-myc expression, but was independent of proliferation. To evaluate interactions of telomere-binding protein expression on telomerase expression in non-Hodgkin lymphoma, the mRNA levels of TRF1, TRF2, tankyrase and hPif1 were assessed by real-time RT-PCR. We demonstrate here that the magnitude of telomerase upregulation does not necessarily reflect the requirement of telomere compensation caused by proliferation. Telomerase regulation in non-Hodgkin lymphomas is therefore uncoupled from proliferative stimuli found in reactive lymphoid tissue. We suggest that the upregulation of specific telomere-binding proteins like TRF2 may contribute to telomere maintenance in malignant lymphoma.

Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents: analysis and outlook.

BACKGROUND: In 5 consecutive pediatric and adolescent Hodgkin's disease trials DAL-HD since 1978 the invasive diagnostic procedures and the radiotherapy have gradually been reduced and chemotherapy modified to minimize toxicity and the risk of late effects. Since 1982 the overall survival increased up to 95%. In this trial the possibility of reducing local radiation doses to 20 Gy in patients with good response to chemotherapy and omitting radiotherapy totally for patients with complete remission after chemotherapy was tested. PATIENTS AND METHODS: Over a period of 6 years, from August 1995 to July 2001, 1018 children and adolescents with Hodgkin's disease from Germany, Austria,Switzerland, the Netherlands, Sweden, Norway and Denmark were enrolled in this trial. The chemotherapy was equivalent to previous trial DAL-HD 90. The treatment group (TG) 1 (stages I and IIA) received 2 cycles OPPA for girls and 2 cycles OEPA for boys, TG2 (stages IIEA, IIB, IIIA) and TG3 (stages IIEB, IIIEA, IIIB, IV) received additional 2 or 4 cycles COPP respectively. In contrast to trial DAL-HD 90 boys in stage IIIB and IIIEB received OPPA instead of OEPA. The initial staging as well as the restaging for evaluating tumor volume reduction after chemotherapy was reviewed by the study center. Radiotherapy was planned accordingly: patients with complete remission after chemotherapy were not irradiated (21.9%); all other patients received local radiotherapy to the initially involved sites, depending on the tu-mor response. Patients with a partial remission of> 75 tumor regression were irradiated with 20 Gy (50AX), partial remission of< 75% with 30 Gy (4.1 %), and residual masses of > 50 ml were boosted up to 35 Gy (20.2 %). RESULTS: 36 tumor progressions and 49 relapses occurred over a period of 7 1/2 years (median followup 3 years, data deadline 12/19/02). Kaplan-Meier-analysis after 5 years showed a probability for event-free survival (pEFS) for all patients of 0.88 and for overall survival (pOS) of 0.97. For the total group the pDFS (disease free survival) was lower in 222 non irradiated patients than in the 758 irradiated patients (0.88 vs. 0.92,p - 0.049). But there was a difference between the individual treatment groups. In TG 1 there was no difference between nonirradiated and irradiated patients (0.97 vs. 0.94) and the non-ir-radiated patients showed a better trend. In TG 2, and in TG 2 and TG 3 combined, the pDFS was significantly worse for non irradiated patients in comparison with the irradiated patients (TG2:0.78 vs. 0.92; TG 2 +3:0.79 vs. 0.91). Compared to former DAL-HD trials the pOS stayed stable despite therapy reduction. CONCLUSIONS: A reduction of radiotherapy to 20 Gy for patients in all stages with good response to chemotherapy is possible without deterioration of the results. The omission of radiotherapy for patients in complete remission after chemotherapy is recommended only for patients in early stages (TG1). In future trials the possibility of a wider selection for chemotherapy alone for this group needs to be evaluated. In intermediate (TG2) and advanced (TG3) stages omission of radiotherapy for patients incomplete remission results in a lower pEFS, but the pOS is not significantly reduced. Only with knowledge of the long term effects of today's therapy we can give a satisfactory answer to the question whether in future trials the primary aim should be pEFS as high as possible due to front-line-therapy or reduction of late effects.

Primary mediastinal large B-cell lymphoma with sclerosis in pediatric and adolescent patients: treatment and results from three therapeutic studies of the Berlin-Frankfurt-Münster Group.

PURPOSE: Primary mediastinal large B-cell lymphoma with sclerosis (PMLBL) is a rare entity of non-Hodgkin's lymphoma (NHL) arising from thymic mature B cells. Optimal treatment strategies remain to be established, especially in pediatric patients. PATIENTS AND METHODS: This study analyzes clinical characteristics and treatment outcome of 30 pediatric patients with PMLBL, diagnosed in multicenter therapy NHL-Berlin-Frankfurt-Münster Group (BFM) trials. Treatment was stratified by stage and serum lactate dehydrogenase (LDH) and consisted of four to six 5-day courses of chemotherapy using steroids, oxazaphosphorine alkylating agents, methotrexate, cytarabine, etoposide, and doxorubicin. Radiation was not part of the protocol. RESULTS: From April 1986 to August 1999, 1,650 patients with newly diagnosed NHL were enrolled in the NHL-BFM trials; 30 patients (1.8%) had PMLBL. Median age was 14.3 years (range, 1.4 to 16.7 years); 15 patients were male and 15 patients were female. With a median observation time of 5 years (range, 1 to 12 years), probability of event-free survival (pEFS) at 5 years was 0.70 (SE, 0.08). Two patients erroneously diagnosed as T-cell NHL received non-B-cell therapy and died from progress of disease. Events in 28 patients receiving B-cell therapy included early progress during therapy (n = 1) and relapse (n = 6). Residual mediastinal masses were present in 23 patients after two courses of therapy and in 15 patients after the end of therapy. LDH > or = 500 U/L was associated with increased risk of failure in multivariate analysis. CONCLUSION: PMLBL mainly is found in adolescents. Dose-intense chemotherapy including high-dose methotrexate yields a pEFS at 5 years of 0.70 (SE, 0.08). LDH is of prognostic value in pediatric patients with PMLBL.

Regulation of telomerase activity by alternate splicing of human telomerase reverse transcriptase mRNA in a subset of neuroblastomas.

It has been proposed that the regulation of telomerase takes place at the transcriptional level, the expression of the catalytic subunit human telomerase reverse transcriptase (hTERT) being crucial for telomerase activity (TA). Recently, differential splicing of hTERT mRNA has been demonstrated in various tissues during embryonal development, and it has been suggested that only full-length transcripts translate into functionally active telomerase. With this in view, we analyzed the different hTERT transcripts by reverse transcriptase-polymerase chain reaction in neuroblastic tumors and compared the results with the TA, the tumor growth fraction, and the MYCN status. In a series of 38 neuroblastic tumors, high TA and full-length hTERT transcripts were found in nine samples, whereas nine samples showed absence of both enzymatic activity and hTERT transcripts. Interestingly, in another eight samples, low or absent TA coincided with a lack of full-length hTERT transcripts. Eleven samples contained hTERT transcripts with low or undetectable TA and one sample had low TA but no hTERT transcripts. TA correlated with MYCN amplification and was weakly associated with the proliferative activity. Moreover, a significant correlation with tumor progression was observed. Our findings point at a posttranscriptional regulation of TA in a subset of neuroblastic tumors. Because high TA was detected only in tumors with full-length hTERT transcripts, reverse transcriptase-polymerase chain reaction analysis of archival neuroblastic tumor samples might help to appraise the malignant potential in individual cases.

Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92.

PURPOSE: The study was initiated to obtain epidemiologic data and information on anatomic and histologic distribution, clinical features, and treatment results in patients with primary gastrointestinal non-Hodgkin's lymphomas (PGI NHL). PATIENTS AND METHODS: Between October 1992 and November 1996, 371 PGI NHL patients were eligible to evaluate clinical features. Radiotherapy and chemotherapy were stratified according to histologic grading, stage, and whether surgery had been carried out or not. RESULTS: A total of 74.8% patients had gastric NHL (PGL). Within the intestine, the small bowel and the ileocecal region were involved in 8.6% and 7.0% of the cases, respectively. Multiple GI involvement (MGI) was 6.5%. Approximately 90% of the GI NHL were in stages IE/IIE. Aggressive NHL accounted for the majority, with a distinguishable pattern in several sites. Forty percent of PGL were of low-grade mucosa-associated lymphatic tissue type. One third of large-cell lymphomas had low-grade components. Most intestinal NHL were germinal-center lymphomas. The site of origin was prognostic. In gastric and ileocecal lymphoma, event-free (EFS) and overall survival (OS) were significantly higher as compared with the small intestine or MGI (median time of observation, 51 months). In PGL, localized disease was prognostic for EFS and OS. Histologic grade influenced only EFS significantly. Numbers in intestinal lymphomas were too small for subanalyses. CONCLUSION: PGI NHL are heterogeneous diseases. The number of localized PGL allowed for detailed analyses. Larger studies are needed for stages III and IV and for intestinal NHL. A uniform reporting system for PGI NHL, in terms of definitions and histologic and staging classifications, is needed to facilitate comparison of treatment results.

Primary gastrointestinal non-Hodgkin's lymphoma: II. Combined surgical and conservative or conservative management only in localized gastric lymphoma--results of the prospective German Multicenter Study GIT NHL 01/92.

PURPOSE: The aim of the study was to obtain data on anatomic and histologic distribution, clinical features, and treatment results of patients with primary gastrointestinal non-Hodgkin's lymphomas, particularly combined surgical and conservative treatment (CSCT) versus conservative treatment (CT) alone for primary gastric lymphoma (PGL) in localized stages. PATIENTS AND METHODS: Whether the treatment included surgery was left to the discretion of each participating center. Radiotherapy (Rx) and chemotherapy were stratified according to histologic grading, stage, and the inclusion or omission of surgery as follows: patients with low-grade PGL were treated with extended-field (EF) Rx (30 Gy). In case of residual tumor after surgery or in case of CT only (in stage IIE after six cycles of cyclophosphamide, vincristine, and prednisone), an additional boost of 10 Gy was given. All patients with high-grade PGL were treated with four (stage IE) or six (stage IIE) cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by EF Rx (stage IE) or involved-field (IF) Rx (stage IIE). Rx dosage corresponded to low-grade NHL. RESULTS: Between October 1992 and November 1996, 106 patients had CT only. The survival rate (SR) after 5 years was 84.4% and was influenced neither by patients' characteristics nor by stage or histologic grade. Seventy-nine patients had CSCT. Their SR was 82.0%. Complete resection of the tumor (R0) was prognostic for the overall survival (P =.0165) as compared with incomplete resection. CONCLUSION: Although the study was not randomized, a stomach-conserving approach may be favored.