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David Blumberg

Publications and source records attributed to David Blumberg.

11 recordsLinked to original sources
PubMed2006

Should completely intracorporeal anastomosis be considered in obese patients who undergo laparoscopic colectomy for benign or malignant disease of the colon?

BACKGROUND: The outcome of laparoscopic colectomy with completely intracorporeal anastomosis (LCIA) in obese and nonobese patients is assessed. METHODS: Forty-five consecutive patients who underwent LCIA for benign or malignant disease of the right and proximal left colon were reviewed prospectively. Obesity was defined as a body mass index of >30 kg/m(2). RESULTS: There were 24 men (53%) and 21 women (47%) with a mean age of 67 years (46-84 years). The mean body mass index was 27 kg/m(2) (16-38 kg/m(2)); 13 patients (29%) were obese. One procedure was converted to a laparoscopic-assisted colectomy. The mean operative time, estimated blood loss, and duration of stay were 218 minutes (110-420 minutes), 82 mL (50-250 mL), and 5 days (2-11 days), respectively. The mean length of the larger incision (extraction site) and the sum of all port incisions was 4 cm (3-8 cm) and 7 cm (6-10 cm), respectively. Complications occurred in 8 of 45 patients (18%), with no deaths. The mean number of harvested lymph nodes per specimen was 11 (3-30 lymph nodes). Obesity had no effect on operative time (obese patients, 232 minutes; nonobese patients, 213 minutes), incision length (obese patients, 4 cm; nonobese patients, 4 cm) estimated blood loss (obese patients, 100 mL; nonobese patients, 76 mL), complications (obese patients, 15%; nonobese patients, 19%), duration of stay (obese patients, 5 days; nonobese patients, 5 days), or number of harvested lymph nodes (obese patients, 11 lymph nodes; nonobese patients, 11 lymph nodes). There were no port-site hernias or metastases during a mean follow-up period of 5 months (1-18 months). CONCLUSIONS: LCIA can offer smaller incisions, improved cosmesis, and low conversion rates while oncologic principles are preserved. LCIA is a feasible and safe technique with equally successful outcomes in thin and obese patients.

Aged↗
PubMed2006

Microdissection-based allelotyping: a novel technique to determine the temporal sequence and biological aggressiveness of colorectal cancer.

Pathologic staging in colorectal adenocarcinoma (CA) is based on the concept that the timing of metastatic tumor spread is directly related to the depth of the primary tumor invasion. To evaluate the temporal sequence of CA metastasis, we performed microdissection mutational profiling at multiple microscopic sites of primary and metastatic CA specimens. Twenty-one cases of CA were selected from fixed-tissue archives. Primary tumors were microdissected at the deepest point of invasion. Comparative mutational profiling for different genomic loci [1p36(CCM = cutaneous malignant melanoma], 3p26(OGGI = 8 oxoguanine DNA glycosylase), 5q23 (APC, MCC = mutated in colorectal cancer), 9p21(p16/CDKN2A = cyclin-dependent kinase 2A), 10q23(PTEN = phosphatase and tensin homolog [mutated in multiple advanced cancers 11), 12p12(K-ras-2 point mutation), 17p13(TP53), 18q25(DCC= deleted in colorectal cancer) was carried out on each microdissected tissue target using microsatellite loss of heterozygosity determination or DNA sequencing. All primary and metastatic sites of CA manifested acquired mutational change in 18 to 91 per cent of the genomic markers. In 15/21 (71%) cases, metastatic sites lacked a specific allelic loss seen in the corresponding primary tumor, indicating that the metastasis occurred before maximal depth of primary invasion. This was further supported by discordant mutational profiles between primary and secondary tumors, requiring divergent clonal evolution. This is the first report describing the temporal sequence and significance of sequential mutational acquisition in clinical tissue specimens with potential implications for a new molecular pathology approach to classify human cancer.

Adenocarcinoma↗
PubMed2004

Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53.

Nitric oxide (NO) is a potent tumor radiosensitizer; however, its clinical use is limited by systemic side effects. We have demonstrated previously that gene transfer of the human inducible NO synthase (iNOS) gene into tumor cells and tumors induces high-output NO production that significantly enhances tumor radioresponsiveness, with no observed side effects. Notably, iNOS gene transfer enhances tumor radioresponsiveness via apoptotic cell death. Because NO and ionizing radiation are both known to promote p53-dependent apoptosis, we hypothesized that p53 activation might be a primary mechanism for the synergy of these two genotoxic stresses. We report that NO and ionizing radiation synergistically activate p53 in colorectal cancers grown in athymic mice by augmenting phosphorylation of p53 at serine 15. The effect of NO and ionizing radiation on tumor cell apoptosis and tumor radioresponsiveness is significantly reduced in p53 knockout isogenic cancer cell lines. Furthermore, the transfer of both p53 and iNOS genes into tumor cells lacking functional p53 enhanced their radioresponsiveness more than transfer of either gene alone.

Adenoviridae↗
PubMed2004

Adenoviral gene transfer of the human inducible nitric oxide synthase gene enhances the radiation response of human colorectal cancer associated with alterations in tumor vascularity.

Nitric oxide is a potent radiosensitizer of tumors, but its use clinically is limited by serious side effects when administered systemically. We have demonstrated previously that gene transfer of the inducible nitric oxide synthase gene (iNOS) into colorectal cancer cells enhances radiation-induced apoptosis in vitro. The objectives of this study were to further characterize the effects of iNOS gene transfer on the radiosensitivity of human colorectal cancer cells in vitro and tumors grown in athymic nude mice. Adenoviral gene transfer of iNOS (AdiNOS) into human colorectal cancer cell lines (HCT-116 and SNU-1040 cells) significantly enhanced the effects of radiation with sensitizing enhancement ratios (0.1) of 1.65 and 1.6, respectively. The radiation enhancement induced by iNOS was associated with increased iNOS expression and nitric oxide production and prevented by L-NIO, an enzymatic inhibitor of iNOS. AdiNOS treatment of HCT-116 tumors combined with radiation (2 Gy x three fractions) led to a 3.4-fold greater (P < 0.005) tumor growth delay compared with radiation (RT) alone. AdiNOS plus RT also caused significant (P < 0.01) tumor regression with 63% of tumors regressing compared with only 6% of tumors treated with RT. AdiNOS plus RT significantly (P < or = 0.001) increased the percentage of apoptotic cells (22 +/- 4%) compared with either tumors treated with control vector plus RT (9 +/- 1%), AdiNOS alone (9 +/- 3%), or no treatment (2 +/- 1%). These radiosensitizing effects of AdiNOS occurred at low infection efficiency (4% of tumor infected), indicating a significant bystander effect.

Adenoviridae↗
PubMed2003

Prognostic significance of depth of gross or microscopic perirectal fat invasion in T3 N0 M0 rectal cancers following sharp mesorectal excision and no adjuvant therapy.

BACKGROUND AND AIMS: Although the standard of care for T3 and/or N1-2 rectal cancers includes adjuvant chemoradiation, it is unclear whether T3 N0 patients with limited microscopic perirectal fat invasion warrant further therapy. Our aim was to determine the prognostic significance of gross perirectal fat invasion, or depth of microscopic perirectal fat invasion, in T3 N0 rectal cancers following sharp mesorectal excision and no adjuvant therapy. PATIENTS AND METHODS: Utilizing a prospective database, the medical records of 108 patients who underwent a potentially curative resection for T3 N0 rectal cancer between June 1986 and December 1994 were analyzed. All pathological specimens were re-reviewed by a single pathologist, and extent of perirectal fat invasion was measured in millimeters. Patients who received either preoperative or postoperative adjuvant therapy were excluded. RESULTS: Macroscopic perirectal fat invasion (T3 gross) was present in 49 cases, absent in 40 cases (T3 microscopic), and not reported in 19 cases. Rectal cancers were stratified by extent of measured perirectal fat invasion into 3 mm or less and more than 3 mm. Five-year overall and local recurrence rates for the entire group were 19% and 8%, respectively. The disease-free survival, disease-specific survival, and overall recurrence for rectal cancers with 3 mm or less invasion vs. more than 3 mm invasion, or T3 gross vs. T3 microscopic, were not statistically different. CONCLUSION: Our data suggest that the extent of gross, or microscopic perirectal fat invasion (defined as >3 or </=3 mm), determined in the resected specimen, does not predict outcome in select T3 N0 rectal cancers.

Adipose Tissue↗
PubMed2003

Overexpression of the human inducible nitric oxide synthase gene enhances radiation-induced apoptosis in colorectal cancer cells via a caspase-dependent mechanism.

Nitric oxide (NO) has been reported to sensitize cancer cells to radiation. Since delivery of NO to tumors is limited in vivo by systemic toxicity of NO, we examined the potential of gene delivery of the human inducible nitric oxide synthase (iNOS) gene as a means of achieving high output NO production. We successfully transduced two colorectal cancer cell lines as evidenced by increased iNOS protein accumulation and nitrite production. We found that overexpression of iNOS enhanced the effects of radiation on apoptosis in both cell lines in a caspase-dependent fashion. Gene transfer of iNOS holds much promise as a potential radiosensitizer of cancer cells since it increases apoptosis in an additive manner with radiation.

Amino Acid Chloromethyl Ketones↗
PubMed2003

Gene transfer of human manganese superoxide dismutase protects small intestinal villi from radiation injury.

Small bowel toxicity represents a major dose-limiting side effect of radiation treatment for many malignancies. We examined the effects of overexpressing human manganese superoxide dismutase (MnSOD) in the small intestine in mice to prevent radiation enteritis. Mice were treated with the human MnSOD gene delivered enterally using a nontoxic, replication-defective herpes simplex virus (HSV)-1-based vector. HSV vectors containing the human MnSOD transgene and green fluorescent protein (GFP) transgene, or GFP transgene alone, were constructed and injected intraluminally into a 2cm length of small intestine of C3H/HeNsd mice. Total body irradiation of 15 Gy was delivered to mice inoculated 24 hours earlier with either HSV-MnSOD (10(3) to 10(8) plaque-forming units), control HSV-GFP, or no vector. At 24 or 72 hours after irradiation, mice were killed and villi areas were measured from appropriate segments of the small intestine. Control irradiated mice showed a decreased villi area of 82% by day 3 after irradiation, whereas treatment of mice with HSV-MnSOD 10(8) plaque-forming units led to only a 16% decrease in villi area (P < 0.001) before radiation. Similar findings were seen on day 3 and were associated with a significant (P < 0.001) preservation of enteric protein content in HSV-MnSOD-treated mice. A dose-dependent effect of MnSOD in preventing radiation-induced small bowel injury was evident. These data demonstrate that overexpression of human MnSOD via a replication-defective herpes viral vector is an efficacious method of protecting the small intestine from ionizing radiation damage.

Analysis of Variance↗
PubMed2002

Surgery for ulcerative colitis.

The type of surgery performed for UC varies from patient to patient and must take into account the nutritional status and health of the patient, the presence of dysplasia or cancer, the desire of the patient to maintain continence, the preoperative anorectal function, the degree of confidence in the diagnosis of UC, and the technical constraint because of certain body habituses. A total proctocolectomy is the surgical procedure of choice for UC. A restorative proctocolectomy is the preferred surgical approach that not only cures the patient of the disease and prevents the development of colorectal cancer, but also maintains continence with an improved quality of life.

Colitis, Ulcerative↗
PubMed2002

Long-term results of local excision for rectal cancer.

OBJECTIVE: To review the authors' experience with local excision of early rectal cancers to assess the effectiveness of initial treatment and of salvage surgery. SUMMARY BACKGROUND DATA: Local excision for rectal cancer is appealing for its low morbidity and excellent functional results. However, its use is limited by inability to assess regional lymph nodes and uncertainty of oncologic outcome. METHODS: Patients with T1 and T2 adenocarcinomas of the rectum treated by local excision as definitive surgery between 1969 to 1996 at the authors' institution were reviewed. Pathology slides were reviewed. Among 125 assessable patients, 74 were T1 and 51 were T2. Thirty-one patients (25%) were selected to receive adjuvant radiation therapy. Fifteen of these 31 patients received adjuvant radiation in combination with 5-fluorouracil chemotherapy. Median follow-up was 6.7 years. One hundred fifteen patients (92%) were followed until death or for greater than 5 years, and 69 patients (55%) were followed until death or for greater than 10 years. Recurrence was recorded as local, distant, and overall. Survival was disease-specific. RESULTS: Ten-year local recurrence and survival rates were 17% and 74% for T1 rectal cancers and 26% and 72% for T2 cancers. Median time to relapse was 1.4 years (range 0.4-7.0) for local recurrence and 2.5 years (0.8-7.5) for distant recurrence. In patients receiving radiotherapy, local recurrence was delayed (median 2.1 years vs. 1.1 years), but overall rates of local and overall recurrence and survival rates were similar to patients not receiving radiotherapy. Among 26 cancer deaths, 8 (28%) occurred more than 5 years after local excision. On multivariate analysis, no clinical or pathologic features were predictive of local recurrence. Intratumoral vascular invasion was the only significant predictor of survival. Among 34 patients who developed tumor recurrence, the pattern of first clinical recurrence was predominantly local: 50% local only, 18% local and distant, and 32% distant only. Among the 17 patients with isolated local recurrence, 14 underwent salvage resection. Actuarial survival among these surgically salvaged patients was 30% at 6 years after salvage. CONCLUSIONS The long-term risk of recurrence after local excision of T1 and T2 rectal cancers is substantial. Two thirds of patients with tumor recurrence have local failure, implicating inadequate resection in treatment failure. In this study, neither adjuvant radiotherapy nor salvage surgery was reliable in preventing or controlling local recurrence. The postoperative interval to cancer death is as long as 10 years, raising concern that cancer mortality may be higher than is generally appreciated. Additional treatment strategies are needed to improve the outcome of local excision.

Adenocarcinoma↗
PubMed2002

Treatment of colon and rectal cancer.

During the past two decades, remarkable progress has been made in the treatment of cancers of the colon and rectum. Both oncologic and functional outcomes for this disease have improved dramatically. The reasons for the improved patient outcome in this disease include advances in knowledge of the biology of the disease, advances in surgical instrumentation and techniques, and ongoing advances in multimodality therapy, with the use of radiation and chemotherapy as an adjuvant to surgical resection. This review details many of these advances in a comprehensive manner and illustrates the necessity of a multidisciplinary approach for optimizing outcome for patients with these cancers.

Colonic Neoplasms↗