Schlomo Schneebaum

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: A consensus statement

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement

Clinical applications of gamma-detection probes – radioguided surgery

Abstract.Radioguided surgery (RGS) is a surgical technique that enables the surgeon to identify tissue ”marked” by a radionuclide before surgery, based on the tissue characteristics, the radioactive tracer and its carrying molecule, or the affinity of both. Thus, yet another tool has been added to the inspection and palpation traditionally used by the surgeon. Current clinical applications of radioguided surgery are: radioimmunoguided surgery (RIGS) for colon cancer, sentinel-node mapping for malignant melanoma (which has become state-of-the-art), sentinel-node mapping for breast, vulvar and penile cancer, and detection of parathyroid adenoma and bone tumour (such as osteid osteoma). Although the same gamma-detecting probe (GDP) may be used for all these applications, the carrier substance and the radionuclide differ. MoAb and peptides are used for RIGS, sulphur colloid for sentinel-node mapping, iodine-125 for RIGS, technetium-99m for sentinel node, parathyroid and bone. The mode of injection also differs, but there are some common principles of gamma-guided surgery. RIGS enables the surgeon to corroborate tumour existence, find occult metastases, and assess the margins of resection; this may result in a change on the surgical plan. Sentinel lymph-node (SLN) scintigraphy for melanoma guides the surgeon to find the involved lymph nodes for lymph-node dissection. SLN for breast cancer is being investigated with promising results. This procedure has also changed the outlook of lymph-node pathology by giving the pathologist designated tissue samples for more comprehensive examination. Gamma-guided surgery will result in more accurate and less unnecessary surgery, better pathology and, hopefully, in better patient survival.

Gamma probe-guided sentinel node biopsy--optimal timing for injection.

Aims. We initiated a Phase I feasibility study using a gamma-detecting probe (GDP) and radiolabelled colloid to localize the sentinel lymph node (SLN) in breast cancer. The aim of the study was to establish the ideal timing for injection and examine any possible exclusion criteria for this method. Methods. Thirty breast cancer patients diagnosed by fine needle aspiration (FNA) were included in this study. All were injected with 60 M Bq rhenium colloid labelled with 99m Tc (Tck-17). Scintigraphy was done 20 min, 2, 6 and 25 hours post-injection. Patients were then taken to surgery where they were injected with patent blue dye. During surgery, the SLN was located with a GDP (Neoprobe ® Model 1000). In 28 patients, the SLN was identified by scintigraphy 2 hours after injection, identical to the images seen after 24 hours. Results. In all 28 patients, the SLN was found by the GDP during surgery. In 26 patients the SLN was dyed blue. The two patients with no SLN localization had received prior radiation. Pathology disclosed SLNs with metastases in seven patients. Two patients had a negative SLN but had an axillary lymph node replaced by tumour. Conclusions. Two to 24 hours prior to surgery is suitable timing for injection. Previous radiotherapy predicts failure for this procedure. Further studies are needed to find the exact false-negative rate of this method for breast cancer.

Radioimmunoguided surgery benefits for recurrent colorectal cancer.

AbstractBackground: Despite new adjuvant therapy, 50% of patients with colon cancer will have recurrent disease. This study investigated the use of a radiolabeled monoclonal antibody in locating occult tumor during surgery for recurrent colorectal cancer. Methods: Twenty-two patients with recurrent colorectal cancer underwent surgery using the radioimmunoguided surgery (RIGS) system. All patients were subjected to abdominal and chest computed tomography (CT). Before surgery, patients were injected with the CC49 monoclonal antibody (MoAb), anti-TAG antibody labeled with125I. Ten patients with elevated carcinoembryonic antigen (CEA) levels and no CT findings had a scintigraphy scan with an anti-CEA MoAb labeled with99Tc. Human antimouse antibody levels of these patients were within normal limits. Surgical exploration including liver ultrasound examination was followed by survey with a gamma-detecting probe (GDP). Results: There was MoAb tumor localization in 100% of the patients. CT found nine tumor sites, traditional surgical exploration 30, and the GDP 51, with 44 confirmed by pathology (hematoxylin and eosin). The RIGS system found occult tumor in 10 patients (45.4%) and resulted in major changes in surgical procedure in 11 patients. In the 10 patients who had scintigraphy scans, 10 tumor sites were identified, whereas RIGS found an additional eight sites. Conclusion: RIGS technology offers a substantial benefit for patients undergoing surgery for recurrent colorectal cancer and a better chance of finding recurrent tumor intraoperatively in patients who have elevated CEA levels with no other CT findings.

Current management practice of breast borderline lesions—need for further research and guidelines

BACKGROUND Breast borderline lesions are usually diagnosed on needle biopsies of imaging abnormalities. The natural history of these lesions is unclear, and the literature is divided on appropriate management. It was hypothesized that management varies among surgeons and may be associated with surgeon and practice characteristics. METHODS A survey of 477 members of the American Society of Breast Surgeons was completed. Results were analyzed according to various surgeon and practice characteristics. RESULTS Most respondents recommended routine excision for atypical ductal and lobular hyperplasia. Excision of radial scars and papillomas was much more variable, with only 50% recommending routine excision. Results differed by surgical dedication to breast surgery and fellowship training. Management of atypical ductal or lobular hyperplasia found at the margin varied significantly. The lack of a routine tumor board, low breast case volume, and low percentage of breast cases were associated with routine excision in these cases. CONCLUSIONS Breast borderline lesions pose a clinical dilemma, with practice varying greatly among surgeons.

Malignant melanoma and pregnancy: second thoughts.

Malignant melanoma (MM) was considered a hormone-sensitive tumour, and pregnancy was thought to increase its risk and cause faster progression and earlier metastasis. Several controlled studies demonstrated similar survival rates between pregnant and non-pregnant patients and concluded that early reports of advanced MM of pregnancy were probably due to late diagnosis. We retrieved information from our database between 1997 and 2006 on all patients diagnosed as having MM during and up to 6 months after pregnancy (n=11) and compared them to age-matched, non-pregnant, MM patients (n=65, controls) treated by us during that period. The mean Breslow thickness was 4.28mm for the pregnant patients and 1.69mm for the controls (p=0.15). The sentinel nodes were metastatic in five pregnant patients compared to four controls (p<0.0001). Two patients in the pregnancy group and one control died of MM (p=0.0532). Our results indicate a negative effect of pregnancy on the course of MM.

Immunoguided Lymph Node Dissection in Colorectal Cancer: A New Challenge?

AbstractKnowledge of lymphatic involvement in patients with colorectal cancer is important in surgery and in the postoperative decision-making process. Fifty-eight patients with recurrent colorectal cancer underwent operation with the RIGS® (Radioimmunoguided Surgery) technology. Preoperatively, patients were injected with 1 mg monoclonal antibody (MoAb) CC49 (anti-TAG-72-tumor-associated glycoprotein) labeled with 2 mCi of iodine 125. Traditional surgical exploration was followed by survey with a gamma-detecting probe. Localization of MoAb on tumor was noted in 54/58 patients (93%). Traditional exploration identified 117 suspected tumor sites. With RIGS, 177 suspected tumor sites were detected. In 17 of the 58 patients (27.5%), at least one occult tumor site identified by RIGS was confirmed by pathology with hematoxylin & eosin (H & E) staining. This finding resulted in 16 major changes in surgical plan. RIGS performance varied between lymphatic and non-lymphatic tissue, with a positive predictive value (PPV) of 95.6% and negative predictive value (NPV) of 90% in non-lymphoid tissue compared to PPV of 40% and NPV of 100% in lymphoid tissue. In patients with tumors that localize, no RIGS activity in lymph nodes signifies no tumor, while decisions based on RIGS activity in lymph nodes requires H & E confirmation. Using this guideline, additional information acquired by RIGS can help the surgeon in making an informed decision during surgery and in planning postoperative therapy.

Effect of photodynamic therapy on normal fibroblasts and colon anastomotic healing in mice.

Photodynamic therapy as an adjuvant modality to surgical resection of colon cancer is feasible provided that it does not affect healing of the anastomosis. The aim of this study was to evaluate the effects of photodynamic therapy on the viability of normal fibroblasts and on the healing process of colonic anastomosis in mice. Both in vitro and in vivo methods were employed. For in vitro study, 2 x 105 human fibroblasts were incubated in triplicate with 5-aminolevulinic acid (2.5 μ g/well) for 48 hours. Cells then underwent photoradiation at light doses of 50,100, and 200 joules/cm2 using a nonlaser light source. Viability was assessed by methylene blue dye exclusion. For in vivo studies, 60 mice were randomized into study and control groups and underwent laparotomy involving colonic anastomosis. The anastomosis underwent photodynamic therapy using 5-aminolevulinic acid (60 mg/kg) as a photosensitizer and a nonlaser light (40 joules/cm2). On postoperative days 1, 4, 7, 14, and 21, six mice were killed and subjected to bursting pressure and histologie examinations. Results of in vitro study showed pretreatment cell viability to be 96% to 99% in both groups. Photodynamic therapy caused no significant change in fibroblast viability at all light doses. Results of in vivo studies showed that the mean bursting pressure of both groups dropped to a low peak on day 4. Subsequently there was a gradual increase in bursting pressure along the examined time points (P <0.001). There was no difference in bursting pressure between the two groups for all time points examined. It was concluded that photodynamic therapy has no effect on viability of normal human fibroblasts and no adverse effects on healing of colonic anastomosis.

Identification of lymph node metastases in recurrent colorectal cancer.

Lymph node metastases are an important prognostic prediction factor in patients with recurrent colorectal cancer, particularly those with liver metastasis. Fifty-six patients with recurrent colorectal cancer were operated by us using the RIGS (radioimmunoguided surgery) technology. Patients were injected with 1 mg monoclonal antibody (MoAb) CC49 labeled with 2 mCi 125I. In surgery, traditional exploration was followed by survey with a gamma-detecting probe. Sixty of 151 patients enrolled in the Neo2-14 Phase III study for recurrent colorectal cancer were diagnosed with liver metastases based on preoperative CT. In 17/56 patients (30%), RIGS identified at least one tumor site confirmed by pathology (H&E). This resulted in 16 major changes in surgical plan. RIGS performance varied between lymphatic and non-lymphatic tissue, with positive predictive value (PPV) of 100% and negative predictive value (NPV) of 94% for non-lymphoid tissue, compared to PPV of 46.5% and NPV of 100% for the lymphoid tissue. Thirty-five out of 60 patients were considered resectable after traditional evaluation. RIGS identified occult tumor in 10 of these patients (28.5%). 7/10 occult patients expired (70%), while only 7/25 of the non-occult patients expired (28%) (P = 0.046). In localizing patients, no RIGS activity in lymph nodes signifies no tumor, while H&E confirmation is needed for decisions based on RIGS activity in the lymph nodes. RIGS provides important staging information, identifying patients for whom surgery may be done with curative intent.