Sentinel node lymphocytes: tumour reactive lymphocytes identified intraoperatively for the use in immunotherapy of colon cancer

The sentinel node is the first lymph node to receive lymphatic drainage from a tumour and is usually the first site of metastases. Today, the sentinel node is used for tumour staging. Here, we focus on its immunological role and investigate lymphocytic function in sentinel nodes, identified intraoperatively by peritumoural dye injection, from 15 patients with colon cancer. Tumour infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and peripheral blood leukocytes were studied by flow cytometry, proliferation assays and interferon-γ secretion after activation with autologous tumour homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the proliferation assays, lymphocytes from sentinel nodes proliferated dose dependently and secreted interferon-γ upon stimulation with tumour homogenate. The responses were of varying magnitude and tended to be weaker in metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched source of tumour reactive lymphocytes, and may be useful in future trials of adoptive immunotherapy

A shift from distal to proximal neoplasia in the colon: a decade of polyps and CRC in Italy

<p>Abstract</p> <p>Background</p> <p>In the last years a trend towards proximalization of colorectal carcinomas (CRC) has been reported. This study aims to evaluate the distribution of CRC and adenomatous polyps (ADP) to establish the presence of proximalization and to assess the potential predictors.</p> <p>Methods</p> <p>We retrieved histology reports of colonic specimens excised during colonoscopy, considering the exams performed between 1997 and 2006 at Cuneo Hospital, Italy. We compared the proportion of proximal lesions in the period 1997-2001 and in the period 2002-2006.</p> <p>Results</p> <p>Neoplastic lesions were detected in 3087 people. Proximal CRC moved from 25.9% (1997-2001) to 30.0% (2002-2006). Adjusting for sex and age, the difference was not significant (OR 1.23; 95% CI: 0,95-1,58). The proximal ADP proportion increased from 19.2% (1997-2001) to 26.0% (2002-2006) (OR: 1.43; 95% CI: 1.17-1.89). The corresponding figures for advanced proximal ADP were 6.6% and 9.5% (OR: 1.48; 95% CI: 1.02-2.17). Adjusting for gender, age, diagnostic period, symptoms and number of polyps the prevalence of proximal advanced ADP was increased among people ≥ 70 years compared to those aged 55-69 years (OR 1.49; 95% CI: 1.032.16). The main predictor of proximal advanced neoplasia was the number of polyps detected per exam (> 1 polyp versus 1 polyp: considering all ADP: OR 2.16; 95% CI: 1.59-2.93; considering advanced ADP OR 1.63; 95% CI: 1.08-2.46). Adjusting for these factors, the difference between the two periods was no longer significant.</p> <p>Conclusions</p> <p>CRC do not proximalize while a trend towards a proximal shift in adenomas was observed among people ≥ 70 years.</p

Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation exists between the expression of EGFR and treatment outcome in a group of patients with rectal adenocarcinoma who had undergone preoperative radiotherapy (RT). METHODS: Within a six-year period, 138 patients underwent preoperative radiotherapy and curative surgery for rectal cancer (UICC stages II-III) at our institute. Among them, 77 pretherapeutic tumor biopsies were available for semi-quantitative immunohistochemical investigation evaluating the intensity and the number (extent) of tumor stained cells. Statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of loco-regional recurrences. RESULTS: Median age was 64 years (range: 30–88). Initial staging showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal-cancer patients the primary tumor received a boost dose of up to 16 Gy for a sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the cases. All patients underwent complete total mesorectal resection. Positive staining (EGFR+) was observed in 43 patients (56%). Median follow-up was 36 months (range: 6–86). Locoregional recurrence rates were 7 and 20% for EGFR extent inferior and superior to 25%, respectively. The corresponding locoregional recurrence-free survival rate at two years was 94% (95% confidence interval, CI, 92–98%) and 84% (CI 95%, 58–95%), respectively (P = 0.06). Multivariate analyses showed a significant correlation between the rate of loco-regional recurrence and three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17–46, P = 0.037), rectal resection with microscopic residue (hazard ratio = 6.92, CI 95%, 1.18–40.41, P = 0.032), and a total dose of 44 Gy (hazard ratio = 5.78, CI 95%, 1.04–32.05, P = 0.045). CONCLUSION: EGFR expression impacts on loco-regional recurrence. Knowledge of expression of EGFR in rectal cancer could contribute to the identification of patients with an increased risk of recurrences, and to the prediction of prognosis

Short-term natural history of isolated gastrocnemius and soleal vein thrombosis

AbstractObjective: Lower extremity deep vein thrombosis is often isolated to the sinusoidal veins draining the gastrocnemius and soleus muscles. The purpose of this study was to establish the incidence rate of propagation of isolated gastrocnemius and soleal vein thrombosis (IGSVT) into the deep veins of the calf and thigh. Methods: All patients who were referred for color flow duplex ultrasonography (CFDU) for suspected deep vein thrombosis were prospectively evaluated for IGSVT. Patients with IGSVT received no systemic anticoagulation therapy and underwent serial CFDU at 5, 9, 14, 30, and 90 days after recruitment. The incidence and extent of IGSVT propagation were noted. Factors predictive of IGSVT extension were sought, including age, gender, side, symptoms, ambulatory status, and the presence of comorbid illness, including cardiac disease, cancer, hypercoagulable states, recent surgery or trauma, and previous venous disease. Results: One hundred thirty-five limbs with IGSVT were studied for 3 months, and 16.3% of cases with IGSVT extended the thrombus to the level of the adjacent tibial, or peroneal, veins or higher. Only 3% of the cases with IGSVT propagated as cephalad as the popliteal vein, and 90.9% of IGSVT propagation occurred within 2 weeks of CFDU diagnosis. No IGSVT propagated to the level of the popliteal vein beyond 2 weeks from the time of CFDU diagnosis. No IGSVT extended into the deep veins of the thigh. By the end of the 3-month study period, 45.9% of thrombi had completely resolved. Only the presence of cancer was prognostic for IGSVT progression. Conclusion: During the 3-month study period, the short-term incidence rate of untreated IGSVT propagation to the level of the popliteal vein, even in the presence of cancer, was only 3%. Follow-up imaging to detect IGSVT propagation beyond 2 weeks from the time of diagnosis may not be necessary. (J Vasc Surg 2003;37:523-7.

Venous duplex scanning for unilateral symptoms: When do we need a contralateral evaluation?

Objectives:Determine the need for bilateral duplex scanning (DS) in patients with unilateral symptoms of acute DVT of the leg.Design:Prospective study.Materials:One thousand, one hundred and sixty-one consecutive patients with recent unilateral symptoms of pain or swelling.Methods:Bilateral DS were performed and demographic data including risk factors for DVT were entered into a computerised database.Results:Of the 250 cases (22%) of acute DVT, thrombus was confined to the symptomatic limb in 80% (200/250) and to the asymptomatic limb (AL) in 5% (12/250), while bilateral DVT was found in 15% (38/250). The management was not altered by the contralateral DS findings in any patient with bilateral thrombus. Ten of the 12 cases of DVT confined to the AL were localised to the infrapopliteal level; advanced malignancy, recent joint surgery or hypercoagulability were noted in nine patients, including all those requiring treatment.Conclusions:In the presence of unilateral symptoms of DVT, we recommend DS of the symptomatic extremity only; bilateral examination should be confined to patients with normal duplex findings in the symptomatic limb following recent joint surgery, or in the presence of advanced malignancy or hypercoagulability. Bilateral DS would therefore be required in approximately 11% of cases with unilateral symptoms of DVT