Perioperative FOLFOX 4 Versus FOLFOX 4 Plus Cetuximab Versus Immediate Surgery for High-Risk Stage II and III Colon Cancers: A Phase II Multicenter Randomized Controlled Trial (PRODIGE 22).

BACKGROUND: Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC). OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients with locally advanced nonmetastatic CC. METHODS: This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery. RESULTS: A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P < 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group. CONCLUSIONS: Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients.

Biliary structures lead to tumour recurrences after laser-induced interstitial thermotherapy.

BACKGROUND AND OBJECTIVE: Thermal diffusion during laser-induced interstitial thermotherapy (LITT) has not yet been fully investigated in heterogeneous tissue architecture such as liver. LITT was performed on rabbit liver tumours to analyse the role of biliary structures in thermal diffusion. STUDY DESIGN/MATERIALS AND METHODS: Twenty-four VX2 tumours were grafted onto 12 rabbit livers. The animals were randomly separated into two groups when tumour size reached 8 mm. Thermotherapy was performed by delivering the 830-nm output of a diode laser to the centre of the tumour with a 300-,microm fibre. Irradiation conditions were 1.5 W over 900 sec. On day 7 or 14, the tumours were removed and stained with haematoxylin-eosin and picrosirius red F3BA (PR). Thermal damage was evaluated by PR and electron microscopic examinations. RESULTS: Among the treated tumours, recurrences were found both at the periphery (one on day 7, seven on day 14) and within the treated area (two on day 7, two on day 14). All recurrences were located in the vicinity of the biliary structures, which are frequently spared from thermal injury. CONCLUSION: Biliary ducts lead to a heat sink, thereby facilitating tumour recurrences.

[Pneumatosis cystoides of the colon. Apropos of 7 cases]. / Pneumatose kystique du côlon. A propos de 7 observations.

Seven cases of pneumatosis cystoides intestinalis affecting the colon (PKC) revealed 5 times by a nonspecific symtomatology and 2 times by an occlusion were reported. In three of the patients the disease was found as a primary idiopathic form free of clinical antecedents. In 4 of the patients the pneumatosis was found to be secondary to a pulmonary disease, a gastric ulcer, a connectivite of a corticotherapy. The PKC was generally diagnosed either by barium enema or by computed tomography and less frequently by colonoscopy with deep biopsy allowing differential diagnosis with colonic polyposis. The mechanism and etiology of the PKC were not fully understood. The illness is a benign condition that often responds to a conservative management--i.e. abstention, oxygenotherapy, diet or antibiotherapy- or exceptionally to surgical colonic resection in case of acute complication.

Interstitial diode laser hyperthermia in the treatment of subcutaneous tumor.

BACKGROUND AND OBJECTIVE: Interstitial Laser Hyperthermia (ILH) has been investigated since the early 80s in the treatment of deep seated tumors. The purpose of this study was to evaluate the efficiency of diode ILH (830 nm) in a subcutaneous tumor model. STUDY DESIGN/MATERIALS AND METHOD: The antitumoral effect of diode ILH was assessed in a randomized study performed on 80 Swiss nu/nu mice. The tumor model was a subcutaneously implanted HT29 colonic carcinoma. The animals were assigned to four groups of 20 mice: Groups 1 and 3 were treated by ILH, groups 2 and 4 were not treated (control groups). Tumors were removed on day 3 in groups 1 and 2, and on day 30 in groups 3 and 4. The treatment was performed on tumors of 8 mm in diameter and a volume of 140 mm3. A laser irradiation of 360 J (power: 0.2 W; irradiation time: 1800 s) was delivered through a 300 microns optical fiber implanted in the tumor. The laser parameters insured temperatures of 46 degrees C in the central part of the tumor and 42 degrees C at the periphery. Tumor features were evaluated on day 3 and day 30. RESULTS: Untreated tumors grew rapidly up to a mean volume of 241 mm3 on day 3 (group 2) and 2,000 mm3 on day 30 (group 4). Treated tumors regressed to a mean volume of 32 mm3 on day 3 (group 1). On day 30, 40% of the tumors had totally disappeared and 60% showed partial response with small and peripheral residual tumor of 172 mm3 on an average, as to say 11.2 times smaller than in group 4. CONCLUSION: ILH with a low power 830 nm diode laser is an efficient treatment of subcutaneous tumor model. Partial responses are attributed to an insufficient heating at the tumor periphery. More precise control of the peripheral tumor temperature will improve the ILH results.