Pharmacokinetics of pegylated liposomal doxorubicin administered by intraoperative hyperthermic intraperitoneal chemotherapy to patients with advanced ovarian cancer and peritoneal carcinomatosis.

The pharmacokinetics of pegylated liposomal doxorubicin (PLD) were investigated in 17 women undergoing intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced ovarian cancer and peritoneal carcinomatosis. HIPEC was performed immediately after completing debulking surgery, which included a number of peritonectomy procedures. PLD was injected and allowed to equilibrate in peritoneal cavity filled with 4 liters of physiological solution and stabilized at 42°C; next, the outflow line was opened and perfusion proceeded for 1 h. PLD was stable in peritoneal perfusate and plasma. During HIPEC, PLD peritoneal perfusate/plasma gradients averaged ∼600 or ≥1000 for peak concentration or area under the curve. After HIPEC, PLD plasma levels remained stable or decreased. Biopsy samples of residual normal peritoneum or ovarian carcinomatosis were collected at the end of HIPEC and were shown to contain free doxorubicin. Correlating PLD decrements in peritoneal perfusate with plasma exposure to PLD or peritoneal deposition of free doxorubicin showed that the former occurred during preperfusional equilibration of PLD in peritoneal cavity, whereas the latter occurred during 1 h of perfusion. Plasma exposure to PLD correlated negatively with the number of peritonectomy procedures performed during surgery, whereas peritoneal deposition of free doxorubicin correlated positively. Taken together, these results show that PLD administered by intraoperative HIPEC undergoes limited systemic diffusion and releases active free doxorubicin in peritoneum exposed to ovarian carcinomatosis. PLD pharmacokinetics seem to be influenced by peritonectomy procedures.

Magnetic Resonance Assessment of Peritoneal Carcinomatosis: Is There a True Benefit From Diffusion-Weighted Imaging?

PURPOSE: To assess the added value of diffusion weighted imaging (DWI) with intermediate (500 s/mm2) and high (1000 s/mm2) b values when combined to conventional contrast-enhanced magnetic resonance imaging (MRI) in identifying peritoneal neoplastic involvement. METHODS: Twenty-four patients with peritoneal carcinomatosis from gastrointestinal or gynecological tumors were retrospectively evaluated. All patients underwent peritonectomy with hyperthermic intraoperative chemotherapy and 1.5 T MRI including DWI with 500 s/mm2 and 1000 s/mm2 b values within 1 month from surgery. Images were independently reviewed by 2 radiologists with different experience in abdominal MRI in 3 separate reading sessions, the first including conventional MR images alone (T2-weighted, T1-weighted pre- and post gadolinium injection), the second conventional MRI and DWI with a b value of 500 s/mm2 (b 500-DWI), and the third conventional MRI and DWI with a b value of 1000 s/mm2 (b 1000-DWI). Apparent diffusion coefficient maps were included in the DWI analyses. Peritoneal dissemination was assessed in 9 anatomical sites, including right and left subphrenic space, paracolic gutters, small bowel mesentery, greater omentum, gastric-bowel serosa, free peritoneal surfaces, rectosigmoid-colon mesentery, and pelvis. The presence or absence of peritoneal dissemination for each patient and for each site was scored using a 5-point confidence scale. Sensitivity, specificity, and area under the curve (AUC) for identifying per-site peritoneal implants were calculated for each reader at each reading session. Interobserver agreement was evaluated using kappa statistics. RESULTS: For both readers, the sensitivity and AUC values resulting from combined interpretation of conventional MRI and DWI (both b500-DWI and b1000-DWI) were significantly higher than those of conventional MRI alone (P < 0.001). The added value of DWI was greater for the less experienced reader (sensitivity 0.55, specificity 0.73, AUC 0.64 on conventional MRI; sensitivity 0.75, specificity 0.72, AUC 0.74 on b500-DWI; sensitivity 0.87, specificity 0.72, AUC 0.80 on b1000-DWI) than for the more experienced reader (sensitivity 0.63, specificity 0.75, AUC 0.70 on conventional MRI; sensitivity 0.76, specificity 0.77, AUC 0.77 on b500-DWI; sensitivity 0.85, specificity 0.72, AUC 0.79 on b1000-DWI), although the differences between the 2 observers were not statistically significant. Interobserver agreement resulted to be fair (κ = 0.30) when dealing with conventional MRI alone. The addition of b500-DWI and b1000-DWI to conventional MRI allowed to reach a substantial agreement (κ = 0.75). CONCLUSIONS: The combined interpretation of high b value DWI and conventional MRI provides increased sensitivity and diagnostic performance in detection of peritoneal carcinomatosis in oncologic patients.

[Intralobar pulmonary sequestration: a case report]. / Sequestrazione polmonare intralobare: a proposito di un caso.

The authors report a case of intralobar pulmonary sequestration diagnosed accidentally in a 64-year-old woman. The patient subsequently underwent surgery. The authors were prompted by this fairly rare case to describe and discuss its anatomopathological, clinical, diagnostic and therapeutic aspects.