Predicting the Response to FOLFOX-Based Chemotherapy Regimen from Untreated Liver Metastases on Baseline CT: a Deep Neural Network Approach.

In developed countries, colorectal cancer is the second cause of cancer-related mortality. Chemotherapy is considered a standard treatment for colorectal liver metastases (CLM). Among patients who develop CLM, the assessment of patient response to chemotherapy is often required to determine the need for second-line chemotherapy and eligibility for surgery. However, while FOLFOX-based regimens are typically used for CLM treatment, the identification of responsive patients remains elusive. Computer-aided diagnosis systems may provide insight in the classification of liver metastases identified on diagnostic images. In this paper, we propose a fully automated framework based on deep convolutional neural networks (DCNN) which first differentiates treated and untreated lesions to identify new lesions appearing on CT scans, followed by a fully connected neural networks to predict from untreated lesions in pre-treatment computed tomography (CT) for patients with CLM undergoing chemotherapy, their response to a FOLFOX with Bevacizumab regimen as first-line of treatment. The ground truth for assessment of treatment response was histopathology-determined tumor regression grade. Our DCNN approach trained on 444 lesions from 202 patients achieved accuracies of 91% for differentiating treated and untreated lesions, and 78% for predicting the response to FOLFOX-based chemotherapy regimen. Experimental results showed that our method outperformed traditional machine learning algorithms and may allow for the early detection of non-responsive patients.

Comparison of bupivacaine and 2-chloroprocaine for spinal anesthesia for outpatient surgery: a double-blind randomized trial.

BACKGROUND: We have always been searching for the ideal local anesthetic for outpatient spinal anesthesia. Lidocaine has been associated with a high incidence of transient neurological symptoms, and bupivacaine produces sensory and motor blocks of long duration. Preservative-free 2-chloroprocaine (2-CP) seems to be a promising alternative, being a short-acting agent of increasing popularity in recent years. This study was designed to compare 2-CP with bupivacaine for spinal anesthesia in an elective ambulatory setting. METHODS: A total of 106 patients were enrolled in this randomized double-blind study. Spinal anesthesia was achieved with 0.75% hyperbaric bupivacaine 7.5 mg (n = 53) or 2% preservative-free 2-CP 40 mg (n = 53). The primary endpoint for the study was the time until reaching eligibility for discharge. Secondary outcomes included the duration of the sensory and motor blocks, the length of stay in the postanesthesia care unit, the time until ambulation, and the time until micturition. RESULTS: The average time to discharge readiness was 277 min in the 2-CP group and 353 min in the bupivacaine group, a difference of 76 min (95% confidence interval [CI]: 40 to 112 min; P < 0.001). The average time for complete regression of the sensory block was 146 min in the 2-CP group and 329 min in the bupivacaine group, a difference of 185 min (95% CI: 159 to 212 min; P < 0.001). Times to ambulation and micturition were also significantly lower in the 2-CP group. CONCLUSION: Spinal 2-chloroprocaine provides adequate duration and depth of surgical anesthesia for short procedures with the advantages of faster block resolution and earlier hospital discharge compared with spinal bupivacaine. (ClinicalTrials.gov number, NCT00845962).

Evaluation of the addition of bupivacaine to intrathecal morphine and fentanyl for postoperative pain management in laparascopic liver resection.

BACKGROUND: Optimal modality of pain management after liver resection has been controversial. Epidural analgesia is often avoided because of transient coagulopathy and the associated risk of epidural hematoma. Single-dose intrathecal morphine has been shown to be an effective alternative in open liver resection. The purpose of this trial was to compare the analgesic efficacy of intrathecal morphine and fentanyl versus intrathecal bupivacaine 0.5%, morphine, and fentanyl for patients undergoing laparoscopic liver resection. METHODS: This prospective randomized controlled double-blind trial compared morphine consumption between control (CTRL) group receiving a spinal injection of fentanyl 15 µg and morphine 0.4 mg and bupivacaine (BUPI) group receiving the same medications in addition to bupivacaine 0.5% (15 mg). Forty patients scheduled for laparoscopic liver resection were enrolled. Primary outcome was intravenous patient-controlled analgesia morphine consumption measured at 6, 9, 12, 18, 24, 36, and 48 hrs after spinal injection. Secondary outcomes were pain scores at rest and with movement, sedation, nausea, pruritus, and respiratory rate. RESULTS: Cumulative doses of morphine were significantly lower for all time intervals in the BUPI group: 54 (30) versus 94 (47) mg (P = 0.01) at 48 hrs. Morphine consumption was significantly lower for each time interval up to 18 hrs. Pain scores with movement were significantly lower in the BUPI group up to 24 hrs after injection. Pain score at rest was significantly lower in the BUPI group 9 hrs after injection. There were no differences in adverse effects. CONCLUSIONS: The addition of bupivacaine to intrathecal morphine and fentanyl significantly reduced intravenous morphine consumption after laparoscopic liver resection.

Hypertrophy of the non-embolized liver after chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NC(+)) and portal vein embolization (PVE) enables curative resection in more patients with colorectal-liver metastases (CRLM). However, after NC(+), structural alterations have been reported with the risk of post-operative hepatic failure. We undertook to determine if NC(+) toxicity limits future remnant liver (FRL) hypertrophy after PVE. METHODS: PVE was performed in 20 patients, 13 (65%) of whom previously received a mean FOLFIRI (5-fluorouracil + leucovorin + irinotecan) regimen (NC(+)) of 6.6 cycles. The seven remaining patients served as the control group without NC (NC(-)). RESULTS: CRLM were bilateral in 69% (NC(+)) and 57% (NC(-)), and synchronous in 84% (NC(+)) and 14% (NC(-)). The FRL hypertrophy rate was 54.1% (NC(+)) and 43.7% (NC(-)) (P= 0.3). CRLM were unresectable in four of our 20 patients, i.e. group NC(+): one insufficient FRL hypertrophy and one severe steatosis; and group NC(-): two tumoral progressions. In both groups, the operative parameters were comparable except for pedicular clamping: 8 (NC(+)) and 36 min (NC(-)), respectively (P < 0.05). Also, the surgical outcome rate and hospital stay were comparable. No significant pathological difference was observed between the two groups. No mortality occurred in either group. CONCLUSION: In view of our limited experience, we conclude that hypertrophy of the non-embolized liver (FRL) is not altered after FOLFIRI-based NC.

Nuclear FGF-2 facilitates cell survival in vitro and during establishment of metastases.

Nuclear-targeted high molecular weight 24 kDa fibroblast growth factor 2 (FGF-2) may induce specific cell functions through intracrine mechanisms. The role of nuclear FGF-2 on the metastatic potential of carcinoma cells was examined by conditional FGF-2 expression, which demonstrated that spontaneous metastasis in nude mice is a direct consequence of its expression. The lung colonizing capacities of fluorescent nuclear FGF-2-expressing cells following intravenous injection was also investigated. All cells reaching the lung extravasated as soon as 5 min following injection with similar in vivo behavior during the first 24 h. However, after 2 days, dramatic differences were observed between the FGF-2 and parental cells: most control cells underwent apoptosis, while the FGF-2-producing cells instigated a survival program and proliferated. Therefore, sustained apoptosis in vivo prevents growth of metastatic foci, while nuclear FGF-2 induction of a survival program is responsible for growth of the lung metastases. In vitro serum deprivation assays also established that 24 kDa FGF-2 expression improves carcinoma cell survival. This study provides both in vitro and in vivo evidence that the role of the nuclear 24 kDa FGF-2 isoform in carcinoma is the promotion of cell survival, thereby defining its association with poor prognosis in some human carcinomas.