Changes in apparent diffusion coefficient and pathological response in colorectal liver metastases after preoperative chemotherapy.

BACKGROUND: The pathological response to preoperative chemotherapy of colorectal liver metastases (CRLMs) is predictive of long-term prognosis after liver resection. Accurate preoperative assessment of chemotherapy response could enable treatment optimization. PURPOSE: To investigate whether changes in lesion-apparent diffusion coefficient (ADC) measured with diffusion-weighted magnetic resonance imaging (MRI) can be used to assess pathological treatment response in patients with CRLMs undergoing preoperative chemotherapy. MATERIAL AND METHODS: Patients who underwent liver resection for CRLMs after preoperative chemotherapy between January 2011 and December 2019 were retrospectively included if they had undergone MRI before and after preoperative chemotherapy on the same 1.5-T MRI scanner with diffusion-weighted imaging with b-values 50, 400, and 800 s/mm2. The pathological chemotherapy response was assessed using the tumor regression grade (TRG) by AJCC/CAP. Lesions were divided into two groups: pathological responding (TRG 0-2) and non-responding (TRG 3). The change in lesion ADC after preoperative chemotherapy was compared between responding and non-responding lesions. RESULTS: A total of 27 patients with 49 CRLMs were included, and 24/49 lesions showed a pathological chemotherapy response. After chemotherapy, ADC increased in both pathological responding (pretreatment ADC: 1.26 [95% confidence interval (CI)=1.06-1.37] vs. post-treatment ADC: 1.33 [95% CI=1.13-1.56] × 10-3 mm2/s; P = 0.026) and non-responding lesions (1.12 [95% CI=0.980-1.21] vs. 1.20 [95% CI=1.09-1.43] × 10-3 mm2/s; P = 0.018). There was no difference in median relative difference in ADC after chemotherapy between pathological responding and non-responding lesions (15.8 [95% CI=1.42-26.3] vs. 7.17 [95% CI=-4.31 to 31.2]%; P = 0.795). CONCLUSION: Changes in CRLM ADCs did not differ between pathological responding and non-responding lesions.

Perioperative liver and spleen elastography in patients without chronic liver disease.

AIM: To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. METHODS: Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. RESULTS: Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s (P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more (P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy (n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin (R2 = 0.154, Pearson's r = 0.392, P = 0.032) and international normalized ratio (R2 = 0.285, Pearson's r = 0.534, P = 0.003). CONCLUSION: Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.

Significance of poor performance status after resection of colorectal liver metastases.

BACKGROUND: Performance status (PS) is known as one of the strongest prognostic factors for survival in metastatic colorectal cancer patients. The aim of the present study was to analyze factors associated with poor PS assessed after resection for colorectal liver metastases and the impact on survival. METHODS: All patients undergoing curative resection for colorectal liver metastases between 2010 and 2015 in a single center were reviewed retrospectively. RESULTS: A total of 284 patients were included, out of whom 74 patients (26%) presented with a postoperative PS WHO > 2 precluding administration of adjuvant chemotherapy. These patients had a shorter recurrence-free survival (P = 0.002) and shorter overall survival (P < 0.001). Multivariable analysis showed that patients with PS > 2 after surgery had higher preoperative ASA score, had a higher frequency of major complications after surgery, and had more frequently synchronous liver and lung metastases. PS was found to be the strongest independent factor predicting survival (hazard ratio 0.45). When patients with postoperative PS > 2 developed recurrent disease (54 of 74), 43 (80%) received tumor specific treatment. CONCLUSIONS: Patients with postoperative PS > 2 who did not receive adjuvant chemotherapy had decreased recurrence-free and overall survival after liver resection for colorectal liver metastases. After recurrence, a large majority of these patients had had improvement in PS allowing for administration of tumor specific treatment.

The impact of neoadjuvant chemotherapy on skeletal muscle depletion and preoperative sarcopenia in patients with resectable colorectal liver metastases.

BACKGROUND: Preoperative skeletal muscle depletion or sarcopenia has been suggested to predict worse outcome after resection of colorectal liver metastases. The aim of the present study was to investigate the impact of neoadjuvant chemotherapy on preoperative skeletal muscle mass prior to liver resection. METHODS: Patients operated with liver resection for colorectal liver metastases between 2010 and 2014 were retrospectively reviewed. Muscle mass was evaluated by measuring muscle area on a cross-sectional computed tomography image at the level of the third lumbar vertebra, and normalized for patient height, presenting a skeletal muscle index. RESULTS: Preoperative skeletal muscle mass was analysed in 225 patients, of whom 97 underwent neoadjuvant chemotherapy. In total 147 patients (65%) were categorized as sarcopenic preoperatively. Patients receiving neoadjuvant chemotherapy decreased in skeletal muscle mass (decrease by 5.5 (-1.1 to 11) % in skeletal muscle index, p < 0.001). Patients with muscle loss >5% during neoadjuvant chemotherapy were less likely to undergo adjuvant chemotherapy than others (68% vs 85%, p = 0.048). A >5% muscle loss did not result in worse overall (p = 0.131) or recurrence-free survival (p = 0.105). CONCLUSION: Skeletal muscle mass decreases during neoadjuvant chemotherapy. Skeletal muscle loss during neoadjuvant chemotherapy impairs the conditions for adjuvant chemotherapy.

Liver-first strategy for synchronous colorectal liver metastases - an intention-to-treat analysis.

BACKGROUND: The liver-first strategy signifies resection of liver metastases before the primary colorectal cancer. The aim of the present study was to compare failure to complete intended treatment and survival in liver-first and classical strategies. METHODS: All patients with colorectal cancer and synchronous liver metastases planned for sequential radical surgery in a single institution between 2011 and 2015 were included. RESULTS: A total of 109 patients were presented to a multidisciplinary team conference (MDT) with un-resected colorectal cancer and synchronous liver metastases. Seventy-five patients were planned as liver-first, whereas 34 were recommended the classical strategy. Twenty-six patients (35%) failed to complete treatment in the liver-first group compared to 10 patients in the classical group (P = 0.664). Reason for failure was most commonly disease progression. A total of 91 patients had the primary tumor resected before the liver metastases of which 67 before referral and 24 after allocation at MDT. Median survival after diagnosis in this group was 60 (48-73) months compared to 46 (31-60) months in the group operated with liver-first strategy (n = 49), (P = 0.310). DISCUSSION: Up to 35% of patients with colorectal cancer and synchronous liver metastases do not complete the intended treatment of liver and bowel resections, irrespective of treatment strategy.

Concurrent biliary drainage and portal vein embolization in preparation for extended hepatectomy in patients with biliary cancer.

BACKGROUND: Patients with perihilar cholangiocarcinoma and gallbladder cancer extending into the hilum often present with jaundice and a small future liver remnant (FLR). If resectable, preoperative biliary drainage and portal vein embolization (PVE) are indicated. Classically, these measures have been performed sequentially, separated by 4-6 weeks. PURPOSE: To report on a new regime where percutaneous transhepatic biliary drainage (PTBD) and PVE are performed simultaneously, shortening the preoperative process. MATERIAL AND METHODS: Six patients were treated with concurrent PTBD and PVE under general anesthesia. RESULTS: Surgical exploration followed the combined procedure after 35 days (range, 28-51 days). The FLR ratio increased from 22% to 32%. Three patients developed cholangitis after the procedure. CONCLUSION: The combined approach of PTBD and PVE seems feasible, but more studies on morbidity are warranted.

Non-invasive imaging of microcirculation: a technology review.

Microcirculation plays a crucial role in physiological processes of tissue oxygenation and nutritional exchange. Measurement of microcirculation can be applied on many organs in various pathologies. In this paper we aim to review the technique of non-invasive methods for imaging of the microcirculation. Methods covered are: videomicroscopy techniques, laser Doppler perfusion imaging, and laser speckle contrast imaging. Videomicroscopy techniques, such as orthogonal polarization spectral imaging and sidestream dark-field imaging, provide a plentitude of information and offer direct visualization of the microcirculation but have the major drawback that they may give pressure artifacts. Both laser Doppler perfusion imaging and laser speckle contrast imaging allow non-contact measurements but have the disadvantage of their sensitivity to motion artifacts and that they are confined to relative measurement comparisons. Ideal would be a non-contact videomicroscopy method with fully automatic analysis software.

Laser speckle contrast imaging for intraoperative assessment of liver microcirculation: a clinical pilot study.

BACKGROUND: Liver microcirculation can be affected by a wide variety of causes relevant to liver transplantation and resectional surgery. Intraoperative assessment of the microcirculation could possibly predict postoperative outcome. The present pilot study introduces laser speckle contrast imaging (LSCI) as a new clinical method for assessing liver microcirculation. METHODS: LSCI measurements of liver microcirculation were performed on ten patients undergoing liver resection. Measurements were made during apnea with and without liver blood inflow occlusion. Hepatic blood flow was assessed by subtracting zero inflow signal from the total signal. Zero inflow signal was obtained after hepatic artery and portal vein occlusion. Perfusion was expressed in laser speckle perfusion units, and intraindividual and interindividual variability in liver perfusion was investigated using the coefficient of variability. RESULTS: Hepatic microcirculation measurements were successfully made in all patients resulting in analyzable speckle contrast images. Mean hepatic blood flow was 410±36 laser speckle perfusion units. Zero inflow signal amounted to 40%±4% of the total signal. Intraindividual and interindividual coefficients of variability in liver perfusion were 25% and 28%, respectively. CONCLUSION: Under the conditions of this pilot study, LSCI allows rapid noncontact measurements of hepatic blood perfusion over wide areas. More studies are needed on methods of handling movement artifacts.

Microcirculation changes during liver resection--a clinical study.

BACKGROUND: In this study we aimed to evaluate effects of liver resection on hepatic microcirculation. In addition we wanted to study if histological liver damage could be detected intra-operatively. PATIENTS AND METHODS: 40 patients undergoing hepatic resection were included and grouped according to if they were operated with a major or minor resection. Hepatic microcirculation measurements were made intra-operatively before and after liver resection with sidestream dark-field (SDF) imaging. Red blood cell velocity (RBCV), sinusoidal diameter and functional sinusoidal density were determined. RESULTS: After hepatic resection RBCV increased in both the minor and major groups (44 µm/s, P=0.016 and 121 µm/s, P=0.002). RBCV in patients with histological damages was 225 (148-464) µm/s vs. 161 (118-329) µm/s in patients with no damage (P=0.016). CONCLUSION: A hepatic resection leads to an increase of sinusoidal RBCV. SDF imaging could potentially be used to intraoperatively identify histological damages.

Limiting factors for liver regeneration after a major hepatic resection for colorectal cancer metastases.

BACKGROUND: Chemotherapy before resection of colorectal metastases in the liver is extensively used and has been shown to induce histopathological changes in the liver parenchyma, although little is known about the effect of chemotherapy on liver regeneration. The aim of this study was to determine if pre-operative chemotherapy influences the regenerated liver volume after a major liver resection. PATIENTS AND METHODS: This retrospective cohort study included 74 patients subjected to a major liver resection for colorectal metastases. Patients were divided into two groups depending on whether they had been treated with chemotherapy less than 3 months before surgery or not. Liver volumes were measured before and 1 year after resection. RESULTS: Pre-operative chemotherapy reduced volumetric liver regeneration (83 ± 2% versus 91 ± 2%; P = 0.007) as compared with patients without chemotherapy. There was a linear correlation between regenerated volume and time interval between the end of chemotherapy to resection (P = 0.031). CONCLUSIONS: Pre-operative chemotherapy in patients with colorectal liver metastases negatively affects volume regeneration after a partial hepatectomy. The time interval between chemotherapy and surgery determines the impact of these affects.