Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy: a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and 1H-MR spectroscopy compared with histology (subgroup in the RAXO trial).

BACKGROUND: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. PATIENTS AND METHODS: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan-Meier estimates of overall survival (OS). RESULTS: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. CONCLUSIONS: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.

Centralized repeated resectability assessment of patients with colorectal liver metastases during first-line treatment: prospective study.

BACKGROUND: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. METHODS: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. RESULTS: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. CONCLUSION: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Differences in Prognostic Factors and Recurrence Patterns After Curative-Intent Resection of Perihilar and Distal Cholangiocarcinomas.

BACKGROUND: Perihilar cholangiocarcinoma and distal cholangiocarcinoma arise from the same tissue but require different surgical treatment methods. It remains unclear whether these cholangiocarcinoma types have different outcomes, prognostic factors, and/or recurrence patterns. METHODS: This retrospective study evaluated patients who underwent curative-intent resection for perihilar cholangiocarcinoma or distal cholangiocarcinoma at a tertiary academic hospital during 2000-2015. Survival and prognostic factors were identified using Kaplan-Meier and Cox regression analyses. RESULTS: The 90-day mortality rates were 0% for perihilar cholangiocarcinoma (36 patients) and 4% for distal cholangiocarcinoma (47 patients). There were no significant differences between perihilar cholangiocarcinoma or distal cholangiocarcinoma in median overall survival (30.9 vs 40.4 months) or median disease-free survival (14.2 vs 21.4 months). Among perihilar cholangiocarcinoma patients, age > 65 years was an independent predictor of poorer overall survival (hazard ratio: 2.45, 95% confidence interval: 1.07-5.64), while requiring bile duct re-resection was an independent predictor of disease-free survival (hazard ratio: 2.76, 95% confidence interval: 1.01-7.51). Among distal cholangiocarcinoma patients, a pN1 category independently predicted poorer overall survival (hazard ratio: 3.40, 95% confidence interval: 1.14-10.11), while preoperative CA19-9 levels >30 U/mL (hazard ratio: 2.51, 95% confidence interval: 1.09-5.79) and pN1 category (hazard ratio: 2.51, 95% confidence interval: 1.09-5.79) predicted a shorter disease-free survival. Local recurrence was more common with perihilar cholangiocarcinoma (50% of recurrences), while multiple synchronous sites were more common for distal cholangiocarcinoma (41% of recurrences). CONCLUSION: Perihilar cholangiocarcinoma and distal cholangiocarcinoma patients have similar survival outcomes. However, local control appears to be more prognostic for perihilar cholangiocarcinoma patients, while positive lymph nodes are critical prognostic factor for distal cholangiocarcinoma patients.

Modified distal metatarsal osteotomy for hallux valgus.

Sixty-three feet in 44 patients with a hallux valgus, which had been operated on using a modified distal osteotomy were reviewed after a mean follow-up of 4.6 years. A modification of Mitchell's and Mommsen's osteotomies was used without any fixation material. The mean correction of the intermetatarsal angle was 2.6 degrees and of the hallux valgus angle 5.2 degrees. Good subjective result was achieved in 90% of the feet. In six (9.5%) cases the hallux valgus angle was worse after the operation. The method used seems to be too unreliable to be continued. Patient selection was found to be of great importance. Hallux valgus angle of more than 40 degrees was less suitable for this kind of operation.

Investigation of suspected intra-abdominal sepsis: the contribution of nuclear medicine.

The diagnosis of abdominal infections and inflammations often presents considerable difficulty, and various imaging techniques may be required to localize them accurately. At present, radiolabelled leucocytes offer the most widely accepted radionuclide method for imaging inflammation. Because of the many advantages of technetium-99m (99mTc) over indium-111 (111In), 99mTc-HMPAO-leucocyte scintigraphy is preferred for the investigation of acute abdominal sepsis and inflammatory bowel disease, and 111In-leucocyte scintigraphy for more chronic infections and renal sepsis. The 99mTc-HMPAO-labelled leucocytes technique is highly accurate within the first few hours postinjection, and is therefore useful also in acutely ill patients. It is sensitive in detecting abdominal abscesses in all locations except the liver and spleen. By whole body imaging, unsuspected sites and types of infection can be found. 99mTc-HMPAO-leucocyte scan is valuable also in the investigation of acute cholecystitis in problematic situations in which ultrasound is known to give misleading results, especially in acute acalculous cholecystitis. In inflammatory bowel disease it can reliably assess disease activity, but a normal scintigraphy does not exclude mild inflammation. Leucocyte scan is useful also in suspected acute appendicitis, acute diverticulitis, pelvic inflammatory disease, aortic graft infection, etc. But infection and inflammation cannot reliably be differentiated, which may cause misinterpretations in the early postoperative period. Radionuclide techniques have an important role to play in the investigation of abdominal sepsis if the nuclear medicine department can offer instant investigations when the clinical problem is acute.

Postoperative graft incorporation after aortic reconstruction--comparison between computerised tomography and Tc-99m-HMPAO labelled leucocyte imaging.

Aortic graft infection may result in high mortality ranging up to 88%. Therefore, early diagnosis is imperative in the treatment of this serious complication. Computerised tomography (CT) is considered as a sensitive tool in the diagnosis of aortic graft infection. Some findings used as the criteria for infection, such as periprosthetic gas and fluid are, however, normal postoperative findings. The aim of this prospective study was to compare CT-scan and Tc-99m-HMPAO labelled leucocytes in the early diagnosis of aortic graft infection. The present study includes 24 consecutive patients (all men, age 70 +/- 8 years, range 55-85 years), who were operated on for abdominal aortic aneurysm. Prosthetic and suture materials were the same in all operations. Each patient was examined with the aid of CT-scan and imaged with Tc-99m-HMPAO labelled leucocytes 2 weeks and 3, 6 and 12 months after the reconstructive aortic surgery. Two radiologists and two specialists in nuclear medicine examined the data independently without knowing the clinical picture of the results of any other examinations of the patients. Seven patients (7/24; 29%) showed significant accumulation of labelled leucocytes in the first imaging (2 weeks postoperatively) with Tc-99m-HMPAO labelled leucocytes. Three months after the surgery only four patients (4/24; 17%) were positive in this respect. One of these patients had clinically proven aortic graft infection and another positive was a patient with resected and reconstructed mycotic aneurysm. CT-examination in all scans was suggestive for aortic graft infection in two cases (2/24; 8%), but neither of these patients showed any signs of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium-99m hexamethyl propylene amine oxine leucocytes in the assessment of disease activity in inflammatory bowel disease.

The inflammatory activity in 108 bowel segments of 40 patients with suspected or known inflammatory bowel disease was assessed macroscopically by endoscopy, histology and technetium-99m hexamethyl propylene amine oxine (99mTc-HMPAO) leucocytes using a numerical grading system (scores 0-3). A 4-h series of scintigrams showed a significant correlation with both histological and macroscopical assessment of disease activity (rho = 0.850, P less than 0.001 and rho = 0.773, P less than 0.001, respectively). Sensitivity, specificity and accuracy of scintigraphy in detecting active inflammatory segments were 85%, 92% and 89%, respectively. A normal scintigram did not completely exclude mild inflammatory activity, especially in the rectosigmoid area. 99mTc-HMPAO leucocytes offer an accurate and non-invasive alternative for the assessment of disease activity in ulcerative colitis and Crohn's disease.

Fast diagnosis of abdominal infections and inflammations with technetium-99m-HMPAO labeled leukocytes.

The diagnostic value of early 99mTc-HMPAO-leukocyte images (2 min, 0.5 hr, 2 hr and 4 hr) was studied in 87 prospectively performed investigations in 80 patients with a suspicion of abdominal inflammation or infection. Sensitivity, specificity and accuracy were 74%, 85% and 77% in the 2-min scans, 88%, 81% and 86% in the 0.5-hr scans, 95%, 85% and 92% in the 2-hr scans, and 96%, 92% and 95% in the 4-hr scans. Nonspecific bowel accumulation was seen in 7% of patients at 2 hr and in 28% at 4 hr but was easily distinguishable from pathologic activity. The uptake in early images represents an active accumulation of granulocytes at the site of inflammation rather than nonspecific blood-pool activity judged by results of 99mTc-HMPAO-RBC imaging. We found that imaging within 2 hr from injection has a high diagnostic value, and that the activity accumulates in areas of infection and inflammation faster than in the intestinal background.

Scintigraphy with 99mTc-HMPAO labeled leukocytes in acute cholecystitis.

99mTc-HMPAO labeled leukocyte scanning was performed on 38 patients with clinically suspected acute cholecystitis (AC) to evaluate its diagnostic value. The typical finding was an increasing accumulation of the tracer in the gallbladder wall in a 4 hour series of scintigrams. Leukocyte scan was positive in 16 of 17 patients with surgically and histologically confirmed AC. There were no false-positive findings. The sensitivity, specificity, and accuracy of scintigraphy were 94, 100, and 96%, respectively. In 2 patients with acute acalculous cholecystitis true-positive findings were observed. Scintigraphy with 99mTc-HMPAO labeled leukocytes is a valuable new imaging method in AC.

Leucocytes labelled with 99mTc-HMPAO in the detection of abdominal abscesses.

To assess the value of 99mTc-HMPAO-labelled-leucocyte scintigraphy in the detection of abdominal abscesses, the results of 74 examinations in 69 patients suspected of having abscesses on clinical grounds were reviewed retrospectively. Of a final total of 29 abscesses in 28 patients, leucocyte scanning diagnosed 26, giving a sensitivity, specificity, and accuracy of 90%, 91%, and 91%, respectively. In 22 patients abscesses were diagnosed within 30 min. In 13 of the 74 examinations (18%) an infection or inflammatory lesion other than an abscess was diagnosed. 99mTc-HMPAO-labelled-leucocyte scintigraphy is an accurate and rapid method of diagnosing abscesses in acutely ill patients.

Accumulation of leucocytes labelled with technetium-99m hexamethylpropylene amine oxime in malignant abdominal tumours.

A total of 343 leucocyte scans labelled with technetium-99m hexamethylpropylene amine oxime were reviewed that had been performed in 338 patients suspected of having abdominal infection or inflammation. There was uptake by malignant abdominal tumours in 10 cases (2.9%), which represents 62.5% of known malignancies at the time of the scintigram. Accumulation was seen in 8 patients with adenocarcinoma of the colon associated with a secondary infection in the tumour or pericolic inflammation. A large tumour that had spread beyond the bowel wall was related to a positive scintigram. Accumulation was also found twice in a malignant fibrous histiocytoma in which bleeding and an inflammatory reaction to necrosis were probably responsible for the uptake. The relevant treatment was delayed for 2 weeks-2 months in 4 patients with adenocarcinoma of the colon in whom the positive uptake was regarded as confirmation of the clinically suspected acute diverticulitis.