Surveillance factors change outcomes in patients with hepatocellular carcinoma due to chronic hepatitis C virus infection in New Zealand.

Although surveillance for Hepatocellular Carcinoma (HCC) with 6 monthly imaging is recommended for patients with cirrhosis secondary to chronic hepatitis C virus (HCV) infection, international studies report poor adherence and there is paucity of data on its effect on patient outcomes. The primary aim of this study was to review cases of HCC secondary to HCV to determine the impact of adherence with HCC surveillance on survival. A total of 520 patients with confirmed HCC secondary to chronic HCV from 31 January 2001 to 31 May 2018 were identified from a prospective national HCC database. Computerized clinical records, general practitioner referral letters and secondary care clinic letters were subsequently retrospectively analysed for methods of HCC detection. HCC was detected through routine surveillance in only 224 patients (44%). HCC was detected either incidentally or following the onset of symptoms in nonadherent (12%), suboptimal surveyed (3%), undiagnosed cirrhotic (12%) or recently diagnosed HCV patients (21%) or were never offered surveillance (2%). Routine surveillance improved overall survival, OR 0.41 (95% CI [0.32, 0.53], P < .0001), with an overall mean survival of 91.5 months (95% CI 76.4, 106.6) compared to 43.0 (95% CI 34.2, 51.9) for those patients not receiving regular surveillance Outcome following diagnosis of HCC secondary to chronic HCV is determined by early detection when curative intervention is possible. Lack of diagnosis of HCV and nonadherence to HCC surveillance results in late diagnosis and poor outcomes. Under-diagnosis of HCV infection and lack of diagnosis of cirrhosis in patients known to have HCV infection reduce the benefit of current HCC surveillance strategies.

Artificial intelligence improves adenoma detection rate during colonoscopy.

BACKGROUND: Artificial intelligence-assisted colonoscopy (AIAC) has gained attention as a tool to assist with polyp detection during colonoscopy. Uncertainty remains as to the clinical benefit, given limited publications using different modules. METHOD: A single-centre retrospective study was performed at Waitemata Endoscopy, a private endoscopy centre in Auckland, New Zealand. An Olympus Endo-AID module was utilised for the first time by 13 experienced endoscopists. Outcomes from AIAC between 10 March 2021 to 23 April 2021 were compared to a subsequent non-AI conventional colonoscopy (CC) control group from 27/4/21 to 20/6/21. RESULTS: A total of 213 AIACs were compared with 213 CCs. Baseline patient age, gender, indication for procedure, bowel preparation scores and specialty of proceduralist (gastroenterologist or surgeon) were well matched (p>0.05). The withdrawal time was significantly longer in the AIAC group compared to CC controls (15 vs 13 minutes; p<0.001). The adenoma detection rate (ADR) was significantly higher in the AIAC group compared to CC group (47.9% vs 38.5%; odds ratio 1.59; 95% CI [1.05-2.41]; p=0.03). The overall polyp detection rate (PDR) was similar between groups (70% vs 70%; p=0.79). Analysis by polyp size, location and other histology was not significant between groups. CONCLUSION: AI-assisted colonoscopy significantly improved ADR compared with conventional colonoscopy. Further research is required to understand its utility and impact on long-term clinical outcomes.

Dysregulated Erythropoietin, Hepcidin, and Bone Marrow Iron Metabolism Contribute to Interferon-Induced Anemia in Hepatitis C.

Anemia is a complication of interferon-containing hepatitis C treatments. We characterized effects of interferon-based therapy on hepcidin and erythropoietin (EPO) production, iron metabolism, hemolysis, and hematopoiesis. Standard hemopoiesis [reticulocyte hemoglobin (Hb), reticulocyte production index (RPI), free Hb, and haptoglobin], iron biochemistry, hepcidin, and EPO levels were measured in 10 subjects over 12 weeks. There was a rapid decline in Hb during treatment, from a mean pretreatment (t = 0 weeks) Hb of 158.6 to 125.2 g/L at week 4 (P = 0.003) and 122.8 g/L at week 12 (P = 0.005). Paradoxically, the RPI (a measure of bone marrow responsiveness to EPO) decreased on initiation of hepatitis C virus treatment from 0.78% to 0.53% (P = 0.04). Despite worsening anemia, there was no significant increase in EPO levels. Hepcidin levels increased to >20 nM in 3 subjects from 5.8 to 27.5 nM (P = 0.009) compared with 9.6 to 12.3 nM (P = 0.5) for the remainder of subjects. Hepcidin levels peaked at week 1 before returning to baseline levels at week 4. Subjects who responded with a rise in serum hepcidin levels to >20 nM had a significantly greater drop in Hb (27.2 g/L, P = 0.008) and reticulocyte Hb (-1.4 g/L, P = 0.013) compared with the subjects who did not exhibit any change in hepcidin production. In conclusion, 30% of subjects treated with interferon exhibited significant transient increase in serum hepcidin levels, which was associated with more extreme anemia and decreased iron availability as evidenced by decreased reticulocyte Hb. In addition, there was a failure to upregulate EPO production in response to anemia and hemolysis ( https://clinicaltrials.gov trial NCT01726400).

CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer.

PURPOSE: The CpG island methylator phenotype (CIMP) is observed in approximately 30% of colorectal cancer (CRC) cases and is characterized by the concurrent methylation of multiple CpG islands in tumor DNA. This phenotype (CIMP+) is more frequently observed in tumors with proximal location, microsatellite instability, and normal p53. Because it has previously been observed that each of these features is associated with a good survival benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy, we investigated in the present study whether CIMP+ has independent predictive value. EXPERIMENTAL DESIGN: CIMP+ status was evaluated in 103 stage III CRCs from patients treated with surgery alone and for an additional 103 cases from patients treated with surgery and adjuvant 5-FU-based chemotherapy. The two cohorts were randomly pair-matched for age, sex, and tumor site, and the median length of follow-up time was 39 months. RESULTS: CIMP+ status predicted survival benefit from 5-FU treatment independently of microsatellite instability and p53 mutation status (relative risk = 0.22; 95% confidence interval, 0.06-0.84; P = 0.027). Unmeasured, high-risk confounding factors could only account for this association if they were unequally distributed between the two patient cohorts by a factor of at least 2-fold. CONCLUSIONS: CIMP+ has independent predictive significance for the survival benefit from 5-FU chemotherapy in CRC. This molecular marker should be incorporated into prospective clinical trials of fluorouracil-based therapies to confirm its clinical value.

The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects.

PURPOSE: We investigated the efficacy of hyperbaric oxygen therapy (HBOT) in the management of patients with radiation-induced late side effects, the majority of whom had failed previous interventions. METHODS AND MATERIALS: Of 105 eligible subjects, 30 had either died or were not contactable, leaving 75 who qualified for inclusion in this retrospective study. Patients answered a questionnaire documenting symptom severity before and after treatment (using Radiation Therapy Oncology Group criteria), duration of improvement, relapse incidence, and HBOT-related complications. RESULTS: The rate of participation was 60% (45/75). Improvement of principal presenting symptoms after HBOT was noted in 75% of head-and-neck, 100% of pelvic, and 57% of "other" subjects (median duration of response of 62, 72, and 68 weeks, respectively). Bone and bladder symptoms were most likely to benefit from HBOT (response rate, 81% and 83%, respectively). Fifty percent of subjects with soft tissue necrosis/mucous membrane side effects improved with HBOT. The low response rate of salivary (11%), neurologic (17%), laryngeal (17%), and upper gastrointestinal symptoms (22%) indicates that these were more resistant to HBOT. Relapse incidence was low (22%), and minor HBOT-related complications occurred in 31% of patients. CONCLUSION: Hyperbaric oxygen therapy is a safe and effective treatment modality offering durable relief in the management of radiation-induced osteoradionecrosis either alone or as an adjunctive treatment. Radiation soft tissue necrosis, cystitis, and proctitis also seemed to benefit from HBOT, but the present study did not have sufficient numbers to reliably predict long-term response.

Early detection markers in Pancreas Cancer.

The role of early detection in cancer has shown improved survival for certain cancers, including colon cancer, cervical cancer and breast cancer. The possibility for early detection of pancreatic cancer may be realized by an improved understanding of the histology and molecular genetics of precursor lesions and cancerous lesions in pancreatic cancer and the development of sensitive and specific screening tests (both invasive and non-invasive) to detect early pancreatic cancer. The NIH-NCI Early Detection Research Network (EDRN) in Pancreatic Cancer has been focussed on the development and validation of new biomarkers for the detection of early pancreatic cancer. This review will focus on our understanding of the histologic and molecular model of pancreatic carcinogenesis, current strategies and limitations of screening for pancreatic cancer and the development and validation of new biomarkers for the early detection of pancreatic cancer.

Prognostic significance of microsatellite instability and Ki-ras mutation type in stage II colorectal cancer.

OBJECTIVES: The survival of stage II colorectal cancer (CRC) patients is approximately 70% at 5 years. Identification of the patient subgroup at high risk for tumour recurrence and death would allow more informed use of chemotherapy for this stage of disease. Several clinical and pathological factors have been reported to associate with worse survival. In the present study we investigated the prognostic significance of two major genetic alterations in CRC: microsatellite instability (MSI+) and the type of Ki-RAS mutation. METHODS: PCR-based molecular techniques were used to screen for MSI+ and Ki-RAS mutation in 396 stage II CRC patients with an average follow-up time of 75 months. Clinicopathological information was obtained by retrospective review of pathology reports. RESULTS: Prominent vascular invasion was identified in 19% of cases and was found to be an independent prognostic factor for poor outcome (relative risk = 2.08, 95% confidence interval: 1.22-3.57, p = 0.008). The MSI+ phenotype was found in 23% of proximal tumours and Ki-RAS mutations in 38% of the overall series. Neither MSI+ nor the type of Ki-RAS mutation showed prognostic significance in this cohort of stage II CRC. CONCLUSIONS: MSI+ and Ki-RAS mutation type are not useful markers for the identification of high-risk stage II CRC patients. Further prospective and/or cohort studies are required to determine whether these molecular changes have predictive value for survival benefit from 5-fluorouracil-based adjuvant chemotherapy.