Regional chemotherapy in the treatment of advanced pancreatic cancer--is it relevant?

The treatment of pancreatic cancer is still problematic for physicians. Only 15% of patients present with resectable tumours, and systemic chemotherapy is of limited effectiveness. In order to achieve higher local drug concentrations in the tumour without causing the side-effects of a comparable level of systemic treatment, regional chemotherapy has been introduced as an alternative treatment. Several techniques have been developed over recent years, these include: celiac axis infusion (CAI), CAI with microspheres or haemofiltration, aortic stop flow (ASF) and isolated hypoxic perfusion (IHP). Whilst several authors have reported improved response rates and a prolongation of median survival time, these results have not been confirmed by others. In addition, the incidence of side-effects and the rate of technical complications have been reported to be high during regional chemotherapy. Except for a single trial containing 14 patients, no randomised trial comparing systemic and regional chemotherapy has been conducted. For these reasons, none of the reported treatment regimens can be considered to be standard treatment and in order to evaluate, if regional chemotherapy is indeed superior to systemic chemotherapy, randomised trials must be conducted.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: Is it justified?

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients.

Methods

This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75 years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed.

Results

Median PCI was 16 (range 6–39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I–II and 17% were grade III–IV. Disease-free survival at 1 and 3 years was 67 and 44%, respectively. Overall survival at 1 and 3 years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p = 0.007) and multivariate (OR 11.639, 95% CI 1.24–109.74, p = 0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p = 0.046).

Conclusion

Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes.

Trial registration

researchregistry1587 (retrospectively registered).

     

The association of H. pylori and colorectal adenoma: does it exist in the US Hispanic population?

Background

Although data on the association between colorectal adenomas and Helicobacter pylori (H. pylori) exists in White and Black patients, there is no data on this association in a US Hispanic population. Our aim was to study the association of adenoma detection and biopsy proven H. pylori infection in a cohort of US Hispanics.

Methods

Data were collected from Nassau University Medical Center, a 530-bed tertiary care teaching hospital in East Meadow, New York. Patients who underwent both an esophagogastroduodenoscopy (EGD) and colonoscopy from July 2009 to March 2011 were pulled from an electronic database. A total of 1,737 patients completed colonoscopies during this time with 95 excluded: 17 inflammatory bowel disease, 12 malignancy, 22 prior history of colorectal adenoma, and 44 incomplete. Among the colonoscopies, 799 patients had EGD’s performed prior to colonoscopies that were eligible for our study.

Results

H. pylori prevalence was highest in Hispanics 40.9%, followed by Blacks 29.1% (OR 0.59, 95% CI: 0.42-0.84), then Whites 7.9% (OR 0.12, 95% CI: 0.06-0.24). The adenoma detection rate was significantly higher in Whites 23.2% and Blacks 21.8% compared to Hispanics 14.5%, P=0.0002 respectively. Smoking and alcohol were lower in the H. pylori group, 18.6% (n=44) vs. 26.1% (n=147) for smoking (P=0.02) and 14.4% (n=34) vs. 19% (n=107) for alcohol (P=0.12), respectively. There was no evidence in the Hispanics for an association between adenoma detection and H. pylori infection. Furthermore size, location, and multiple polyps did not differ between the two groups.

Conclusions

While data has shown an association between H. pylori and colorectal adenomas, we did not find this in our Hispanic population. With the growing population of Hispanics in the U.S, large scale studies are needed to conclusively characterize the role of H. pylori infection in colorectal adenoma and adenocarcinoma in this group of patients.     

What have we learned and where are we going in the treatment of colorectal and gastric cancer?

Clearly increasing knowledge of the timing of administration of new chemotherapy combinations coupled with an improvement in technical skills in the surgical setting has improved the outcome for patients with colorectal and gastric cancer. Of the newer cytotoxic chemotherapy agents irinotecan in particular represents the cornerstone of the new treatment regimens that are leading to a better prognosis for patients with colorectal and gastric cancer. The systematic study of agents like irinotecan and the integration of novel targeted agents into combination chemotherapy regimens can only serve to improve still further the benefits we are beginning to see for the treatment of these patients.     

Immunonutrition and prehabilitation in pancreatic cancer surgery: A new concept in the era of ERAS® and neoadjuvant treatment

Pancreatic cancer (PC) is an aggressive disease, with a growing incidence, and a poor prognosis. Neoadjuvant treatments in PC are highly recommended in borderline resectable and recently in upfront resectable PC. PC is characterized by exocrine insufficiency and nutritional imbalance, leading to malnutrition/sarcopenia. The concept of malnutrition in PC is multifaceted, as the cancer-related alterations create an interplay with adverse effects of anticancer treatments. All these critical factors have a negative impact on the postoperative and oncological outcomes. A series of actions and programs can be implemented to improve resectable and borderline resectable PC in terms of postoperative complications, oncological outcomes and patients’ quality of life. A timely nutritional evaluation and the implementation of appropriate evidence-based nutritional interventions in onco-surgical patients should be considered of importance to improve preoperative physical fitness. Unfortunately, nutritional care and its optimization are often neglected in real-world clinical practice. Currently available studies and ERAS® guidelines mostly support the use of pre- or perioperative medical nutrition, including immunonutrition, in order to decrease the rate of postoperative infections and length of hospital stay. Further data also suggest that medical nutrition should be considered proactively in PC patients, to possibly prevent severe malnutrition and its consequences on disease and treatment outcomes. This narrative review summarizes the most recent data related to the role of prehabilitation, ERAS® program, medical nutrition, and the timing of intervention on clinical outcomes of upfront resectable and borderline PC, and their potential implementation within the timeframe of neoadjuvant treatments.     

Is community treatment best? a randomised trial comparing delivery of cancer treatment in the hospital,home and GP surgery

Background:

Care closer to home is being explored as a means of improving patient experience as well as efficiency in terms of cost savings. Evidence that community cancer services improve care quality and/or generate cost savings is currently limited. A randomised study was undertaken to compare delivery of cancer treatment in the hospital with two different community settings.

Methods:

Ninety-seven patients being offered outpatient-based cancer treatment were randomised to treatment delivered in a hospital day unit, at the patient''s home or in local general practice (GP) surgeries. The primary outcome was patient-perceived benefits, using the emotional function domain of the EORTC quality of life (QOL) QLQC30 questionnaire evaluated after 12 weeks. Secondary outcomes included additional QOL measures, patient satisfaction, safety and health economics.

Results:

There was no statistically significant QOL difference between treatment in the combined community locations relative to hospital (difference of −7.2, 95% confidence interval: −19·5 to +5·2, P=0.25). There was a significant difference between the two community locations in favour of home (+15·2, 1·3 to 29·1, P=0.033). Hospital anxiety and depression scale scores were consistent with the primary outcome measure. There was no evidence that community treatment compromised patient safety and no significant difference between treatment arms in terms of overall costs or Quality Adjusted Life Year. Seventy-eight percent of patients expressed satisfaction with their treatment whatever their location, whereas 57% of patients preferred future treatment to continue at the hospital, 81% at GP surgeries and 90% at home. Although initial pre-trial interviews revealed concerns among health-care professionals and some patients regarding community treatment, opinions were largely more favourable in post-trial interviews.

Interpretation:

Patient QOL favours delivering cancer treatment in the home rather than GP surgeries. Nevertheless, both community settings were acceptable to and preferred by patients compared with hospital, were safe, with no detrimental impact on overall health-care costs.     

MR-imaging of the brain of neurologic asymptomatic patients with large cell or adenocarcinoma of the lung. Does it influence prognosis and treatment?

Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurologist is of little value to provide information of the neurologic status.     

Escape from negative regulation of growth by transforming growth factor β and from the induction of apoptosis by the dietary agent sodium butyrate may be important in colorectal carcinogenesis

There are a number of lines of evidence suggesting that transforming growth factor (TGF) has an important role in the control of intestinal growth and differentiation.In vivo localization studies show that TGF expression occurs predominantly in the differentiated non proliferating cells of the intestinal epithelium. The use of an antisense expression vector for TGF resulted in an increased tumorigenicity in an antisense-transfected cancer cell line.In vitro proliferation studies showed colorectal premalignant adenoma cells to be more sensitive to the growth inhibitory effects of TGF than colorectal cancer cells. Furthermore the conversion of an adenoma to a carcinoma was accompanied by a reduced response to the inhibitory effects of TGF. The acquisition of partial or complete resistance to the inhibitory effects of TGF may be an important late event in colorectal carcinogenesis.Of further interest is the possibility that clonal selection could occur even more rapidly in colorectal tumour cells which not only had lost response to TGF inhibition but produced TGF and were growth stimulated by it. This could have the advantage of not only inhibiting the growth of surrounding less malignantly advanced cells but of also escaping from their potential growth suppressive influence. Carcinogenesis is not, however, simply losing response to negative regulators of growth; the fully malignant cell has to acquire new characteristics of invasiveness and metastatic potential. Growth factors including TGF may have a role in the complex cascade of events leading to the activation of proteolytic enzymes which are involved in progression to an invasive phenotype.Cell proliferation in the large bowel, as well as being under the control of endogenous growth factors, is also under the influence of dietary components in the lumen such as the naturally occurring fatty acid sodium butyrate. Sodium butyrate at physiological concentrations induces apoptosis (programmed cell death) in colonic tumour cell lines. Since sodium butyrate occurs naturally in the colorectum, being produced by bacterial fermentation of dietary fibre, it may be involved in the control of cell death in human colorectal epithelium. This could, in part, explain the apparent protective effects of dietary fibre. Clonal evolution and tumour progression in colorectal carcinogenesis could therefore involve loss of response to endogenous growth factors such as TGF and an escape from the induction of programmed cell death by dietary factors.     

Reply to the article “Metronomic therapy with cyclophosphamide induces rat lymphoma and sarcoma regression,and is devoid of toxicity” by V. R. Rozados et al. (Ann Oncol 2004; 15: 1543–1550): … and in humans?

We congratulate Rozados et al. [1] on conducting this importantclinical trial, which investigates the antitumour effect ofa metronomic administration of low-dose cyclophosphamide (CTX)in sarcoma rat tumour models. The use of ‘metronomic’ drug delivery is increasingin solid     

SDF-1/CXCR4 promotes epithelial–mesenchymal transition and progression of colorectal cancer by activation of the Wnt/β-catenin signaling pathway

Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in angiogenesis and are associated with tumor progression. This study aimed to investigate the role of SDF-1/CXCR4-mediated epithelial–mesenchymal transition (EMT) and the progression of colorectal cancer (CRC) as well as the underlying mechanisms. The data showed that expression of CXCR4 and β-catenin mRNA and protein was significantly higher in CRC tissues than in distant normal tissues. CXCR4 expression was associated with β-catenin expression in CRC tissues, whereas high CXCR4 expression was strongly associated with low E-cadherin, high N-cadherin, and high vimentin expression, suggesting a cross talk between the SDF-1/CXCR4 axis and Wnt/β-catenin signaling pathway in CRC. In vitro, SDF-1 induced CXCR4-positive colorectal cancer cell invasion and EMT by activation of the Wnt/β-catenin signaling pathway. In contrast, SDF-1/CXCR4 axis activation-induced colorectal cancer invasion and EMT was effectively inhibited by the Wnt signaling pathway inhibitor Dickkopf-1. In conclusion, CXCR4-promoted CRC progression and EMT were regulated by the Wnt/β-catenin signaling pathway. Thus, targeting of the SDF-1/CXCR4 axis could have clinical applications in suppressing CRC progression.