Ischaemic colitis and colorectal cancer: some problems and pitfalls

Four cases out of 204 new cases of colorectal carcinoma seen in a 24 month period were proven to have concomitant proximal ischaemic colitis. Ischaemic colitis associated with obstructing carcinoma of the colorectum may present dramatically with gangrene or colonic perforation if the acute vascular insufficiency is severe. Less severe degrees of ischaemic insult must be recognised intra-operatively as the incorporation of ischaemic colon in a colonic anastomosis may result in an anastomotic leak. Two other patients with ischaemic colitis were wrongly diagnosed as colorectal carcinoma on colonoscopy. Endoscopic features of ischaemic colitis may mimic colonic carcinoma and endoscopic biopsy is essential where any doubt exist as to the possibility of ischaemic colitis so that unnecessary surgery may be avoided.

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Résumé 4 cas parmi 204 nouveaux cas de cancers colorectaux vus dans une période de 24 mois, montraient une colite ischémique proximale concomitante. La colite ischémique associée avec un cancer colorectal ischémique, peut se présenter dramatiquement avec gangrene et perforation colique si l'insuffisance vasculaire aigue est sévère. Les lésions moins sévères d'ischémie doivent être reconnues au cours de l'intervention car une anastomose colique sur un colon ischémique peut provoquer un lâchage anastomotique. Deux autres patients avec des colites ischémiques furent faussement diagnostiqués comme cancer colorectal à la coloscopie. Les aspects endoscopiques de la colite ischémique peuvent simuler le cancer colique et les biopsies endoscopiques sont essentielles si le moindre doute existe quant à la possibilité de colite ischémique afin qu'une chirurgie inutile soit évitée.

     

Human papillomavirus and cervical cancer

Cervical cancer is the second most common cancer in women worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual activity. Persistent infections and precancer are established, typically within 5-10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35-55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings.     

Human papillomavirus and gastrointestinal cancer: A review

Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention.     

Clinical and molecular diagnosis of hereditary non-polyposis colorectal cancer: problems and pitfalls in an extended pedigree

Hereditary non-polyposis colorectal cancer (or Lynch syndrome) is an autosomal dominant disease in which early onset colorectal carcinomas aggregate in families together with tumours of other organs. The genetic basis of the syndrome has been clarified with the identification of mutations in several DNA mismatch repair genes (MSH2, MLH1, PMS1, PMS2 and MSH6). We describe the clinical features and molecular characterization of a large hereditary non-polyposis colorectal cancer family which has been followed for almost 10 years. The kindred showed a striking aggregation of colorectal tumours in 3 successive generations; most of these neoplasms developed before the age of 50 years and were localized in the proximal colon. Molecular tests (carried out in ten individuals) showed specific alterations at the MLH1 gene, consisting in the insertion of a T nucleotide between bases 2,269 and 2,270; the mutation caused frameshift of the open reading frame and synthesis of a polypeptide longer than normal. The only tumour that could be analysed was positive for microsatellite instability. Physicians should become more confident with hereditary tumours and their implications, which are not limited to a single individual but concern all family members at risk of cancer. This family approach is different, and requires more expertise than the traditional individual approach. Common problems encountered in Hereditary Non-polyposis Colorectal Cancer families include: A) poor collaboration of subjects at risk (a situation which may cause some conflict between the doctor's duty to inform patients about their risk of disease and the rights of patients to choose and decide about their health); B) definition of the most appropriate surveillance programme for a given family (how many investigations to propose to the patients, and how often); C) possible interaction between genes and environmental factors (for instance, a gene carrier--in this family--developed an endometrial carcinoma after standard tamoxifen adjuvant therapy for breast cancer).     

Oral chemotherapy in colorectal cancer treatment: review of the literature

Recent advances in anticancer treatment have focused on the development of oral anticancer agents with the intention of improving the patients' quality of life as well as providing therapeutic alternatives to intravenous chemotherapy. Until agents such as oxaliplatin and irinotecan became available, the treatment of colorectal cancer, one the most common cancers diagnosed in industralized countries, was mainly based on 5-fluorouracil modulation. The overwhelming majority of these new drugs are pyrimidine analogues intended to replace intravenous treatment or to make the therapy more acceptable to the patients. In this article, the use of oral chemotherapy, alone or in combination with radiotherapy, in colorectal cancer is reviewed and updated. The rationale for using oral compounds is discussed and newer agents, such as oral camptothecin analogues and antiangiogenic agents, are presented with the results of their clinical and preclinical developments.     

Adjuvant chemotherapy for resected colorectal cancer metastases:literature review and meta-analysis

Surgical resection is the only option of cure for patients with metastatic colorectal cancer(CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence(based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.     

Management of peritoneal carcinomatosis from colorectal cancer: review of the literature

Background

Today, we do not have a universally accepted evidence on how to treat peritoneal carcinomatosis (PC) from colorectal cancer (CRC) in international guidelines.

Methods

The present study is a review of the literature investigating current strategies to treat CRC PC.

Results

Despite the progresses of systemic chemotherapy, the presence of PC among patients with metastatic CRC reduces the overall survival to 30 %, and only 4 % of patients with PC from CRC treated are alive for 5 years. Many trials evaluate the combined treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC PC, suggesting a survival benefit in highly selected patients. Only one trial is randomized and presents some biases. The two main prognostic factors are Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC score). There is no universal agreement on how to approach the synchronous presence of PC and liver metastasis with a curative intent during the same procedure. A growing interest among the scientific community has arisen about systematic second-look surgery and HIPEC treatment in high-risk patients.

Conclusion

Current evidences suggest that CRS and HIPEC might be beneficial in highly selected patients affected with PC from CRC. Anyway, today, there is a shortage of well-designed phase 3 trials.     

Tertiary stent-in-stent for obstructing colorectal cancer: A case report and literature review

BACKGROUND Self-expandable metal stents(SEMSs) are frequently used in the setting of palliation for occluding, inoperable colorectal cancer(CRC). Among possible complications of SEMS positioning, re-obstruction is the most frequent. Its management is controversial, potentially involving secondary stent-in-stent placement, which has been poorly investigated. Moreover, the issue of secondary stent-in-stent re-obstruction and of more-than-two colonic stenting has never been assessed. We describe a case of tertiary SEMS-in-SEMS placement, and also discuss our practice based on available literature.CASE SUMMARY A 66-year-old male with occluding and metastatic CRC was initially treated by positioning of a SEMS, which had to be revised 6 mo later when a symptomatic intra-stent tumor ingrowth was treated by a SEMS-in-SEMS. We hereby describe an additional episode of intestinal occlusion due to recurrence of intra-stent tumor ingrowth. This patient, despite several negative prognostic factors(splenic flexure location of the tumor, carcinomatosis with ascites, subsequent chemotherapy that included bevacizumab and two previously positioned stents(1 SEMS and 1 SEMS-in-SEMS)) underwent successful management through the placement of a tertiary SEMS-in-SEMS, with immediate clinical benefit and no procedure-related adverse events after 150 d of post-procedural follow-up. This endoscopic management has permitted 27 mo of partial control of a metastatic disease without the need for chemotherapy discontinuation and, ultimately, a good quality of life until death.CONCLUSION Tertiary SEMS-in-SEMS is technically feasible, and appears to be a safe and effective option in the case of recurrent SEMS obstruction.     

Aspirin and clopidogrel response variability: review of the published literature

Antiplatelet resistance has been proposed as a possible mechanism to explain recurrent cardiovascular events in patients who have coronary artery disease and who are undergoing dual antiplatelet therapy. A comprehensive search on PubMed was conducted for literature that was printed in the English language between January 1996 and November 2007 on aspirin and clopidogrel resistance. Significant traits for aspirin hyporesponsiveness were female sex, older age, and lower levels of hemoglobin. Diabetes mellitus and elevated body mass index showed trends toward a higher incidence of resistance in some aspirin trials but did not reach statistical significance. Clopidogrel studies suggested that patients with type-2 diabetes mellitus are more likely to manifest inadequate response to the medication. Although 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors were initially suspected to decrease response to clopidogrel, later studies refuted this possibility. Patients with a suboptimal response to aspirin or clopidogrel seem to be at increased risk of recurrent cardiovascular events. Large clinical trials with standardized laboratory methods and well-defined protocols are needed to determine whether common features exist in patients with suspected hyporesponsiveness to antiplatelet therapy, and to validate the clinical relevance of response variability. A concise nonarbitrary definition of physiologic "resistance" is needed, and investigators should identify patients as having a variable response to antiplatelet therapy.     

Human papillomavirus DNA: physical map.

Human papillomavirus (HPV) DNA form I (supercoiled) was prepared from plantar warts. HPV DNA was cleaved with restriction enzymes obtained from the following sources: escherichia coli (EcoRI), Hemophilus influenzae strain Rd (both unfractionated Hind and aeparated HindII and HindIII enzymes) and Hemophilus parainfluenzae (HpaI). The cleavage products were analyzed by polyacrylamide gradient slab gel electrophoresis and electron microscopy. HPV DNA was cleaved into two fragments by EcoRI (87% and 13% of the genome) and into six fragments, ranging in size from 33.5 to 1.2% of the genome, by Hind endonucleases. The six Hind fragments result from the cleavage of three sequences recognized by HindII, two of which are also cleaved by HpaI, and of three sequence recognized by HindIII. The order of these fragments was determined by comparing their size with that of the fragments obtained with HindII, HindIII, HpaI, and the mixture of HindIII + Hpal. The two EcoRI cleavage sites were located on two adjacent Hind fragments and one of these sites has been taken for the zero point to construct a physical map. The treatment of superhelical HPV DNA with bacteriophage T4 gene 32 protein yields circular structures with a denaturation loop. The cleavage of these complexes with EcoRI and HindIII has shown two easily denatured regions which were located on the cleavage map.