Current guidelines in the surgical management of hereditary colorectal cancers.

Incidence of colorectal cancer (CRC) is on rise. While approximately 70% of all CRC cases are sporadic in nature, 20%-25% have familial aggregation and only < 5% is hereditary in origin. Identification of individuals with hereditary predilection for CRC is critical, as it has an impact on their overall surgical management including surgical timing, approach & technique and determines the role of prophylactic surgery and outcome. This review highlights the concept of hereditary CRC, provides insight into its molecular basis, possibility of its application into clinical practice and emphasizes the current treatment strategies with surgical management, based on the available international guidelines.

Complicated Pylephlebitis Secondary to Perforated Appendicitis in an Adolescent.

Septic thrombophlebitis of the portal vein or pylephlebitis is a rare cause of morbidity and mortality in children. The common causes include infective intra-abdominal pathology (acute appendicitis or diverticulitis) or inflammatory conditions (acute pancreatitis and inflammatory bowel disease). Management involves a multidisciplinary team approach for favorable outcome. We present a case report of pylephlebitis secondary to perforated appendicitis with incomplete resolution of thrombosis.

Rare case of perforated appendicitis presenting as persistent perineal discharge following laparoscopic abdominoperinal excision of rectum (APER).

Abdominoperineal excision of rectum (APER) is one of the widely used surgical procedures to treat low rectal cancer, benign conditions like Crohn's proctitis with anal involvement and as a salvage procedure for anal cancer. Perineal wound infection is a well-recognised complication following such major surgery. Occurrence of appendicitis in a few weeks' time following such a major surgery is uncommon. However, here we present a rare case report of perforated appendicitis presenting as persistent perineal discharge in an elderly man, following laparoscopic APER for a low rectal tumour. To our knowledge, this is the first time such a rare clinical presentation of appendicitis is reported in the history of medical literature. Through this case report, we aim to highlight the importance of considering such an uncommon presentation in patients with perineal discharge, following APER.

Role of colonic stents in the management of colorectal cancers.

Colorectal cancer is one of the commonly encountered cancers across the Western World. In United Kingdom, this constitutes third most common ranked cancer and second most common ranked cause of cancer related deaths. Its acute presentation as a malignant colonic obstruction imposes challenges in its management. Colonic stent has been used for many years to alleviate acute obstruction in such cases allowing optimisation of patient's physiological status and adequate staging of cancer. In this review, current literature evidence regarding use of colonic stent in acute malignant colonic obstruction is critically appraised and recommendations on the use of colonic stent are advocated.

A rare presentation of complication arising from Meckel's diverticulum in the form of diverticulotransverse colonic fistula in an adult.

Meckel's diverticulum is a common congenital malformation of the gastrointestinal tract, reported to be present in 2-4% of the population. Although most patients with Meckel's diverticulum remain asymptomatic throughout life, reports of acute inflammation, perforation, haemorrhage, intussusception, intestinal obstruction, vesicodiverticular fistulae and primary tumours are described. We present a rare diagnosis of diverticulotransverse colonic fistula and its management.

Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). This Guideline was also reviewed and endorsed by the Governing Board of the American Society for Gastrointestinal Endoscopy (ASGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 Prophylactic colonic stent placement is not recommended. Colonic stenting should be reserved for patients with clinical symptoms and imaging evidence of malignant large-bowel obstruction, without signs of perforation (strong recommendation, low quality evidence). 2 Colonic self-expandable metal stent (SEMS) placement as a bridge to elective surgery is not recommended as a standard treatment of symptomatic left-sided malignant colonic obstruction (strong recommendation, high quality evidence). 3 For patients with potentially curable but obstructing left-sided colonic cancer, stent placement may be considered as an alternative to emergency surgery in those who have an increased risk of postoperative mortality, I. e. American Society of Anesthesiologists (ASA) Physical Status ≥ III and/or age > 70 years (weak recommendation, low quality evidence). 4 SEMS placement is recommended as the preferred treatment for palliation of malignant colonic obstruction (strong recommendation, high quality evidence), except in patients treated or considered for treatment with antiangiogenic drugs (e. g. bevacizumab) (strong recommendation, low quality evidence).

Posterior tibial artery aneurysm: a case report with review of literature.

BACKGROUND: Aneurysms infra-patellar region are uncommon. Of them, true aneurysms are very rare and that of posterior tibial artery are extremely rare. The more common, pseudoaneurysms are commonly associated with trauma whereas the true ones are linked with either inflammatory or mycotic origins. CASE PRESENTATION: We reported another case of true aneurysm of posterior tibial artery without any evident aetiology. This was repaired with resection of aneurysm followed by interposition vein graft. CONCLUSION: Through this report, we discussed the rarity, review of literature and management of this unusual condition.

Safety and efficacy of endoscopic colonic stenting as a bridge to surgery in the management of intestinal obstruction due to left colon and rectal cancer: a systematic review and meta-analysis.

INTRODUCTION: Colorectal carcinoma can present with acute intestinal obstruction in 7%-30% of cases, especially if tumor is located at or distal to the splenic flexure. In these cases, emergency surgical decompression becomes mandatory as the traditional treatment option. It involves defunctioning stoma with or without primary resection of obstructing tumor. An alternative to surgery is endoluminal decompression. The aim of this review is to assess the effectiveness of colonic stents, used as a bridge to surgery, in the management of malignant left colonic and rectal obstruction. METHODS: We considered only randomized trials which compared stent vs surgery for intestinal obstruction from left sided colorectal cancer (as a bridge to surgery) irrespective of their size. No language or publication status restrictions were imposed. A systematic search was conducted in Medline, Cochrane Central Register of Controlled Trials and the Science Citation Index (from inception to December 2011) RESULTS: We identified 3109 citations through our electronic search and 3 through other sources. Initial screening of the titles and abstracts resulted in the exclusion of 3104 citations. A further 5 citations were excluded after detailed screening of full articles. Three published studies were included in this systematic review. A total of 197 patients were included in our analysis, 97 of them had colorectal stent vs 100 who had emergency surgery. Clinical success has been defined in different manners. In included trials the clinical success rate was significantly higher in the emergency surgery group (99%) compared with the stent group (52.5%) (p < 0.00001). There was no difference in the overall complication rate in the stent group (48.5%) vs emergency surgery group (51%) (p = 0.86). There was no difference in 30-days postoperative mortality (p = 0.97). The overall survival was analyzed in none trial. When used as a bridge to surgery, colorectal stents provide some advantages: the primary anastomosis rate was significantly higher in the stent group (64.9%) vs emergency surgery group (55%) (p = 0.003); the overall stoma rate was significantly lower in the stent group (45.3%) compared with the emergency surgery group (62%) (p = 0.02). There were no significant differences between the two groups as to permanent stoma rate (46.7% in stent group vs 51.8% in surgical group, p = 0.56), anastomotic leakage rate (9% in stent group vs 3.7% in surgical group, p = 0.35) and intra-abdominal abscess rate (5.1% in stent group vs 4.9% in surgical group, p = 0.97). CONCLUSION: Although colonic stenting appears to be an effective treatment of malignant large bowel obstruction, the clinical success resulted significantly higher in the emergency surgery group without any advantages in terms of overall complication rate and 30-days postoperative mortality. On the other hand, the colonic stenting as a bridge to surgery provides surgical advantages, as higher primary anastomosis rate and a lower overall stoma rate, without increasing the risk of anastomotic leak or intra-abdominal abscess. However, these results should be interpreted with caution because few studies reported data on these outcomes. Due to the small and variable sample size of the included trials, further RCTs are needed including a larger number of patients and evaluating long term results (overall survival and quality of life) and cost-effectiveness analysis.

Colorectal stents for the management of malignant colonic obstructions.

BACKGROUND: Colorectal cancer is one of the most common cancer in the western world. Acute colonic obstruction is one of the common presentations of colon cancer. Emergency surgical decompression is the traditional treatment of choice but is associated with high morbidity and mortality. In recent years colonic stents have been used to relieve the obstruction. OBJECTIVES: The aim was to compare the colonic stenting versus emergency surgical decompression with regards to benefits and risks. SEARCH METHODS: Searches were carried out May 2010 in the Cochrane Colorectal Cancer Specialised Register, the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid EMBASE and Ovid CINAHL. SELECTION CRITERIA: Randomised clinical trials comparing colonic stenting versus surgical decompression for obstructing colorectal cancers were considered for inclusion. DATA COLLECTION AND ANALYSIS: Data on the characteristics of the trial, methodological quality of the trials, mortality, morbidity, technical and clinical success rate, operating time, hospital stay and other measured secondary outcomes from each trial were collected. And the data were analysed with both the fixed-effect and the random-effects models using RevMan Analysis. For each outcome, odds ratio (OR) with 95% confidence intervals (CI) based on available data analysis was calculated. MAIN RESULTS: Five randomised trials were identified with a total of 207 participants, 102 to colorectal stenting and 105 to emergency surgery. There was statistically significant higher clinical success rate in the emergency surgery group. The average time of clinical relief of obstruction was 0.66 day in the colonic stent group and was 3.55 days in the emergency surgery group. The stent insertion was successful in 86.02% of attempted stent placements. There was no statistically significant difference in the 30-day mortality between two groups. The 30 day mortality rate was similar, 2.3% in both groups. The stent related perforation rate was 5.88%. The stent migration rate was 2.13%. The stent obstruction rate was 2.13%. There was no statistically significant difference in overall complication rate in both groups. The complication rate was 39.22% in the colonic stent group and was 45.71% in the emergency surgery group. The mean hospital stay was 11.53 days in the colonic stent group and was 17.15 days in the emergency surgery group. The mean procedure/operating time was 113.93 minutes in the colonic stent group compared to 143.85 minutes in the emergency surgery group. The median blood loss was 50 ml in the colonic stent group and 350 ml in the emergency surgery group. AUTHORS' CONCLUSIONS: The use of colonic stent in malignant colorectal obstruction seems to have no advantage over emergency surgery. The clinical success rate was statistically higher in emergency surgery group. However, use of colorectal stents seems to be as safe in the malignant colorectal obstruction as the emergency surgery with no statistically significant difference in the mortality and morbidity. Colorectal stents are associated with acceptable stent perforation, migration and obstruction rates. The advantages of colorectal stent includes shorter hospital stay and procedure time and less blood loss. However, due to the variability in the sample size and trial designs in the included studies, further randomised trials with bigger sample size and well defined trial design are needed to achieve the robust evidence.

Intranodal palisaded myofibroblastoma originating from retroperitoneum: an unusual origin.

BACKGROUND: Intranodal palisaded myofibroblastoma is one of the primary mesenchymal tumours. The inguinal region is the commonest site of this rare tumour. As there are only about 55 such cases reported in the literature, the precise aetiology and pathogenesis have yet to be explained adequately. Here we report a case of a 72 year old man presented with incidental finding of intranodal palisaded myofibroblastoma in the retroperitoneal region. CASE PRESENTATION: A 72-year old man presented with abdominal pain in right upper quadrant with an incidental finding of abdominal mass in the right flank. The computerised tomogram scan of abdomen confirmed acute cholecystitis with a 5 x 5 cm retroperitoneal mass. He underwent cholecystectomy with excision of this mass. He recovered well following his operation and was discharged from the hospital. Histological examination confirmed the diagnosis of intranodal palisaded myofibroblastoma. CONCLUSION: To our knowledge, this is the first case of intranodal palisaded myofibroblastoma originating from retroperitoneum. Along with the rarity of this case, we also discussed its typical histopathological findings, aetiology and pathogenesis.

Doxycycline in mitochondrial mediated pathway of apoptosis: a systematic review.

Tetracyclines have been long known for their antimicrobial role. They are one of the most widely used antibiotics in clinical practice since last 5 decades. Recently their role as matrix metalloproteinase inhibitor and in apoptosis has widely attracted attention in biological field. Of them, doxycycline is one with long duration of actions and has recently been shown to have various anti-cancer properties, especially cytotoxic and anti-proliferative activities. Here, we systematically reviewed the role of doxycycline in the mitochondrial mediated apoptosis in various tissues. MEDLINE and EMBASE databases were searched using a formal search strategy with definite inclusion and exclusion criteria. Data extraction was performed for each included study using a custom designed data extraction form. A total of 81 references were identified through MEDLINE and 5 were identified through EMBASE. 74 references from MEDLINE and all 5 in EMBASE were excluded through reading titles, abstracts and full text. In total, 7 studies fulfilled inclusion criteria. Following systematic review of these studies, we concluded that doxycycline induces apoptosis through mitochondrial mediated pathway in different tissue cells however it may be cell specific. The caspase independent apoptosis as one of the mechanisms of actions of doxycycline needs further studies for better understanding.

Lowering the apoptotic threshold in colorectal cancer cells by targeting mitochondria.

BACKGROUND: Colorectal cancer is the third most-common cancer and the second most-common cause of cancer related death in UK. Although chemotherapy plays significant role in the treatment of colorectal cancer, morbidity and mortality due to drug resistance and cancer metastasis are yet to be eliminated. Recently, doxycycline has been reported to have cytotoxic and anti-proliferating properties in various cancer cells. In this study, whether doxycycline was apoptosis threshold lowering agent in colorectal cancer cells by targeting mitochondria was answered. RESULTS: This study showed dose-dependent cytotoxic effects of cisplatin, oxaliplatin and doxycycline in HT29 colorectal cancer cells. Doxycycline showed inhibition of cytochrome-c-oxidase activity in these cells over a time-period. The pre-treatment of doxycycline reported statistically significant increased cytotoxicity of cisplatin and oxaliplatin compared to cisplatin and oxaliplatin alone. The caspase studies revealed significantly less expression and activity of caspase 3 in HT29 cells pre-treated with doxycycline compared to the cells treated with cisplatin and oxaliplatin alone. CONCLUSIONS: It was concluded that doxycycline lowered the apoptotic threshold in HT 29 cells by targeting mitochondria. This also raised possible caspase-independent mechanisms of apoptosis in HT29 cells when pre-treated with doxycycline however this needs further research work.

Does doxycycline work in synergy with cisplatin and oxaliplatin in colorectal cancer?

BACKGROUND: In recent years, apart from antibacterial properties, doxycycline is reported to have cytotoxic and anti-proliferative actions in various cancers including colorectal cancer. Colorectal cancer constitutes one of the most common cancers in the western population. Apart from surgery, chemotherapy plays crucial role in the treatment of colorectal cancer. Cisplatin and oxaliplatin are most commonly used platinum compounds for the cancer chemotherapy. This study has looked for any impact of doxycycline on the cytotoxic effects of platinum compounds in colorectal cancer including its mechanisms of actions. METHODS: HT 29 colorectal cancer cells were used for this study. These cells were treated with cisplatin and oxaliplatin with or without doxycycline treatment. The caspase 3 gene expression was quantitated by gel electrophoresis and qualitated by real time polymerase chain reactions. The caspase 3 activity was assessed in HT 29 cells with fluorescence kit. RESULTS: The results revealed increased caspase 3 gene expressions and activities in HT 29 cells treated with cisplatin, oxaliplatin and doxycycline; however the combination of doxycycline with cisplatin and oxaliplatin did not report increased caspase 3 gene expressions and activity compared to cisplatin and oxaliplatin alone. CONCLUSION: We concluded that doxycycline has role in apoptosis induction in the colorectal cancer. However, it did not show any synergy with platinum compounds in the colorectal cancer cells. This study also pointed towards possible caspase-independent actions of doxycycline with cisplatin and oxaliplatin. However, further work is required to underpin the mechanisms of actions of doxycycline.

Massive penoscrotal haematoma following inguinal hernia repair: a case report.

INTRODUCTION: Inguinal hernia is one of the commonest surgical conditions that one comes across in a surgical career. Operative repair is the only successful treatment for hernias. As with other surgical procedures, this is also associated with possible complications. Scrotal haematoma is one of the well-known complications following hernia repair, but massive penoscrotal haematoma requiring surgical intervention is very rare. CASE PRESENTATION: A 53-year-old black man had undergone elective hernia repair. He underwent standard open hernia repair with a prolene mesh and developed massive scrotal haematoma which required drainage. Eventually he recovered well, although slowly. CONCLUSION: To achieve adequate bleeding control during and at the end of operation is the key preventive measure to avoid scrotal haematoma. Here, we report a case of massive penoscrotal haematoma following repair of a moderate sized inguinal hernia. We strongly emphasize the importance of adequate control of bleeding, even in small to moderate sized inguinal hernias in order to avoid such disastrous complications with long-term cosmetic disfigurement.

Role of stem cells in cancer therapy and cancer stem cells: a review.

For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The recent concept of 'cancer stem cells' has directed scientific communities towards a different wide new area of research field and possible potential future treatment modalities for the cancer. Aim of this review is primarily focus on the recent developments in the use of the stem cells in the cancer treatments, then to discuss the cancer stem cells, now considered as backbone in the development of the cancer; and their role in carcinogenesis and their implications in the development of possible new cancer treatment options in future.