Yunus Alif Gul

Pharmacotherapy for chronic hemorrhagic radiation proctitis

Endoscopic thermal therapy and formalin are being increasingly recommended for the treatment of chronic hemorrhagic radiation proctitis. It may be too early, however, to discard pharmacologic agents from the management process, especially in medical institutions where specialized equipment is unavailable. We prospectively assessed the effectiveness of medical therapy in 14 consecutive patients with chronic hemorrhagic radiation proctitis from July 1999 to June 2001. All 14 subjects were women (mean age 56 years), 13 of whom had had radio-therapy for Cancer of the cervix. The median time to onset of Symptoms following irradiation was 16 months. Six patients had a hemoglobin level of<8 g/dl, and blood transfusion was required in 11 patients. In five patients (36%) initially treated with hydrocortisone enemas prior to referral, this treatment continued; and the remaining nine patients were commenced on sucralfate enemas. Two patients given rectal hydrocortisone continued to bleed and were treated with sucralfate enemas and topical formalin, respectively. Rectal sucralfate Suspension effectively procured symptomatic alleviation in all 11 patients. Rectal bleeding recurred in two patients who had been managed exclusively with hydrocortisone and sucralfate enemas, respectively, over a mean follow-up of 6 months. Both patients were managed with topical formalin, which con-trolled their Symptoms. Even though the number of subjects in this study is small, sucralfate enema can be recommended as an effective first-line agent for managing patients with chronic hemorrhagic radiation proctitis. The use of more specialized therapy can therefore be reserved for cases where primary treatment failure occurs with sucralfate therapy.RésuméOn recommande de plus en plus souvent la thermothérapie (argon-beamer) et l’injection formolée par voie endoscopique dans le traitement de la rectite chronique post-irradiation hémorragique. Cela dit, il est peut-être trop tôt pour se débarrasser complètement des agents pharmacologiques dans le traitement de ces rectites, surtout dans les établissements médicalisés qui manquent d’équipements spécialisés. Nous avons prospectivement évalué l’efficience du traitement médical chez 14 patients consécutifs porteurs de rectite radique chronique hémorragique entre juillet 1999 et juin 2001: il s’agissait de 14 femmes (âge moyen 56 ans), 13 ayant eu de la radiothérapie pour cancer du col utérin. L’intervalle médian entre la radiothérapie et le début des symptômes a été de 16 mois. Six patientes avaient un taux d’hémoglobine <8 g/dl et des transfusions sanguines ont été nécessaires chez 11 patientes. Chez les cinq patientes (36%) qui avaient été traités initialement par des lavements à l’hydrocortisone avant d’être adressés chez nous, ce traitement est resté sans changement: les neuf autres patients ont eu des lavements au sucralfate. Deux patients ont continué de saigner malgré les lavements à l’hydrocortisone et ont été ensuite traités par des lavements au sucralfate. La suspension au sucralfate a été efficace chez 11 patientes en ce qui concerne l’amélioration symptomatique. On a constaté une récidive d’hémorragie chez deux patientes traitées initialement exclusivement par les lavements à l’hydrocortisone et sucralfate sur un suivi moyen de 6 mois. Toutes deux ont été traitées par des lavements locaux au formol, ce qui a contrôlé les symptômes. Bien que le nombre de sujets soit petit, les lavements au sucralfate peuvent être recommandés en première ligne pour le traitement de proctite radique chronique hémorragique. L’utilisation de traitements plus spécifiques est réservée aux patients pour qui le traitement par des lavements au sucralfate a échoué.ResumenEn el tratamiento de la hemorragia crónica por una proctitis secundaria a irradiación, se recomienda cada vez más la terapia térmica endoscópica y el tratamiento con formalina. Sin embargo, parece que todavía es pronto para descartar los agentes farmacológicos hasta ahora empleados, especialmente en centros médicos que carecen del equipamiento necesario para aplicar esta nueva terapia. Evaluamos prospectivamente la eficacia del tratamiento médico en 14 pacientes con radioproctitis con hemorragia crónica, atendidos entre julio de 1999 y junio de 2001. Todos los pacientes eran mujeres (edad media 56 años), 13 de las cuales fueron sometidas a radioterpia por padecer un cáncer de cervix. Los síntomas aparecieron a los 16 meses (como promedio) de la irradiación. 6 pacientes presentaban una hemoglobina<8 g/dl y 11 enfermas requiriern transfusión sanguínea. 5 pacientes (36%) al sernos remitidos estaban siendo tratados con enemas de hidrocortisona y este tratamiento se mantuvo, mientras que en los 9 casos restantes se inició un tratamiento con enemas de sucralfato. Dos pacientes tratados con hidrocortisona continuaron sangrando y por ello se indicaron enemas de sucralfato. La suspensión rectal de sucralfato fue eficaz en 11 pacientes, mejorándose considerablemente su sintomatología. Durante un periodo de seguimiento superior a 6 meses se constataron recidivas de hemorragia rectal en 2 pacientes tratados uno, exclusivamente con hidrocortisona, y otro con sucralfato. En ambos la aplicación tópica de formalina controlô su sintomatología. Aunque la casuística de este estudio es escasa parece evidente, que el enema de sucralfato debe recomendarse como tratamiento inicial de pacientes con hemorragia crónica por proctitis por irradiación. Otras terapias más especializadas deberán reservarse para cuando fracase el tratamiento con sucralfato.

A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D1 in colorectal carcinoma

Background and aimsIt is well accepted that activation of Wnt signalling occurs in colorectal carcinoma (CRC), but the correlation amongst the various proteins involved in primary tumours are still unclear. The expression of the inducer of this pathway, Wnt-1, and the downstream effectors, WISP-1, cyclin-D1 and survivin proteins, was compared in a series of CRC tissues with the apparently normal adjacent tissues to determine the relationship of these proteins.Patients and methodsFormalin-fixed, paraffin-embedded tissue samples of 47 CRCs surgically resected at the Kuala Lumpur Hospital (KLH) between 1999 and 2000 were used. Immunohistochemical staining with monoclonal antibodies against cyclin-D1 and survivin and polyclonal antibodies against Wnt-1 and WISP-1 was performed. Results of immunohistochemistry were analysed for correlation between biomolecules and histopathological data of the patients.ResultsOf the 47 CRCs, 26 (55.3%), 15 (31.9%), 5 (10.6%) and 28 (59.6%) of the tumours exhibited positivity for Wnt-1, WISP-1, cyclin D1 and survivin, respectively. A lower percentage of the 40 apparently normal adjacent tissues were found to be positive for Wnt-1 (7, 17.5%), WISP-1 (±5, 12.5%) and survivin (13, 32.5%), but cyclin D1 was not detected in any of them. Interestingly, the total scores of Wnt-1, WISP-1 and survivin were significantly higher in CRC tissues (p=0.001, 0.034 and 0.044, respectively). Using the Spearman rank correlation test, a positive linear relationship was found between total Wnt-1 score with total WISP-1 score (rho=0.319, p=0.003) and total survivin score (rho=0.609, p=<0.001). The expression of WISP-1 in the CRC tissues was found to be positively correlated with patients older than 60 years old (p=0.011). In addition, nuclear cyclin-D1 expression was found to be associated with poorly differentiated CRC tissues (p<0.001, Table 5) and right-sided CRC tumour (p=0.019, Table 6). Total WISP-1 score was associated with well-differentiated CRC tissues (p=0.029).ConclusionsOverexpression and interplay between Wnt-1, WISP-1, survivin and cyclin-D1 may play a role in tumorigenesis, possibly by promoting cell cycle checkpoint progression, accelerating cell growth and inhibiting apoptosis. Our data may provide useful information towards the search for potent therapeutic targets towards the development of novel treatment strategies for CRC.

Postoperative venous thromboembolism in Asia: a critical appraisal of its incidence.

OBJECTIVES Venous thromboembolism (VTE) has historically been perceived to be a rare disorder in Asia. However, new evidence has emerged recently that contradicts this perception. The question of routine VTE prophylaxis has been hotly debated in Asia due to disagreement on its incidence. We reviewed and analysed studies on postoperative VTE in Asian patients to determine if the condition was indeed rare and if the routine prophylactic measures as recommended by internationally accepted guidelines should be adopted in Asia. METHODS A review of published reports, from 1966 to December 2002, on deep vein thrombosis (DVT) and pulmonary embolism (PE) in the Asian population was made. A literature search of studies published in English was conducted via a detailed MEDLINE search. Studies had to attain a minimum inclusion and quality criteria to be accepted for the review, including the diagnostic modality used for the diagnosis of VTE. The appraisal was carried out independently and accepted by at least two of the three authors. The study population was classified into orthopaedic and general surgical/colorectal groups. RESULTS Twelve orthopaedic publications reviewed revealed an incidence of postoperative DVT of 10% to 63%. Six general and colorectal surgical publications reported an incidence of DVT ranging from 3% to 28%. The incidence was slightly lower than the reported incidence of 40% to 80% following orthopaedic surgery and 28% to 44% following general surgical operations in studies reporting on Caucasian populations. CONCLUSION While there is a wide variation in the incidence of DVT and VTE as reported in the Asian population, these diseases are by no means rare. The wide variation could be due to the study designs, heterogeneity of the procedures performed and the application of different diagnostic criteria. Results based on prospective studies with objective diagnostic criteria confirm the incidence of VTE as common. Routine chemoprophylaxis must be seriously considered in high-risk patients.

Adult Intussusception Secondary to Inflammatory Polyps

Adult intussusception is a rare entity that may present in the acute and subacute setting principally related to the degree of bowel obstruction. Preoperative diagnosis of this condition may be difficult. The intussusception is usually due to a definable intraluminal lesion, most probably neoplasia, unlike intussusception in children. We present the cases of two adult male patients with intussusception. The first presented with acute small-bowel obstruction secondary to a retrograde ileojejunal intussusception with a pseudopolyp as the lead point. This was possibly due to a retrograde ball-valve effect. The intussuscepting segment was resected. The second patient presented with unexplained chronic diarrhoea and an intussusception occurring within the caecum, as demonstrated at colonoscopy, with a terminal ileal pedunculated fibroid polyp as the lead point. A limited right hemicolectomy was performed. Both patients recovered uneventfully and have remained well. A brief literature review of adult intussusception complements the case reports, with an emphasis on the pathogenesis of inflammatory polyps and recommended surgical management.

Mucinous adenocarcinoma of the rectum with breast and ocular metastases.

We present the case of a 32-year-old woman who, 10 months after abdominoperineal resection and total mesorectal excision for a locally advanced mucinous adenocarcinoma of the rectum, presented with local recurrence and metastases to the breast, spine, the left eye and orbit. Following surgery, due to the patients personal reasons, adjuvant chemoradiation was not given. The patient died 2 months later, with disseminated cancer. To the best of our knowledge, breast as well as ocular metastasis in a patient with mucinous adenocarcinoma of the rectum has never been reported and, therefore, needs to be documented.

Antibiotic prophylaxis in elective colorectal surgery

Background: Antibiotics are often administered in elective colorectal surgery to prevent wound infection. The tendency for surgeons to prolong the administration of prophylactic antibiotic therapy in the postoperative period is a well‐known fact. The aim of this study was to elucidate the pattern of prophylactic antibiotic utilization in elective colorectal surgery and to determine if evidence‐based medicine is employed in relation to this practice.

Diagnostic value of plain abdominal radiographs in patients with acute abdominal pain

OBJECTIVE A prospective study was performed over a 3-month period in a tertiary referral centre to evaluate the appropriateness and contribution of plain abdominal radiographs (PAR) in the diagnosis and management of adult patients presenting with acute abdominal pain. METHODS Forward stepwise logistic regression was used to examine the correlation between PAR findings and the final diagnosis. The Chi-squared test was used to determine any changes in patient management including requirement for surgical intervention based on PAR findings (p < 0.05). RESULTS Of 168 patients (246 PAR), 59 (35%) had positive findings on PAR. PAR were most sensitive in cases of intestinal obstruction (odds ratio, OR = 33.548, r = 0.561). The sensitivity was further increased if three of the following predictive signs were present: exaggerated bowel sounds (OR = 13.350, r = 0.154), abdominal distension (OR = 2.993, r = 0.234) and age over 50 years (OR = 2.301, r = 0.027). PAR were non-diagnostic in 82% of patients with acute abdominal pain (p < 0.001). CONCLUSION PAR do not play a major role in influencing the management of patients with acute abdominal pain without coexisting bowel obstruction.

Expression of Beta-catenin, COX-2 and iNOS in Colorectal Cancer: Relevance of COX-2 and iNOS Inhibitors for Treatment in Malaysia

BACKGROUND Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS. METHODS A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral. RESULTS COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores. CONCLUSIONS the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

Appropriateness of colonoscopy in a tertiary referral centre.

The aim of this study was to determine the appropriateness of colonoscopy in relation to its diagnostic yield, with reference to the guidelines set by the American Society of Gastrointestinal Endoscopy (ASGE). A prospective 90-day audit was performed at Hospital Kualal Lumpur, which is a tertiary referral centre in Malaysia, to examine the appropriateness of colonoscopy by indication. During that time, 257 colonoscopies were performed in 244 patients. The predominant indications for colonoscopy were altered bowl habit (37%) and rectal bleeding (18%). Of the 257 colonoscopies, 216 (84%) were judged to be appropriate by ASGE guidelines. Only 43% of all colonoscopies had positive findings. Positive findings were found in 93% of cases judged appropriate compared with only 7% found in cases deemed inappropriate. There were statistically significant relationships between appropriateness and overall positive yield and between appropriateness and neoplastic findings (p < 0.05). Colonoscopy performed for appropriate indications yield more significant findings, this, we advocate the use of accepted guidelines to maintain or improve the standard colonoscopy services.

Ruptured ectopic pregnancy presenting as an irreducible inguinal hernia.

Abstract An inguinal hernia that suddenly becomes irreducible may be secondary to a variety of other underlying conditions which can occasionally mislead the attending surgeon. Benign, inflammatory or neoplastic processes, as well as surgical emergencies such as intraperitoneal or retroperitoneal haemorrhage, have all been previously reported to mimic an inguinal hernia that suddenly becomes irreducible with or without clinical features of strangulation. We add an additional interesting presentation to this list in the form of a ruptured ectopic pregnancy, which is the first such case reported in the literature. A swelling in the groin may be much more complicated than it seems on superficial consideration and good clinical acumen is constantly required in managing such cases if a satisfactory outcome without any morbidity is to be expected.