BRAF Inhibitors for BRAF V600E Mutant Colorectal Cancers: Literature Survey and Case Report.

The main method of fighting against colon cancer is targeted treatment. BRAF inhibitors, which are accepted as standard treatment for V600E mutant malign melanomas, are the newest approach for targeted treatment of V600E mutant colorectal cancers. In this case report, we share our experience about the use of BRAF inhibitor vemurafenib on a V600E mutant metastatic right colon adenocarcinoma patient. A 59-year-old male with only lung multiple metastatic V600E mutant right colon cancer presented to our clinic. The patient was evaluated and FOLFOX + bevacizumab treatment was initiated, which was then continued with vemurafenib. A remarkable response was achieved with vemurafenib treatment in which the drug resistance occurred approximately in the sixth month. Even though the patient benefited majorly from vemurafenib, he died on the 20th month of the diagnosis. The expected overall survival for metastatic V600E mutant colon adenocarcinoma patients is 4.7 months. BRAF inhibitors provide new treatment alternatives for V600E mutant colorectal cancers, with prolonged overall survival. BRAF inhibitors in combination with MEK inhibitors are reported as feasible treatment to overcome BRAF inhibitor drug resistance on which phase studies are still in progress. To conclude, BRAF inhibitors alone or in combination with other drugs provide a chance for curing BRAF V600E mutant colorectal cancer patients.

The value of combined elevation of D-dimer and neopterin as a predictive parameter for early stage acute mesenteric ischemia: An experimental study.

Background The diagnosis of acute mesenteric ischemia is variable. Early diagnosis is important for reducing the mortality and morbidity rates. Aim This experimental study aims to investigate the diagnostic utility of D-dimer and neopterin as a marker for the early stage of acute mesenteric ischemia caused by occlusion of superior mesenteric artery. Methods The levels of D-dimer and neopterin were measured using an animal acute mesenteric ischemia model in 21 male rabbits. Superior mesenteric artery occlusion (Group 1, n = 14) and control (Group 2, n = 7) groups were identified. Blood samples at different times are collected from each rabbits. Blood samples from superior mesenteric artery occlusion group were taken 30 min after anesthesia but before laparotomy, 1, 2, and 3 h after superior mesenteric artery ligation. Blood samples from control group were taken 1 h before, 1 and 3 h after anesthesia and laparotomy. The D-dimer and neopterin levels of each blood sample were measured. Results The probability of acute mesenteric ischemia was found to be 36 times higher when the D-dimer level was over 0.125 ng/L, whereas the probability was 19.2 times higher when the neopterin level was over 1.25 nmol/L. Conclusions In this experimental study, the combined elevation of two significant markers, D-dimer and neopterin, may be helpful for the early diagnosis of acute mesenteric ischemia.

Role of alkaline phosphatase intestine-isomerase in acute mesenteric ischemia diagnosis.

BACKGROUND: The aim of the present study was to investigate the diagnostic value of alkaline phosphatase (ALP) intestine-isomerase, plasma lactate dehydrogenase (LDH), and D-dimer levels in acute mesenteric ischemia. METHODS: Thirty Wistar rats were divided into 5 groups of 6 rats each. In Group 1, blood samples were obtained to determine normal parameter levels. In the sham group, Group 2, blood samples were obtained following laparotomy. In Group 3, blood samples were obtained 2 hours after ligation. In Groups 4 and 5, blood samples were obtained at 4 and 6 hours after ligation, respectively. Ischemic damage was assessed using a pathological scoring system. Blood samples were analyzed for hourly changes in parameters. RESULTS: No statistically significant difference in D-dimer levels was found between ischemia groups (p=0.337). A statistically significant difference in LDH levels was found between the control group, Group 1, and Group 4 (p=0.018). ALP intestine-isomerase enzyme levels were not statistically significant in other groups (p=0.077). CONCLUSION: Findings indicate that plasma LDH levels higher than 1900 IU/L may be a useful marker in the early diagnosis of acute mesenteric obstruction. However, ALP intestine-isomerase enzyme and D-dimer plasma levels were not found to contribute to the diagnosis.

A simple novel technique for enteroatmospheric fistulae: silicone fistula plug.

Enteroatmospheric fistulae (EAFs), a rare condition that develops in patients treated with an open abdomen, present serious problems for the surgeon. There are no fixed algorithms for treatment of EAF, and treatment options are determined based on the experience of the surgeon and status of the patient. We developed a 'suspended silicone fistula plug' for treating a patient who developed an EAF after undergoing multiple operations in a short period of time. Used in conjunction with negative pressure wound therapy, application of this novel therapy resulted in EAF closure and patient discharge.

Use of self-expanding covered stent and negative pressure wound therapy to manage late rectal perforation after injury from an improvised explosive device: a case report.

Blast injuries, caused by explosions accompanied by high-pressure waves, produce tissue damage in the acute period, followed in the later period by circulatory disorders due to vascular endothelial damage and related tissue necrosis. Blunt rectal perforation is rare and difficult to diagnose. In the acute period following blast pelvic injuries, the main objectives are to stop bleeding, minimise contamination and preserve the patient's life. The patient in this report had major vascular injuries, severe pelvic injury and, in the later period, rectal perforation because of vascular endothelial damage caused by the blast effect. Our aim was to treat the patient conservatively because of his poor general condition. We placed a self-expanding covered stent (SECS) into the rectum and then applied negative pressure wound therapy (NPWT; V.A.C.® Therapy, KCI) to the pelvic region and perirectal area. At the end of the treatment, the rectal perforation was closed, and the patient was discharged with healing. In this article, we discuss the novel use of an SECS with NPWT and review related literature.

[Analysis of the pediatric trauma score in patients wounded with shrapnel; the effect of explosives with high kinetic energy: results of the first intervention center]. / Pediatrik travma skorunun yüksek kinetik enerjiye sahip parça etkili yaralanmalardaki analizi: Ilk müdahale merkezi sonuçlari

BACKGROUND: We aimed to assess the pediatric trauma score analysis in pediatric trauma cases due to shrapnel effect of explosives material with high kinetic energy. METHODS: The data of 17 pediatric injuries were reviewed retrospectively between February 2002 and August 2005. The information about age, gender, trauma-hospital interval, trauma mechanism, the injured organs, pediatric Glasgow coma score (PGCS), pediatric trauma score (PTS), hemodynamic parameters, blood transfusion, interventions and length of hospital stay (LHS) were investigated. RESULTS: While all patients suffered from trauma to the extremities, only four patients had traumatic lower-limb amputation. Transportation time was <=1 hour in 35% of cases, and >1 hour in 65% of cases. While PTS was found as <=8 in 35.3% of cases (n=6), the score was found to be higher than 8 in 64.7% of them (n=11). Median heart rate in patients with PTS <=8 was 94 beats/min. This value was 70 beats/min in those with PTS >8 (p=0.007). Morbidity rates of PTS <=8 cases and PTS >8 cases were 29.4% and 5.9%, respectively (p=0.026). While LHS was 22.8 days in PTS <=8 cases, LHS was found to be only 4 days in PTS >8 cases. This difference was found to be statistically significant (p=0.001). CONCLUSION: PTS is very efficient and a time-saving procedure to assess the severity of trauma caused by the shrapnel effect. The median heart rate, morbidity, and LHS increased significantly in patients with PTS <=8.

Biliary fistula after treatment for hydatid disease of the liver: when to intervene.

AIM: To determine the outcome of patients with biliary fistula (BF) after treatment for hydatid disease of the liver. METHODS: Between January 2000 and December 2010, out of 301 patients with a diagnosis of hydatid cyst of the liver, 282 patients who underwent treatment [either surgery or puncture, aspiration, injection and reaspiration (PAIR) procedure] were analysed. Patients were grouped according to the presence or absence of postoperative biliary fistula (PBF) (PBF vs no-PBF groups, respectively). Preoperative clinical, radiological and laboratory characteristics, operative characteristics including type of surgery, peroperative detection of BF, postoperative drain output, morbidity, mortality and length of hospital stays of patients were compared amongst groups. Multivariate analysis was performed to detect factors predictive of PBF. Receiver operative characteristics (ROC) curve analysis were used to determine ideal cutoff values for those variables found to be significant. A comparison was also made between patients whose fistula closed spontaneously (CS) and those with intervention in order to find predictive factors associated with spontaneous closure. RESULTS: Among 282 patients [median (range) age, 23 (16-78) years; 77.0% male]; 210 (74.5%) were treated with conservative surgery, 33 (11.7%) radical surgery and 39 (13.8%) underwent percutaneous drainage with PAIR procedure A PBF developed in 46 (16.3%) patients, all within 5 d after operation. The maximum cyst diameter and preoperative alkaline phosphatase levels (U/L) were significantly higher in the PBF group than in the no-PBF group [10.5 ± 3.7 U/L vs 8.4 ± 3.5 U/L (P < 0.001) and 40.0 ± 235.1 U/L vs 190.0 ± 167.3 U/L (P = 0.02), respectively]. Hospitalization time was also significantly longer in the PBF group than in the no-PBF group [37.4 ± 18.0 d vs 22.4 ± 17.9 d (P < 0.001)]. A preoperative high alanine aminotransferase level (> 40 U/L) and a peroperative attempt for fistula closure were significant predictors of PBF development (P = 0.02, 95%CI: -0.03-0.5 and P = 0.001, 95%CI: 0.1-0.4), respectively. Comparison of patients whose PBF CS or with biliary intervention (BI) revealed that the mean diameter of the cyst was not significantly different between CS and BI groups however maximum drain output was significantly higher in the BI group (81.6 ± 118.1 cm vs 423.9 ± 298.4 cm, P < 0.001). Time for fistula closure was significantly higher in the BI group (10.1 ± 3.7 d vs 30.7 ± 15.1 d, P < 0.001). The ROC curve analysis revealed cut-off values of a maximum bilious drainage < 102 mL and a waiting period of 5.5 postoperative days for spontaneous closure with the sensitivity and specificity values of (83.3%-91.1%, AUC: 0.90) and (97%-91%, AUC: 0.95), respectively. The multivariate analysis demonstrated a PBF drainage volume < 102 mL to be the only statistically significant predictor of spontaneous closure (P < 0.001, 95%CI: 0.5-1.0). CONCLUSION: Patients with PBF after hydatid surgery often have complicated postoperative course with serious morbidity. Patients who develop PBF with an output < 102 mL might be managed expectantly.

The role of 2-[f-18] fluoro 2-deoxy d-glucose positron emission tomography in the preoperative staging of gastric cancer.

OBJECTIVE: FDG-PET can contribute significantly to the preoperative period of patients with planned curative resections or with isolated liver or lung metastasis. In this study, we analyze the importance and diagnostic value of FDG-PET in the preoperative evaluation of gastric cancers by correlating its value with computerized tomography (CT). MATERIALS AND METHODS: A prospective study was conducted. Abdominal and pelvic CTs were obtained for preoperative staging in each patient. Separate stagings were performed according to the findings of conventional methods and PET scans, and the results were compared with the operative and histological findings. RESULTS: When the patients were evaluated according to the pathological stage, eight patients were Stage 1 (26.7%), five were Stage 2 (16.7%), eight were Stage 3 (26.7%), and nine were Stage 4 (30%). FDG-PET and CT down-staged the disease in eight (26.7%) and twelve (40%) patients, respectively. FDG-PET and CT up-staged the disease in two (6.7%) and five patients (16.7%), respectively. FDG-PET accurately staged the disease in eighteen patients (60%) (p= 0.182). CONCLUSION: To develop highly sensitive radioactive tests that show invasive local lymph node and peritoneal metastases, more studies in the preoperative staging of gastric cancer are needed. FDG-PET indicates a high specificity in the staging of gastric cancer. In patients who are planned for curative surgery, FDG-PET provides better staging when used with CT.

[The affecting factors on the complication ratio in abdominal gunshot wounds]. / Karin içi atesli silah yaralanmalarinda komplikasyon oranlarini etkileyen faktörler.

BACKGROUND: We aimed to investigate the affecting factors on the complication ratio in abdominal gunshot wounds. METHODS: Twenty-one patients with abdominal gunshot wounds were analyzed between February 2002 and May 2005. The effects of the interval between trauma and presentation to the hospital, the number of injured abdominal and extra-abdominal organs, penetrating abdominal trauma index (PATI), and blood transfusion were evaluated. RESULTS: 90.4% of all patients were transported to the hospital and underwent their first evaluation in the first two hours. The complication rate was 7.1% in patients who had <3 injured organs and 71% in the others (p<0.0001). 71.4% of the patients had isolated abdominal trauma, while 28.6% had additional extra-abdominal organ trauma. The complication rate was 7.7% in 13 patients with PATI score <25 and 62.5% in 8 patients with a PATI score ≥25 (p<0.0001). In 10 patients who underwent blood transfusion of ≥3 units, the complication rate was 50% (p<0.0001). CONCLUSION: In our study, PATI score, multiple blood transfusions and the number of injured intra-abdominal organs were the most important factors affecting the rate of postoperative complications in penetrating abdominal gunshot wounds. We found that the interval between trauma and presentation to the hospital and number of injured extra-abdominal organs did not affect the complication rate.

Comparison of hyperbaric oxygen and medical ozone therapies in a rat model of experimental distal colitis.

OBJECTIVES: Previous studies have shown that hyperbaric oxygen (HBO) is effective in reducing the severity of acute distal colitis (ADC). Ozone therapy (OT) reduces inflammation in several pathological conditions. We aimed to compare the effects of HBO therapy and OT in an experimental ADC rat model. MATERIALS AND METHODS: Forty rats were randomly divided into four groups: Sham, ADC, ADC + HBO, and ADC + OT. Rats in the sham group were given isotonic saline. In the remaining groups, ADC was created by intracolonic administration of 4% acetic acid. No treatment was given to the ADC group. The rats in the ADC + HBO and ADC + OT groups were given HBO and ozone treatments, respectively. The administration of acetic acid caused an inflammatory response in all animals. Distal colons and blood samples were obtained. RESULTS: The histopathological score was significantly higher in the ADC group compared to the other groups. The histopathological scores in the ADC + HBO and ADC + OT groups were significantly lower compared to the ADC group (both p < 0.001). The most pronounced therapeutic effect was observed in the ADC + OT group. Malondialdehyde and neopterin levels and superoxide dismutase and glutathione peroxidase activities in the ADC group were significantly higher compared to the other groups (p < 0.001). CONCLUSION: Our data showed that the therapeutic effect of OT is more pronounced than that of HBO therapy. Its possible effect is by means of decreasing inflammation, edema, and oxidative stress. These findings also suggest that it is possible to improve the outcome of ADC by using ozone therapy as an adjuvant therapy.

Comparison of modified darn repair and Lichtenstein repair of primary inguinal hernias.

OBJECTIVE: This study was designed to compare the results of the Modified Darn Repair through Lichtenstein procedure in inguinal hernias. MATERIALS AND METHODS: The study involved 322 patients with inguinal hernia, operated in General Surgery Departments of Gulhane Military Medical Academy and Sirnak Military Hospital between 1998 and 2004. The durations of operation time, hospitalization, and time to return to daily activities and postoperative complication and recurrence rates were evaluated. Lichtenstein procedure was applied on 170 patients (Group 1), and modified darn repair was applied on 152 patients (Group 2). RESULTS: The average follow-up period was 56 months. For the Lichtenstein procedure, the average duration of operation was 56 min; the average time to return to routine activities was 20 days. The number of patients with postoperative complications was 20 (11.7%), and the number of patients with recurrence was 1 (0.6%). For modified darn repair, the average duration of operation was 48 min; the time to return to daily activities was 20 days. The number of patients with postoperative complication was three (1.9%), and no recurrences were noted. The hospitalization time of the groups was similar. DISCUSSION: Modified darn repair is a reliable method for inguinal hernia repair with short hospitalization time, low rate of postoperative complications, and recurrence.

D-dimer levels in the prediction of the degree of intestinal necrosis of etrangulated hernias in rats.

PURPOSE: The aim of this study was to investigate the time-dependent relation between plasma D-dimer levels and the degree of intestinal necrosis and to compare these parameters with leukocyte counts in an experimental etrangulated hernia model in rats. RESULTS: When the duration of intestinal ischemia was prolonged, serum D-dimer levels increased relative to the control group, with the difference being statistically significant at hour 2 (P = 0.027). In contrast, leukocyte counts in the 2- and 4-h strangulation group were higher that those of the control group, but the difference was not statistically significant (P = 0.625 and P = 0.846, respectively). However, in the 6-h strangulation group the levels of leukocytes were significantly higher that those of the control group (P = 0.015). CONCLUSION: Serum D-dimer measurements may be used as a more valuable diagnostic parameter than leukocyte count in the early diagnosis of intestinal ischemia, including strangulated hernia.

Appropriate approach to bronchobiliary fistulas: a case series with hydatid disease and algorithm of case-based management.

Bronchobiliary fistula caused by liver echinococcosis is a relatively unusual but severe complication of hydatid disease. Optimal management of cases is crucially important in establishing rapid recovery and avoiding additional complications. The use of an algorithmic guide is essential because of an ongoing dilemma that involves a large variety of therapeutic options. We present four patients with bronchobiliary fistulas caused by liver hydatid disease to discuss the management of therapeutic options through a case-based approach and an extent review to finally generate an algorithm. In this series, two patients were treated surgically, and the remaining were treated with conservative methods. To date, they have developed neither recurrence nor need for additional intervention. Although treatment of bronchobiliary fistulas is traditionally thought to be surgical, most of the less severe cases can be treated nonoperatively. Making an accurate selection among less invasive methods and/or open surgical interventions seems to be a key component of management.

Comparison of Urografin versus standard therapy in postoperative small bowel obstruction.

Water-soluble contrast media (Urografin) cause redistribution of intravascular and extracellular fluid into intestinal lumen due to their hyperosmolarity. As a consequence, these media decrease intestinal wall edema and act as a direct stimulant to intestinal peristalsis. In this prospective study, we aimed to examine objectively the therapeutic role and ability of Urografin in patients with postoperative small bowel obstruction for whom failed to respond to conservative treatment. Three hundred and seventeen patients with postoperative small bowel obstruction due to intraperitoneal adhesions were included prospectively in this study. In the Urografin group, 40 mL Urografin diluted in 40 mL distilled water was administered through the nasogastric tube. No contrast media were administered in the control group, but the patients were decompressed via a nasogastric tube continuously. The number of obstruction episode in 317 patients was 338. In total, 199 patients were in the Urografin group, and 118 patients were in the control group. In the Urografin group, 178 (89.4%) patients responded successfully to the treatment, but 21 (11.6%) patients underwent surgical operation. Intensive intraabdominal adhesions and obstructing fibrous bands were observed and repaired in 15 (71.4%) patients at the operation, while 6 patients underwent segmental small intestine resection in control group, conventional management was successful in only 89 (75.4%) patients, and the remaining 29 (24.6%) patients underwent surgical intervention. In conclusion, it was suggested that in patients with intestinal obstruction due to postoperative intra-abdominal adhesion, water-soluble contrast media such as Urografin may be safely administered via a nasogastric tube or oral route and may decrease the need for surgical operation; furthermore, they may help the physician to operate the patients who needs surgery as early as possible.

Role of anorectal myectomy in the treatment of short segment Hirschsprung's disease in young adults.

Basic pathological disorder in Hirschsprung's disease (HD) comes into being by the abnormal innervations of the aganglionic distal intestine. The nonserious forms of this congenital disease may reach the young by proceeding with chronic, obstinate constipation that does not respond to diet. Myectomy of the short segment of aganglionic part may provide diagnostic and therapeutic value. Between 1993 and 2003, anorectal posterior myectomy was performed in 19 patients diagnosed with HD. The mean age of patients was 23 years. Previous or concomitant anterior resection was added to the procedure in seven cases due to dolicomegacolon. In addition to the deficiency of anorectal inhibitor reflex (ARIR) among all patients, the frequency of defecation was 12.5 days (range, 6-30 days) before operation. Anorectal length before widening was an average of 5.5 cm (range, 2-8 cm). All pathologic specimens were found to be aganglionic. Postoperatively, the mean of first regular defecation interval was 1.5 days (range, 1-3 days). Involution of rectum was evaluated with a rectal examination and barium enema X-rays during follow-up. ARIR of patients also returned to normal. In conclusion, anorectal posterior myectomy is an effective operation in diagnosis and treatment of short-segment HD. Furthermore, colon resection annexed to this operation, in the condition of dolicomegacolon, is also used to remove obstinate constipation.