The Impact of Preoperative Radiation Therapy on Locoregional Recurrence in Patients with Stage IV Rectal Cancer Treated with Definitive Surgical Resection and Contemporary Chemotherapy.

PURPOSE: Definitive resection of primary rectal cancers is frequently incorporated, with or without preoperative radiotherapy and perioperative chemotherapy, in the management of selected patients with metastatic rectal adenocarcinoma. This study reviews the impact of preoperative radiotherapy and perioperative chemotherapy on locoregional recurrence and overall survival in these patients. METHODS AND MATERIALS: This retrospective study with an Institutional Review Board (IRB) waiver included 109 patients with metastatic rectal adenocarcinoma who underwent definitive primary resection between 1998 and 2011. In addition to resection, 64 patients were treated with preoperative radiotherapy and perioperative chemotherapy and 45 patients were treated with perioperative chemotherapy alone. Radiotherapy dose was typically 50.4 Gy. Baseline variables were compared using chi-square and unpaired t tests. Overall survival was calculated using Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards regression. RESULTS: There were no significant baseline differences between the two groups. There was no significant difference in locoregional recurrence (10.9 vs. 11.1%; p = 0.90) or overall survival (34.5 vs. 34.8 months; p = 0.89) for patients treated with preoperative radiotherapy compared to those treated with perioperative chemotherapy alone, respectively. Patients who underwent radiotherapy were less likely to have a positive margin (10.9 vs. 20.0%; p = 0.19), lymphovascular invasion (32.8 vs. 53.3%; p = 0.03), and pathologic stage N2 disease (25.0 vs. 42.2%; p = 0.02). Grade 2 postoperative complications were more common in the preoperative radiotherapy group (32.8 vs. 15.6%; p = 0.04). Multivariate analysis demonstrated that patients with poorly differentiated tumors (HR 2.19; p = 0.009) and those that did not undergo liver-directed therapy (HR 2.20; p = 0.005) had inferior survival. CONCLUSIONS: Locoregional recurrence is modest in patients with metastatic rectal adenocarcinoma receiving definitive primary resection, irrespective of the use of radiotherapy. Preoperative radiotherapy may enhance pathologic downstaging at the expense of increased grade 2 postoperative complications. Its use should be reserved for patients at high risk for locoregional recurrence.

A 58-year-old lady presented as an emergency with right upper quadrant pain and loss of 5 stones in weight. What does the X-ray show?

KEY CLINICAL MESSAGE: Renal cell cancers are among the great mimics in surgery as they present with myriad symptoms unrelated to the renal cancer. This patient also interestingly had an incidental finding of porcelain gall bladder.

Management and outcome of pouch-vaginal fistulas after IPAA surgery.

BACKGROUND: After IPAA, the timing, management, and outcome of pouch-vaginal fistulas are poorly defined. OBJECTIVE: The purpose of this study was to evaluate the frequency, management, and outcome of patients who develop a pouch-vaginal fistula. DESIGN: This was a retrospective analysis of a prospectively maintained database. SETTINGS: The study was conducted in a single-center, high-volume tertiary referral colorectal unit. PATIENTS: Women with a pouch-vaginal fistula after IPAA from 1983 to 2010 were included in the study. MAIN OUTCOME MEASURES: The healing rate of pouch-vaginal fistulas was measured. RESULTS: Of 152 patients with a pouch-vaginal fistula after IPAA, 59 fistulas occurred at <12 months, constituting the early onset group, and 43 occurred at >12 months, constituting the late-onset group. Seventy-five patients (77.3%) underwent local repair (48 (49.5%) had ileal pouch advancement flap and 27 (27.8%) had transvaginal repair). The healing rate after ileal pouch advancement flap performed as a primary procedure was 42% and 66% when performed secondarily after a different procedure. The healing rate for transvaginal repair was 55% when done as a primary procedure and 40% when performed secondarily. Nineteen patients underwent redo ileal pouch construction, with an overall pouch retention rate of 40%. At median follow-up of 83 months (range, 5-480 months), 56 (57.7%) of the 102 patients had healed the pouch-vaginal fistula, whereas pouch failure occurred in 34 women (35%, 12 early onset and 22 late onset). Healing of the fistula was significantly lower (22% versus 73%; p < 0.001) and pouch failure higher (52.7% versus 22.7%, p < 0.001) when compared with Crohn's disease. On multivariate analysis, a postoperative delayed diagnosis of Crohn's disease was associated with failure (p = 0.01). No other factors were associated with pouch failure. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Pouch-vaginal fistula after IPAA surgery is indolent and may persist after repairs. A delayed diagnosis of Crohn's disease is associated with a poor outcome and a higher chance of pouch failure.

Ischemic preconditioning of small bowel mitigates the late phase of reperfusion injury: heme oxygenase mediates cytoprotection.

BACKGROUND: Ischemia and reperfusion (IR) injury of the intestine is a major cause of morbidity and mortality following small bowel transplantation. The current study evaluates the effect of ischemic preconditioning (IPC) on the intestinal microcirculation in the late phase of IR injury of the intestine. METHODS: Sixty rats were randomly allocated to 5 study groups (n = 12 per group): (1) sham, (2) IR (3) IPC, (4) pyrrolidine dithiocarbamate (PDTC) (HO-1 inducer), and (5) zinc protoporhyrin (ZnPP) (HO-1 inhibitor). Mucosal perfusion and leukocyte-endothelial interactions were measured with the aid of an intravital microscope. At the end of the experiments, blood samples for lactate dehydrogenase (LDH) levels and biopsies of ileum for histologic evaluation were obtained. RESULTS: IPC significantly improved the mucosal perfusion and decreased the leukocyte-endothelial interactions. Histologic examination showed that ileal mucosa was significantly less injured in the IPC and PDTC groups as compared with the IR group. CONCLUSIONS: IPC protects the intestine from late reperfusion injury. HO-1 is involved in this protection. These findings may be of significant importance in clinical small bowel transplantation.

Rupture of urinary bladder: a case report and review of literature.

INTRODUCTION: Spontaneous rupture of the urinary bladder is a rare event. Patients usually present with features of peritonitis and diagnosis is usually made at operation. The morbidity and mortality rate is very high in these groups of patients. CASE PRESENTATION: We present a case of a 47-year-old caucasian woman who was known to have transitional cell carcinoma of the urinary bladder who presented with features of peritonitis. An exploratory laparotomy revealed free perforation of the urinary bladder. The perforation was closed. However, on the second post-operative day she started draining urine from the abdominal drain and was taken back to the operating theatre. The stitches in the urinary bladder had given off and she underwent radical cystectomy along with double barrel cutaneous ureterostomies. Peritoneal biopsies revealed disseminated transitional cell carcinoma in the peritoneum. She made a slow postoperative recovery. CONCLUSION: Perforation of the urinary bladder should be considered in patients presenting with peritonitis particularly with a previous history of urinary bladder cancer.

The in-vivo effect of pyrrolidine dithiocarbamate on hepatic parenchymal microcirculation and oxygenation of the rat liver.

OBJECTIVE: Pyrrolidine dithiocarbamate has been shown to be a potent inducer of haemeoxygenase-1. This study investigated its in-vivo effects on systemic and hepatic microcirculatory perfusion. METHODS: Male Sprague-Dawley rats (n=12) were administered intravenously with pyrrolidine dithiocarbamate (10, 20 and 50 mg/kg body weight) or vehicle (0.2 ml physiological saline) served as control. Systemic and hepatic haemodynamics including arterial oxygen saturation, heart rate, mean arterial blood pressure and portal blood flow were monitored. Microcirculation in skeletal muscle and liver was measured by laser Doppler flowmetry and intravital fluorescence microscopy, whereas hepatic tissue oxyhaemoglobin and cytochrome oxidase CuA redox state, which is an indicative of extracellular and intracellular oxygenation were measured by near infrared spectroscopy. RESULTS: Pyrrolidine dithiocarbamate induced a dose-dependent increase in mean arterial blood pressure and skeletal muscle microcirculation. The hepatic parenchymal microcirculation was significantly improved and an increase in sinusoidal diameter and reduction in RBC velocity were observed. Pyrrolidine dithiocarbamate also showed beneficial effect on hepatic tissue oxygenation showed by an increase in oxyhaemoglobin and cytochrome oxidase CuA redox state as well. CONCLUSION: Pyrrolidine dithiocarbamate improves hepatic parenchymal microcirculation and tissue oxygenation, suggesting that it may be used as a potential agent in pharmacological preconditioning in the liver.

Massive gastrointestinal haemorrhage due to gastritis cystica profunda.

INTRODUCTION: Gastritis Cystica Profunda is a well recognized entity which may occur several years after previous gastric surgery. This is a premalignant condition and may lead on to carcinoma of the stomach. CASE PRESENTATION: We report a case of a 50-year-old man with epigastric pain and haematemesis. 28 years ago he had undergone partial gastrectomy and gastroenterostomy for benign gastric ulcer. An Upper gastrointestinal endoscopy showed a possible bleeding vessel on the anterior wall lesser curve of the stomach. The lesion was injected with adrenaline 1 in 100,000. In spite of the intervention he continued to have haemetemesis with significant haemodynamic impairment. At exploratory laparotomy, an oedematous ridge on the posterior wall with a bleeding point on the posterior gastric wall. Histology showed features consistent with gastritis cystica profunda. He made an excellent post-operative recovery. CONCLUSION: We suggest that patients who are diagnosed with gastritis cystica profunda should be regularly followed up as this is a premalignant condition.

Pyrrolidine dithiocarbamate protects the small bowel from warm ischaemia/reperfusion injury of the intestine: the role of haem oxygenase.

IR (ischaemia/reperfusion) injury of the intestine occurs commonly during abdominal surgery. We have previously shown that PDTC (pyrrolidine dithiocarbamate), an HO-1 (haem oxygenase-1) donor, improves intestinal microvascular perfusion. In the present study, we have investigated the effects of PDTC on the intestinal microcirculation following IR (ischaemia/reperfusion) injury of the intestine. Male Sprague-Dawley rats (n=72) were randomly assigned to four groups (n=18/group): (i) sham-operated group, who underwent laparotomy without induction of IR of the intestine; (ii) IR group, who were subjected to 30 min of superior mesenteric artery occlusion and 2 h of reperfusion; (iii) PDTC+IR group, who received PDTC prior to IR; and (iv) ZnPP group, who received the HO-1 inhibitor ZnPP (zinc protoporphyrin) followed by procedures as in group (iii). The ileum was evaluated for changes in tissue cytochrome c oxidase redox status, RBC (red blood cell) dynamics and leucocyte-endothelial interactions. The expression of HO-1 in the ileal tissue was examined at the end of the reperfusion. PDTC significantly improved the intestinal tissue oxygenation, mucosal perfusion index and RBC velocity compared with the IR and ZnPP groups. PDTC also decreased the leucocyte-endothelial interactions (P<0.05 compared with the IR and ZnPP groups). PDTC induced the expression of HO-1, whereas ZnPP abolished this effect.

Situs inversus abdominus and malrotation in an adult with Ladd's band formation leading to intestinal ischaemia.

Situs inversus abdominus with rotational anomaly of the intestines is an extremely rare condition. Although intestinal malrotation has been recognized as a cause of obstruction in infants and children and may be complicated by intestinal ischaemia, it is very rare in adults. When it occurs in the adult patient, it may present acutely as bowel obstruction or intestinal ischaemia or chronically as vague intermittent abdominal pain. Herein, we present an acute presentation of a case of situs inversus abdominus and intestinal malrotation with Ladd's band leading to infarction of the intestine in a 32 year old woman.

Protective effects of ischemic preconditioning on the intestinal mucosal microcirculation following ischemia-reperfusion of the intestine.

OBJECTIVE: The small bowel villi are extremely sensitive to ischemia-reperfusion (IR) injury and a range of microcirculatory disturbances contribute to structural and functional changes. The aim of this study was to determine the protective effects of ischemic preconditioning (IPC) of the intestine on the mucosal villous microcirculation during IR injury of the intestine and whether heme oxygenase (HO) is involved in the protection. METHODS: Rats were allocated into 4 groups: (1) sham, (2) IR consisting of 30 min of ischemia followed by 2 h of reperfusion, (3) IPC, as in IR group, but preceded by 10 min of ischemia and 10 min of reperfusion, and (4) with administration of zinc protoporphyrin, an HO inhibitor before IPC and IR. The mucosa of an exteriorized segment of ileum was visualized. Mucosal perfusion index (MPI), red blood cell (RBC) velocity and leukocyte-endothelial interactions during reperfusion were assessed continuously using in vivo fluorescence microscopy. HO activity in the ileum was assessed at the end of the reperfusion period. RESULTS: IPC improved the MPI by 26% and the RBC velocity by 29% on comparison to IR. IR led to a 52% increase in leukocyte-endothelial interactions on comparison to IPC. The administration of zinc protoporphyrin reversed the beneficial effects of IPC. There was a two fold increase of HO activity in IPC compared to IR, whereas zinc protoporphyrin significantly reduced the HO activity. CONCLUSIONS: IPC conferred a protective effect on the villous microcirculation possibly via HO and might prove to be an effective strategy for the amelioration of IR injury.

Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine.

AIM: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO production, attenuates intestinal IR injury. METHODS: Eighteen male rats were randomly allocated into three groups: (a) sham; (b) IR, consisting of 30 min of intestinal ischemia, followed by 2-h period of reperfusion; and (c) PDTC treatment before IR. Intestinal microvascular perfusion (IMP) was monitored continuously by laser Doppler flowmetry. At the end of the reperfusion, serum samples for lactate dehydrogenase (LDH) levels and biopsies of ileum were obtained. HO activity in the ileum was assessed at the end of the reperfusion period. RESULTS: At the end of the reperfusion in the IR group, IMP recovered partially to 42.5% of baseline (P<0.05 vs sham), whereas PDTC improved IMP to 67.3% of baseline (P<0.01 vs IR). There was a twofold increase in HO activity in PDTC group (2 062.66+/-106.11) as compared to IR (842.3+/-85.12) (P<0.001). LDH was significantly reduced (P<0.001) in PDTC group (585.6+/-102.4) as compared to IR group (1 973.8+/-306.5). Histological examination showed that the ileal mucosa was significantly less injured in PDTC group as compared with IR group. CONCLUSION: Our study demonstrates that PDTC improves the IMP and attenuates IR injury of the intestine possibly via HO production. Additional studies are warranted to evaluate the clinical efficacy of PDTC in the prevention of IR injury of the small intestine.

Pancreatic trauma from a book.

CONTEXT: An early diagnosis of pancreatic trauma can be challenging and difficult because of the lack of correlation between the initial presenting features, radiological and laboratory findings, and the severity of the trauma. A high degree of suspicion is essential to diagnose pancreatic injury particularly in patients with blunt trauma to the abdomen. A computerised tomography scan is useful in making an early diagnosis of pancreatic trauma, localizing the site of the injury and in the identification of main pancreatic duct injury which has major implications in the management of the patient. CASE REPORT: Here in, we report an interesting case of a 40-year-old woman who sustained a tear in the tail of the pancreas following a blunt injury to the pancreas while she was carrying a book in front of her abdomen and collided against an edge of a door-frame. She was managed conservatively without any complications. CONCLUSIONS: A history of abdominal trauma, however trivial it may sound, needs to be appropriately investigated.