KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer?

KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR) monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE) samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27%) and specificity (64%) in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100%) and specificity (100%) in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer.

JCV-specific T-cells producing IFN-gamma are differently associated with PmL occurrence in HIV patients and liver transplant recipients.

Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LTR.

Giant xanthogranuloma of the pelvis with S1 origin: Complete removal with only posterior approach, technical note.

Xanthogranulomas (XG) are benign proliferative disorder of histiocytes, a non-Langerhans cell histiocytosis. Whose etiology is unknown. The nature of these lesions is controversial and could be either reactive or neoplastic; the presence of monoclonal cells does, however, favor the second hypothesis. Xanthogranuloma is frequently found in young adults and children (under 20 years old), mainly in the skin. In about 5%-10% of all Juvenile XG (JXG) cases xanthogranuloma are extracutaneous. Within this group, the site most frequently involved is the eye. Other involved organs are heart, liver, adrenals, oropharynx, lung, spleen, central nervous system and subcutaneous tissue, although involvement of the spine is uncommon. Isolated lesions involving the sacral region are extremely rare. To date, this is the first reported case of a giant JXG arising from S1 with extension into the pelvic region in an adult spine.

The role of HIPEC in the treatment of peritoneal carcinomatosis from gastric cancer: between lights and shadows.

Gastric cancer is one of the most dreadful neoplastic diseases and remains the second cause of cancer death worldwide. Patients who develop peritoneal metastasis have a poor prognosis, with a median survival of less than 6 months. Despite being the cause of 60% of deaths from gastric cancer, peritoneal metastasis can still be considered a local disease and a local multidisciplinary approach can improve the prognosis even in this end-stage disease. At present, hyperthermic intraperitoneal chemotherapy (HIPEC) is the most widely accepted treatment for peritoneal surface diseases and can be performed in patients with different stages of cancer and with various antitumoral drugs. We performed a systematic review of the current status of HIPEC in the treatment of gastric peritoneal metastasis in an attempt to obtain answers to the questions that still remain: do results differ with these different methods? Does HIPEC exert a significant effect on the intracavitary delivery of drugs? Which patients should be treated and which should not? What can we expect from this approach in terms of survival, morbidity, and mortality? On reviewing the literature, despite the lack of trials comparing the different methods, we found that HIPEC has been shown to be an effective tool whenever a complete or an almost complete resection of the peritoneal implants can be performed. Therefore, it is advisable to refer all at-risk patients to specialized centers to be enrolled in randomized trials to achieve truly reliable results.

Colovesical fistula in sigmoid diverticulitis. A case report.

Colonic diverticulosis has continuously increased, noticeably left-sided disease. Colovesical fistula is an uncommon complication of diverticulitis, and its most common cause is diverticular disease. Pneumaturia and fecaluria are commonly related symptoms. We present the case of a 79-year-old woman complaining pneumaturia and fecaluria. Abdominal CT showed a colovesical fistula due to sigmoid diverticulitis. After surgical adhesiolysis between the sigmoid colon and the bladder, the defect of the bladder wall was repaired by simple closure. The colonic defect was treated by segmental resection including the rectosigmoid junction. Following the operation the patient continuously improved at months 6, 12 and 18 without evidence of recurrences.

Preoperative chemoradiotherapy in elderly patients with locally advanced rectal cancer.

PURPOSE: To evaluate the treatment tolerance and clinical outcomes in patients aged 70 and older with locally advanced rectal carcinoma treated with multimodality approach. METHODS AND MATERIALS: We retrospectively analysed 20 consecutive elderly patients, with histologically proven rectal adenocarcinoma, staged T3-4, and/or node-positive tumour, who received chemoradiotherapy and proceeded to surgical approach. Performance status score and adult comorbidity evaluation-27 score were calculated, and their influence on treatment tolerance and clinical outcomes was analysed. RESULTS: All patients completed programmed chemoradiotherapy treatment. Gastrointestinal toxicity was the most common acute side effects: proctitis in 70% of patients and diarrhoea in 55%, classified as Grade 3 in 3 patients only. Radiation dermatitis was reported in 7 patients (35%) and it was graded G3 in one patient. There was no haematological toxicity. Eighteen patients out of 20 underwent surgery. Sphincter preservation was assured in 13 patients. Comorbidity index was related to higher severe acute toxicity (P = 0.015) but no influenced treatment outcomes. CONCLUSION: Treatment tolerance with combined modality is good in elderly patients. Due to age, no dose reduction for radiation therapy and chemotherapy should be considered.

Analysis of variables predictive of severity in biliary peritonitis.

OBJECTIVE: To analyze clinical and laboratory findings in order to find variables predictive of severity of Biliary Peritonitis (BP). METHODS: Physical findings, course of illness, imaging and laboratory data were evaluated in 22 patients with BP, and statistically analysed to assess their prognostic significance. RESULTS: Serious illness and worse outcome were associated with: age > 60 years (P= 0.034), long time between onset of symptoms and treatment (P= 0.025), fever > 38°C (P= 0.009), WBC count > 17.000 cell/mm3 (P=0.043), diffuse abdominal pain (P= 0.034), and infected bile (P= 0.048). CONCLUSIONS: Most patients become severely ill due to supervening infection, while early bile drainage avoids serious complications. In addition, abdominal pain, fever and WBC count are also predictive of severity of BP.

The role of nutrition in the development of esophageal cancer: what do we know?

Cancer of the esophagus is the eighth most common cancer by incidence worldwide and ranks sixth as the most common cause of cancer death. It is unique among the gastrointestinal tract malignancies because it embodies two distinct histopatologic types, squamous cell carcinoma and adenocarcinoma. Which type of cancer occurs in a given patient or predominates in a given geographic area depends on many variables, including individual lifestyle, socioeconomic pressures, environmental factors and diet and nutrition. Generally for both squamous cell carcinoma and adenocarcinoma of the esophagus case-control studies provide evidence of a protective effect of fruits and vegetables. Here we review the role of nutrition in the etiology of esophageal cancer.

Primary testicular plasmocytoma.

A case of Primary Testicular Plasmocytoma (PTP) in an 81-year-old man with a painless nodule in the left testis is reported. All possible pre-operative investigations were carried out, but the diagnosis of PTP was possible only after microscopic examination of the resected testis.

FOLFOX4 in the treatment of metastatic colorectal cancer in elderly patients: a prospective study.

Elderly patients constitute a subpopulation with special characteristics that differ from those of the general population and have been under-represented in clinical trials. We, prospectively, analyzed the toxicity and efficacy of the original FOLFOX4-regimen in the treatment of elderly patients affected by metastatic (m) colorectal cancer (CRC). Thirty-six consecutive patients aged 67-82 years (median age 72 years), 22 males and 14 females, with mCRC and measurable disease, were enrolled in the study. The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. A total of 36 patients, aged 67-82 years were included. Twenty-two and 14 patients were male and female, respectively. The median age was 72 years (range 67-82). The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The overall response rate (ORR) was 44.4% and similar to original study. Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 16 months. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. Tolerability, however, was manageable and no toxic death occurred. FOLFOX4-regimen maintains its efficacy, and safety ratio in elderly patients with mCRC and good performance status. It would be considered the treatment of choice in the treatment of this particular setting of patients.

Prostate apoptosis response-4 is expressed in normal cholangiocytes, is down-regulated in human cholangiocarcinoma, and promotes apoptosis of neoplastic cholangiocytes when induced pharmacologically.

Prostate apoptosis response-4 (Par-4) is a tumor suppressor protein that sensitizes cells to apoptosis; therefore, Par-4 modulation has therapeutic potential. No data currently exist on Par-4 expression in cholangiocarcinoma (CCA). We evaluated the expression of Par-4 in normal and neoplastic cholangiocytes and the effects of its pharmacological or genetic modulation. The study was performed in human and rat liver, CCA patient biopsies, and two CCA cell lines. PAR-4 was expressed in normal rat and human cholangiocytes, but its expression levels decreased in both human CCA and CCA cell lines. In both intrahepatic and extrahepatic CCA, Par-4 expression (as shown by immunohistochemistry) was inversely correlated with markers of proliferation (eg, proliferating cellular nuclear antigen) and directly correlated with apoptotic markers (eg, Bax and Bax/BCL2 ratio). Par-4 expression was decreased during CCA cell proliferation but was enhanced after apoptosis induction. Pharmacological induction of Par-4 expression in CCA cell lines by diindolymethane or withaferin A promoted activation of apoptosis and inhibition of proliferation. In contrast, specific Par-4 silencing by small-interfering RNA determined activation of CCA cell line proliferation. Par-4 is expressed in rat and human cholangiocytes and is down-regulated in both human CCA and CCA cell lines. Par-4 protein levels decrease during cell proliferation but increase during apoptosis. Pharmacological or genetic induction of Par-4 determines apoptosis of CCA cells, suggesting Par-4 targeting as a CCA treatment strategy.

A case of relapsing secondary bladder adenocarcinoma after right colonic cancer.

BACKGROUND: A 71-year-old woman was referred to a surgical oncology clinic after CT raised suspicion for a bladder neoplasm. She had previously undergone right hemicolectomy and received adjuvant chemotherapy for pT3N1MX cancer of the cecum. A retroperitoneal recurrence had been deemed unsuitable for surgical resection, and had instead been treated with chemoradiation therapy. Follow-up CT raised suspicion for a possible bladder neoplasm. INVESTIGATIONS: CT, physical examination, urinalysis, cystoscopy with biopsy, pathological analysis and immunohistochemical analysis. DIAGNOSIS: Adenocarcinoma of the cecum metastatic to the bladder. MANAGEMENT: The patient underwent open bladder resection with total excision of the neoplasm and was administered adjuvant chemotherapy consisting of irinotecan and cetuximab. Subsequent recurrences at the same site were treated with transurethral resection, while chemotherapy was still in progress. At 7 months' follow-up, the patient remained alive, with no evidence of further recurrence.

Multi-slice tomographic diagnosis of isolated right aortic arch in an elderly patient.

Occasional report of asyntomatic right aortic arch in a 90-year-old man with any congenital defect associated.

Endoscopic retrograde cholangiography for intrabiliary rupture of hydatid cyst.

BACKGROUND: Hydatid disease affects most commonly the liver, and rupture into the bile ducts is a frequent complication, occurring in 5% to 25% of cases. These complications can cause major clinical problems either preoperatively or postoperatively with post-resectional abscess or prolonged biliary fistula. We reviewed our experience with preoperative endoscopic retrograde cholangiography (ERC) and the diagnosis of major cyst-biliary fistula. METHODS: During a 7-year period, 78 patients underwent surgery for hepatic hydatid disease. Ten patients, in whom a major intrabiliary rupture of the cyst was suspected on the basis of clinical and radiological criteria, underwent preoperative ERC, with clearing of the biliary tree. Endoscopic sphincterotomy was performed in 7 cases when the fluid contained daughter cysts or pus. Three patients, in whom the biliary content was fluid only, did not undergo sphincterotomy. One patient in whom a preoperative ERC was not feasible underwent operative transduodenal sphincterotomy. In all 11 patients the cyst was resected. Two patients underwent preoperative ERC, but no fistula was detected . They were compared with the remaining group of 67 patients who underwent resectional surgery during the same period, for apparently uncomplicated echinococcal cysts, and with an historical group of 569 patients operated on from January 1966 to January 1995. RESULTS: According to the clinical and radiological preoperative criteria, there were 2 false positives. Preoperative ERC allowed visualization of the fistula, clearing of the biliary tree, and sphincterotomy in selected cases. The incidence of postoperative fistula was significantly decreased after the introduction of selective preoperative ERC, on the basis of preoperative clinical and radiological criteria. CONCLUSIONS: Preoperative ERC is very helpful in patients with cyst-biliary fistula, allowing visualization of the fistula and drainage of the biliary tree, and reducing the incidence of postoperative complications from 11.1% to 7.6%. In selected cases it can solve the problem, without further surgical therapy.

Surgical treatment of severe late radiation injury to the bowel: a retrospective analysis of 83 cases.

BACKGROUND/AIMS: The aim of this study was to determine the best surgical approach for the treatment of late radiation injury to the bowel. METHODOLOGY: Clinical and follow-up charts of 83 patients operated in our institution for late radiation injury to the bowel were retrospectively reviewed. The type of operation (resection-anastomosis or bypass) mortality, postoperative complications and reoperation rate were recorded. Seventy-six underwent resection with immediate anastomosis. A bypass or viscerolysis was performed in only 7 patients. RESULTS: Postoperative mortality was 2.4%, morbidity was 23. Twenty-seven patients underwent further surgery; early reoperation (within 1 month) was necessary in 12 (morbidity 41%). A late reoperation has been performed in 15 patients (no mortality, morbidity 53.5%). CONCLUSIONS: From the results of our study it can be concluded that resection with immediate anastomosis for late radiation injury to the bowel is safe and should be the first option for these patients.