Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Total intravenous anesthesia (TIVA) with propofool and remifentanil during operative endoscopy tracheobronchial laser therapy.

Background: The aim of our study was to assess how total intra-venous anaesthesia (TIVA) achieved by propofol and remifentanil continuous infusion could ensure proper success of the endobronchial laser therapy, in optimal conditions for the endoscopist, determining at the same time an adequate hypnosis and a good analgesia. Methods: We studied 50 patients (28M - 22F), ASA class I-IV, mean age 42 ± 32.5 years , subjected to laser endoscopy to repair tracheal stenosis. TIVA was performed in all patients, and spontaneous breathing was maintained. Results: 10.2% of patients experienced episodes of coughing during induction. The depth of the anaesthesia plan, monitored by BIS, was 55 ± 5. The awakening was fast in all patients, with an Aldrete score of 7.71 ± 1.14 at 1 minute and 9.31 ± 1.12 at 10 minutes. Conclusion: The results of this study allow us to state that the continuous infusion of propofol and remifentanil proved to be the gold standard in patients ASA I-II-III undergoing endobronchial laser therapy. The use of TIVA has also allowed to perform endoscopic intervention on patients who suffered from a significant decrease of both cardiac and respiratory functions.

Fracture and migration in right atrium of a permanent venous central access system in a elderly patient: case report and literature review.

Abstract: Catheter dislocation and fracture with migration of central venous lines have been reported in the International literature. Catheter fracture with consequent migration has been observed in 0.5-3.0% and may either be consequent to catheter removal or it can occur spontane-ously. Our case report concerns the migration of a Hickman catheter connected to a venous port to the right atrium in a 61-year old patient. A literature up-to-date has been performed to assess the risk of port-a-cath positioning. The position of catheter tip is considered critical for the risk of migration, that is greater as higher the tip localization respect to the carina. The aim of our study is to underline the critical role of X-ray to visualize the exact location of the catheter tip, regard-less of the approach used for catheter positioning.

Abdominal scar endometriosis: case report.

Abdominal scar endometriosis, corresponding to the presence of an endometrial tissue near or inside an abdominal surgical incision, is a rare clinical event that can occur in women after gynecological or obstetric surgery. Generally, a triad consisting of underlying mass at the incision, cyclic menstrual scar pain, and history of previous gynecological or obstetric surgery leads to the preoperative diagnosis. In rare cases, the clinical presentation is atypical and the differential diagnosis with incarcerated incisional hernia, granuloma, abscess or other soft tissue tumors can be difficult. The authors describe the case of 39-year-old woman who underwent three previous cesarean sections, with a 20-week history of underlying palpable mass at the Pfannenstiel incision, associated to continuous pain. In this case, a surgical excision followed by the histology definitely clarified the diagnosis.

Statins reduce levels of metalloproteinases in patients with carotid occlusive disease.

AIM: Pharmaceutical stabilization of an unstable low-grade carotid artery stenosis delays surgery and improve outcome. Statins can be used to reduce intimal media thickness. Our aim was to determine the clinical and biological effects of rosuvastatin on plaque stabilization or regression. METHODS: Forty-two consecutive male patients presenting with an asymptomatic internal carotid artery plaque uniformly anechogenic (group 1) 40-50% lumen diameter reduction formed the basis of the study. A group of 35 patients affected with a uniformly echogenic carotid artery stenosis (40-50%) served as control (group 2). Patients were followed-up every 8-month for 2 years with B-mode ultrasonography and color imaging. A computed tomography angiography (CTA) was performed before the initiation of the study period and at the end to confirm plaque characteristics and the degree of stenosis. Ticlopidine (250 mg/day) and rosuvastatin (10 mg/day) were administered. One blood sample was drawn at every control to assess the release of matrix metallopoteinases (MMPs)-1, -2, -3, -9, tissue inhibitors of metalloproteinases (TIMPs)-1 and -2. RESULTS: After the administration of rosuvastatin plasma level of MMP-1, -2, -3 and -9 significantly decreased in both groups (P<0.001). Conversely, plasma level of TIMP-1 and -2 significantly increased in both groups (P<0.001). B-mode ultrasonography and color imaging and CTA failed to demonstrate a stabilization or regression of uniformly anehogenic carotid plaque during follow-up. CONCLUSION: Rosuvastatin decreases the plasma level of MMPs and increases those of TIMPs. However, neither progression nor stabilization of low-grade unstable carotid plaques was seen.

Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases.

PURPOSE: A major problem in treating patients with peritoneal spread from colorectal cancer is that at diagnosis wide peritoneal involvement often precludes all curative attempts. A possible solution is to identify those patients at risk for peritoneal metastases and intervene early to prevent locoregional disease spread before it develops and, thus, to improve outcome. METHODS: We analyzed long-term results from a previous study and compared outcomes in 25 patients with advanced colon cancer considered at high risk for peritoneal spread (pT3/pT4 and mucinous or signet ring cell histology) prospectively included and managed with a proactive surgical approach including target organ resection for peritoneal spread plus hyperthermic intraperitoneal chemotherapy (HIPEC) and in 50 retrospectively well-matched controls who underwent standard surgical resection during the same period and in the same hospital by different surgical teams. RESULTS: At 48 months after the study closed, peritoneal metastases and local recurrence developed significantly less often in proactively managed patients than in controls (4 vs 28%) (p < 0.03). Patients in the proactive group also survived longer than control patients (median overall survival 59.5 vs 52 months). Despite similar morbidity, Kaplan-Meier survival curves disclosed significantly longer disease-free and overall survival in the proactive than in the control group (p < 0.05 and <0.04). CONCLUSIONS: In patients with advanced colon cancer at risk for peritoneal recurrence, the proactive surgical approach plus HIPEC seems to achieve good locoregional control preventing peritoneal spread thus improving outcome without increasing morbidity. These advantages merit investigation in a multicentric randomized trial.

Axillary lymph node metastasis as first presentation of peritoneal carcinomatosis from serous papillary ovarian cancer: case report and review of the literature.

Ovarian cancer usually spreads into abdominal cavity and to the loco-regional lymph nodes. Extra-abdominal metastases are less frequent and isolated axillary metastases are very rare. The authors describe the case of a 49-year-old woman who was diagnosed with a peritoneal carcinomatosis from ovarian cancer by mean of an enlarged axillary lymph node biopsy, whose histological examination identified as a ovarian cancer metastasis. Patient was treated by peritonectomy and intraperitoneal chemohyperthermic perfusion (HIPEC). Although patients with axillary lymph node metastasis from ovarian cancer are though to be metastatic (FIGO Stage IV), surgical radical treatment and adjuvant systemic chemotherapy can achieve the same prognosis of Stage IIIb-c patients, suggesting they could be a particularly good prognosis subset of patients. Early differential diagnosis between ovarian or breast cancer in axillary lymph node metastasis is crucial but not always very simple, because of the very different course and treatment of these tumours.

Two synchronous adenocarcinomas of the small bowel in a patient with undiagnosed Crohn's disease of the terminal ileum.

A small but significant excess of deaths for tumors of the digestive system has been described in Crohn's disease. In a study analyzing all cancers of the small intestine within a defined population, Crohn's disease was the major underlying factor for cancer of the small intestine. Areas of the small intestine containing strictures are unusually prone to malignant transformation. We report the rare case of a patient in whom surgery for intestinal occlusion disclosed Crohn's disease of the distal ileum complicated by two adenocarcinomas arising within distinct areas of the inflamed bowel.

[Prognostic factors and results of surgical treatment of pelvic recurrence of rectal cancer]. / Fattori prognostici e risultati del trattamento chirurgico delle recidive pelviche da cancro del retto.

From 1990 to 2003 have been admitted 105 patients with pelvic recurrence from rectal cancer. Fifty-nine patients have been selected and 25 patients underwent surgery. We evaluate the prognostic factors and the 3 years disease-free survival. The 60% of the patients after R0 resection and the 20% of the patients who underwent R1-R2 resection are alive. The evaluation of the prognostic factors allows early diagnosis of recurrence with a better long time survival.

[Molecular epidemiologic analysis of the levels of metalloproteases and cyclooxygenase-2 in colorectal cancer]. / Analisi epidemiologico molecolare dei livelli di metalloproteasi e cicloossigenasi-2 nel cancro del colon/retto.

The aim of this work is the investigation of the level of expression of the vascular endothelial growth factor (VEGF) and metalloproteases (such as Cox-2) in the colon rectal cancer. The final goal is the correlation with liver metastases. Molecular biology approaches will be adopted: in particular: RT-PCR, quantitative real time PCR with fluorescent probes, immunolocalizations and Western blotting This is a proposal of research. The work is under development and results and conclusions cannot be at the moment anticipated. However, in recent publication we found human polyomavirus DNA sequences in colorectal tumors.

The role of Echo Colour/Power Doppler and magnetic resonance in expansive parotid lesions.

The purpose of this research was to evaluate the role of Echo Colour/Power Doppler and Magnetic Resonance Imaging (MRI) in the diagnosis of expansive parotid lesions, and to establish criteria for differential diagnosis between benign and malignant forms. Forty nine patients (23 males and 26 females), aging from 30 to 85 years, with an expansive pathology of parotid gland were enrolled in our study from February 1999 through August 2004. Each patient was carefully assessed employing both ultrasonography integrated with Color/Power Doppler and MRI. Eventually, all patients received echo-guided needle-biopsy and surgical excision of the parotid lesion. Preliminary ultrasound assessed site, size, echoic appearance and margins of the lesion. In order to assess blood supply by means of Colour/Power Doppler, we divided the patients in four groups. Our MRI diagnostic criteria included site, size, intensity of signal, behaviour of the lesion after i.v. contrast, relationship with facial nerve and retromandibular vein, detection of margins and proximity to adjacent structures. On the basis of our results, the Authors concluded that both Echo Colour/Power Doppler and MRI play a very important role in the diagnosis and surgical planning of parotid gland lesions.

[Physiopathological bases and the role of oncologic surgery in the formation of general surgeon]. / Basi fisiopatologiche e ruolo della chirurgia oncologica nella formazione del chirurgo generale.

Surgical oncology can currently be definite "bio-surgery" in as more frequently uses in pre-, intra and postoperative phase biological substances what growth factors, cytokines, anti-adhesion and neoangiogenesis inhibiting molecules with a potential reduction of the local recurrences and improvement of survival rates. The increasing and continuous development of the genic therapy, cellular therapies, immunotherapy, chemotherapy and radiotherapy in the cancer treatment, "force" surgeon to interrogate himself on the role of the radical surgery through the "advanced" tumors of the digestive tract. Surgery alone, continuous to be in terms of recovery, the most effective treatment against tumor, (62% of the recoveries), also if its combination with other therapies improve the results especially in the advanced tumors. Chemotherapy has had positive results in the treatment of solid tumors, sometimes like adjuvant or neoadjuvant treatment to a radical surgery, improving the survival rates. Surgical oncology of "tomorrow" must be necessarily a quality surgery performed from a surgeon possessing some necessary requisite: technical ability, specific base-formation on physiopathologic knowledge in constant evolution, standardization ability of surgical techniques and therapeutic protocols. Such requisite will allow surgeon reach the main goal of surgical oncology what the local control of tumor, reduction of local recurrences, offer an good enough quality of life getting all the possible information on the local development of tumor and on the ways of diffusion. All these elements will be necessary for formulate a reliable prognostic judgment, more and more requested from the patients.

Videoassisted transhiatal esophagectomy for cancer.

Blunt transhiatal esophagectomy is largely performed in selected cases of esophageal cancer according to the experience of Mark Orringer. We have recently performed eleven consecutive videolaparoscopy assisted transhiatal esophagectomies in order to help esophageal dissection and to avoid injuries to mediastinal structures. In our experience the routine use of laparoscopic assistance during transhiatal esophageal dissection improves the safety of this technique and lowers postoperative complications. The results of neoadjuvant treatments (radio-chemotherapy) recently reported emphasize the role of transhiatal esophagectomy for cancer.

[Video-assisted closed-thorax esophagectomy in cancer. A technical proposal]. / L'esofagectomia a torace chiuso videoassistita per cancro. Una proposta di tecnica.

Blunt transhiatal esophagectomy is largely performed in selected cases of esophageal cancer following the experience of Mark Orringer. We have recently performed five consecutive video-laparoscopy-assisted transhiatal esophagectomies in order to help the esophageal dissection and to avoid injuries to mediastinal structures. In our experience a routine use of laparoscopic assistance during transhiatal esophageal dissection improves the safety of this technique and lowers postoperative complications. The results recently reported from neoadjuvant treatments (radio-chemotherapy) emphasize the role of transhiatal esophagectomy for cancer.