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.

Local repair of a trans-stomal ileocecal prolapse by stapler device.

The creation of a stoma, although considered a simple surgical procedure, is burdened by various complications, one of the most common being prolapse. Usually prolapse increases gradually, involving generally limited functional disorders and it can be well managed with non-operative measures. Occasionally it requires major surgery, for severe skin excoriation, bleeding or incarceration of the bowel. However, for critical clinical conditions of patients, often is not possible to use classical techniques, as bowel-pexy fixation or resection of the prolapse. Maeda has described a simple method for the correction of prolapse of the transverse colon using a stapler device that can be applied in this type of patients. In this report, we describe the first application of this technique to treat the prolapse of the ileocecal loop in an 81-year old woman, suffering from Parkinson's disease. A definitive ciecum stoma was performed the previous year for an Olgivie syndrome. At 6 months, follow-up showed no recurrence of prolapse with a functional stoma and without any skin irritation. In conclusion, this approach is recommended especially for high-risk patients who cannot be submitted to a much more invasive treatment. In fact, the main advantages consist of a minimally invasive technique, with minimal blood loss and with a rapid recovery of a normal quality of life.

The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of ovarian cancer relapse.

Nowadays the standard clinical management for advanced epithelial ovarian cancer is constituted by primary cytoreductive surgery associated to adjuvant systemic chemotherapy. Even if this first-line chemotherapy shows a high rate of complete responses, the disease recurrences occur especially in stage-III patients. Actually an option for this subset of patients is represented by secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy that represents a promising therapy, having shown positive results in terms of median overall survival, progression free survival and overall survival. However, a much more research is still required especially by prospective randomised trials to improve outcomes in recurrent ovarian cancer.

Apoptotic-induced cleavage shifts HuR from being a promoter of survival to an activator of caspase-mediated apoptosis.

Little is known about the cellular mechanisms modulating the shift in balance from a state of survival to cell death by caspase-mediated apoptosis in response to a lethal stress. Here we show that the RNA-binding protein HuR has an important function in mediating this switch. During caspase-mediated apoptosis, HuR is cleaved to generate two cleavage products (CPs). Our data demonstrate that the cleavage of HuR switches its function from being a prosurvival factor under normal conditions to becoming a promoter of apoptosis in response to a lethal stress. In the absence of an apoptotic stimuli, HuR associates with and promotes the expression of caspase-9 and prothymosin α (ProT) mRNAs, and pro- and antiapoptotic factors, respectively, both of which have been characterized as important players in determining cell fate. During the early steps of caspase-mediated apoptosis, however, the level of caspase-9 protein increases, while ProT remains unchanged. Under these conditions, the two HuR-CPs selectively bind to and stabilize caspase-9 mRNA, but do not bind to ProT. Hence, taken together, our data show that by maintaining a threshold of expression of proapoptotic factors such as caspase-9 in response to a lethal stress, the HuR-CPs help a cell to switch from resisting death to undergoing apoptosis.

Whole lung lavage for pulmonary alveolar proteinosis after surgery for spontaneous pneumothorax.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a relatively rare lung disorder, probably under diagnosed, characterized by the accumulation of lipoproteinaceosus material in the lung alveoli. The primary (acquired or idiopathic) form occurs in more than 90% of all cases. Whole lung lavage is considered the golden standard of treatment. In this report, we describe a rare case of pulmonary alveolar proteinosis with severe and incapacitating respiratory, in which whole lung lavage followed the thoracotomy for spontaneous pneumothorax. CASE PRESENTATION: A 34-year-old white male patient presented at the respiratory intensive care with severe respiratory failure, aggravated in the last two months, cough, night sweats and important weight loss and left spontaneous pneumothorax. The initial diagnosis of diffuse interstitial pneumopathy was revised to Pulmonary Alveolar Proteinosis after bronchoalveolar lavage. Active pleural drainage of the pneumothorax was unsuccessful and after two months, surgical suture of the lung was performed under general anaesthesia. One month later a whole left lung lavage was performed. The same procedure was also performed on the right lung. Eight months later the patient had a good exercise tolerance, normal arterial blood gas (ABG) values, and persistent ground-glass opacities in some of the pulmonary segments on CT scan. CONCLUSIONS: The most severe forms of pulmonary alveolar proteinosis, in which hypoxemia and cyanosis occur, have a high mortality risk during anaesthesia and whole lung lavage. When a rare complication like spontaneous pneumothorax occurs, the suturing of the pulmonary apical blebs seems to be the only viable solution, despite the high risk of dehiscence of the sutures due to the poor pulmonary tissue integrity at the time of the whole lung lavage and during postoperative care.

Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi-institutional study.

OBJECTIVE: To assess the efficacy and morbidity and mortality of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (EOC). DESIGN: A retrospective study conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs). Setting Four Italian centres specializing in locoregional treatment of PSM. POPULATION: Patients with recurrent EOC. METHODS: Fifty-six patients underwent 57 combined procedures. CRS was performed using peritonectomy procedures and HIPEC using the closed-abdomen technique with cisplatin and doxorubicin or cisplatin and mitomycin-C. MAIN OUTCOME MEASURES: Overall survival (OS), progression-free survival (PFS), morbidity and mortality rates. RESULTS: The median age of the patients was 55.2 years (range 30-75 years). The median peritoneal cancer index was 15.2 (range 4-30). Forty-seven patients had microscopic residual disease (completeness of cytoreduction, CC-0), seven had residual disease ≤2.5 mm (CC-1) and one had residual disease >2.5 mm (CC>2). Major complications occurred in 15 patients (26.3%), and procedure-related mortality occurred in three patients (5.3%). The median follow-up time was 23.1 months. The median OS and PFS were 25.7 (95% CI 20.3-31.0) and 10.8 (95% CI 5.4-16.2) months, respectively. The 5-year OS and PFS were 23% and 7%, respectively. Independent prognostic factors affecting OS according to the multivariate analysis were Eastern Cooperative Oncology Group performance status, preoperative serum albumin, and completeness of cytoreduction. CONCLUSIONS: Patients with recurrent EOC treated with CRS and HIPEC showed promising results in terms of outcome. The combined treatment strategy could benefit subsets of patients wider than that defined for conventional secondary debulking surgery without HIPEC. These data warrant further evaluation in randomised clinical trials.

[Intestinal perforation by ingested foreign bodies in the digestive tract: an insidious pathology always of interest. Our experience]. / La complicanza perforativa da ingestione di corpi estranei alimentari: una patologia insidiosa sempre attuale. Nostra esperienza.

The authors want to present five cases (from May 1999 to May 2009) of acute abdomen from perforation of the foreign body introduced with food. They highlight how the accidental ingestion is very common but the perforation is rare. The preoperative diagnosis, in these cases, is always very difficult and the radiological examinations are not always able to resolve the diagnostic doubt with other acute intestinal diseases that are responsible of perforation. Then, the surgery procedure is, necessarily, the only possible diagnostic and therapeutic means. The mortality and the morbidity remain still high first of all for the delay in the diagnosis and the advanced age of patients.

Quintuple primitive malignant neoplasms. A case report.

The authors describe the case of a patient who developed during 31 months, five malignant tumours, three synchronous and two metachronous. The primitive origin and the long interval of time between the occurrence of each tumour, allow to set them in the group of Multiple Primitive Malignant Neoplasm. The authors, reviewing the classifications and the pathogenesis of these tumours, underline the importance of the follow-up in oncology patients and emphasize the role of nosographic setting in order to plan the most suitable therapeutic approach.

Evaluation of quality of life of patients submitted to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinosis of gastrointestinal and ovarian origin and identification of factors influencing outcome.

BACKGROUND: The prognosis of patients with peritoneal tumors has been improved by the association of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, though still with an unclear impact on patients' quality of life. The purpose of our study was to evaluate the quality of life in 18 cases submitted to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and particularly to identify the factors that influence it. PATIENTS AND METHODS: Quality of life was evaluated using the functional assessment of cancer therapy; the results were correlated with 25 parameters. RESULTS: The study demonstrated that the patients'quality of life was not modified by treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy; the dose of mitomycin C, the site of the primary tumor, gastrointestinal, renal and neurological toxicity, adjuvant chemotherapy, the patients' age and leukopenia were factors that influenced the quality of life. CONCLUSION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy allows conservation of preoperative quality of life.

[Multiple primitive lipoma of the transverse mesocolon: a rare disease]. / Lipoma primitivo multiplo del mesocolon: una patologia rara.

The Authors describe a case of multiple lipomatosis of the mesocolon and, after a careful review of the literature, they examine particular findings and discuss diagnostic difficulties, anatomopathological features and treatment. Intraabdominal lipoma is very rare and presents difficulties in diagnosis, both for aspecific symptoms and for the unusual site which does not allow early identification. As it is a tumor which arises from primitive and totipotent mesenchymal cells, radical surgery is the only therapeutic option. The correct diagnosis depends on histological testing which can differentiate the lesion from other mesenchymal tumors.

[Endoscopic prosthetic treatment of the esophagojejunal leaks after total gastrectomy: clinical experience]. / Il trattamento endoscopico protesico delle fistole anastomotiche esofago-digiunali dopo gastrectomia totale per cancro dello stomaco: esperienza clinica.

The Authors, on the basis of their experience on the use of self-expanding prostheses in abdominal surgery, report on the use of these prostheses in two patients who, having undergone a gastrectomy for cancer, developed a fistula of the esophago-jejunal anastomosis. Given recent data from literature, using a prosthesis for an anastomotic fistula may be a valid alternative to a second operation, which, apart from obvious difficulties, has a high mortality rate in patients in weakened general health conditions. In these cases, after the application of a stent, excellent results can be obtained and, after some days, the patients can begin a semi-liquid diet, then proceeding to a semi-solid diet, improving quality of life; in addition, within a reasonable time span, after the healing of the fistula, the prosthesis can easily be removed by endoscopy.

Serum levels of interleukin 1beta, interleukin 8 and tumour necrosis factor alpha as markers of gastric cancer.

Despite the efforts made, a serum marker reliable for the screening and follow-up of patients with gastric cancer has not yet been identified. The aim of this preliminary study was to test the role of pro-inflammatory cytokines interleukin 1beta, interleukin 8 and tumour necrosis factor alpha in patients with gastric cancer and in control groups. The statistical analysis of cytokines serum levels in the group with gastric cancer versus control groups has shown considerable differences (p < 0.001) in their mean rates. The results indicate that the cytokines interleukin 1beta, interleukin 8 and tumour necrosis factor alpha might perhaps act as diagnostic markers in patients with gastric cancer. Therefore, it is hypothesized that after more extended trials, their use in the screening and prognostic assessment of these patients could be a possibility.

Acute gallstone cholecystitis in the elderly: treatment with emergency ultrasonographic percutaneous cholecystostomy and interval laparoscopic cholecystectomy.

BACKGROUND: The treatment of acute cholecystitis in the elderly is still a subject of debate, particularly with reference to the timing of surgery and the role of laparoscopy. PATIENTS: From January 1994 to June 2002 we observed 27 patients aged over 70 years with acute calcolous cholecystitis. The patients were submitted to ultrasonographic percutaneous cholecystostomy within 12 h of the acute attack. For two patients (7.4%) at high operative risk, we chose a conservative treatment. Twenty-five patients (92.6%) were submitted, in 15 cases (60%) within 5 days and in 10 patients (40%) within 8 days, to a laparoscopic cholecystectomy. Statistical significance was accepted when the value of p was less than 0.05. RESULTS: Ultrasonographic percutaneous cholecystostomy was performed successfully in all patients, without major morbidity or mortality, and complete resolution of clinical symptoms was obtained within 48 h. The conversion rate of laparoscopy was 20% (13.3% in patients submitted to surgery within 5 days and 30% in the group submitted within 8 days--p > 0.05). The postoperative morbidity rate was 24%; it was higher (40% versus 15%) in patients converted to laparotomy (p > 0.05); mortality was 4%. The period of hospitalization was 11 days in patients operated laparoscopically and 21 days in those converted to open cholecystectomy (p < 0.001). CONCLUSIONS: The more rational treatment of acute calcolous cholecystitis in elderly patients is represented by ultrasonographic percutaneous cholecystostomy followed, within 5 days, by laparoscopic cholecystectomy using an abdominal insufflation maximum to 12 mmHg and a limited 10-15 degrees head-up tilt.

[Diagnostic and therapeutic implications in two cases of pancreatic cystic tumours: mucinous and serous]. / Implicazioni diagnostiche e terapeutiche in due casi di tumori cistici del pancreas: mucinoso e sieroso.

Cystic tumours of the pancreas include a pathologically heterogeneous and rare group of tumours, which however have many common clinical features. They represent about 10% of pancreatic cystic lesions and 1% of all forms of neoplasms, thus having a certain relevance in organ surgery. So far two distinct categories of cystic tumours have been identified, the basically benign serous form and the potentially malign mucinous form, which may sometimes show malignant features as early as the diagnostic stage. As neoplasms are very difficult to interpret before operation, it is essential that diagnosis is as accurate as possible in order to streamline surgery, which will have to be carried out after histological tests have been performed on an adequate number of tumour sections. Basing on these two cases of cystic tumours of the pancreas and on current literature, the Authors discuss the effectiveness of imaging techniques, such as contrast echography, dosage of specific tumour markers and histological tests backed up by immunohistochemistry in identifying these neoplasms, in order to study this rare but interesting pathology more accurately.

[The capillary hemangioma of the stomach: an unusual cause of haemorrhage. Case report]. / L'emangioma capillare dello stomaco: una rara fonte di sanguinamento. Caso clinico.

Gastric haemorrhages are common clinical emergencies which often directly involve the surgeon in diagnosis and treatment; among these, rare vascular neoplasms deserve particular attention. The Authors report a rare case of benign vascular tumour of the stomach, a capillary angioma. After a literature review they highlight the importance of specific exams to reveal these small neoformations which, generally, show up clinically with acute bleeding, which may be severe, and which may not be discovered if the clinical evaluation is not very detailed. The surgical excision supported by a frozen sections is the most effective treatment.