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.

Prognostic factors in gastric cancer patients: a 10-year mono-institutional experience.

Introduction: Gastric cancer (GC) is one of the main causes of death from cancer globally. Long-term survival, especially in Western countries, remains dismal, with no significant improvements in recent years. Therefore, precise identification of clinical and pathological risk factors is crucial for prognosis, as it allows a better selection of patients suitable for oncologically radical treatments and contributes to longer survivals. Methods: We devised a retrospective observational longitudinal study over 10 years of experience with GC patients operated with curative intent. Results: Several factors were thoroughly investigated in a multivariate analysis to look for significance as independent risk factors for disease-free survival. Our results showed that only BMI, pTNM, and lymph node ratio expressed hazard ratios with implications for survival in our series of patients. Discussion: Although limited by the retrospective nature of the study, this is one of the few cancer reports from Northern Italy showing results over 10 years, which may in our view, have an impact on decision-making processes for multidisciplinary teams dedicated to the care of gastric cancer patients.

Strong impact of sarcopenia as a risk factor of survival in resected gastric cancer patients: first Italian report of a Bicentric study.

Gastric cancer (GC) accounts for 4% of all cancers in Europe. Sarcopenia is a complex syndrome characterized by a loss of muscle mass and function associated with age, often present in neoplastic patients. Recently, several studies have shown a significant association between sarcopenia and poor prognosis in various pathological conditions. The current observational retrospective study investigates the association between sarcopenia and overall survival (OS) and recurrence-free survival (RFS) in patients with GC undergoing up-front surgery with curative intent. Resected GC patients' clinical records and CT images were retrospectively assessed. The preoperative CT calculation of the skeletal muscle index (SMI) at L3 level allowed us to categorize patients as sarcopenic or not. Kaplan-Meyer and univariate and multivariate Cox regression analyses were performed to determine the difference in survival and presence of independent prognostic factors. Fifty-five patients, 28 male and 27 female, out of 298 studied for gastric cancer were enrolled in the current study from two cancer referral centers in Italy. The preoperative CT calculation of the SMI at L3 level allowed us to identify 39 patients with and 16 without sarcopenia. A statistically significant difference between the sarcopenic and non-sarcopenic groups was observed in both OS and RFS (p < 0.023; p < 0.006). Moreover, sarcopenia was strongly correlated to a higher risk of recurrence in univariate and multivariate analysis (p < 0.02). Sarcopenia can be considered a critical risk factor for survival in patients with resectable GC treated with up-front surgery. Identifying sarcopenic patients at the time of diagnosis would direct selection of patients who could benefit from early nutritional and/or physical treatments able to increase their muscle mass and possibly improve the prognosis. More extensive multicenter studies are needed to address this issue.

Role of poorly differentiated cluster in gastric cancer: is it a new prognosis factor?

BACKGROUND: Poorly differentiated Clusters (PDCs) of tumor cells composed of more than five elements have been recently described in gastrointestinal cancers and correlate with a worse prognosis. Our study aims to investigate PDC occurrence in a series of patients with gastric cancer and correlate it with lymph node status and clinical outcome. MATERIAL AND METHODS: 50 patients were included in the study; PDCs count was graduated as G1, G2, and G3 according to Ueno classification (PDCs count at 20× <5, 5-9 and ≥10 respectively). We collected several clinicopathologic variables such as tumor location, pTNM stage, vascular or perineural invasion, and lymph-node ratio for each case. RESULTS: The presence of PDCs was related to vascular invasion (p < .013) and recurrence event (p < .027). When the population was categorized according to the number of PDCs, a significant correlation was found with the presence of lymph node metastasis (p < .000), the Lymph Node Ratio (p < .002), WHO stage at the diagnosis (p < .000) and vascular invasion (p < .001). At the univariate and multivariate analysis, PDCs were found as an independent risk factor for recurrence (HR 1.94; CI 95% 1.209-3.121; p < .006 and HR 0.401; CI 95% 0.187-0.862; p < .017 respectively). The Kaplan-Meier curves for OS and DFS showed a significant association between PDCs and shorter time to recurrence or survival. CONCLUSION: PDC is a strong prognostic factor in gastric cancer, easily detectable, and feasible. As far as we know, this is the first report in Literature of a strong correlation between PDC and survival in patients with operated gastric cancer.

Negative pressure wound therapy (NPWT) after cytoreductive surgery (CRS) and intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies: preliminary report.

AIM: Surgical site (SSI) infection is a common complication that occurs in the post-operative period because it still has a decisive impact on the morbidity and mortality of patients and the costs associated with therapy and prolongation of hospitalization. In recent years, therefore, several authors have published their experience in the use of negative pressure prevention systems (NPWT) for the management of surgical wounds. Few authors in the literature have discussed the use of NPWT in patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies associated with hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Nineteen patients undergoing open surgery, of which 15 underwent CRS+HIPEC operations; in 2 cases the dressing was applied to patients undergoing colon surgery, 1 case after emergency laparotomy for intestinal occlusion in a patient with a BMI of 29 and 1 case after gastric surgery for a tumour. At the and of the surgery, NPWT was placed on the surgical site; the therapy includes a closed and sealed system which maintains a negative pressure between at -125 mmHg on the surgical wound and which remains in place for five days. RESULTS: The rationale for using an NPWT is to determine a barrier between the wound and external contamination, reducing wound tension and reducing the formation of seroma and hematoma. Moreover, during the HIPEC, several litres of water are used to wash the patient's abdominal cavity and then the patient is sutured again without the peritoneum, losing the function of protection from external microorganism and also of reabsorbing the intra-abdominal serum. A recent Cochrane collaboration about the application of NPWT demonstrates that it may reduce the rate of SSI compared with SSD, even if there is no sure evidence about the reduction of complications like seromas or dehiscence. CONCLUSION: After the analysis of the preliminary data, we confirm the possibility to start with a randomised clinical trial, as suggested by the literature.

Role of sentinel node in differentiated thyroid cancer: a prospective study comparing patent blue injection technique, lymphoscintigraphy and the combined technique.

PURPOSE: The purpose of the present study was to evaluate the feasibility and reproducibility of the sentinel lymph node (SLNs) biopsy in differentiated thyroid cancer using patent blue injection, lymphoscintigraphy and the combined techniques. METHODS: Between January 2011 and January 2013, 82 consecutive patients were enrolled in our prospective multicentre study. Inclusion criteria were 18 years of age, preoperative diagnosis of differentiated thyroid carcinoma, no evidence of lymph node enlargement and multifocal neoplasm. To investigate the benefits of each procedure, all patients underwent total thyroidectomy plus central compartment lymphadenectomy, and in all cases, the SLN was identified via one of three techniques using the same protocol. RESULTS: Lymphoscintigraphy was used in five patients, patent blue injection was used in 40 patients, and a combined technique was used in 40 patients to identify sentinel lymph nodes (SLN). SLNs were identified in 61 cases. In the patent blue injection technique, the sensitivity, specificity and false negative rates were 88.9, 94.4 and 3.8%, respectively. In the lymphoscintigraphy technique, the percentages of sensitivity and specificity were 100%, and the percentage false negative was 0%. For the combined techniques, the corresponding values were, respectively, 69.2, 90, and 17.4%. Metastases were detected in nine cases of lateral-cervical nodes, ipsilateral tumour metastases were observed in eight cases, and contralateral tumour metastasis was observed in one case. CONCLUSION: Additional well-designed randomized studies are needed to validate and further optimize the SLN biopsy in patients with differentiated thyroid cancer.

Laparoscopic treatment of paraesophageal and mixed diaphragmatic hernias. Report of two cases.

Hiatal hernias are classified into 3 types: sliding hernia (type I), paraesophageal hernia (type II) and mixed hernia (type III), that is a combination of type I and II. The paraesophageal and mixed hernias represent about 5-10% of the surgically treated hiatal hernias. The surgical treatment of the paraesophageal and mixed hernias is unavoidable because of the high risk of severe complications and it has to be considered in a high percentage of cases. The most important technical difficulty in the video-laparoscopic treatment is represented by the hugeness of the hernial defect and by the challenging reduction of the stomach into the abdomen. A cautious dissection of hernial sac and diaphragmatic cruses as well as a careful crural repair make the video-laparoscopic procedure feasible. The operative times are not prolonged and the results are similar to the open technique ones. In literature, the incidence of both intra and postoperative complications doesn't exhibit statistically significant differences between laparoscopic and open techniques. Because of the complexity of the laparoscopic procedure, the minimally invasive access has to be reserved to surgeons who are well trained in those techniques. In this paper we describe 2 cases: one of paraesophageal hernia and the other of mixed hernia which were video-laparoscopically treated with the help, in the second case, of a Gore-Tex mesh. In both cases the technical results were positive. Intra and postoperative complications didn't occur and, one year after the surgical procedure, both patients were in good health and recurrence-free.

Sutureless and stapleless laparoscopic splenectomy using radiofrequency: LigaSure device.

BACKGROUND: Bleeding is the main complication and cause of conversion during laparoscopic splenectomy (LS). We present the advantages of the LigaSure vessel sealing system added to the lateral approach for achieving safe vascular control. METHODS: We performed 63 consecutive LS in a 3-year period using LigaSure in two affiliated university hospitals. We employed a right semilateral position technique with dissection of the spleen and vessel sealing using LigaSure. Forty-two patients had benign hematological disease, 19 had malignant disease, and two had splenic cysts. RESULTS: A total of 58 LS were completed with five conversions due to hilar bleeding (three cases), difficult dissection (one), and massive splenomegaly (one). In all but five patients, blood loss was less than 100 ml. No transfusions were needed. There were five postoperative complications: portal thrombosis (one case), hemoperitoneum (two), surgical wound infection (one), and pleural effusion (one). CONCLUSIONS: The use of LigaSure, and the semilateral position, results in a gain of time and safety. Furthermore, average intraoperative bleeding is very low.

Literature overview on artificial liver support in fulminant hepatic failure: a methodological approach.

Artificial liver support is a therapeutic option for subjects with fulminant hepatic failure. Results of these studies suggest a possible favourable effect on this condition. The aim of the present review is to evaluate not the results of the different artificial systems available but the methodology used to achieve these results. A computer and manual search of the literature was performed; 832 pertinent references were retrieved. Seventy-seven were full papers reporting the application of artificial liver support in animals or humans (15 RCTs (3 in humans, 12 in animals), 53 uncontrolled phase I trials, 9 case reports). The results of this review indicate that, although the rationale of artificial liver support as shown by animal studies is acceptable, the widespread use in clinical practice is not justified and a controlled design for the studies on artificial liver support systems is mandatory.

[The surgery of non-small-cell bronchogenic carcinoma in stage IIIA. An analysis of 150 treated cases]. / La chirurgia del carcinoma broncogeno non a piccole cellule in stadio IIIA. Analisi di 150 casi trattati.

BACKGROUND AND AIM: The authors report the findings of a retrospective study made of 150 cases of bronchogenic non-small-cell carcinoma at stage IIIA. METHODS: Of the 150 patients treated 130 were male and 20 female. The mean age of the population examined was 55, with a minimum of 28 and maximum of 76. The techniques of exeresis used were pneumonectomy in 70 cases (33.3%) (simple in 50 cases--33.3% and intrapericardial ligation of pulmonary vessels in 20--13.3%), lobectomy in 61 cases (40.6%), lobectomy with associated atypical resection in 9 cases (6%), atypical resection in 6 patients (4%) and bilobectomy in 4 (2.6%). RESULTS: The 5-year survival rate was 16.9%. It was also found that the 5-year survival rate was 20.7% higher for epidermoid carcinoma compared to other histiotypes. The technique used also influenced survival and subjects undergoing pneumonectomy presented a 5-year survival of 29.7% compared to 26.8% for lobectomies associated with atypical resection. CONCLUSION: Surgery of bronchogenic carcinoma at stage IIIA has not obtained promising results in terms of survival. However, no other alternative treatment permits an average 5-year survival rate of 15% to be achieved.

Mesenteric cystic neoformations: report of two cases.

The authors present two case reports of mesenteric cystic neoformations which they themselves observed and, with the help of the literature regarding this pathology, discuss the problems of both diagnosis and treatment.

[Video laparoscopy in patients with pain in the right iliac region]. / La videolaparoscopia nel paziente con dolore in regione iliaca destra.

The authors report on their experience of 235 laparotomy operations and 125 laparoscopic operations performed on patients with right lower abdominal pain. Concerning each of these different approaches, the authors analyzed and compared preoperative diagnosis, anatomo-pathological findings, intraoperative and early post operative morbidity and hospital stay. The ratio of negative open-appendectomies was 24.1% (56 cases out of 233). The laparoscopic approach, performed on 88 cases of suspected appendicitis, allowed to document and to treat other pathologies, real causes of the lower right abdominal pain, in 42 cases (47.7%). The rate of conversion from laparoscopic appendectomy to open appendectomy was only 2.19% (2 cases out of 91). The morbidity rate of laparoscopic appendectomy was estimated at 6.5% (4.4% major complications, 2.2% minor complications). The morbidity rate of open appendectomy was estimated at 8.9% (0.4% major complications, 8.5% minor complications). Though the median postoperative stay, after laparotomy approach, was slightly longer (2.6 days versus 2.4 days), the difference was not statistically significant. Based on these results, the authors conclude that the laparoscopic approach should be reserved for fertile female patients, especially when the diagnosis of appendicitis is uncertain.

[Surgery of anal fistulas]. / La chirurgia delle fistole anali.

The authors report a study on 120 patients with anal fistula (111 males and 9 females). The average age was 44.3 years (median 44, SD +/- 14.807). 64.1% of patients had an intersphincteric fistula, 23.3% hanal transphincteric fistula, 1.6% a suprasphincteric fistula, 7.5% a horseshoe fistula and the 3.3% an extrasphincteric fistula. We treated 14 patients (11.66%) with direct surgical treatment. The other 106 had various types of treatment depending on the localisation and the involvement of the anorectal sphincter. We had 11 cases (9.1%) of complications, such as recurrence in 5 patients (4.1%) transitory incontinence in 2 cases (1.6%) and finally postoperative bleeding in 3 patients (2.5%).

[Evaluation of costs in surgery of inguinal hernia. Day surgery and one day surgery versus ordinary admission]. / Valutazione dei costi nella chirurgia dell'ernia inguinale. Day surgery e one day surgery versus ricovero ordinario.

The authors have completed an analytic research about costs of hospitalization and treatment for inguinal hernioplasty and costs of anesthesiologic and surgical techniques and hospitalization regimen. The authors consider possible in about 50% of cases the tension-free hernioplasty carried out with local anesthesia and day or one day surgery regimen and they have estimated that it is very less costly then traditional herniorraphy carried out with general anesthesia and hospitalization: L. 1.056.075 versus L. 2.252.650. In Emilia-Romagna we could have a considerable cost-saving, even if only the 50% of patients treated for uncomplicated inguinal hernia every year (7.133 patients with mean hospital stay = 5,8 days and total hospitalization = 41.731 days during 1993) could benefit by treatment in one day surgery regimen. In fact, leaving out of account the advantage of the rapid return the patient to work, the costs of hospital stay, esteemed in L. 25.038.600.000, would be L. 8.558.700.000. A considerable increase of one day surgery hernioplasties should be expected by the hospital administration in budget planning.

[Costs of cholecystectomy after the arrival of video-laparoscopic surgery]. / Costi della colecistectomia dopo l'avvento della chirurgia video-laparoscopica.

The authors proceeded to point out the hospital stay costs and the operating-room costs of the cholecystectomy after the introduction of the laparoscopic technique, underlining the higher economic advantages. The total unit cost for laparoscopic cholecystectomy, even if there are higher costs due to the surgical equipment, thanks to the mini-invasive approach and to the reduced hospital stay, results lower (17%) then the total unit cost for laparotomic cholecystectomy (L. 3.982.489 vs. L. 4.825.300). Let us suppose that in the Emilia Romagna Region an 80% of patients underwent to laparoscopic cholecystectomy and only a 20% underwent to laparotomic cholecystectomy: in this case there could be the economic savings of L. 3.777.478.902 and concerning the hospital stay there could be the savings of 17.928 days too. This cost estimation is important if we consider that the rate of cholecystectomy procedures, in our local area, per 1000 inhabitants, increased from 2.29 in 1990 to 3.99 in 1992 (rate of increase: 74%).

[Costs of video-laparoscopic surgery in the treatment of ovarian cysts]. / Costi della chirurgia video-laparoscopica nel trattamento delle cisti ovariche.

The authors proceeded to point out the hospital stay costs and the operating-room costs of the operations for benign adnexal pathologies, especially concerning the ovarian cysts, after having introduced the laparoscopic technique. The highly costs, due to the laparoscopic surgical equipment, are compensated by the reduced hospital stay. The total unit cost for laparoscopic approach results lower then the total unit cost for laparotomic approach (L. 3.253.923 versus L. 4.662.892). If we consider that, in our local area, in 1993, 1212 operations were performed, with 5454 days of postoperative hospital stay, we could suppose that the laparoscopic approach affords higher savings. This cost estimation is important if we consider the diffusion of the mini-invasive procedures.