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.

Empty pelvis syndrome: the use of breast prosthesis in the prevention of complications.

AIM: Empty pelvis syndrome and radiation-induced bowel injury are two major clinical issues resulting from the pelvic dead space after pelvic exenteration (PE). In order to avoid these complications, different methods of pelvic floor reconstruction have been proposed. We report our experience on the use of breast prosthesis. METHOD: Fifty-three patients who underwent PE and three who underwent palliative surgery with silicone breast prosthesis placement were included. RESULTS: Forty-seven posterior PE, six total PE and three palliative procedures were identified. Sphincter preservation was feasible in 34 patients (62.3%). There were no deaths. Overall morbidity was 37.5%. There were no complications such as sepsis or obstruction related to the prosthesis. Adjuvant radiotherapy was delivered in 16 cases (30.1%) without any side-effects. Reconstruction of intestinal continuity was possible in 12 patients (36.3%) with sphincter preservation and the prosthesis allowed a prompt identification of the rectal stump. CONCLUSION: Breast prosthesis placement is a simple and safe method to minimize complications resulting from empty pelvis syndrome and can be adopted to exclude bowel loops from the radiation field. Reconstruction of intestinal continuity after resection is also simplified.

Limb saving procedure in metastatic leiomyosarcoma of the femoral vein: case report and literature review.

Primary venous leiomyosarcoma is very rare and first description was made by Perl in 1871. Most cases are from venous system and half of them are reported to originate in inferior vena cava. We report the case of a 77-year-old Caucasian man with a leiomyosarcoma of the femoral vein. A leg preservation surgery was decided. Eight months later, the patient died of tumor progression. A PubMed search using the terms "leiomyosarcoma femoral vein" and "leiomyosarcoma vein" was performed. All cases of composite iliac-femoral leiomyosarcoma were excluded, and as far as possible, only well-documented cases were included. Median age was 55 years, seven men and six women, tumor resection was performed by six authors, six others performed a vascular resection, and one preferred for a thigh excision. Prognosis remains poor if metastasis is present, and in these cases, a conservative surgery is recommended to preserve patients' quality of life.

Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: proposal and results from a prospective protocol study of prevention, surveillance and treatment.

The incidence of infectious complications due to several contributory causes is particularly elevated and life-threatening in patients undergoing peritonectomy and HIPEC procedure for peritoneal carcinomatosis. Following a previous experience, we started a prospective protocol study of preoperative screening, perioperative prophylaxis and postoperative surveillance and treatment. A total of 111 patients with peritoneal carcinomatosis of various origin underwent CRS with HIPEC between April 2004 and December 2012. The group was divided into a pilot group of 30 patients (04/04 to 05/08) and a main group of 81 patients (06/08 to 12/12). Overall postoperative morbidity rate was 44%, with 35.8% of symptomatic infections. No post-operative mortality was observed. Microorganisms were isolated in 24 patients (80.0%) in the first group and 54 (66.7%) in the second. They were symptomatic in 18 cases (75.0%) and 25 (46.3%) cases respectively. In addition, 7 invasive candidosis were recorded (25.9%). Colon resection (P = 0.01) and duration of surgery (P = 0.0008) were associated with infection at logistic regression model. Concerning symptomatic infections, only Infection Risk Index (P = 0.009) showed significance at multivariate analysis. Despite a significant incidence of infectious complications, establishment of a prevention, surveillance and treatment protocol lead to a zero mortality rate in the observed patients of our experience. Owing to the obtained results, we suggest the use of a standardized protocol for the prevention, monitoring and treatment in all patients enrolled for cytoreductive surgery and HIPEC.

Subtotal gastrectomy for gastric cancer: long term outcomes of Billroth I reconstruction at a single European institute.

BACKGROUND/AIMS: The role of Billroth I (BI) subtotal gastrectomy (SG) for gastric cancer (GC) remains controversial in Western countries. The aim of the study is to critically analyze the long term outcomes of this procedure in a large single-institution experience. METHODOLOGY: Between 1990 and 2004, 158 patients underwent BI SG for GC at the Regina Elena Cancer Institute of Rome. Evaluation focused on cancer recurrence of the gastric stump, functional outcome and endoscopic findings. RESULTS: Actuarial survival rate 10 years after resection in stage I-II was 70.7 per cent. After curative resection, primary cancer of the gastric stump occurred in one patient seven years after resection (0.7 per cent), whereas two patients had early recurrence (1.4 per cent) one and three years postoperatively. There were no oesophageal cancers. In survivors, Visick grades I and II achieved 95 per cent, and postoperative endoscopy showed no evidence of mucosal changes in 85 per cent of the patients. Twelve per cent of the patients took acid blocker regularly, however, the incidence of functional failure was 5 per cent. CONCLUSIONS: In selected patients, Billroth I subtotal gastrectomy is a safe and effective procedure that provides long-term survival and very good functional outcome.

Long-term Evaluation of a Modified Double Staple Technique for Low Anterior Resection.

BACKGROUND: When performing low anterior resection for rectal cancer with the double staple technique, -closing the rectum with a linear stapler in the abdomen can be challenging, especially when dealing with a narrow pelvis. For such instances we proposed to modify this technique by pulling the rectal stump through the anus, doing an extra-anal resection of the tumor and linear suture of the rectal stump, before performing a standard, stapled colorectal anastomosis. The purpose of this study was to assess the adequacy of this modification of the double staple technique. METHODS: Retrospective review of 108 patients undergoing a stapled, low colorectal or coloanal anastomosis, after -eversion, extra-anal resection of the tumor and linear closure of the rectal stump for colorectal cancer, from January 1990 to December 2012. RESULTS: Operative mortality was 0.9%. Fourteen patients (13%) presented early, surgery-related complications -consisting of 7 anastomotic leaks, 5 wound infections, 1 ureteral lesion, and 1 peristomal abscess. Late complications related to surgery included 5 incisional hernias (4.6%), 4 anastomotic strictures (3.7%), 4 neurogenic bladders (3.7%) and 2 fecal incontinences (1.8%). The incidence of local disease recurrence was 10%. CONCLUSIONS: Surgical and oncological results validate the proposed modification of the double staple technique, when facing difficulties in suturing the rectum from the abdomen.

miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer.

Micro RNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Here, we aim to identify miRs whose deregulated expression leads to the activation of oncogenic pathways in human gastric cancers (GCs). Thirty nine out of 123 tumoral and matched uninvolved peritumoral gastric specimens from three independent European subsets of patients were analyzed for the expression of 851 human miRs using Agilent Platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by qPCR. miR-204 falls into a group of eight miRs differentially expressed between tumoral and peritumoral samples. Downregulation of miR-204 has prognostic value and correlates with increased staining of Bcl-2 protein in tumoral specimens. Ectopic expression of miR-204 inhibited colony forming ability, migration and tumor engraftment of GC cells. miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil. Altogether, these findings suggest that modulation of aberrant expression of miR-204, which in turn releases oncogenic Bcl-2 protein activity might hold promise for preventive and therapeutic strategies of GC.

Sexual function in women undergoing hemodialytic treatment assessed using the female sexual function index (FSFI) and the somatic inkblot series (SIS) test.

AIMS: Female sexuality in end-stage renal disease has so far only been explored using non-validated tools. The aim of this study was to compare sexual function among hemodialyzed (HD) patients and healthy controls using validated questionnaires. MATERIAL: Two internationally validated tests have been administrated: the female sexual function index (FSFI) questionnaire and a set of tables from the somatic inkblot series (SIS) test which focus specifically on the area of sexuality. METHODS: 25 consecutive HD patients were assessed for sexual function using the FSFI. Nine SIS inkblots concerning sexuality were also administered to obtain more detailed information about the psychological component of sexuality. An equal number of control healthy volunteers perfectly matched for age, marital status and educational level underwent the same evaluations, and the results of the two groups were compared. RESULTS: HD patients had significantly lower scores than the controls for all FSFI domains except sexual desire even when stratified by age and marital status. All sexually related thematic areas of the SIS except body perception were significantly affected in the HD group compared to the control group. CONCLUSIONS: Chronic renal failure requiring HD treatment adversely affects female sexual function. The psychological impact on patients is significant when compared to an age-matched control group. Both the FSFI questionnaire and the SIS test may be considered useful tools for an integrated medical and psychological screening of FSD.

Clinicopathological features and prognosis of gastric cancer in young European adults.

BACKGROUND: The aims of this study were to define the clinicopathological features and prognosis of gastric cancer in young European adults. METHODS: Between 1990 and 2004, 603 patients with gastric cancer were enrolled in a prospective database. The findings for 51 (8.5 per cent) patients aged 45 years or less were compared with those of 457 aged between 46 and 75 years. RESULTS: In the younger group there were significantly more women (57 versus 36.3 per cent; P = 0.004), Laurén diffuse-type carcinomas (73 versus 42.7 per cent; P < 0.001), N2-3 lymph node metastases (59 versus 38.9 per cent; P = 0.005), stage IV disease (49 versus 35.7 per cent; P = 0.085) and resections that were non-curative (36 versus 18.5 per cent; P = 0.007) than in the older patients. Actuarial survival rates in younger patients at 5 and 10 years after resection were 40 and 32 per cent respectively, similar to those in older patients (P = 0.540). Unfavourable prognostic factors associated with poor 5-year survival were the degree of gastric wall invasion (T3-4 versus T1-2; P < 0.001), lymph node invasion (positive versus negative; P < 0.001), disease stage (III-IV versus I-II; P < 0.001) and curability of resection (non-curative versus curative; P < 0.001). CONCLUSION: Gastric cancer in young adults tends to be more advanced; however, when matched for stage, the prognosis does not differ from that of older patients.

Malignant insulinoma presenting as metastatic liver tumor. Case report and review of the literature.

Insulin-secreting tumors are the commonest hormone-producing neoplasm of the gastrointestinal tract. They occur with an incidence of 4 cases per million per year. About 10% of them are metastatic and malignant insulinomas very rarely observed in children and in elderly. We report a rare case of very large malignant insulinoma in a 71-year-old woman admitted in our Oncological Institute on October 2005. She presented with fasting hypoglicemia (blood glucose 35 mg/dl) and high serum insulin levels (insulin 115.9 microU/ml). A computerized tomographic scan showed a pancreatic tail lesion of about 6 cm in max diameter and multiple liver metastases. A whole body scintiscan using 111In-DTPA-D-Phe1-octreotide was made and an increased uptake in the tail of the pancreas has been found. The patient was submitted to liver biopsy and the diagnosis of a metastatic insulin-secreting tumor was immunoistochemically confirmed. Due to the presence of some hypoglicemic episodes uncontrolled by medical treatment, on December 2005 the patient was admitted to surgical intervention with a body and tail pancreatic resection. Post-operatively the patient experienced again syncope with hypoglycemia and hyperinsulinemia. It was then decided to start a schedule of treatment with somatostatin analog (octreotide subcutaneously 500 microg three times a day) with a good control of blood glucose levels (101 mg/dl). A trans-arterial chemioembolization was planned but the patient died for pancreatic and cardiovascular complications before this treatment started.

Cystic pancreatic neoplasms: 12-year surgical experience.

Cystic pancreatic neoplasms have been increasingly diagnosed in the last years. Resection is recommended in most cases, but their management has not been standardized since an accurate nonoperative differentiation is often difficult. A retrospective review of 30 patients undergoing surgical resection for cystic pancreatic neoplasms between 1993 and 2005 was performed. Median age of the patients was 63 years and 63.5% were female. Twelve patients (40%) were asymptomatic. Twenty-nine had curative resections. Pathologic analysis revealed 13 serous cystadenomas, 9 mucinous cystadenomas, 3 mucinous cystadenocarcinomas, 4 intraductal papillary mucinous neoplasms and 1 solid pseudopapillary neoplasm. Overall mortality was 6.5% (2 patients). Postoperative complications occurred in 12 patients (41%). Pancreatic fistula occurred in 7 cases (24%). Reoperation was required in 2 patients (6.5%). Two patients operated for mucinous cystadenocarcinoma and invasive intraductal papillary mucinous neoplasms died of recurrence at 24 and 7 months postoperatively. Excluding another patient died from other cause, all others are currently alive with no evidence of disease. Diagnostic accuracy for cystic pancreatic neoplasms is still limited. Considering the good prognosis and acceptable morbidity and minimal mortality after surgical treatment in specialized centers, resection seems still justified in most cases.

[Isolated resection of the caudate lobe in metastasis of colorectal cancer]. / Resezione isolata del lobo caudato per metastasi da cancro colorettale.

The presence of metastatic lesions confined to the caudate lobe (CL or segment I) is quite a rare event. Even more rare is the decision to perform an isolate CL resection. Segmental resection in the liver is justified by the evidence that primary and secondary lesions, in early stage, are confined to the originating segment, and therefore a segmentectomy can be considered for the CL as well. Anatomy of the CL was deeply studied through the years since the surgical approach to this liver segment requires a detailed knowledge of its surgical anatomy and only after 1985 the surgical technique for CL isolate resection was established. We report our experience with 1 case of isolate colo-rectal metastasis confined to the caudate lobe and describe the surgical technique employed.

Pancreaticoduodenectomy for pancreatic metastatic melanoma.

Isolated pancreatic metastatic melanoma is a rare occurrence. Even more rare is the surgical treatment of this lesion. However, considering the lack of effective systemic treatment and the decreasing morbidity and mortality rates of pancreatic resections in specialized centers, selected patients, especially if symptomatic, may be considered for surgical resection to achieve good palliation or improve survival. We performed a pancreaticoduodenectomy in a patient with a bleeding pancreatic metastasis from cutaneous melanoma excised 10 years before and reviewed the recent literature.

Gastrointestinal stromal tumors of the stomach. A ten-year surgical experience.

Gastrointestinal stromal tumors show an increasing incidence. Immunohistochemistry is mandatory to make differential diagnosis with other mesenchimal tumors. We retrospectively reviewed 15 primary stomach GISTs operated during the last decade. Gastroscopy, Ultrasonography and CT scan were employed to obtain the diagnosis. Tumor size ranged from 1.5 to 30 cm in diameter. Treatment consisted of curative surgical resection without sistematic lymph node dissection. A wedge resection was sufficient in 8 cases. In 2 patients a distal subtotal gastrectomy was required and in 1 a total enlarged gastrectomy with pancreaticosplenectomy was performed. 4 GISTs were incidentally discovered and removed during surgical procedures for other gastrointestinal malignancies. In 4 cases a laparoscopic wedge resection was possible. In all cases postoperative course was uneventful. No adjuvant treatment was administered. Concerning the follow-up, two patients died for local and distant relapse while 13 are still alive (most of them operated during the last three years). GISTs show a very unpredictable clinical course and curative surgery is the only potential effective curative treatment.

[The modified "hanging maneuver" during orthotopic liver transplantation using a technique for conserving the inferior vena cava]. / Manovra di "hanging" modificata durante trapianto ortotopico di fegato con tecnica di conservazione della vena cava inferiore.

We describe a modification of Belghiti's "liver hanging maneuver" applied to the last phase of hepatectomy during OLT with IVC preservation. The proposed maneuver provides a better exposition of the suprahepatic veins allowing an ortogonal clamping of the suprahepatic confluence and avoiding caval clamping. It allows, moreover, an increase of venous surface available for the anastomosis that results wider and easier to perform. This provides a large outflow anastomotic cloaca and prevents outflow problems of the graft.

Adrenal glands metastases from malignant melanoma. Laparoscopic bilateral adrenalectomy.

Adrenal metastases from Malignant Melanoma (MM) represent a debated therapeutical problem particularly in the case of disseminated disease. Surgical treatment, however, seems to be able to provide improvement on survival. Laparoscopic adrenalectomy is considered a gold standard procedure in benign adrenal disease but its value in malignancy, in terms of oncological effectiveness, is not known. A case of bilateral adrenal malignant melanoma metastases is reported. The patient, affected by superficial spreading melanoma of the right foot, eleven years after the primary developed a right adrenal metastasis. The relapse was treated by laparoscopic right adrenalectomy. One year later the patient had a new metastasis in the left adrenal gland and was submitted to laparoscopic left adrenalectomy. The two step laparoscopic bilateral adrenalectomy showed to be quite easy to perform, providing a complete removal of the whole glands, without adrenal tissue crushing and without neoplastic tissue dissemination in abdominal cavity. The postoperative course was excellent and the patient was discharged within about 72 hours after the two procedures. In literature only few reports indicate the feasibility of laparoscopic adrenalectomy for malignancy. In the reported case of malignant melanoma metastasis, minimally invasive adrenalectomy was very satisfactory and the good results obtained suggest its routine use.

Resection and transplantation: evaluation of surgical perspectives in HIV positive patients affected by end-stage liver disease.

PURPOSE: The aim of this study was to evaluate the opportunity of surgical treatment in terms of liver resection or liver transplantation in HIV positive patients affected by an end stage liver disease that referred to our liver unit. METHODS: Among 1350 outpatients who referred to our liver unit from January 2002 to September 2003, thirty-two (2,4%) were HIV positive. The routes of transmission of the viral infection, the related co-infections and the underlying liver disease were recorded. The therapeutic pathway was analysed. The kind and the duration of the surgical procedures were assessed. RESULTS: Fourteen (44%) of these thirty-two patients were not suitable for surgical treatment. Surgery was planned in 9 of 32 HIV positive patients (28%). Four patients (12%) were submitted to liver resection and OLT was performed in five patients (15%). Hepatocellular Carcinoma was present in 4 (44%) of the HIV positive patients considered for surgery. CONCLUSIONS: In conclusion in our centre the 28% of HIV positive out patients had the opportunity to receive a surgical treatment. The candidate to this surgery is mostly young, HCV and/or HBV coinfected and affected by HCC in 44% of cases.