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.

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.

Debris production in bovine bone during implant site preparation. A comparative in vitro study: ultrasonic and drilling procedures.

The aim of this study was to compare the size and shape of bone fragments produced by the ultrasonic and drilling procedures in implant site preparation. Six pieces of rib selected as experimental animal model of 15 cm in length and at least 13 mm of thickness were used. The samples were treated and divided into 2 groups as follows: group A (GA) ultrasonic implant site preparation technique; group B (GB) traditional surgical drill technique. Ultrasonic implant site preparation (GA) was carried out using a sequence of progressive diameter (1.00 mm, 2.00 mm and 3.00 mm) conical inserts at a depth of 10 mm. Standard drill implant site procedure (GB) was carried out with a sequence of 1.00 mm, 2.00 mm, and 3.00 mm cylindrical twist drills, for preparing an implant site at a depth of 10 mm. From each group bone fragments (0.1 gr) were collected from both cortical and cancellous bone preparation and their dimensions were evaluated by optic microscope analysis. The bone debris dimensions procured by cortical bone of Group A and Group B were, respectively, 0.14×0.16 mm (±0.13) and 1.15 ×0.92 mm (±0.68). The bone debris dimensions procured by cancellous bone of Group A and Group B were, respectively, 0.15×0.10 mm (±0.10) and 1.98×1.27 mm (±0.94). Ultrasonic implant site preparation technique was able to micronize bone and to remove all debris with cooling system. Surgical drills tend to fracture bone, creating a weaker structure and fragments of larger size, which remain in considerable quantity over bone walls during site preparation. Within the limits of the present study, the ultrasonic implant preparation was able to produce reduced bone sediments and a clear bed implant favoring osseointegration.

A longitudinal study of painless and painful intercostobrachial neuropathy after breast cancer surgery.

Intercostobrachial neuropathy, often resulting in neuropathic pain, is a common complication of breast cancer surgery. In this 1-year longitudinal study, we aimed at seeking information on the frequency, clinical features, and course of painless and painful intercostobrachial neuropathy. We enrolled 40 women previously undergoing breast cancer surgery. In these patients, we collected, at 3, 6 and 12 months after surgery, clinical and quantitative sensory testing (QST) variables to diagnose intercostobrachial neuropathy, DN4 questionnaire to identify neuropathic pain, Neuropathic Pain Symptom Inventory to assess the different neuropathic pain symptoms, the Beck Depression Inventory to assess depressive symptoms, and SF36 to assess quality of life and Patient Global Impression of Change. Clinical and QST examination showed an intercostobrachial neuropathy in 23 patients (57.5%). Out of the 23 patients, five experienced neuropathic pain, as assessed with clinical examination and DN4. Axillary surgery clearance was associated with an increased risk of intercostobrachial neuropathy. Whereas sensory disturbances improved during the 1-year observation, neuropathic pain did not. Nevertheless, Beck Depression Inventory, SF36, and the Patient Global Impression of Change scores significantly improved over time. Our study shows that although intercostobrachial neuropathy is a common complication of breast cancer surgery, neuropathic pain affects only a minor proportion of patients. After 1 year, sensory disturbances partially improve and have only a mild impact on mood and quality of life.

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.

Peritoneal carcinomatosis: imaging with 64-MDCT and 3T MRI with diffusion-weighted imaging.

Peritoneal carcinomatosis is usually associated with a poor overall survival rate. Recently, introduction of more aggressive surgical treatment and intraperitoneal chemotherapy appears to significantly increase the overall survival rate for these patients. A detailed preoperative assessment of peritoneal carcinomatosis could be very challenging in the field of imaging, but a new aggressive surgical approach requires an accurate preoperative assessment of the disease. Cross-sectional imaging using CT and MRI with diffusion-weighted imaging (DWI) sequences is important for appropriate management of patients with peritoneal carcinomatosis. Appreciation of the spectrum of diagnostic patterns and pitfalls as well as different sites of involvement of peritoneal carcinomatosis using CT and DWI is crucial for appropriate surgical treatment.

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.

Functional results of a personal technique of reconstruction after pancreaticoduodenectomy.

The aim of the study is to propose a new technique of reconstruction after pancreaticoduodenectomy with more attention to the functional aspects. From 1995 and 2003, 25 patients underwent pancreaticoduodenectomy for pancreatic or periampullary cancer. The reconstruction was carried out by: end-to-end gastro-jejunal anastomosis (first jejunal loop); a Roux-en-Y T-T pancreatico-jejunal anastomosis leaving a silastic catheter in the Wirsung; hepatico-jejunostomy and jejuno-jejunostomy below the biliary anastomosis; superselective vagotomy. Mortality was 8%. Regarding the complications, we observed 3 biliary fistulas, mean duration 5 days, with spontaneous healing; 8 pleural effusions and 7 wound infections. Postoperative 3 months reevaluation showed weight gain in 14 patients with no other digestive symptoms (vomiting, fullness, dumping). With a scintigraphic meal we observed a good rythmic and regular gastric emptying. No jejunal peptic ulcers were noted in all patients after the gastric protonic pump inhibitors were discontinued. Fecal fats were evaluated in all cases for malabsorption 3 months after operation with low fat fecal levels. The preliminary results of our recent experience seem to be encouraging. This technique may have a useful application in the clinical setting as far as radicality and quality of life of the patients with pancreaticoduodenectomy.

[Immunomorphology of lymph nodes and prognosis in lung cancer]. / Immunomorfologia linfonodale e prognosi nel cancro del polmone.

BACKGROUND: Many studies have investigated locoregional immune responses and long-term survival in various types of cancer; few have focused on lung cancer. This study was designed to assess the prognostic value of immunomorphologic changes in locoregional lymph nodes in patients resected for bronchogenic carcinoma. METHODS: In a retrospective analysis, immune responses in locoregional lymph nodes were studied histologically in 172 selected patients. Lymph node morphology was studied according to the system of Cottier et al.: sinus histiocytosis (SH) and paracortical lymphoid cell hyperplasia (PCA) were considered as a cellular immune response, and follicular hyperplasia of the cortical area (CA) as a humoral reaction. The survival rate was estimated by the Kaplan-Meier product-limit method. Log-rank test and Cox proportional-hazards model were used to determine statistical significance in univariate and multivariate survival analysis. RESULTS: 35.5% of the patients had no evident response in regional nodes; 19.8% had a marked cellular response; 11% a marked humoral response; and 33.7% a mixed cellular-humoral response. A nodal cellular response improved long-term survival rates even in patients with regional node metastases. Multivariate analysis identified an independent variable as having high prognostic value: lymph node immunoreactivity. CONCLUSIONS: Lymph node immunoreactivity significantly influences long-term survival after curative surgery for lung cancer and may be useful in stratifying patients for prospective trials of adjuvant treatment including immunotherapy.

Host defense and survival in patients with lung carcinoma.

BACKGROUND: Numerous studies have investigated locoregional immune responses and long term survival in patients with various types of cancer; few have focused on patients with lung carcinoma. The current study was designed to assess the prognostic value of immunomorphologic changes in locoregional lymph nodes and lymphocytic infiltration of primary tumor (LI) in patients who undergo resection for bronchogenic carcinoma. METHODS: In a retrospective analysis, immune responses in locoregional lymph nodes and at primary tumor sites were studied histologically in 172 selected patients. Lymph node morphology was studied according to the system of Cottier et al. Sinus histiocytosis and paracortical lymphoid cell hyperplasia were considered to be cellular immune responses, and follicular hyperplasia of the cortical area was considered to be a humoral reaction. LI was classified with Black's method. The survival rate was estimated by using the Kaplan-Meier product-limit method. The log rank test and the Cox proportional-hazards model were used to determine statistical significance in univariate and multivariate survival analyses. RESULTS: Among the 172 patients, 35.5% had no evident response in regional lymph nodes, 19.8% had a marked cellular response, 11% had a marked humoral response, and 33.7% had a mixed cellular and humoral response. LI was intense in 36.6% of patients and was absent or scarcely evident in 63.4%. A lymph node cellular response and marked LI improved long term survival rates even in patients with regional lymph node metastases. Multivariate analysis identified two independent variables that had high prognostic value: lymph node immunoreactivity and LI. CONCLUSIONS: Lymph node immunoreactivity and LI significantly influence long term survival after curative surgery for patients with carcinoma of the lung and may be useful in stratifying patients for prospective trials of adjuvant treatment, including immunotherapy.

Topographic diagnosis and surgical treatment of insulinoma.

AIM: Controversy continues to reign with regard to the need for preoperative localization of insulinomas and to which are the most sensitive and accurate diagnostic imaging modalities. Our aim was to determine the role of diagnostic procedures and suggest which of them are really useful. METHODS: Over a 12-year period 34 patients underwent several preoperative diagnostic procedures to localize the insulinoma: ultrasonography (US) in 20 cases, computed tomography (CT) in 26, magnetic resonance imaging (MRI) in 28, selective angiography in 8, arterial stimulation venous sampling (ASVS) in 23 and Octreoscan in 26. All patients underwent surgical palpation and in 32 cases intraoperative ultrasonography (IOUS) was performed. Twenty-six cases underwent enucleation, six had distal pancreatic resections and two patients had only exploratory laparotomy with liver biopsies. We compared the findings of the diagnostic procedures and analyzed the surgical treatment chosen according to the pancreatic site of the tumor. RESULTS: In 32 (94.1%) of the 34 patients with clinically suspected pancreatic insulinoma the tumor was found at surgery. Preoperative US achieved 5.2% sensitivity, CT 29.1%, selective angiography 28.5% and MRI 76.9%. ASVS achieved 91.3% sensitivity and diagnostic accuracy whereas Octreoscan achieved only 65.3% diagnostic accuracy. Surgical palpation performed before IOUS identified the tumors in 30/34 patients: in the other four cases, one was a false-positive result (a cyst in the pancreatic head), two were true negatives and one was a false negative. Surgical palpation therefore yielded 88.2% diagnostic accuracy. IOUS was performed in 32 cases and localized the tumors in 29/32 cases (sensitivity: 96.6%) with one false-negative result (diagnostic accuracy: 96.8%). The operative mortality was 2.9% and the morbidity 24.6% (30.7% in patients treated by tumor enucleation). CONCLUSIONS: No single diagnostic imaging modality is reliable for localizing insulinoma. We therefore suggest combined MRI, ASVS and IOUS. ASVS provides particularly useful information for planning manual palpation and intraoperative ultrasonography.

Gastrointestinal emergencies in patients with acute intestinal graft-versus-host disease.

Acute intestinal graft-versus-host disease (GVHD) develops in about 30-50% of allogeneic bone-marrow transplant recipients: 10-20% have gastrointestinal emergencies (hemorrhage or perforation). Mortality reaches 30-60% in patients with acute, grade 2-4 GVHD. We studied 36 bone marrow recipients in whom acute intestinal GVHD developed. Seven had gastrointestinal emergencies: 4 severe gastrointestinal bleeding and 3 acute peritonitis. Three patients with gastrointestinal bleeding and one patient with peritonitis responded to medical therapy. Three needed surgery: one with bleeding and two with peritonitis, while 1 patient had embolization. Of the 7, two patients died, one after embolization and one after surgery. Two of the three surgically-treated cases are still alive several years after operation. From this experience we feel that surgery for gastrointestinal bleeding in acute GVHD is indicated only when medical treatment fails. Severe neutropenia, thrombocytopenia (<10.000 x mm3) and blood cultures positive for CMV have an unfavorable prognostic value.

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.

[Intravenous omeprazole versus ranitidine in the treatment of hemorrhagic duodenal ulcer: a prospective randomized study]. / Oméprazole versus ranitidine intraveineux dans le traitement de l'ulcére duodénal hémorragique: une étude randomisée prospective.

This prospective randomized trial compares the results of i.v. omeprazole and i.v. ranitidine in 45 patients admitted as an emergency with an endoscopic diagnosis of bleeding duodenal ulcer. The patients were randomized to receive i.v. omeprazole, 40 mg bolus followed by 80 mg/day by continuous infusion for 3 days (group A), or ranitidine 50 mg i.v. bolus followed by 400 mg/day i.v., continuous infusion for 3 days (group B). Follow-up endoscopy on day 4 demonstrated successful therapy, except when more than 4 units of blood/day had to be transfused to maintain hemoglobin level above 10 g/l. Bleeding stopped in 20/21 patients in group A (95.2%), and in 17/24 patients in group B (70.80%) (p < 0.05). From the results of the study, it can be concluded that intravenous omeprazole seems to be effective in the control of bleeding duodenal ulcer.

[The role of colonoscopy in early diagnosis of intraluminal recurrences in patients already treated for colorectal cancer]. / Ruolo della colonscopia nella diagnosi precoce delle recidive intraluminali nei pazienti già trattati per carcinoma colorettale.

It is a common opinion that the more often and the more rigorously the colon is examined, the more lesions will be discovered and diagnosed. However it has not been shown which methods of colonic examination and which regimen of surveillance should be used. Chart review was conducted on 481 patients who underwent curative resection for colorectal cancer between 1980 and 1990. Colonoscopy was performed preoperatively, after 12-15 months from surgical treatment, and then at an interval of 12-24 months, or when symptoms appeared. About ten percent of patients developed intraluminal recurrences, and more than 25% adenomatous polyps. More than one half of the metachronous lesions arise within the first 24 months. The median time to diagnosis was 25 months for intraluminal recurrences and 22 months for adenomatous polyps. Patients with left sited tumor at an advanced stage run a higher risk of developing recurrent intraluminal disease, and patients who presented associated polyps at the time of the operation for the index cancer have a higher risk of developing new polyps. About 50% of recurrences were detected when patients were asymptomatic. Colonoscopy must be performed within the first 12-15 months after operation, while an interval of 24 months between each examination seems sufficient to guarantee an early detection of metachronous lesion. Asymptomatic patients are more frequently reoperated for cure and thus have a better survival rate.

Prognostic significance of postoperative empyema in lung cancer.

Four hundred sixty patients who had undergone resection for lung cancer, with a minimum follow-up of 10 years, were analyzed retrospectively. Thirty-eight cases developed postoperative empyema. A comparative evaluation of the long-term survival rate was made of two groups: one in which the patients had developed empyema and one in which the patients had developed no empyema complications. The survival rate was estimated by the Kaplan Meyer Product Limit Method. The prognostic significance of empyema and other factors was analyzed by the Log Rank Test, the chi 2 test in homogeneous series of patients and the Cox Hazard Model. Overall, the ten-year survival rate was 23.7% in the empyema group and 15.9% in the control group. After stratification by post-surgical stage, lymphocytic infiltration of primary-tumor (LI), and histological type, no significant differences in survival between the two groups were demonstrated by the Log Rank Test. The same results were found when the survival distribution of the empyema cases was compared with two control groups of patients without empyema, individually paired to the empyema group for Immune Response (LI), post-surgical stage, and histological type. In the end, after multivariate analysis empyema was not shown to be a factor of prognostic significance.