Riccardo Rosati

Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer

Purpose: The outcome of patients with colorectal cancer is more favorable when the tumor exhibits high-frequency microsatellite instability (MSI). Although associated with earlier-stage tumors, MSI has been proposed as an independent predictor of survival. We tested the prognostic value of MSI in a large series of patients diagnosed with colorectal cancer in the last decade. Experimental Design: The survival of 893 consecutive patients with colorectal cancer characterized by microsatellite status was analyzed. The 89 (10%) patients with MSI cancer were classified according to tumor mismatch repair (MMR) defect, MMR germ-line mutation, hMLH1 and p16 promoter methylation, BRAF and K-ras mutations, and frameshifts of target genes. Results: The colorectal cancer–specific survival was significantly (P = 0.02) better in patients with MSI cancer than in those with stable tumor (MSS). MSI did not predict a significantly lower risk of cancer-related death if tumor stage was included in the multivariate analysis [hazard ratio, 0.72; 95% confidence interval (95% CI), 0.40-1.29; P = 0.27]. Instead, MSI was strongly associated with a decreased likelihood of lymph node (odds ratio, 0.31; 95% CI, 0.17-0.56; P < 0.001) and distant organ (odds ratio, 0.13; 95% CI, 0.05-0.33; P < 0.001) metastases at diagnosis, independently of tumor pathologic features. Molecular predictors of reduced metastatic risk, and then of more favorable prognosis, included TGFβRII mutation for all MSI tumors, hMSH2 deficiency for hereditary non-polyposis colorectal cancer, and absence of p16 methylation for sporadic hMLH1-deficient cancers. Conclusions: Tumor MSI is a stage-dependent predictor of survival in patients with colorectal cancer. The decreased likelihood of metastases in patients with MSI cancer is associated with specific genetic and epigenetic changes of the primary tumor.

Endoscopic submucosal dissection in patients with early esophageal squamous cell carcinoma: results from a prospective Western series

BACKGROUND Although endoscopic submucosal dissection (ESD) is becoming accepted as an established treatment for superficial esophageal squamous cell neoplasia, the majority of data on this endoscopic modality has been provided by Japanese series. OBJECTIVE To assess the efficacy and safety of ESD for esophageal squamous cell neoplasia in a consecutive series of patients treated in a Western setting. DESIGN AND SETTING Single-center, prospective observational study. PATIENTS AND INTERVENTION From January 2005 to July 2008, 20 patients with superficial esophageal squamous cell neoplasia were treated by ESD. MAIN OUTCOME MEASUREMENTS Rates of en bloc resection, complete resection, and complications were evaluated as short-term outcomes. Overall survival, local or distant recurrence, and postoperative stricture rates were evaluated as long-term outcomes. RESULTS ESD was performed in 20 patients (mean age 64 years, range 46-81 years; 16 men). The mean size of the lesion was 32 mm (range 15-60 mm); it was 30 mm or larger in 14 patients (70%). The mean time of ESD was 89 minutes (range 58-180 minutes). En bloc resection with resection-free margins was achieved in 18 patients (90%), whereas 2 patients presented with incomplete or indeterminate resection. Two cases (10%) of mediastinal emphysema without overt perforation and 1 case (5%) of post-ESD symptomatic stricture were reported. No local or distant post-ESD recurrence occurred in those with resection-free margins at a median follow-up of 18 months. LIMITATIONS Small number of patients and limited follow-up. CONCLUSION This Western series study confirms that ESD is a potentially curative treatment for superficial esophageal squamous cell neoplasia. Early and late complication rates were comparable to those of Japanese series. ESD should be probably considered as the treatment of choice in all large lesions amenable to endoscopic treatment.

Laparoscopic approach to esophageal achalasia

Certain technical details are considered important to ease the laparoscopic performance of a Heller myotomy combined with a Dor antireflux procedure for esophageal achalasia. A special emphasis is given to intraoperative esophagoscopy combined with a mild balloon distension of the esophagogastric junction. These maneuvers prove helpful in identifying the esophagogastric region, easing the myotomy, and controlling its completeness.

Diverticulectomy, myotomy, and fundoplication through laparoscopy: A new option to treat epiphrenic esophageal diverticula?

OBJECTIVE To describe the technique and the results of laparoscopic diverticulectomy combined with esophageal myotomy and antireflux wrap for epiphrenic diverticula of the esophagus. SUMMARY BACKGROUND DATA The epiphrenic diverticulum of the esophagus is a rare disease probably caused by a longstanding impairment of the esophageal motor activity. Although there is almost universal agreement to operate only on symptomatic patients, the optimal treatment is controversial. The best-accepted guideline is to treat the underlying motor disorder. This is generally done through a left thoracotomic approach that allows diverticulectomy, esophageal myotomy, and partial fundoplication. METHODS From January 1994 through February 1996, 4 patients underwent laparoscopic transhiatal diverticulectomy, esophageal myotomy, and partial fundoplication at our institution. A thorough preoperative study was done with barium swallow, esophagoscopy, and manometry in all patients; 24-hour pH monitoring was done in one case. RESULTS No postoperative complications were observed. Short- and medium-term results are satisfactory. CONCLUSIONS No theoretical objection should be made to this approach, because the principle of treatment of the diverticular pouch and the underlying motor disorder and the prevention of reflux is respected. Longer follow-up and a wider series are mandatory to substantiate these initially favorable results.

Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection

Hepatitis C virus (HCV) persistence in the host results from inefficiencies of innate and adaptive immune responses. Most studies addressing the role of innate immunity concentrated on peripheral blood (PB) natural killer (NK) cells, whereas only limited information is available on intrahepatic (IH) NK cells. We therefore examined phenotypic and functional features of IH and PB NK cells in paired liver biopsy and venous blood samples from 70 patients with chronic HCV infection and 26 control persons subjected to cholecystectomy for gallstones as controls. Ex vivo isolated IH NK cells from HCV‐infected patients displayed unique phenotypic features, including increased expression of NKp46‐activating receptor in the face of reduced tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL) and cluster of differentiation (CD) 107a expression, which resulted in impaired degranulation compared with controls. To gain insights into the effect of HCV on NK cells, we exposed peripheral blood mononuclear cells (PBMCs) from patients and healthy donors to cell‐culture–derived HCV (HCVcc) and measured NK cell degranulation, TRAIL, and phosphorylated extracellular signal‐regulated kinase 1/2 (pERK1/2) expression. Exposure of PBMCs to HCVcc significantly boosted NK degranulation, pERK1/2, and TRAIL expression in healthy donors, but not in patients with chronic HCV infection, a defect that was completely reversed by interferon‐alpha. Purified NK cells showed a minimal, though significant, increase in degranulation and TRAIL expression, both in patients and controls, after exposure to HCVcc. Conclusions: These findings indicate dysfunctional IH NK cell cytotoxicity associated with TRAIL down‐regulation in chronic HCV infection, which may contribute to virus persistence. PB NK cell impairment upon exposure to HCVcc suggests the existence of an accessory cell‐dependent NK cell lytic defect in chronic HCV infection predominantly involving the TRAIL pathway. (HEPATOLOGY 2012;56:841–849)

Evaluating results of laparoscopic surgery for esophageal achalasia

AbstractBackground: Extramucosal myotomy of the lower esophagus and cardia, combined with anterior fundoplication, is, in our opinion, the procedure of choice to treat stage I–III esophageal achalasia. Methods: After a successful experience with open surgery in over 280 patients, from January 1992 through February 1997, 61 patients underwent laparoscopic Heller-Dor for stage I–III achalasia. Conversion to laparotomy was done in three cases. All procedures were performed under intraoperative endoscopic control. Intraoperative complications were seven mucosal tears, which were sutured laparoscopically in five cases. The sole postoperative complication was bleeding from an acute gastric ulcer (conservative treatment). Results: Follow-up consisted of clinical and radiographic study 1 month after surgery, and endoscopy and manometry within 1 year. After a mean follow-up (F.U.) of 21 months (1–62), clinical results range from excellent to good in 98.2%. One patient (1.7%) complaining of recurrent dysphagia improved after endoscopic dilation. Esophageal diameter reduced from 52 to 27 mm. LES pressure reduced from 30.3 ± 12.4 to 10.7 ± 3.5 mmHg (basal) and from 14.8 ± 9.3 to 2.9 ± 2.1 mmHg (residual). Conclusions: Laparoscopic Heller-Dor operation is feasible, safe, and effective. Special care should be taken in patients with previous endoscopic dilations.

Age- and sex-related changes in the normal human ear.

The objective of this study was to supply information about: (1) normal sex-related dimensions of ears (linear distances and ratios, area); (2) left-right symmetry; and (3) growth changes between childhood and old age. The three-dimensional coordinates of several soft-tissue landmarks on the ears and face were obtained by a non-invasive, computerized electromagnetic digitizer in 497 male and 346 female healthy subjects aged 4-73 years. From the landmarks, paired ear width and length, the relevant ratios, ear areas and angles relative to the facial midline, as well as indices of left-right symmetry, were calculated, and averaged for age and sex. Comparisons were performed by factorial analysis of variance. All ear dimensions were significantly larger in men than in women (p<0.001). A significant effect of age was found (p<0.001), with larger values in older individuals. The ear width-to-length ratio and the sagittal angle of the auricle significantly decreased as a function of age (p<0.001) but without sex-related differences. On average, the three-dimensional position of ears was symmetric, with symmetry coefficients ranging between 92% and 96%. Asymmetry was found in the sagittal angle of the auricle (both sexes), in the ear width-to-length ratio and ear width (men only). Data collected in the present investigation could serve as a data base for the quantitative description of human ear morphology and position during normal growth, development and aging. Forensic applications (evaluations of traumas, craniofacial alterations, teratogenic-induced conditions, facial reconstruction, aging of living and dead persons, personal identification) may also benefit from age- and sex-based data banks.

Accuracy and Reproducibility of a 3-Dimensional Stereophotogrammetric Imaging System

PURPOSE To test the accuracy and reproducibility of a 3-dimensional (3D) stereophotogrammetric imaging system for measuring the facial soft tissues of healthy subjects. MATERIALS AND METHODS Three-dimensional soft tissue facial landmarks were obtained from the faces of 10 adult subjects, by use of a 3D stereophotogrammetric imaging system (Vectra; Canfield Scientific, Fairfield, NJ). Sixteen linear measurements were computed. Systematic and random errors between operators, calibration steps, and acquisitions were calculated. RESULTS No systematic errors were found for all performed tests (P > .05, paired t test). The method was repeatable, and random errors were always lower than 1 mm, except for the distance from cheilion to cheilion. Repeated sets of acquisition showed random errors up to 0.91 mm, without systematic biases. CONCLUSION The 3D stereophotogrammetric imaging system can assess the coordinates of facial landmarks with good precision and reproducibility. The method is fast and can obtain facial measurements with few errors.

Laparotomic vs. laparoscopic rectopexy in complete rectal prolapse.

Aim: The aim of this study was to compare the functional and clinical results of laparotomic and laparoscopic rectopexy in 2 homogeneous groups of patients with complete rectal prolapse and fecal incontinence. Methods: Between January 1989 and December 1997, twenty-three patients underwent abdominal rectopexy. Thirteen patients (group A, 12 females and 1 male, mean age 57.3, range 22–76 years), and 10 patients (group B, 10 females, mean age 52.3, range 26–70 years) were submitted respectively to either Wells laparotomic or laparoscopic rectopexy by the same surgical team using the same surgical technique and materials. Before the operation a detailed clinical history was collected, and the patients were studied by inspection and digital examination of the anorectum, proctosigmoidoscopy, pancolonic transit time, dynamic defecography, anorectal manometry and anal electromyography. After the operation all patients underwent perineal physiotherapy, external electric stimulation, and perineal biofeedback. Mean follow-up was 37.1 (range 6–90) months in group A and 25.7 (range 6–49) months in group B. Values were compared by χ2, Mann-Whitney U, and Wilcoxon tests as appropriate. Differences were considered significant at p < 0.05. Results: In both groups dyschezia and fecal incontinence improved significantly (p < 0.05) after the operation. The basal pressure of the anal sphincter, squeezing pressure and rectoanal reflex improved without significance, and anal-perineal pain was not significantly reduced. In group B the postoperative hospital stay was lower than in group A, with a reduction in costs. Conclusion: Laparoscopic Wells rectopexy has the same clinical and functional results as laparotomic rectopexy, but with a shorter postoperative hospital stay and lower costs.

Thoracoscopic esophagectomy: Are there benefits?

Between 1991 and 1995, 18 patients affected by a resectable intramural tumor of the esophagus underwent esophagectomy with thoracoscopic dissection of the esophagus. All patients had a relative contraindication to transthoracic esophagectomy with radical lymphadenectomy. All esophagectomies were completed thoracoscopically and reconstruction of the digestive tract was performed in 17 cases through cervical gastroplasty, and in 1 case, through cervical coloplasty. One cirrhotic patient died in the postoperative period due to a cervical anastomotic leak. Six other patients experienced a postoperative complication (mortality rate, 5.5%; morbidity rate, 33.3%). After a median follow-up of 17 months, 14 patients are alive without evidence of disease. One patient, who had excision of a cutaneous metastasis at a trocar insertion site 6 months postoperatively, eventually died with locoregional recurrence 14 months postoperatively. Another patient died 20 months after surgery with mediastinal recurrence. One patient died 28 months postoperatively after massive hematemesis with a suspect abdominal recurrence. The results of the present series, and those reported by other authors, do not seem to indicate evident advantages at present for the minimally invasive procedure during resection of the esophagus for cancer. Currently, there is no indication that this procedure should be used for standard clinical use. Wider randomized trials, performed in selected centers only, and longer follow-up are needed to further evaluate the procedure.