A small intestinal organoid model of non-invasive enteric pathogen-epithelial cell interactions.

Organoids mirror in vivo tissue organization and are powerful tools to investigate the development and cell biology of the small intestine. However, their application for the study of host-pathogen interactions has been largely unexplored. We have established a model using microinjection of organoids to mimic enteric infection, allowing for direct examination of pathogen interactions with primary epithelial cells in the absence of confounding variables introduced by immune cells or the commensal microbiota. We investigated the impact of Paneth cell α-defensin antimicrobial peptides on bacterial growth. We demonstrate that organoids form a sealed lumen, which contains concentrations of α-defensins capable of restricting growth of multiple strains of Salmonella enterica serovar Typhimurium for at least 20 h postinfection. Transgenic expression of human defensin 5 in mouse organoids lacking functional murine α-defensins partially restored bacterial killing. We also found that organoids from NOD2(-/-) mice were not impaired in α-defensin expression or antibacterial activity. This model is optimized for the study of non-invasive bacteria but can be extended to other enteric pathogens and is amenable to further genetic manipulation of both the host and microbe to dissect this critical interface of host defense.

[Hormone replacement therapy after total thyroidectomy. Can the combined treatment be considered effective to get metabolic adequacy? Preliminary results]. / Terapia ormonale sostitutiva dopo tiroidectomia totale. Il trattamento ormonale combinato può essere considerato efficace strumento di adeguatezza metabolica? Risultati preliminari.

INTRODUCTION: Even if T4 is standard treatment for hypothyroidism after thyroidectomy, a treatment with T4 plus T3 has been proposed as an alternative reproducing carefully the physiology of the thyroid. We performed an observational study about the effects of the combined replacement therapy with T4 and T3 in patients who underwent total thyroidectomy. PATIENTS AND METHODS: Fifty thyroidectomized patients (not for cancer), in T4 replacement therapy, were included in the study. Such a therapy has been changed by administering T3 and T4 in proportion 1/16. Adverse effects, clinical parameters and general health perceptions (SF36 Questionnaire) have been considered at the time of enrollment (T0), after 30 days (T1) and after 60 days (T2). RESULTS: No differences in weight, cardiac frequency and blood pression have been found between T0 and T2. A not statistically significant reduction has been found in total cholesterol (3 mg/dL) and triglycerides (3.29 mg/dL) levels. A reduction of complaints referred by the patients at T0 has been revealed in T2: anxiety from 21 to 13 patients; headache from 22 to 13; tiredness from 17 to 8 (p<0.05); sleepiness from 25 to 15 (p<0.05). About the questionnaire, in the General Health Perception sub-score has been found a not significant increase of the parameter. DISCUSSION AND CONCLUSIONS: T4 replacement therapy is of proved efficacy, notwithstanding some complaints afflict a share of patients. To improve the quality of life of these patients, we consider relevant the reduction of complaints and the improvement of well-being and cognitive function obtained by the combined T4 and T3 treatment. Moreover, even if the production of T3 from T4 usually ensures euthyroidism in all tissues, contemporary pathologies and alterations determined by the oldness can disturb the enzymatic activity, which is the essential requirement of T4 therapy. These preliminary findings in a small group of patients encourage further studies on a larger patient population.

[Colorectal carcinoma in the young. Prognostic factors]. / Il carcinoma colo-rettale nel giovane. Fattori prognostici.

Colorectal carcinoma is the third most frequently diagnosed malignant neoplasm. Usually patients affected by this neoplasia belong to VI decade of life. However approximately 2-8% of tumors arise in patients with age under 40 years. Aim of the study was to analyse the results of surgical treatment of colorectal cancer in patients aged under forty. From January 1987 to December 2002, 46 patients under forty years with colorectal cancer underwent surgical procedure. No perioperative mortality was registered, and complications were evidenced in nine patients (20%). Actuarial five years survival was 33%, and overall mean survival was 53 months. Univariate and multivariate analyses identified as prognostic factors the tumor grade, Dukes' stage, nodal status, and length of symptoms.

[Primary adenocarcinoma of the ureter. Case report]. / Adenocarcinoma primitivo dell'uretere: caso clinico.

Primary ureteral adenocarcinoma is an infrequent histological type of urinary neoplasm. Many authors consider intestinal metaplasia the pivotal event of the pathogenetic process, whether it occurs on a pre-existing urothelial carcinoma or on a normal urothelium. Diagnosis is essentially based on case history and clinical findings (hematuria and pain) and on diagnostic imaging. Treatment is surgical and the ideal procedure is nephroureterectomy with excision of a bladder margin adjacent to the ureteral opening and ispilateral para-aortoiliac lymphadenectomy. A 76-year-old man with primary adenocarcinoma of the ureter case is reported.

Lymphadenectomy in gastric cancer: influence on prognosis of lymph node count.

To better understand the role of the number of lymph nodes retrieved on long-term outcome of gastric cancer treatment, 154 patients who had undergone curative resection, with dissection of >15 nodes were retrospectively studied. Dissection of perigastric and extraperigastric lymph nodes, defined as 'extended' (>26 nodes dissected) in 39 cases and 'limited' (< or = 26 nodes dissected) in 115 cases, was performed. A total of 3479 lymph nodes (mean 22.6 per specimen), were dissected and of these 721 showed metastases. A mean of 8.1 lymph node metastases, per metastatic case, was found. Regression analysis showed no independent factor associated with the extent of lymphadenectomy. Depth of wall invasion (p=0.000) and histological growth pattern (p=0.044) were independently associated with the number of lymph nodes involved (pN0, pN1 1-7, pN2 >7). The cumulative 5-year survival rate was 47% in patients without lymph node metastases; 29% in those with 1-7 nodes involved and 17% in those with >8 nodes involved (p=0.002). Receiver operating characteristic (ROC) curve analysis, in 65 nodenegative cancer cases, demonstrated an area under the curve for vital status (alive or dead) of 0.602 (95% CI: 0.473 - 0.721). All node-negative cases with a number equivalent to or exceeding the cutoff point of 23 nodes were alive. ROC analysis showed 11 to be the cutoff number of metastasized lymph nodes in correlation with vital status. Almost all those patients in whom the number of positive nodes was equivalent to, or exceeded the cutoff point had died (area under the ROC curve 0.633; 95% CI: 0.524 - 0.733). ROC analysis showed that the cutoff lymph node ratio, in relation to vital status, was 0.33. The majority of patients at or above this cutoff point had died (area under ROC curve 0.682; 95% CI: 0.574 - 0.776). Multivariate survival analysis showed that lymph node ratio was the only independent prognostic factor (p=0.001). The present findings suggest that, in lymphadenectomy with at least 15 nodes, the number and status of regional nodes dissected, irrespective of the location, provide reliable prognostic information on curatively resected gastric carcinomas.

Clinical significance of serum gastrin levels in patients with colorectal cancer.

AIMS: An association between elevated serum gastrin levels and the presence of human colorectal cancer has been reported, and gastrin has been shown to stimulate the growth of experimentally induced colon neoplasia. The aim of this study was to determine the preoperative and postoperative concentrations of serum gastrin in 53 patients with colorectal cancer and to assess the correlation between gastrin levels and tumor characteristics and prognosis. MATERIALS AND METHODS: A prospective study was performed over a six-year period during which 53 patients received potentially curative surgery for colorectal cancer. The prognostic variables used for the analysis included age, sex, tumor site, stage and degree of differentiation, preoperative and postoperative serum values of carcinoembryonic antigen (CEA) and gastrin, cancer-related mortality, and survival. CEA and gastrin serum values were determined using radioimmunological methods. Follow-up was carried out with clinical and radiological tests. RESULTS: The mean preoperative gastrin concentration was 51.2+/-27.4 pg/mL (range 12-146). Significantly increased serum gastrin concentrations, which returned to normal after surgery, were detected only in patients with well-differentiated cancer (74.2+/-28.3 pg/mL; moderately differentiated, 52.1+/-23.8; poorly differentiated, 29.9+/-12.3, p=0.02). The prognosis was unrelated to serum gastrin level; instead, tumor stage, preoperative CEA value, and degree of differentiation affected patient survival. CONCLUSIONS: This study showed that the serum gastrin concentration is not an appropriate clinical oncogenic factor. Although occurring only in well-differentiated tumors, serum gastrin is unrelated to the prognosis of patients with colorectal cancer.

Cancer precursor lesions in intact stomach Helicobacter pylori gastritis and in resected stomach gastritis.

Hemigastrectomy for benign disease and Helicobacter pylori infection are risk conditions for the development of gastric cancer. Aim of the study was to compare gastric histology and precursor lesions of malignancy in these two conditions. The hemigastrectomy group included 351 consecutively endoscoped subjects operated for gastroduodenal benign disease. Six to ten biopsy specimens were routinely taken from the residual gastric mucosa. The intact stomach group included 2097 consecutively endoscoped symptomatic subjects, who did not receive eradication therapy against H. pylori. The histological findings were classified as normal mucosa (NM), chronic non atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS). One thousand and three intact stomachs were H. pylori negative, and 1094 showed H. pylori colonization. The age over fifty was a significant risk factor for the occurrence of IM (OR 2.52, P < or = 0.001) and DYS (OR 3.46, P < or = 0.001), while Hp-positivity was a risk factor for CNAG (OR 1.81, P < or = 0.001) and CAG (OR 3.88, P < or = 0.001). Gastroresection was associated to higher risk for CNAG (OR 1.53, P < or = 0.001) and DYS (OR 4.31, P < or = 0.001) and to a lower risk of CAG (OR 0.49, P < or = 0.001). Both in males and females the risk for CNAG was significantly higher in Hp-positive (males OR 1.92, P=0.000; females OR 1.70, P=0.000) and gastrectomized subjects (males OR 2.06, P=0.000; females OR 2.43, P=0.000). Gastrectomized males, furthermore, showed an increased risk for DYS (OR 5.82, P=0.000). The aged Hp-negative and Hp-positive subjects evidenced a significant risk for IM (respectively OR's 3.42, P=0.000 and 4.85, P=0.000); the risk for DYS was significant in aged Hp-negative subjects (OR 4.09 P < or = 0.020). The Hp-positive individuals evidenced a significant risk for metaplastic mucosal changes (OR 38.17, P=0.000). Subjects aged over forty at the time of surgery and those with a longer postoperative follow up endoscopy presented an increased risk for CNAG of the residual mucosa (respectively OR's 2.75, P=0.000 and 5.25, P=0.000). CNAG and IM were the most frequently observed mucosal lesions both in subjects operated for duodenal and gastric ulcer (respectively OR's 4.02, P=0.000 and 3.00, P=0.000). Our data support that hemigastrectomy for benign disease and H. pylori infection may induce an increased incidence for histological precursor lesions for gastric malignancy and suggest that carcinogenesis in a resected stomach may be different from that in the intact stomach.

[Rectal cancer in women]. / Il cancro del retto nella donna.

A retrospective chart review was performed utilizing the First Department of Surgery of the University of Rome "La Sapienza" Medical School database. Ninety-two women who underwent abdominal surgery between 1980 and 1993 for rectal cancer were identified. Data collected included demographics, history, intraoperative findings and complications, cancer histology and stage and follow up. Special attention was focused on intraoperative incidental gynecological findings and follow up. Twenty-two patients being previously submitted to hysterectomy and three with oral intake of hormones were dismitted from the study. Of the remaining 67 patients gynecological procedure was associated to rectal surgery because of a previously undiagnosed gynecological condition. No prophylactic oophorectomies were performed. At follow up 7 patients experienced further surgery for gynecologic disease. The necessity to offer these patients the benefit of a preoperative informed decision about adjunctive gynecologic surgery and indications for bilateral oophorectomy is discussed.

Maximum gastric cancer diameter as a prognostic indicator: univariate and multivariate analysis.

It was suggested that there are no stronger prognostic factors in gastric cancer than nodal involvement or depth of wall invasion. The present paper evaluated the influence of maximum tumor diameter (MTD) value, measured on fixed resected specimens, on the extent of disease progression and the outcome in gastric cancer patients. Clinicopathological data were retrospectively retrieved from records of 122 patients who underwent curative gastrectomy. The patients' MTD values were grouped as follows: MTD1, up to 26 mm; MTD2, between 26 and 50 mm; and MTD3, over 50 mm. The three groups evidenced significant differences with regard to 5 year survival (MTD1: 54%, MTD2: 31%, MTD3: 20%; p = 0.00027), furthermore they were significantly different with respect to the type of gastrectomy (p = 0.021), depth wall invasion (p = 0.000), lymphatic microinvasion (p = 0.014), perineural microinvasion (p = 0.017), stromal reaction (p = 0.025), and stage (p = 0.035). ROC curve analysis individuated a best accurate MTD threshold value for nodal involvement of 32 mm (sensitivity = 56.6%; specificity = 60.9%; positive predictive value = 52.6%; negative predictive value = 64.6%). The logistic regression analysis suggested that the depth of wall invasion was the only independent variable associated with MTD value (p = 0.0005). Multivariate analysis showed that independent prognostic risk factors were sex (p < 0.0025), number of involved nodes (p < 0.001) and MTD (p < 0.001). In conclusion, the maximum tumor diameter value of gastric cancer may be a factor with greater prognostic implications than previously believed.

[Pancreatic anastomotic fistula after pancreaticoduodenectomy: incidence, significance and treatment]. / La fistola anastomotica pancreatica dopo duodenocefalopancreasectomia: incidenza, significato e trattamento.

The Authors reviewed the complications, and outcomes in a consecutives series of 97 patients undergoing pancreaticoduodenectomy. The clinical leak rate in this series was 21.8%. There was a difference in the pancreatic leak rate in those patients who underwent pancreatic ductal closure or end to end pancreaticojejunal invagination compared with end to side pancreaticojejunal anastomosis. The postoperative complication rate was 41.8% and the most common complications were pancreatic fistula. 9 deaths occurred in hospital or within 30 days from operation. Univariate and multivariate analysis revealed that operative technique, the pathological status of the pancreatic remnant, and mayor complications were the significant risk factors for the development of pancreatic anastomotic leak. In the 2000s pancreatic leak remains a potentially lethal problem. After pancreaticoduodenectomy, pancreatic remnant management by end to side pancreaticojejunostomy appeared safe in low-risk patients. Morbidity was greatest after pancreatic duct closure without anastomosis.

[Use of ileostomy and colostomy as temporal derivation in colorectal surgery]. / L'impiego della ileostomia e della colostomia come derivazioni temporanee in chirurgia colo-rettale.

A retrospective study on 41 patients with primary stoma creation after low anterior resection of the rectum was made. Among the 41 patients 24 had a loop colostomy (Group A) and 17 had a loop ileostomy (Group B). The two groups were well matched for each of the data analysed and there was no significant difference in the rate of complications related to stomas creation and closure. In this study the Authors suggest that loop ileostomy is the best procedure to electively defunctionate colorectal anastomoses.

Unusual breakage of a plastic biliary endoprosthesis causing an enterocutaneous fistula.

OBJECTIVE: The objective of our study was to illustrate a case of endoscopically placed biliary stent breakage. METHODS: A72-year-old woman with a prolonged history of cholangitis following laparoscopic cholecistectomy was referred to our institution 8 years ago. Dilatation of the intra- and extrahepatic biliary tree and a benign stricture at the cystic confluence were observed at US and endoscopic retrograde cholangiopancreatography (ERCP). A 12-F gauge plastic endoprosthesis was placed. In the absence of any symptoms, breakage of the stent was revealed 18 months later at plain radiology. Eight years later an enterocutaneous fistula occurred originating from a jejunal loop containing the indwelled distal part of the stent. Surgery was undertaken and the distal part of the stent removed with the perforated jejunal loop. The proximal part was successively endoscopically removed. CONCLUSIONS: Disruption of a biliary endoprosthesis is observed in patients in whom the stent is kept in situ for a long period or consequent to exchange. The removal and exchange is mandatory when the stent disruption is followed by cholangitis. In the current case, because of the absence of any symptoms the removal of the stent was not attempted. Immediate endoscopic removal of the prosthetic fragments seems to be the treatment of choice for replacement of a new stent.

[Cecal volvulus]. / Il volvolo del cieco.

A retrospective study on 18 patients with cecal volvulus surgically treated was made. Demographics and clinical data, as well as treatment were determined from clinical reports. The operative procedures employed were cecostomy (56%), cecopexy (22%) and right colectomy (22%). The length of follow up averaged 63 months and there was one recurrence. The Authors suggest that cecostomy should be employed in patients with viable bowel, and resection should be limited to cases with gangrene.

[Carcinoma of the male breast. Prognostic factors and outcome of surgical treatment]. / Il carcinoma della mammella nell'uomo. Fattori prognostici e criteri di trattamento.

A retrospective study was made on 18 male patients with breast carcinoma treated at the Department of Surgery "Pietro Valdoni" of the University "La Sapienza" of Rome, Medical School. Demographics, pathology, stages, and treatment were determined from clinical reports. All patients but one underwent modified radical mastectomy. The length of follow up averaged 57.5 months. Five years actuarial survival rate was 62%. In the current study the Authors suggest that the clinical, prognostic and treatment features of breast carcinoma in men are similar to those reported in literature for post-menopausal women.

Presacral myelolipoma in a patient with colon carcinoma.

Myelolipoma is an uncommon benign tumor, composed of an admixture of adipose tissue and hematopoietic cells, usually discovered within the adrenal glands. Extra-adrenal myelolipomas are rare and approximately half of the reported cases were presacral. We report a case of an asymptomatic presacral myelolipoma measuring 9x8x7 cm, incidentally found in a 71-year-old woman with a stenosing colon cancer. Ultrasonography, computed tomography and magnetic resonance imaging of the presacral mass evidenced a well circumscribed tumor with heterogeneous features due to a nonuniform composition. Surgical excision of the mass was performed.

[Ambulatory closed surgery for the treatment of pilonidal sinus]. / Il trattamento chirurgico ambulatoriale del sinus pilonidalis con tecnica chiusa.

Pilonidal disease (PD) is a common chronic disorder of the sacrococcygeal region afflecting young people. Despite several methods for treating PD have been described, the management remains controversial. Recent reports have advocated different surgical approaches such as open or closed technique, but recurrence plagues all forms of therapy. We conducted this case review to evaluate the validity of an outpatient closed technique in the treatment of chronic pilonidal disease. Between January 1997 and July 1999, 65 consecutive patients with quiescent chronic PD were electively treated by surgical excision of the cyst and primary closure. There were 47 men (72%) and 18 women (28%) in this study. Patients ranged in age from 14 to 47 years, the average age being 21 years. The median healing time was 8 days and the median time to return to full work was 20 days (range 10-25). Infection and recurrence rates were 1.5% and 4.6% respectively. There was no correlation among recurrence rate, postoperative infection, or prior surgery. Cyst excision and primary closure is a safe, low cost operation with a very high long-term success rate and a negligible rate of complications. It can successfully be performed under local anaesthesia in an outpatient facility.

Preservation of the inferior mesenteric artery in colorectal resection for complicated diverticular disease.

BACKGROUND: Preservation of the inferior mesenteric artery (IMA) and consequential blood flow to the rectum would reduce the risk of leakage of a colorectal anastomosis. METHODS: One hundred and sixty-three patients undergoing left colectomy for complicated diverticular disease of the colon were randomly placed into two groups: A, n = 86; and B, n = 77. In group A, the integrity of the IMA was preserved by artery skeletization (IMAS); in group B, the IMA was divided at its origin. Variables recorded included duration of the surgical procedure, need for blood transfusion, length of hospital stay, operative mortality and morbidity, staple-ring disruption, and radiologic and clinical leakage. Anastomotic stenosis and recurrence of diverticular disease were noted. RESULTS: Surgical time was superior in the IMAS group. Radiologic and clinical leakages were significantly higher in group B (P = 0.02, P = 0.03, respectively). In group A a significant lower number of staple-ring disruptions was observed, evolving into clinical dehiscence. CONCLUSION: Preserving the natural blood supply to the rectum and the ensuing use of a healthy well-nourished rectal stump are suggested as the main aspects of IMAS in preventing and healing leakage of colorectal anastomosis.

Late development of bile duct cancer in patients who had biliary-enteric drainage for benign disease: a follow-up study of more than 1,000 patients.

OBJECTIVE: To evaluate the correlation between biliary-enteric surgical drainage and the late development of cholangiocarcinoma of the biliary tract. SUMMARY BACKGROUND DATA: In patients with biliary-enteric drainage, reflux of intestinal contents into the bile duct may occur and cause cholangitis, which is regarded as the most serious complication of these procedures. Lithiasis of the biliary tract and a previous biliary-enteric anastomosis have both been suggested to favor the late onset of cholangiocarcinoma. METHODS: Consecutive patients (n = 1,003) undergoing three different procedures of biliary-enteric anastomosis (transduodenal sphincteroplasty, choledochoduodenostomy, and hepaticojejunostomy) between 1967 and 1997 were included in this study. The postoperative clinical course and long-term outcome were evaluated by a retrospective review of the hospital records and follow-up. Mean follow-up was 129.6 months. RESULTS: Fifty-five (5.5%) cases of primary bile duct cancer were found among the 1,003 patients at intervals of 132 to 218 months from biliary-enteric anastomosis. The incidence of cholangiocarcinoma in the three groups was 5.8% in transduodenal sphincteroplasty patients, 7.6% in choledochoduodenostomy patients, and 1.9% in hepaticojejunostomy patients. The incidence of malignancy related to the different underlying diagnosis was 5.9%, 7.2%, and 1.9% in patients with choledocholithiasis, sphincter of Oddi stenosis, and postoperative benign stricture, respectively. Although only one patient who developed cholangiocarcinoma had previous concurrent lithiasis of the biliary tract, 40 patients had experienced mostly severe, recurrent cholangitis. No case of malignancy occurred in patients scored as having no cholangitis in the early and long-term postoperative outcome. Univariate and multivariate analyses have shown the presence of cholangitis as the only factor affecting the incidence of cholangiocarcinoma. CONCLUSIONS: Chronic inflammatory changes consequent to biliary-enteric drainage should be closely monitored for the late development of biliary tract malignancies.

Clinical significance of normobasemia in early post-operative outcome of hepatic resections.

BACKGROUND: Major hepatic resections are usually followed by acid-base unbalance. Adjustment of the acid-base disorders is considered central when dealing with these critical patients and normobasemia is thought to be a favourable prognostic factor when occurring in the immediate postoperative outcome after major surgery. The present study was undertaken to investigate the influence of acid base balance on the early outcome after hepatic resection. METHODS: A series of fifty-seven cirrhotic patients was submitted to liver resection for hepatocellular carcinoma. Forty-eight patients experienced an uneventful early postoperative outcome (CTR group). Nine died in the postoperative course (HD group). In all patients pulmonary, renal and hepatic functions were monitored pre- and postoperatively. The pH values were detected daily preoperatively and in the course of the first three days after hepatic resection. In the same days acid base balance and arterial ketone body ratio were assessed on arterial blood samples. Data were collected in a data base and statistical analysis was performed. RESULTS: A significantly higher metabolic alkalosis was found to characterize the first and second postoperative days (POD1 and POD2) in the CTR group (pH 7.43+/-0.007 vs pH 7.33+/-0.001; pH 7.45+/-0.006 vs pH 7.35+/-0.009; p<0.05). Lower values of pH and an associated impaired energetic status of the liver were found to characterise the postoperative course of the poor prognosis patients. At POD1 AKBR decreased in both groups but while recovering at POD2 in patients of CTR group maintained significantly lower values in HD group (AKBR 1+/-0.3 vs 0.5+/-0.2; p<0.01). A lower energetic status of the liver is associated with an inadequate tricarboxylic acid cycle and is responsible for an impaired production of HCO3-. CONCLUSIONS: Apparent normobasemia is then expressive of liver failure leading to poor postoperative outcome.