Laparoscopic treatment of advanced colonic cancer: a case-matched control with open surgery.

AIM: The safety, feasibility and oncological results of laparoscopic resection for advanced colon cancer were evaluated. METHOD: Seventy consecutive patients with a histologically proven T4 colon cancer who underwent laparoscopic (LPS) right or left colectomy were matched for comorbidity on admission (American Society of Anesthesiologists score), tumour stage and grading with 70 patients who underwent open colectomy over a 10-year period. Short- and long-term outcome measures were evaluated. RESULTS: The overall conversion rate was 7.1%. Less intra-operative blood loss (P = 0.01), a trend toward a longer operation time (P = 0.09) and a lower peri-operative blood transfusion rate (P = 0.06) were observed in the LPS group. A similar number of lymph nodes were retrieved (P = 0.37) and the R1 resection rate (P = 0.51) was no different in the two groups. The overall mortality rate was 1.4%. The overall morbidity rate was 21.4% (15/70 patients) in the LPS group and 27.5% (19/70 patients) in the open group (P = 0.42), with anastomotic leakage rates of 7.1% and 4.2% (P = 0.32). Length of stay was shorter after LPS (P = 0.009). Five-year overall survival rate (P = 0.18) and disease-free survival rate (P = 0.20) did not differ significantly between the two groups. CONCLUSION: Laparoscopic treatment of T4 colon cancer is safe and feasible and provides a similar surgical and oncological outcome compared with the open technique.

Sentinel node mapping during laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: The goal of this study was to evaluate the feasibility and accuracy of sentinel node (SN) mapping with endoscopic submucosal blue dye injection during laparoscopic distal gastrectomy for gastric cancer. METHODS: Thirty-four patients affected by gastric adenocarcinoma without gross clinical serosal invasion and distant metastasis were prospectively enrolled. At the start of the surgery, 2 ml of 2% patent blue was endoscopically injected into the submucosal layer at four points around the site of the primary tumor. Sentinel nodes were defined as nodes that were stained by the blue dye within 5-10 min after the dye injection. After identification and removal of sentinel lymph nodes, each patient underwent laparoscopic distal gastrectomy with D1 (n = 2) or D2 (n = 32) lymphadenectomy. RESULTS: Of the 34 patients, 14 had positive nodules (41%). SNs were detectable as blue nodes in 27 (80%) of 34 patients. The mean number of dissected lymph nodes per patient was 31 +/- 10 (range = 16-64) and the mean number of blue nodes was 1.5 (range = 1-4). Only five (sensitivity 36%) of 14 N(+) patients had at least one metastatic lymph node among the SNs identified. In these 14 patients the sentinel node was traced in 12 cases. Sentinel node status diagnosed the lymph node status with 74% accuracy. In early gastric cancer (n = 18), three patients had lymph node metastasis. These early gastric cancer patients with nodal metastases had at least one metastatic lymph node among the SNs identified (sensitivity 100%). CONCLUSIONS: Blue dye SN mapping during laparoscopic distal gastrectomy seems to be a feasible and accurate diagnostic tool for detecting lymph node metastasis in patients with early-stage gastric cancer in which the accuracy of the method was 100%. However, in more advanced gastric cancer the results are not satisfactory. Validation of this method requires further studies on technical issues, including selection of the tracers.

Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma: a dose-finding study.

The aim of this study was to assess the maximum tolerated dose (MTD) of an intensified PEFG regimen administered every 14 days to patients with Stage III or metastatic pancreatic adenocarcinoma. Twenty-nine patients received fixed doses of both epirubicin (30 mg/m2) and 5-fluorouracil (200 mg/m2/day on Days 1-14) and of escalating doses of cisplatin and gemcitabine. The MTD was cisplatin 30 mg/m2 and gemcitabine 800 mg/m2. With respect to classical PEFG, intensified regimen potentially improved the dose-intensity of both cisplatin and epirubicin by 50 percent and of gemcitabine by 33 percent, reduced Grade 3-4 haematological toxicity and the number of outpatient accesses.

Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma.

BACKGROUND: PEFG regimen (cisplatin and epirubicin 40 mg/m2 day 1, gemcitabine 600 mg/m2 days 1 and 8, 5-fluorouracil (FU) 200 mg/m2/day continuous infusion) significantly improved the outcome of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine in a previous phase III trial. This regimen was subsequently modified in a dose-finding study by increasing dose intensity of cisplatin and epirubicin (both at 30 mg/m2 every 14 days) and of gemcitabine (at 800 mg/m2 every 14 days). Results of a consecutive series treated by dose-intense PEFG regimen are herewith reported. MATERIAL AND METHODS: Dose-intense PEFG was administered to chemotherapy-naive patients with stages III-IV PA, < 75 years, performance status (PS) > 50, till progressive disease or for a maximum of 6 months. RESULTS: Between January 2004 and June 2005, 49 (31 or 63% metastatic) patients, median age 62 years, median PS 80, were treated with dose-intense PEFG. Partial response and stable disease was observed in 24 (49%) and 16 (33%) patients, respectively; 31 patients were progression-free at 6 months (PFS-6 = 63%). Median survival was 10.5 months and 1-year overall survival (OS) was 48% (95% confidence interval: 33-61%). Main grade 3-4 toxicity was: neutropenia in 26% of patients, stomatitis and fatigue in 8%, anaemia, diarrhoea, nausea/vomit in 6%, febrile neutropenia and thrombocytopaenia in 4%, hand-foot syndrome in 2%. CONCLUSION: When compared with 84 patients treated by classical PEFG at the same institution, dose-intense PEFG was not inferior in terms of PFS-6 (63 versus 57%), 1-year OS (48 versus 42%) and response rate (49 versus 49%); it allowed to increase dose intensity for gemcitabine by 32%, for cisplatin and epirubicin by 36% (FU reduced by 3%), to significantly reduce grade 3-4 hematological toxicity (neutropenia: 26 versus 86%; P < 0.00001; thrombocytopaenia: 4 versus 58%; P < 0.00001) and to reduce by one-third the number of outpatient accesses. The new PEFG schedule appears more suitable for clinical use and should be preferred as a basis for further development of therapeutic strategies against pancreatic cancer.

Laparoscopic excision of duodenal schwannoma.

BACKGROUND: Benign duodenal tumours are rare and less common than malignant tumours. They comprise a wide variety of pathologies. Schwannoma is an ectodermal neoplasm arising from the nerve sheath that envelops axons. A duodenal location is extremely rare. Therapy consists in the radical excision of the tumour. Our aim was to describe a minimally invasive technique used for the excision of duodenal schwannoma, so that a laparotomy has been avoided. METHODS: A laparoscopic operation under general anaesthesia was undertaken with the patient in supine position with the legs abducted. No macroscopic peritoneal seedling was found. Therefore, a laparoscopic Kocher maneuver was performed. The retroperitoneum was entered using the harmonic scalpel and the dissection extended beyond the vena cava and the duodenum. The location and the size of the lesion have been confirmed using an intraoperative endoscopic ultrasound examination. The excision of the lesion was performed by use the harmonic scalpel. Then, the duodenal wall was sutured by use endoscopic stitches. The resected lesion was then placed in a retrieval bag and extracted through the port incision. Operating time was 300 min and blood loss 200 ml. RESULTS: The postoperative course was uneventful. Histological findings showed a benign schwannoma. CONCLUSIONS: The minimally invasive technique may be a valid alternative to open surgery in the treatment of benign duodenal tumors.

Impact of recipient and donor ages on patient and graft survival after kidney transplantation.

BACKGROUND: The purpose of the study was to evaluate the impact of donor and recipient ages on patient and graft survival after kidney transplant. METHODS: Patients in a hospital database undergoing kidney transplant for end-stage renal disease (ESRD) during the period 1985 to May 2006 (n = 410; mean age 42 +/- 10 years; 61% men and 39% women) were divided into two groups: group A, patients of 60 years or older (6%, n = 24), and group B, those younger than 60 years (94, n = 386). In 204 patients (49.8%) the pancreas was transplanted simultaneously with the kidney. RESULTS: Overall 1-, 3-, 5-year patient survivals were 92%, 90%, 88% in group A and 95%, 90%, 87% in group B (P = .6, NS). Overall 1-, 3-, 5-year kidney graft was 92%, 75%, 65% in group A and 92%, 84%, 79% in group B (P = .7, NS). Donors were divided into two groups: group 1, 55 years or older (15%, n = 62), versus group 2, those younger than 55 years (85%, n = 348). Overall 1-, 3-, 5-year patient survivals were 91%, 86%, 76% in group 1 and 97%, 94%, 90% in group 2 (P = .0009). Overall 1-, 3-, 5-year kidney graft survivals were 87%, 82%, 76% in group 1 and 94%, 86%, 82% in group 2 (P = .02). CONCLUSIONS: Renal transplantation is an effective option for the treatment of ESRD in elderly patients. The overall rates of patient and kidney graft survival are comparable to those of younger patients. Donor age > or =55 years had a negative effect on patient and kidney graft survival.

Triple arterial reconstruction improves vascularization of whole pancreas for transplantation.

We assessed the effect on duodenal stump vascular supply of reconstruction of the gastroduodenal artery performed before pancreas transplantation. The median pancreas graft and patient survival times were 144 and 72 months for cases with or without gastrointestinal bleeding. Transmural blood flow values were significantly different between the donor duodenal stump and the recipient anastomosed jejunum (P < .01). The rate of gastrointestinal bleeding was lower in patients who received a pancreatic graft with back-table reconstruction of the gastroduodenal artery (P = .005).

Lack of feedback inhibition of insulin secretion in denervated human pancreas.

In this study, pancreas transplantation is used as a clinical model of pancreas denervation in humans. To assess the role of innervation on the feedback autoinhibition of insulin secretion, we studied four groups of subjects--group 1: 16 patients with combined pancreas and kidney transplantation (plasma glucose = 5.1 mM, HbA1c = 6.4%, creatinine = 86 mM); group 2: 8 patients with chronic uveitis on the same immunosuppressive therapy as transplanted patients (12 mg/day prednisone, 5 mg.kg-1.day-1 CsA); group 3: 4 uremic, nondiabetic patients in chronic hemodialysis; group 4: 7 normal, nondiabetic control subjects. The following means were used to study the groups: 1) a two-step hyperinsulinemic euglycemic clamp (insulin infusion rate = 1 mU and 5 mU.kg-1.min-1); and 2) a 0.3 mU.kg-1.min-1 hypoglycemic clamp (steady-state plasma glucose = 3.1 mM). Basal plasma-free IRI (84 +/- 6, 42 +/- 12, 72 +/- 12, and 30 +/- 6 pM in groups 1, 2, 3, and 4, respectively), basal C-peptide (0.79 +/- 0.05, 0.66 +/- 0.05, 3.04 +/- 0.20, and 0.59 +/- 0.06 nM in groups 1, 2, 3, and 4, respectively), and glucagon (105 +/- 13, 69 +/- 4, 171 +/- 10, and 71 +/- 5 pg/ml in groups 1, 2, 3, and 4, respectively) were increased in groups 1 and 3 with respect to groups 2 and 4 (P < 0.01). During euglycemic hyperinsulinemia, plasma C-peptide decreased by 45, 20, and 44% in groups 2, 3, and 4, respectively, but showed no significant change from the basal in patients with transplanted pancreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Laparoscopic assisted duodenopancreatectomy.

BACKGROUND: In the past few years, minimally invasive therapy for pancreatic diseases has made significant strides but the role of laparoscopic pancreaticoduodenectomy is still controversial. METHODS: Four patients with a mean age of 44 +/- 11 years were chosen for a laparoscopic pancreaticoduodenectomy. Pathological diagnoses were ductal adenocarcinoma in one, neuroendocrine tumor in two, and metastatic malignant melanoma in one. RESULTS: The procedure was laparoscopically completed in all with a mean operating time, blood loss, and hospital stay of 416 +/- 77 min, 325 +/- 50 ml, and 12 +/- 2 days, respectively. There were no complications attributable to this surgery and there were no deaths. The average number of dissected lymph nodes was 26 +/- 17 (range 16-47). All the patients remained well at a median follow-up of 4.5 months (range 1-10). CONCLUSIONS: It can be inferred from this small but successful experience that laparoscopic pancreaticoduodenectomy can be considered for the treatment of tumors of the pancreas or periampullary region.

Cardiovascular benefits of simultaneous pancreas-kidney transplant versus kidney alone transplant in diabetic patients.

UNLABELLED: The aim of our study was to demonstrate the cardiovascular benefits of simultaneous pancreas-kidney transplantation when compared to kidney-alone transplants in diabetic recipients. PATIENTS AND METHODS: A total of 386 renal transplants were performed from 1985 to 2004, including 262 (68%) in diabetic recipients and 124 (32%) in nondiabetics. Among the former group, 200 kidneys were transplanted simultaneously to the pancreatic graft (KP group) and 62 were kidney-alone transplants (KA group). The mean time on dialysis was 31 +/- 20 months (range 0-126 months). The duration of diabetes was 24 +/- 7 years (range 5-51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% on hemodialysis and 20% on peritoneal dialysis). RESULTS: Among 262 patients, 28 (11%) died due to a cardiovascular event, which was higher among KA patients compared with the KP group (P = .004). Overall patient survival was significantly higher in the KP group when compared with the KA group (log-rank: P = .0004). Patient survivals were 80% and 70% versus 70% and 40% at 5 and 10 years in the KP and KA groups, respectively. Kidney graft survivals were 81% and 60% versus 63% and 26% at 5 and 10 years in the KP and KA groups, respectively. Pancreas graft survival was 70% and 50% at 5 and 10 years, respectively. CONCLUSIONS: This clinical evaluation, even if retrospective, confirmed that simultaneous pancreas-kidney transplantation has a protective effect against cardiovascular mortality in diabetic recipients affected by end-stage renal disease.

Multivariate analysis of factors affecting patient and graft survival after renal transplant.

AIM: To evaluate factors affecting patient and kidney survival after renal transplant. PATIENT AND METHODS: Among 361 patients undergoing renal transplant: 52% (n = 189) were simultaneous with pancreas transplant (SPKT group) and 48% (n = 172), a kidney transplant alone (KT group). Out of 361 patients, 75% (n = 270) were diabetics. The patients were 220 (61%) men and 141 (39%) women of mean age 41 +/- 9 years. The mean time of dialysis was 42 +/- 21 months (range 0 to 126), and the mean duration of diabetes 24 +/- 7 years (range 5 to 51). A Cox regression analysis was done. RESULTS: The multivariate analysis revealed that in the final model diabetes and donor age were significant predictors of kidney graft survival; moreover, diabetes and recipient age were predictors of patient survival. Overall patient survival was significantly greater among nondiabetic patients (P = .002) or in diabetic patients who received SPKT, when compared with diabetics in whom only the kidney was transplanted (P = .001). CONCLUSIONS: Diabetes and donor age were independent prognostic factors affecting kidney graft survival after renal transplant, and recipient age and diabetes were prognostic factors affecting patient survival. Combined pancreas and kidney transplantation should be offered to patients with end-stage diabetic nephropathy.

Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma.

PURPOSE: To assess the impact on local control and survival of intraoperative radiotherapy (IORT) in resectable pancreatic adenocarcinoma. METHODS AND MATERIALS: The outcome of 127 patients surgically treated with curative intent combined with IORT was compared with the therapeutic results of 76 patients treated with surgery as exclusive treatment. RESULTS: Operative mortality and morbidity were similar in IORT and no-IORT patients. In 49 patients with locally limited disease (Stage I-II; LLD), IORT (n = 30) reduced the local failure rate and significantly prolonged time to local failure (TTLF), time to failure (TTF), and overall survival (OS) with respect to surgery alone (n = 19). The multivariate analyses, stratifying patients by age, tumor grade, resection margins, chemotherapy, and external-beam radiotherapy use, confirmed the independent impact of IORT on outcome. In patients with locally advanced disease (Stage III-IVA; LAD), IORT had an impact on local failure rate and on TTLF when combined with beam energies of greater than 6 MeV, whereas no effect on TTF and OS was observed. CONCLUSION: IORT did not increase operative mortality and morbidity and achieved a significant improvement in local control and outcome in patients with LLD. In patients with LAD, beam energies greater than 6 MeV prolonged TTLF.

Urticaria pigmentosa: a clinical, hematopathologic, and serologic study of 30 adults.

Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated with systemic involvement, most often of the bone marrow. The incidence of systemic involvement is not yet well established, however. To address this question, we subjected a group of 30 adults with histologically proved UP to a retrospective study that included history, physical examination, laboratory tests including cytokine measurements, radiologic examinations, and bone marrow biopsies. The most frequently associated clinical symptoms were recurrent flush episodes in 16 of 30 patients, alcohol intolerance in 13, pruritus in 10, and gastrointestinal problems in 11 (recurrent diarrhea, 8 patients; gastritis, 2 patients; and history of peptic ulcer, 1 patient). Of the 30 patients, 18 (60%) had mast cell infiltrates of the bone marrow (nodular type, 10 patients; diffuse interstitial type, 8 patients). Bone marrow involvement was not correlated with massive cutaneous mast cell infiltration, clinically or histologically, or with the incidence of clinical symptoms and associated hematologic disorders. None of the patients had experienced progression of clinical symptoms, skin or organ involvement, or development of hematologic malignant neoplasms since UP was first diagnosed (10 years on average). Urticaria pigmentosa was found associated with mast cell infiltration of the bone marrow in 18 patients (60%). However, bone marrow involvement does not seem to predict adverse clinical course.

Isolation of the elusive pig islet.

This study describes a procedure for large scale isolation of swine islets. The reported results are from 15 consecutive isolations. The glands were removed from live animals with no warm ischemia, and the pancreata were digested by a modification of the automated method for human islet isolation. It was possible to separate an average of 690,000 +/- 279,429 islets per pancreas corresponding to 10,360 +/- 4034 islets per gram of pancreas with a volume of 714 +/- 480 mm3. After purification the recovery was 255,000 +/- 32,407 islets corresponding to 4,000 +/- 567 islets per gram of pancreas. Purity of the final preparation was 80% to 95% islets. Insulin content resulted in an average of 146.8 +/- 78 U before purification and 71 +/- 53 U after purification. After a 10 mm3 aliquot of the final preparation was transplanted under the renal subcapsular space of seven nude mice with diabetes, normoglycemia occurred in six of the mice. Thirty days after transplantation, nephrectomy of the kidneys bearing the grafts produced a rapid return to the diabetic state in all cases. This method makes it possible to provide large numbers of intact swine islets for preliminary studies of prevention of the rejection of pig islet xenograft by immunoalteration and immunoisolation procedures.

Pathogenesis of hepatic encephalopathy and hyperdynamic syndrome in cirrhosis. Role of false neurotransmitters.

We sought to determine whether false neurotransmitters (FNTs) play an important role as determinants not only of hepatic encephalopathy but also of hyperdynamic syndrome in cirrhosis. A combined biochemical and hemodynamics study of 55 bleeding cirrhotic patients was made. We evaluated the aromatic and aliphatic branched-chain amino acids and octopamine serum levels as well as the hemodynamic measurements. The results show that there is a correlation between levels of serum octopamine and aromatic amino acids and hepatic coma: the higher the octopamine level, the deeper the hepatic coma. There is also a correlation between aromatic amino acids and cardiac index and total peripheral resistance. Furthermore, when a narrowing of arteriovenous difference in oxygen occurs and oxygen consumption decreases, there is an increase not only in the level of aromatic amino acids, but also in octopamine level, suggesting an important linkage between hemodynamic and metabolic impairment.

Factors affecting survival and long-term outcome in the cirrhotic patient undergoing hepatic resection for hepatocellular carcinoma.

AIMS: Prognostic analysis of hepatocellular carcinoma (HCC) in the cirrhotic patient undergoing hepatic resection is necessary in order to determine the clinical effect of hepatectomy on prognosis. PATIENTS AND METHODS: Univariate and multivariate retrospective analyses were performed in 51 cirrhotic patients (38 men, 13 women; mean age 65 years, range 43-81 years) with supervening HCC undergoing hepatic resection between January 1993 and December 1997. RESULTS: Segmental liver resection was performed in 39 patients (76%) with non-anatomical (wedge) resections in the remainder of cases. The post-operative mortality rate was 8%. The tumours recurred in 23 patients (45%), with 12 patients (52% of recurrences) recurring within 1 year of surgery and 22 patients (96% of recurrences) within 3 years. Recurrent disease was most frequently intrahepatic (22 patients). Significant risk factors for recurrence were micro/macro vascular invasion, and symptoms. CONCLUSIONS: The recurrence rate of hepatocellular carcinoma in patients with cirrhosis undergoing surgical resection alone is high and actuarial survival at 4 years is low. Other approaches to the treatment of hepatocellular carcinoma in patients with cirrhosis require consideration.

Causes of anergy in the surgical patient and its relationship to postoperative sepsis.

Between June 1981 and June 1983 the delayed hypersensitivity response (DHR) was studied in 401 patients considered for major surgical procedure: 320 of these patients underwent surgery. The incidence of sepsis and postoperative mortality was higher in anergic and relative anergic patients than in normal responders (p<0.001). To evaluate whether DHR depression in cancer patients was due to the direct effect of cancer or to tumour-linked malnutrition, the 401 patients were divided into 4 groups: 1) 140 malnourished cancer patients, 2) 51 malnourished non-cancer patients, 3) 120 well-nourished cancer patients and 4) 90 well-nourished non-cancer patients. The mean age was not significantly different for the 4 groups. The results showed a relationship between DHR and nutritional status (p<0.001). The tumour-related DHR impairment disappeared when the cancer and non-cancer patient groups were homogeneous with regard to their nutritional status. Therefore, the tumour was able to determine the DHR depression because of the cancer-linked malnutrition. We did not observe any relationship between local extension of the tumour and lymph node involvement and DHR depression. In 90 well-nourished non-cancer patients the relation between DHR and age was investigated. The incidence of anergy and relative anergy was higher in patients over 59 years than in patients under 60 years (p<0.001).