Individual participant data pooled-analysis of risk factors for recurrence after neoadjuvant radiotherapy and transanal local excision of rectal cancer: the PARTTLE study.

BACKGROUND: An organ-preserving strategy may be a valid alternative in the treatment of selected patients with rectal cancer after neoadjuvant radiotherapy. Preoperative assessment of the risk for tumor recurrence is a key component of surgical planning. The aim of the present study was to increase the current knowledge on the risk factors for tumor recurrence. METHODS: The present study included individual participant data of published studies on rectal cancer surgery. The literature was reviewed according to according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data checklist (PRISMA-IPD) guidelines. Series of patients, whose data were collected prospectively, having neoadjuvant radiotherapy followed by transanal local excision for rectal cancer were reviewed. Three independent series of univariate/multivariate binary logistic regression models were estimated for the risk of local, systemic and overall recurrence, respectively. RESULTS: We identified 15 studies, and 7 centers provided individual data on 517 patients. The multivariate analysis showed higher local and overall recurrences for ypT3 stage (OR 4.79; 95% CI 2.25-10.16 and OR 6.43 95% CI 3.33-12.42), tumor size after radiotherapy > 10 mm (OR 5.86 95% CI 2.33-14.74 and OR 3.14 95% CI 1.68-5.87), and lack of combined chemotherapy (OR 3.68 95% CI 1.78-7.62 and OR 2.09 95% CI 1.10-3.97), while ypT3 was the only factor correlated with systemic recurrence (OR 5.93). The analysis of survival curves shows that the overall survival is associated with ypT and not with cT. CONCLUSIONS: Local excision should be offered with caution after neoadjuvant chemoradiotherapy to selected patients with rectal cancers, who achieved a good response to neoadjuvant chemoradiotherapy.

[Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head and papilla of Vater]. / Duodenocefalopancreatectomia per adenocarcinoma della testa del pancreas e della papilla di Vater.

AIM: The authors report their consecutive experience in the surgical management of adenocarcinoma (ADC) of head of pancreas and papilla of Vater, in order to review the available literature. METHODS: One hundred and seventy cases (131 in the head of pancreas and 39 in the papilla of Vater) were operated upon for ADC by radical pancreaticoduodenectomy in the period 1972-2005. The stomach was resected in 81 patients (47.7%) and the pylorus was preserved in 89 (52.3%). Follow-up was completed in all patients. RESULTS: Postoperative morbidity was reported in 66 patients (38.8%) and pancreatic fistulae were observed in 39 patients (22.9%). Postoperative mortality was 9.4% (16 patients), but in the last 10 years it was reduced to 4.1% (4/97 patients). Five-year survival for pancreatic ADC was 75% in stage IA, 43.9% in stage IB and IIA, 3.2% in stage IIB. In ADC of the papilla of Vater, for the same stages, the 5-year survival rates were 54.4%, 51.4%, 0% and 37.5%, respectively. None of the III-staged patients survived at a 5-year follow-up in both groups. CONCLUSIONS: Preoperative studies should include laparoscopy with cytological examination of peritoneal lavage, while preoperative biliary drainage is rarely indicated in case of obstructive jaundice. The Wirsung duct has to be anastomosed directly to the jejunum and the pancreatic section needs to be checked. Extended lymphadenectomy, in addition to the standard peripancreatic excision, is seldom indicated, there is no controindication to pylorus preservation and Wirsung drainage is not necessary. This operation should be performed in Centres with substantial experience.

Conservative surgical treatment in rectal cancer after complete pathological response to neoadjuvant treatment. Prospective observational study.

In 2012 we started a prospective observational study at San Giovanni Addolorata Hospital in Rome for patients with rectal cancer with complete response to neoadjuvant therapy (nCRT). In our, IRB approved protocol, patients are evaluated at time 0 by physical, endoscopic, pathological and radiological examinations. 6 weeks after completion of nCRT they are re-evaluated. In case of persistence or progression of disease patients undergo surgery with Total Mesorectal Excision. In case of complete or major clinical response they are re-evaluated at 12 weeks and subjected to transanal surgical excision to confirm complete pathological response (pCR). If tumor is found in the transanal excision specimen the patient is operated upon whereas patients with pCR are followed up at 3 months interval.

Management of obstructive colorectal cancer with endoscopic stenting followed by single-stage surgery: open or laparoscopic resection?

BACKGROUND: About one-third of patients with colorectal carcinoma present with acute colonic obstruction requiring emergency surgery. Current surgical options are intraoperative lavage and resection of the colonic segment involved with primary anastomosis, subtotal colectomy with primary anastomosis, colostomy followed by resection, and resection of the colonic segment involved with end colostomy (Hartmann's procedure) requiring a second operation to reconstruct the colon. These procedures present risks and a poor quality of life. Endoscopic colonic stent insertion can effectively decompress the obstructed colon, allowing bowel preparation and elective resection. METHODS: The authors present their experience managing 31 patients with obstructing colorectal cancer who underwent endoscopic colonic decompression with self-expanding metallic stents. A total of 16 patients were treated with open resection, and 6 underwent a laparoscopic resection. The remaining 9 patients were managed with endoscopic palliation and adjuvant therapy. Of the 31 patients, 17 were treated with postoperative chemotherapy. RESULTS: The mean interval between stenting and surgery was 11 days (range, 1-21 days). There was no intraoperative morbidity. The incidence of postoperative morbidity was 20% for open surgery and 0% for laparoscopic surgery. The mean postoperative hospital stay was 13 days for the open surgery group, and 7 days for the laparoscopic group (p = 0.003). The hospital mortality rate was 3.2%. Follow-up evaluation was completed for 96% of the patients. The minimum follow-up period was 15 months. All the patients in the palliative group died of disease, with a median survival of 3 months. Of the 22 surgically treated patients, 17 (77%) are alive at this writing. CONCLUSION: This initial experience shows that after successful endoscopic stenting of malignant colorectal obstruction, elective surgical resection can be performed safely. The presence of the endoluminal stent does not prevent a laparoscopic approach. The combined endoscopic and laparoscopic procedures are a less invasive alternative to the multistage open operations and offer a faster recovery.

Outcomes for early rectal cancer managed with transanal endoscopic microsurgery: a 5-year follow-up study.

BACKGROUND: This study aimed to evaluate the long-term risk of local and distant recurrence as well as the survival of patients with early rectal cancer treated using transanal endoscopic microsurgery (TEM). METHODS: The study reviewed 69 patients with Tis/T1/T2 rectal cancer treated using full-thickness excision between 1991 and 1999. The pathology T-stages included 25 Tis, 23 T1, and 21 T2. The median follow-up period was 6.5 years (range 5-10.2 years). RESULTS: The overall local recurrence rate was 8.7%. The 5-year local recurrence rate was 8% for Tis, 8.6% for T1, and 9.5% for T2. All six patients with recurrence were managed surgically. The 5-year disease-specific survival rate was 100% for Tis, 100% for T1, and 70% for T2. The overall cancer-related mortality rate was 7.2%. CONCLUSIONS: After local excision of early rectal cancer, a substantial local recurrence rate is observed. Patients with recurrent Tis/T1 cancers who undergo a salvage operation may achieve good long-term outcome. Local treatment without adjuvant therapy for T2 rectal cancers appears inadequate.

Nuclear DNA analysis of insulinomas and gastrinomas.

The potential for malignancy of an islet cell tumor of the pancreas is difficult to cytologically judge when one evaluates only the primary lesion, because a malignant condition is usually determined by the presence of regional or distant metastases. Nuclear DNA cytometric measurements have proved helpful both in the evaluation of the malignant potential of other endocrine and nonendocrine lesions and in the determination of the "aggressiveness" of these tumors. Thirty-six islet cell tumors or their metastases from 25 patients were studied. Eleven patients had insulinomas and typical insulinoma syndromes, and 14 others had gastrinomas with the Zollinger-Ellison syndrome. Tissue from each tumor was stained by the Feulgen technique, and nuclear DNA cytometry was performed by means of the microTICAS system designed by the Cytopathology Laboratory of the University of Chicago. Ploidy measurements of insulinomas, taken alone, did not discriminate well between benign and malignant states. However, the single malignant insulinoma could be clearly recognized, for it was one of only two lesions in that group with 5N-exceeding rate (5N-ER) values of 1% or greater. (5N-ER is defined as the percentage of aneuploid nuclei with nuclear DNA content greater than 5N.) On the other hand, seven of eight malignant gastrinomas had ploidy values of 2.5N or greater (our definition of an aneuploid state) and/or had 5N-ER values of 1% or greater, while five of six benign gastrinomas had ploidy values of less than 2.5N and had 5N-ER values of 0%. In addition, the two most aggressive tumors had the highest ploidy and 5N-ER values. Nuclear DNA cytometric studies appear to offer promise as an aid in the evaluation of pancreatic islet cell tumors, particularly gastrinomas.

Growth factor production by arterial and vein grafts: relevance to coronary artery bypass grafting.

BACKGROUND: Occlusion caused by myointimal hyperplasia, atherosclerosis, or both is the main reason for late failure of saphenous vein coronary artery bypass grafts. On the other hand, internal mammary artery grafts are usually spared from atherosclerosis. Evidence exists that platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are involved in the genesis of myointimal hyperplasia and atherosclerosis. The aim of this study was to assess the production of PDGF and bFGF by arterial and vein grafts. METHODS: In 20 inbred Lewis rats alpha 1 cm long segment of arterial graft was interposed at the level of the abdominal aorta. In a control group of 20 Lewis rats alpha 1 cm long segment of vein graft was implanted at the level of the abdominal aorta. Animals were killed 4 weeks after operation, and the grafts were studied in serum-free organ culture to assess the production of PDGF and bFGF. RESULTS. Arterial grafts produced a smaller quantity of PDGF and bFGF than vein grafts (p < 0.01) Higher mitogenic activity was present in the conditioned media from vein grafts than in the conditioned media from arterial grafts (p < 0.001). A large amount of myointimal hyperplasia was present in all vein grafts. CONCLUSIONS: This phenomenon could explain the rarity of atherosclerotic changes in internal mammary coronary bypass grafts.

Extended left hepatectomy with vascular exclusion.

Extended left hepatectomy represents the most extensive and difficult type of hepatic resection. The risk of hemorrhage during transection of the hepatic parenchyma and subsequently the risk of biliary complications may be minimized with use of hepatic vascular exclusion.

Renal carcinoma with a solitary synchronous contralateral adrenal metastasis: a case report.

A case of synchronous contralateral adrenal metastasis of renal cell carcinoma occurring in a 64-year-old male is reported herein. The patient underwent a left transperitoneal nephrectomy for renal cell carcinoma and right adrenalectomy. The postoperative course was uneventful. To our knowledge this is the 14th case of contralateral adrenal metastasis of renal cell carcinoma in the international literature.

The role of surgery in the treatment of primary gastric lymphoma.

BACKGROUND: The aim of the study was to analyze the results of surgical treatment in early and advanced primary gastric lymphoma and to evaluate predictive factors for long-term outcome. MATERIAL AND METHODS: A retrospective study of 92 patients resected for primary gastric lymphoma was conducted. Sixty-eight (74%) patients underwent a curative resection 10 (11%) patients had palliative resection and 14 (15%) patients were deemed unresectable: 33 patients (36%) had a stage IE tumor, 12 (13%) stage IIE1, 22 (24%) IIE2 and 25 (27%) stage IVE. RESULTS: Follow-up ranged from 1 to 336 months (means 44 +/- 70 months, median 18 months). Cumulative actuarial 10-year survival rate was 49.1%. Ten-year actuarial survival rates were 78.9% for stage IE and 100% for stage IIE1 whereas 5-years survival rates were 0% for stage IIE2 and 21.7% for stage IVE (P < 0.00001). CONCLUSION: Surgical treatment is the front line therapy for IE and IIE1 stages of primary gastric lymphoma.

Angiogenesis as a prognostic indicator in pancreatic ductal adenocarcinoma.

BACKGROUND: Angiogenesis has gained wide acceptance as a reliable prognostic factor in several solid tumors. However, to date, experience in pancreatic adenocarcinoma is limited. MATERIALS AND METHODS: Specimens from 45 patients radically operated on at our departments from 1988 to 1997 were stained immunohistochemically with the antibodies anti-mutant p53, anti-bcl2, anti Ki67 and anti-CD31. All the slides were reviewed by the same pathologist without knowledge of the patients' outcome. RESULTS: Mutant p53, Ki67 index and vessel count were significantly related to tumoral behaviour and patients' outcome. Among patients with nodal involvement (Stage III), cumulative survival between hypovascular and hypervascular subgroups differed significantly (p = 0.03). Angiogenesis was independent from TNM in assessing the patients'prognosis at COX analysis (p = 0.02). CONCLUSION: In patients with pancreatic adenocarcinoma, angiogenesis is a reliable indicator of tumor extension, lymph node status and survival. Its evaluation as a common procedure may contribute to a further improvement in the management of these patients and to a proper selection of those who could benefit from different follow-up protocols or adjuvant treatment.

The laparoscopic approach with antireflux surgery is superior to the thoracoscopic approach for the treatment of esophageal achalasia. Experience of a single surgical unit.

BACKGROUND: Since its first description in the early 1990s, minimally invasive Heller myotomy has become the treatment of choice for esophageal achalasia. We report the experience of a single unit with thoracoscopic Heller myotomy (THM) and laparoscopic Heller myotomy (LHM) and we analyze the short- and long-term surgical outcomes in patients treated by each of the two approaches. METHODS: We evaluated retrospectively 33 patients who underwent surgical treatment for achalasia. Sixteen patients underwent THM without an antireflux procedure, and 17 patients underwent LHM and partial anterior fundoplication (n = 10) or closure of the angle of His (n = 7). RESULTS: Mean operative time was significantly shorter for LHM than for THM (150 vs 222 min, respectively) (p = 0.0001). Mean hospital stay was significantly shorter after LHM than after THM (2.0 +/- 1.0 vs 5.1 +/- 2.2 days, respectively) (p = 0.0001). Six of 16 patients (37.5%) in the THM group experienced persistent or recurrent dysphagia compared to one of 17 patients (5.8%) in the LHM group (p = 0.04). Heartburn developed in five patients (31.2%) after THM and in one patient (5.8%) after LHM (p = 0.07). Regurgitation developed in four patients (25%) after THM and in one patient (5.8%) after LHM (p = 0.149). Lower esophageal sphincter (LES) basal pressure decreased significantly from 30.1 +/- 5.07 to 15.3 +/- 2.1 after THM and from 32.1 +/- 5.9 to 10.5 +/- 1.7 after LHM (p = 0.0001). Mean esophageal diameter was significantly reduced after LHM compared to THM (from 54.5 +/- 5.7 mm to 27.1 +/- 3.3 mm vs 50.8 +/- 7.6 mm to 37.2 +/- 6.9 mm, respectively) (p = 0.0001). CONCLUSION: In our experience, LHM is associated with a shorter operative time and a shorter hospital stay, and it is superior to THM in relieving dysphagia. LHM with partial anterior fundoplication should be considered the treatment of choice for achalasia.

Selection, establishment and characterization of cell lines derived from a chemically-induced rat mammary heterogeneous tumor, by flow cytometry, transmission electron microscopy, and immunohistochemistry.

In order to isolate, characterize, and establish culture cell lines with different diagnostic and prognostic significance, derived from multiclonal neoplasms, a ductal infiltrating mammary tumor was induced in rats by 7,12-dimethylbenz[a]anthracene. Clones with different DNA/protein content, being the DI of 1.16, 1.30, and 1.60, respectively, were observed in the primary tumor. Biparametric flow cytometry suggested that the clone at 1.30 is made up of two subpopulations with different protein and slightly different DNA contents. The culture, after a few passages, exhibited the presence of aneuploid cells and the absence of diploid components, demonstrating that only tumor cells survived. The limiting dilution method gave rise to four lines with DI of 1.16, 1.25, 1.30, and 1.50; a mean chromosome number of 45, 46, 47, and 88, respectively; and different morphological and ultrastructural features. These characteristics were stable during the experimental procedure, that is, for about 20 passages. Conversely, the detection of cytoskeletal proteins indicated that the tumor epithelial cells underwent early dedifferentiation into sarcoma-like cells showing markers of stromal cell type and thus exhibiting phenotypic instability in vitro, a feature reported in many advanced human breast cancers in vivo. In conclusion, this cellular model represents the in vivo situation and appears suitable for in vitro studies of tumor cell characteristics and might be used to predict clinical behavior.

In vitro proliferation and in vivo malignancy of cell lines simultaneously derived from a chemically-induced heterogeneous rat mammary tumor.

Identification of clones in primary tumors responsible for proliferation, invasion, and metastasis was carried out. Four different aneuploid established cell lines derived from a ductal infiltrating mammary rat tumor induced by 7,12-dimethylbenz[a]anthracene were studied for proliferative and growth features in vitro and for tumorigenic and metastatic potential in vivo in nude mice. Clones, named RM1, RM2, RM3, and RM4, were characterized by different proliferative activity. Clone RM1 showed the highest proliferative activity by both tritiated thymidine incorporation and S-phase flow cytometry, followed by clone RM4. Conversely, clones RM2 and RM3 showed a lower proliferation rate. Growth-promoting activity, tested on 3T3 Swiss cells, was high in all clones, although RM1 showed significantly lower growth factors-releasing activity. Nude mice tumorigenesis demonstrated a strong tumor induction of line RM1 (100% of the mice after 47 +/- 7 d) and a slightly lower tumor induction of line RM4 (70% of the mice after 69 +/- 9 d). Line RM3 showed tumor induction in 40% of the mice after 186 +/- 16 d. Lines RM2 showed no tumor induction. Metastasis occurred in mice treated with line RM1 only. Therefore, tumorigenesis and metastasis correlate with proliferation but not with the release of growth factors. In conclusion, flow cytometry monitoring of clones from heterogeneous primary tumors proved to be a suitable model for the study of in vivo malignancy and in vitro proliferation.

Local excision of rectal tumours with transanal endoscopic microsurgery.

Transanal Endoscopic Microsurgery (TEM) is a novel technique, first introduced by Buess and coworkers in 1983 for the treatment of large sessile polyps of the rectum. Due to the excellent results the indication was then extended also for the removal of low risk early adenocarcinomas (pT1, G1-G2). TEM allows, by using an operative proctoscope of an outside diameter of only 4 cm., all the conventional surgical manoeuvers within the rectal lumen, up to 20 cm. from the anal verge. The Authors report a consecutive series of 53 patients submitted to TEM over a 37 month period; apart from 7 patients excluded for different reasons, postoperative diagnosis showed 30 adenocarcinomas (65.2%), 15 adenomas (32.6%) and 1 epidermoidal carcinoma (2.2%). The low recurrence rate observed both for adenomas (0%) and pT1 adenocarcinomas (9%) coupled with the optimum vision allowed by the 6-fold magnified stereoscopic view, make this technique the method of choice for selected patients with these kind of pathologies.

[Multilocular benign cystic nephroma. Case report and review of the literature]. / Il nefroma cistico multiloculare benigno. Contributo casistico e revisione della letteratura.

The authors report a case of multilocular cystic nephroma. According to the literature this is a rare lesion, which may be diagnosed any time during life, showing the same prevalence in childhood as in adults. Multilocular cystic nephroma is usually an unilateral lesion. Aetiology is unknown and preoperative ultrasonography and roentgenographic studies frequently led to misdiagnosis. Surgical excision of the cyst, with kidney sparing, is the therapy of choice, however nephrectomy is advised when intraoperative biopsy is ambiguous.

[Occlusion of the duct with a fibrin glue and preservation of the pylorus after resection of the duodenum and head of the pancreas for periampullary carcinoma]. / Occlusione del dotto con colla di fibrina e conservazione del piloro dopo duodenocefalopancreasectomia per carcinoma periampollare.

Dehiscence of pancreaticojejunostomy represent the main technical postoperative complication after duodenocephalopancreasectomy for periampullary carcinoma. The incidence of this complication is particularly high in cases of narrow duct and a tender pancreatic gland. In this case the authors suggest a technique of occlusion of the residual pancreatic stump using a fibrin sealant. This approach was utilized in 6 consecutive patients affected by resectable periampullary carcinoma. No postoperative mortality was observed. Pancreatic fistula developed in 5 cases and all of them resolved spontaneously in 1-4 months. The sixth patient underwent, at 3 months p-o, a CT-guided percutaneous aspiration of an intraabdominal fluid collection and with no further complications. 3 patients died at 3, 9 and 11 months because of liver metastases. Currently 3 patients are alive and apparently disease free at 25, 7 and 5 months. Pancreatic endocrine function was assessed in 5 patients at 3 months p-o. Blood glucose and insulin, glucagon and C-peptide plasma levels, all fasting and 1 our after a standard meal, revealed a normal glucose metabolism. The authors conclude that, since fibrin sealant avoids the pancreatic fibrosis which could be induced by non-absorbable polymers and the benign evolution of this type of pancreatic fistula, this method for handling the exocrine secretion is a safe and satisfactory approach which is particularly indicated in case of a pancreatic stump at risk for intestinal anastomoses.

[Ovarian pregnancy]. / La gravidanza ovarica.

A case of ovarian pregnancy in a patient with intrauterine device is reporter. The patient was hemodynamically instable and immediate laparotomy was indicated. The treatment was left oophorectomy. Ovarian pregnancy is a rare form of ectopic pregnancy in which the gestational sac is implanted in the ovary. The incidence appears to be of 1 to 3 per cent of all ectopic gestations with a frequency of one in 7000 to 40000 deliveries and it is now believed to occur four times more frequently than previously thought. It has been suggested that the increasing incidence is caused by the use of IUD. In contrast to patients with tubal pregnancy traditional risk factors such as pelvic inflammatory disease, prior surgical procedure upon the pelvis may not apply. The clinical signs are similar to those found in tubal pregnancies and in hemorrhagic corpus luteum cysts. The treatment is emergency laparatomy followed by oophorectomy in many instances. When the patient is hemodynamically stable laparoscopy and the ovarian wedge resection should be the treatment of choice.

[Sarcomatoid renal carcinoma. A case report]. / Il carcinoma renale sarcomatoso. Presentazione di un caso.

Renal sarcomas are rare tumors. Prognosis is overall dismal. Adjuvant therapies should follow radical nephrectomy but no standardized regimen has been at present defined. We report a case of a patient affected by a sarcomatoid renal tumor to detect the best therapeutic approach to this rare tumor.

[Antibiotic prophylaxis in the surgical treatment of inguinal hernia: need or habit?]. / La profilassi antibiotica nel trattamento chirurgico dell'ernia inguinale: necessità o abitudine?

BACKGROUND: Prophylactic antibiotics are recommended for clean-contaminated and selected contaminated surgery. In clean surgery antibiotics are suggested if the operation involves the insertion of prosthetic devices and a potential infection is expected to cause serious morbidity or mortality. Inguinal hernia repair is a clean operation, infections are rare; they can usually be cured without removing the prosthesis and recurrence is uncommon even after removal of the mesh. Aim of the study is to evaluate whether the lack of antimicrobial prophylaxis increases the risk of postoperative infections in patients treated for groin hernia, compared to those treated with prophylaxis. METHODS: One hundred and forty-eight patients underwent inguinal hernia repair with mesh: 64 patients (43%) received 2 g cefotaxime by intravenous bolus about 30 minutes before the operation, 84 patients (57%) did not receive any antimicrobic prophylaxis. Mean follow-up was 13 months (range 1-31 months) for both groups. RESULTS: We did not observe any major complication. Among both groups, no patient had developed infection at one week and one month after surgery. CONCLUSIONS: In personal experience, any advantage in terms of prevention of infections with antibiotic prophylaxis in patients operated on for groin hernia has been observed. A review of the literature showed no general agreement on this subject with different risk of infections in different trials. A new prospective randomized trial is necessary to clarify this topic.