Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

The role of antral resection in sleeve gastrectomy. An observational comparative study.

OBJECTIVE: The role of antral resection (AR) in laparoscopic sleeve gastrectomy (LSG) is still a greatly debated topic in the literature. The aim of this study was to evaluate the results and complications of AR in LSG. PATIENTS AND METHODS: In this observational comparative study, 101 patients who underwent LSG were divided into two groups based on the extent of antral resection: 1 cm from the pylorus (1-DP group), or 6 cm from the pylorus (6-DP group). The %EWL (%Excess weight loss), resolution of T2D (Type 2 Diabetes Mellitus) and GLP-1 were investigated 48 hours before surgery and 3, 6 and 12 months after LSG. Postoperative complications in the first 30 days after surgery were also compared between the two groups using the Clavien-Dindo (CD) score. RESULTS: A significant difference in %EWL was observed at 3 and 6 months in favor of the 1-DP group (38.9% and 57.8%, respectively) compared to the 6-DP group (31.4% and 49.7%, respectively). No difference in T2D resolution was observed between two groups during the follow-up period, with similar changes in GLP-1. Statistically significant differences were found between 1-DP and 6-DP group for the reintervention rate (CD III, 7.7% and 1.9%, respectively; p = 0.02) and life-threatening complications requiring intensive care unit management (CD IV, 3.8% and 0%, respectively, p = 0.03). CONCLUSIONS: In LSG, sparing the antrum is associated with a significant reduction in the rate of postoperative complications, but the metabolic and weight results are comparable to those for antrum resection.

Successful laparoscopic trans-peritoneal repair of an incisional inguinal hernia, resulting from deep lymph node dissection for melanoma: A case report.

INTRODUCTION: Deep pelvic lymph node dissection for cancer may result in incisional inguinal hernias. We present a case report of successful laparoscopic trans-peritoneal repair of a large ventral inguinal hernia that developed following ileo-inguinal lymph node dissection (CLND) for melanoma. CASE PRESENTATION: A successful 3 port laparoscopic trans-peritoneal procedure was performed on a 56-year-old female for the repair of a left inguinal hernia, developed 13 months following CLND for melanoma. The large oval 18 × 14 cm inguinal defect, with superior margins bordering the conjoint tendon and inferior margins bordering the ileo-psoas muscle, femoral vessels and nerve, was not closed in order to avoid excessive tension and was repaired by fixing a 25 × 20 cm intra-peritoneal mesh to abdominal borders at superior and lateral margins with permanent fasteners and at the inferior margin by a cyanoacrylate-glued overlap to protect femoral vessels and nerves from damage. No hernia recurrence was observed 8 months following this procedure. DISCUSSION: Incisional inguinal hernias, following CLND, are rare but present a challenge to surgeons due to the difficulty in identifying both anatomical plains and safe sites for stable repair. CONCLUSIONS: We report a laparoscopic trans-peritoneal approach for the safe, reproducible and efficacious repair of incisional inguinal hernias that result from CLND. In our opinion prevention of hernia recurrence can be achieved by a intraperitoneal large mesh fixed at superior and lateral margin borders with permanent fasteners and using cyanoacrylate glue to overlap inferior margin borders in order to prevent vessels and/or nerve injury.

Advanced Merkel cell carcinoma of the lower extremity treated with surgery and isolated pelvic and limb perfusion using Melphalan: A case of unexpected long-term survival.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare, neuroendocrine skin tumor, with high frequency of locoregional recurrence, metastases, and poor prognosis. Locoregional MCC recurrence in the extremities can pose considerable treatment challenges. We report a case of long-term survival in a female patient with recurrent MCC of the leg, treated with surgery and locoregional chemotherapy. PRESENTATION OF CASE: A 73-year-old female with cirrhosis and hepatitis C, developed cutaneous MCC in the left inferior limb. This patient initially received surgical treatment, with subsequent negative sentinel lymph-node biopsy in another center, one-month prior recovery in our department, and arrived with 4 new limb nodules, cranially to the previously treated area, without distant metastases or inguinal lymph node recurrence. This patient was not eligible for immunotherapy due to active hepatitis upon treatment with NS5B inhibitors, or eligible for systemic chemotherapy or radiotherapy due to severe neutropenia and was, therefore, subjected to surgical resection combined with Isolated Pelvic and Limb Perfusion (IPLP) with Melphalan. Histological evaluation confirmed MCC diagnosis and during the following 4 months, she developed further locoregional recurrences with homolateral inguinal lymph node involvement and was subjected to two additional rounds of surgery plus IPLP. DISCUSSION: All procedures were tolerated, systemic toxicities were temporary and subsequent clinical and radiological follow-up, following the last combined treatment, indicated that this patient was still alive and disease-free, at 56 months. CONCLUSION: In this case, surgery combined with locoregional Melphalan chemotherapy was an effective and repeatable treatment for recurrent MMC and resulted in unexpected long-term survival.

Hypoxic abdominal stop-flow perfusion in the treatment of advanced pancreatic cancer: a phase II evaluation/trial.

In the past decade, some authors have reported objective responses and prolonged median survival times using hypoxic abdominal perfusion (HAP) for the treatment of advanced pancreatic cancer. However, these promising results have not been confirmed by others, making it difficult to define the effectiveness of this loco-regional chemotherapy. The aim of this study, therefore, was to evaluate the response rate, time to disease progression and overall survival following HAP treatment of 22 consecutive patients with advanced pancreatic tumors. Within the period from 1999 to 2003, 22 patients with histological diagnosis of unresectable stage III/IV pancreatic cancer, not responsive to systemic chemotherapy, were treated with mitomycin C 30mg/m(2) and cisplatin 60mg/m(2) by HAP (stop flow technique). Immediately after perfusion, hemofiltration was performed to reduce systemic side toxic effects. Responses were assessed by CT-scan 30days from the end of treatment. Minor or partial responses were confirmed by a second CT-scan 4weeks later. Following 26 treatment cycles no death or technical complications were recorded; four patients (18.2%) achieved a partial response, 2 (9.1%) a minimal response and 13 (59.1%) stable disease. The remaining 3 patients (13.6%) showed progression of the disease. The median time to disease progression was 3 months (range 1-10). The median survival time from the start of regional chemotherapy was 6 months (range 1.9-16), with a 1-year survival rate of 9%. Our data show that HAP is a relatively effective second-line treatment for advanced stage pancreatic cancer with a low complication rate. We do not concur with the opinion of others that HAP is an inactive treatment approach. However, taking into account the invasiveness of this procedure, and associated morbidity and cost, HAP would not appear to be preferable to less invasive loco-regional chemotherapeutic alternatives.

Hypoxic pelvic perfusion with mitomycin C using a simplified balloon-occlusion technique in the treatment of patients with unresectable locally recurrent rectal cancer.

HYPOTHESIS: To evaluate the role of hypoxic pelvic perfusion in providing therapeutic options for palliation without relevant complications in a homogeneous group of patients with unresectable locally recurrent rectal cancer who are nonresponders or have disease progression after the standard treatments. DESIGN: Nonrandomized and noncontrolled phase II experimental study. SETTING: University hospital, L'Aquila, and the National Cancer Institute, Naples and Milan, Italy. PATIENTS: Eleven patients had symptomatic unresectable pelvic recurrent rectal cancer. The mean +/- SD product of the 2 maximum perpendicular diameters of the recurrent cancer was 24.2 +/- 11.0 cm(2) (range, 10-48 cm(2)). Tumor fixation to the pelvic side walls or proximal sacrum were the main criteria for unresectability. All patients were free from extrapelvic disease and had a life expectancy longer than 3 months. INTERVENTION: Patients were submitted to one course of pelvic perfusion with mitomycin C (MMC) (25 mg/m(2)) by means of a simplified balloon occlusion technique. A pharmacokinetic evaluation of the procedure was also performed. MAIN OUTCOME MEASURES: Response rate and time to disease progression were the primary endpoints; overall survival was the secondary endpoint. RESULTS: Mean +/- SD value of the ratios of pelvic MMC area under the plasma concentration curve (0 to 20 minutes) (AUC(0-20)) to systemic MMC AUC(0-20) was 13.30 +/- 6.52. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery or in the postoperative period. The response rate was 36.3% (95% confidence interval [CI], 6.5%-66.1%). Pain response rate was 45.4% (95% CI, 16.6%-76.2%). Median survival was 12.2 months (range, 5.7-19.5 months). Median time to disease progression was 6 months (range, 3-8 months). Two-year overall survival was 9.1%. CONCLUSIONS: Hypoxic pelvic perfusion with MMC is a safe and good palliative treatment for patients with unresectable locally recurrent rectal cancer. Further studies are necessary to establish if a different sequence in the multimodular treatment of these patients could be more useful.

Pharmacokinetics of mitomycin C in pelvic stopflow infusion and hypoxic pelvic perfusion with and without hemofiltration: a pilot study of patients with recurrent unresectable rectal cancer.

This pilot study was conducted to evaluate the advantage in drug delivery for regional chemotherapy in patients with unresectable recurrent rectal carcinoma by different methods. For this research, the pharmacokinetic advantages of mitomycin C delivery by four different methods were compared: intraaortic infusion with aortic stopflow; intraaortic infusion with inferior vena cava stopflow; intraaortic infusion with aortic and inferior caval vein stopflow (hypoxic pelvic perfusion); and hypoxic pelvic perfusion with hemofiltration. The results of this study indicate that pelvic stopflow infusion followed by hypoxic pelvic perfusion significantly increases mitomycin C concentrations in the blood coming from the tumor site. Also, use of hemofiltration reduces mitomycin C levels in peripheral blood after high-dose regional chemotherapy. Further investigations involving more patients should be carried out in the future to validate these results.

Regional plus systemic chemotherapy: an effective treatment in recurrent non-small cell lung cancer.

AIMS: This study was undertaken to determine the activity and toxicity of regional chemotherapy using an isolated thoracic perfusion (ITP) technique as second-line treatment for patients with advanced and recurrent non-small cell lung cancer (NSCLC). METHODS: Eighteen patients with relapsed NSCLC confined to the thoracic region entered the study and received regional chemotherapy using ITP plus low-dose systemic chemotherapy. All 18 patients had been pre-treated with some form of chemotherapy, surgery and/or radiotherapy. The cytostatic regimen had two components: (1) ITP using mitomycin 10 mg/m(2), navelbine 25 mg/m(2)and cisplatin 30 mg/m(2)on day 1; (2) systemic chemotherapy with 5-fluorouracil 250 mg/m(2)and cisplatin 20 mg/m(2)given as a continuous infusion over 24 h on days 1-4. RESULTS: All 18 patients were assessable for toxicity, tumour response and survival. There were 10/18 responses (CR 0; PR 10): a response rate of 56%. Side-effects were transient and acceptable. No treatment-related death occurred. Median survival was 21 months and the 1-year survival rate was 75%. CONCLUSIONS: Regional chemotherapy using ITP plus low-dose systemic chemotherapy is effective in recurrent advanced NSCLC, with an encouraging survival outcome.

Hemodynamic variations during thoracic and abdominal stop-flow regional chemotherapy.

AIMS: The aim of this study was to study hemodynamic modifications during thoracic and abdominal stop-flow regional chemotherapy and to evaluate the need for routine hemodynamic monitoring during such kind of procedures. METHODS: Thirty patients, aged 17-67 years, ASA physical status II-III, scheduled for thoracic (group A, n = 15), and abdominal (group B, n = 15) stop-flow regional chemotherapy were enrolled. Heart rate (HR), electrocardiogram lead I and V(5), end tidal carbon dioxide (ETCO(2)), arterial oxygen saturation (SaO(2)), systolic, diastolic and mean arterial pressure (SBP, DBP, MAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac output (CO), stroke volume (SV), stroke index (SI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), left cardiac work (LCW), right cardiac work (RCW), left cardiac work index (LCWI), right cardiac work index (RCWI), cardiac index (CI), and body O(2) consumption (VO(2)) were recorded. RESULTS: After aortic and inferior vena cava endovascular occlusion (T(1)), a significant reduction of CO and SV, associated with an increase of CVP, MAP, PAPM and PCWP were observed. A concomitant reduction of CI and increase of SVR and PVR were registered. The VO(2) was significantly reduced compared to basal values in both groups. After deflating aortic and vena cava balloons (T(2)), CO, SV and CI increased with respect to basal value p < 0.05) whereas MAP, CVP, PAPM, PCWP and calculated parameters (SVR, PVR) showed a significant reduction compared to T(1). The oxygen consumption was significantly higher than that of basal values p < 0.05. After hemofiltration (T(3)), all hemodynamic variables were comparable with the basal values. Modifications of direct and calculated parameters, during the stop-flow period, showed a similar trend in both study groups, without any statistically significant difference. No ST modifications at ECG were noted during all perioperative period. CONCLUSIONS: The results of this study have confirmed in both groups, the safety of stop-flow regional chemotherapy procedure, despite endovascular occlusion of the aorta and inferior cava vein. The hemodynamic and oxygenation changes are reversible and did not produce any ST modifications at ECG during all perioperative period. Routine pulmonary artery catheterization is thus unnecessary, except in high cardiac risk patients.

Significance of duplex/colour Doppler sonography in hepatic arterial chemotherapy for patients with liver metastases from colorectal carcinoma.

AIMS: The aim of the study was to evaluate the importance of duplex/colour Doppler ultrasound in a protocol of hepatic regional chemotherapy, by measuring the blood flow in the hepatic artery, portal vein, hepatic veins, and inferior caval vein of patients with unresectable liver metastases from colorectal carcinoma. METHODS: Thirty-nine consecutive subjects were selected for this study, including 21 patients who had unresectable histologically confirmed liver metastases from colorectal carcinoma (Group A), and 18 asymptomatic volunteers as normal controls (Group B). All subjects of Groups A and B were examined using duplex/colour Doppler sonography. After the ultrasound study, all patients of Group A were submitted to the administration of high dose mitomycin C into the hepatic artery, with concomitant detoxication of post-hepatic venous blood. RESULTS: The mean value of the hepatic artery blood flow was significantly higher (P=0.0009) in liver metastases patients (361 ml/min, SEM=24 ml/min) than in normal controls (245 ml/min, SEM=20 ml/min). Also, the mean Doppler perfusion index was higher in liver metastases patients than in normal controls. For each patient of Group A, the total dose of mitomycin C to be infused was calculated based on the blood flow in the hepatic artery. In this way the concentration of mitomycin C in the hepatic artery was always greater than 3 microg/ml. The duration of detoxication was calculated based on the blood flow in the inferior caval vein. For two patients only, the blood flow was lower than 1000 ml/min, with the necessity to protract the duration of detoxication over 2 hours. CONCLUSIONS: The measurement of the blood flow in hepatic vessels of patients with liver metastases seems to be very important in establishing the total dose of drug which has to be infused in hepatic arterial chemotherapy, and to determine the duration of concomitant detoxication of post-hepatic venous blood.

Loco-regional perfusions (stop-flow techniques): state of art and future.

The treatment of primary advanced or unresectable recurrent cancers is still one of the main medical challenges. The Stop-flow perfusion has been used as loco-regional chemotherapy based on blood supply blockage of the tumour-bearing area. The aim of the present paper is to report the personal experience in the clinical use of stop-flow perfusions and discuss about future perspectives of research. Since December 1997 more than 400 Stop-flow perfusions have been performed at University of L'Aquila. The following types of indication have been selected: recurrent unresectable rectal cancer, advanced pancreatic cancer, thoracic lymphomas, recurrent non-small cell lung cancer, recurrent pelvic and limb melanoma, and recurrent limb melanoma. In this paper results are presented in terms of median survival. For recurrent rectal cancer median survival was 12.2 months, for advanced pancreatic cancer 9.6 months, for thoracic lymphomas 16 months, for recurrent non-small cell lung cancer 21 months, for recurrent pelvic and limb melanoma 34.4 months, for recurrent limb melanoma 23.8 months. Based on these encouraging results, Stop-flow perfusion should be considered an effective approach to locally advanced cancers. Future fields of research include personalized chemotherapy and perfusion under hyperthermic conditions.

Thoracic stop-flow perfusion in the treatment of refractory non small cell lung cancer.

This study was undertaken to determine the survival of patients with unresectable and refractory non small cell lung cancer (NSCLC) submitted to thoracic stop-flow perfusion (TSP). Forty-five patients with NSCLC confined to thoracic region entered the study. All 45 patients had been pretreated with some form of chemotherapy and had progression of disease. The cytostatic regimen was mitomycin 10 mg/m2, navelbine 25 mg/m2 and cisplatin 60 mg/m2. In 39/45 patients, immediately after TSP, hemofiltration was performed to reduce systemic side effects There were 16/45 responses to the first TSP (CR 0; PR 16): a response rate of 35.6%. Median time to progression was 4 months. Median survival was 7.5 months.1-year survival rate was 36.4%, 2-year survival rate was 14%, and 3-year survival rate was 5.7%.

Intra-arterial hepatic chemoembolization in liver metastases from neuroendocrine tumors: a phase II study.

Neuroendocrine tumors, particularly those of gastrointestinal tract origin, have a predisposition for metastasizing to the liver, causing parenchymal substitution and paraneoplastic syndrome. Lipiodol embolization combined with anticancer drugs is a recent tool in regional therapy. It has been proven that chemoembolization reduces tumor bulk and hormone levels, and that it palliates the symptoms of many patients with liver-dominant neuroendocrine metastases. Beginning in December 1988, ten patients with unresectable and chemotherapy-refractory liver metastatic neuroendocrine tumors were treated with chemoembolization based on a mixture of lipiodol, mitomycin, cisplatin, epirubicin, followed by gelfoam powder and contrast media. Toxicity encountered included: upper right quadrant pain requiring narcotics, elevation of lactate dehydrogenase, alkaline phosphatase, and transaminases. One patient had liver abscess and persistent fever for 2 weeks. We obtained two complete remissions lasting 12 and 34 months and 5 partial remissions. The median survival was 22 months. Four patients had urinary elevation of 5-hydroxyindolacetic acid (5-HIAA). They showed more than a 75% decrease in urinary secretion after treatment. In a patient with transplanted liver we noticed a partial response lasting 7 months. We conclude that chemoembolization will improve the clinical condition of a significant percentage of patients with liver metastases, that future therapy of carcinoid tumors will be based on specific tumor biology and that treatment will be customized for each individual patient combining the use of cytoreductive procedures including radiofrequency ablation, laser treatment and chemoembolization.

Hepatic intra-arterial chemotherapy (HIAC) of high dose mitomycin and epirubicin combined with caval chemofiltration versus prolonged low doses in liver metastases from colorectal cancer: a prospective randomized clinical study.

A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22).

Pre-operative angiography in gastric cancer surgery with extended lymphadenectomy.

BACKGROUND/AIMS: The value of pre-operative angiographic evaluation in patients undergoing gastric cancer surgery with extended lymphadenectomy was assessed in a prospective study comparing exposed and unexposed groups of patients. METHODOLOGY: During the period from July 1991 to October 1997, 76 patients (Group A--exposed) were pre-operatively submitted to a digital subtraction angiography (DSA) after informed consent. Concurrently, 94 patients (Group B--unexposed) were included as an unexposed reference group. All patients underwent total or subtotal gastrectomy with D2 lymphadenectomy according to the guidelines proposed by the Japanese Research Society for Gastric Cancer (JRSGC). RESULTS: In 34 (45%) exposed patients (Group A), DSA detected an atypical vascular anatomy. Major anatomical variations of the celiac axis, its branches and the superior mesenteric artery were discovered in 4 subjects (5%). Vascular anomalies affecting the surgical tactics of lymphadenectomy were detected in less than 8% of patients. Five post-operative deaths (6.6%) were registered between patients of the Group A, exposed to pre-operative angiography, 8 in the unexposed Group B (8.5%). Post-operative morbidity was significantly higher (P = 0.038) in the Group B (34%) in comparison to Group A (20%) but no difference in risk of individual complications was detected. CONCLUSIONS: Although useful in the presence of major vascular anomalies, it appears that pre-operative angiography did not significantly reduce intra- and post-operative complications associated with radical gastrectomy combined with extended lymphadenectomy. Arteriography is therefore not routinely recommendable but its use is mandatory in specific operations for gastric cancer.

Locoregional therapy for liver metastases from colorectal cancer: the possibilities of intraarterial chemotherapy, and new hepatic-directed modalities.

Liver metastasis of colorectal cancer is a life-threatening prognostic factor. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). The diagnosis has been carried out by clinical examination, abnormal alkaline phosphatase, lactic acid dehydrogenase and tumor markers, abdominal liver echography and computed tomography scan. Angiography and intraoperative echography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems useful combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review reports the possibilities of intraarterial chemotherapy and other novel hepatic directed approaches to the treatment of liver metastases from this common disease.

Stop-flow in mediastinum and thorax for resistant lymphoma.

BACKGROUND/AIMS: Management of patients with heavily pretreated malignant lymphoma failing frontline treatment and salvage high-dose chemotherapy and autologous peripheral stem cell rescue, is problematic. A pilot study was conducted to evaluate isolated thoracic perfusion of drugs by means of stopflow technique. METHODOLOGY: Six patients were enrolled in the study; diagnoses included 4 advanced Hodgkin's disease, 1 primary mediastinal B-cell lymphoma, and 1 anaplastic large cell lymphoma. Patients were aged 18-37 years; 4 presented with bulky mediastinum. They had never achieved a complete response since all had progressed from front-line treatment, and 3 had even failed salvage high-dose chemotherapy with autologous peripheral stem cell rescue. Cisplatin (100 mg/m2) and melphalan (35 mg/m2) were used. Carmustine (100 mg/m2) were added to these 2 drugs and cytarabine (2000 mg/m2) in patients not previously treated by carmustine, etoposide, cytarabine, and melphalan. Epidoxorubicin (70 mg/m2) was added in patients who previously received a suboptimal dosage of antracycline. Drugs were delivered monthly via aortic perfusion performed by means of Aigner's stop-flow technique. RESULTS: Overall 13 cycles of perfusional chemotherapy were administered with a median number of 2 cycles. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery. After 1 month, 6 (100%) objective responses after isolated thoracic perfusion were recorded, 3 (50%) of which were complete. Tolerance to therapy was excellent. Hematological toxicity was mild and transfusional support was needed only in one course. At the last follow-up, 2 patients are alive (1 complete response and 1 very good partial response, maintained). CONCLUSIONS: This new therapeutical approach seems very active in recurrent/refractory malignant lymphoma and may play an important role in this setting.

Gastric juice nitrite and bacteria in gastroduodenal disease and resected stomach.

The N-nitroso-compounds and the bacteriological contamination of gastric juice could represent a risk factor for cancer of the stomach when the mucosal barrier is altered. In the unresected stomach and gastric stump, the hypo-achlorhydria and bilopancreatic reflux permit the development of bacterial flora and the production of N-nitroso-compounds in the presence of nitrite. A survey was performed on 71 patients: 15 normal controls, 31 with gastroduodenal disease (9 gastrites, 10 gastric ulcers, 10 duodenal ulcers, 7 neoplasias), 20 patients with gastric resection (8 BI, 12 BII), using an endoscopic-histopathologic control and a chemical-bacteriological analysis of the gastric juice. We studied the gastric juice for the following parameters: pH, concentration of nitrite, identification of bacterial type, count and nitrate-reductase activity. An inverse relationship was found between the concentration of nitrite and the hydrogen ion concentration. In the alkaline gastric juice, we identified aerobic bacteria with nitrate-reductase activity and anaerobic bacteria. The latter has the ability to transform biliary salts into carcinogenic and cocarcinogenic compounds and to catalyze the nitrosations. The chemicobacteriological characteristics of the gastric juice from gastric ulcers (Johnson type I), atrophic gastrites, and resected stomachs lead one to think that there is a risk of carcinogenesis brought about by the N-nitroso-compounds.

Benign granular cell tumor of the breast: a misleading disease.

Granular cell tumor (GCT) is a relatively rare neoplasm, and almost always benign in its prognostic behavior. Location of this tumor in the breast presents serious problems for differential diagnosis, both from a clinical point of view and at gross pathological examination, because of its resemblance to carcinoma. Fine needle aspiration biopsy and intraoperative frozen section examination may not be of any further help. The histogenesis of these lesions has been widely debated in the past, but no universally accepted conclusion has been reached. Most GCTs appear to be derived from Schwann cells, but many different neoplastic and non-neoplastic lesions show granular cell changes. Therefore, GCT should not be considered as a single entity but as the result of a cytoplasmic change due to still unknown metabolic alterations that may occur in various cell types. No firm conclusions can be drawn regarding the suspected hormonal influence on the development of breast GCT. The authors describe three typical cases of breast GCT that occurred in patients of different ages, and discuss the most important questions concerning this lesion.

Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: results of a phase I clinical study.

BACKGROUND: Hepatic arterial infusion chemotherapy is a promising approach in liver metastases from colorectal cancer, but chemical hepatitis, biliary sclerosis, arterial thrombosis and right upper quadrant pain are limiting factors. Irinotecan (CPT-11) is an active drug in colorectal cancer. We planned a short hepatic arterial infusion of CPT-11 to describe the toxicity, to determine the dose-limiting toxicity, and to define the doses of CPT-11 to be recommended for phase II studies. PATIENTS AND METHODS: Fourteen patients with a median liver substitution of 30% (10-60%) were enrolled. All patients received hepatic arterial infusion chemotherapy with CPT-11 on an outpatient basis every 3 weeks as a short, 30-min infusion. RESULTS: At 240 mg/m2, 2 of 4 patients experienced grade 4 diarrhea and neutropenia, and 3 of them also reported grade 4 abdominal pain of the right upper quadrant. The maximum tolerated dose was reached at 240 mg/m2. The recommended doses of CPT-11 for phase II studies is 200 mg/m2, given every 3 weeks. CONCLUSIONS: CPT-11 presents a low hepatic toxic profile and could be considered a new active drug, suitable for hepatic arterial infusion in liver metastases from colorectal cancer.