Laparoscopic Treatment of Incisional and Ventral Hernia.

BACKGROUND AND OBJECTIVES: Although several large studies regarding patients undergoing minimally invasive repair of incisional hernia are currently available, the results are not particularly reliable as they are based on heterogeneous groups, different surgical techniques, different mesh types, or with a too short follow period. METHODS: We conducted a retrospective observational trial, collecting data from patients who underwent laparoscopic repair of a primary abdominal wall or an incisional hernia using the laparoscopic Intraperitoneal Onlay Mesh technique and a single mesh type, i.e., a composite polyester mesh with a hydrophilic film (Parietex CompositeTM mesh - Medtronic, Minneapolis, MN - USA). All patients signed an informed consent. RESULTS: One thousand seven hundred seventy-seven patients were enrolled. The median surgery time was 50 minutes and the median length of hospital stay was 2 days. Intraoperative complications occurred in 12 patients (0.7%), while early postoperative surgical complications occurred in 115 (6.5%); during follow-up, bulging mesh was diagnosed in 4.5% of cases and hernia recurred in 4.3% of patients. An overlap equal or greater than 4 cm resulted as a significant protective factor, while the use of absorbable fixing devices was a risk factor for recurrence (odds ration: 9.06, p < 0.001, 95% confidence interval: 4.19 - 19.57). CONCLUSIONS: Minimally invasive treatment of primary and postincisional abdominal wall hernias is a safe, effective, and reproducible procedure. An overlap equal or greater than 4 cm, the use of nonabsorbable fixing devices and a postoperative care and follow-up regime are crucial in order to obtain good results and low recurrence rates.

Laparoscopic ventral hernia repair with composite mesh: Analysis of risk factors for recurrence in 185 patients with 5 years follow-up.

BACKGROUND: Laparoscopic ventral hernia repair is widely used although its clinical indications are often debated. The aim of this study is to describe our surgical experience in order to establish the safety, efficacy, feasibility of laparoscopic ventral hernia repair and to identify the factors that influence the risk of recurrence in a group of patients treated with only one type of prosthetic mesh and by the same surgical team. MATERIALS AND METHODS: Between January 2007 and December 2016, 512 patients were admitted to the General and Urgent Surgery Unit, with diagnosis of ventral hernia. Of these, 244 were operated laparoscopically and 268 in a traditional open surgery. In 244 patients treated by laparoscopy we always used a composite mesh: 185 Parietex™ Composite mesh (Medtronic-Covidien, Minneapolis, USA), the remaining other with other types of prosthetic mesh. The type and size of surgical defects, features of surgical technique, length of hospital stay, rate of conversion, morbidity, mortality, and rate of recurrence at 5 years follow-up were retrospective analysed on the 185 patients who underwent surgery with Parietex™ Composite mesh. RESULTS: We performed 185 laparoscopic ventral hernia repair with Parietex™ Composite mesh: 108 (58%) for incisional hernias and 77 (42%) for primary abdominal wall hernias. Mean age was 58 years (19-80). The mean size of abdominal defect was 5 cm (1,5-18), mean BMI was 30,4 kg/m2 (21-47), mean overlap of the mesh was 5 cm (3-6). The mean operative time was 54 min (30-180) and conversion rate was 3,2%. In 61 patients (33%) we performed a transversus abdominis plane block (T.A.P. block) to reduce postoperative pain. The mean length of hospital stay was 5 days (1-26) (2 days, mean value, in patient with preoperative T.A.P. block). The mortality rate was 0%; overall morbidity was 15,6%. At 5-year follow-up we observed 13 (7%) hernia recurrences. The features of patients with recurrence were as follows: mean age 50 years (19-74), mean ASA Score 3 (2-3), mean BMI 31 kg/m2 (21-44), mean size of hernial defect 7,5 cm (larger diameter), mean overlap 4,5 cm (3-6). CONCLUSIONS: Laparoscopic repair of ventral hernia using composite mesh is an effective and safe procedure particularly suitable in the following cases: median and paramedian defects, diameter of defect between 5 and 15 cm, "swiss cheese" defects, obesity. In our experience the factors related to the patient and the surgical technique that may influence the onset of early or late recurrence as the follows: a defect size >5 cm (W2 of EHS Classification), an overlap of the mesh < 5 cm, a BMI of 30 kg/m2 or superior and the presence of significant comorbidities (ASA score: 3). Finally, we observed that the T.A.P. Block preoperative procedure can lead to reduced the clinical costs through a lower administration of analgesics used and a lower length of stay.

Laparoscopic management of non-midline incisional hernia: A multicentric study.

BACKGROUND: The laparoscopic repair of non-midline ventral hernia (LNM) has been debated. The aim of this study is to analyze our experience performing the laparoscopic approach to non-midline ventral hernias (NMVHs) in Northwest Italy for 6 years. METHODS: A total of 78 patients who underwent LNM between March 2008 and March 2014 in the selected institutions were analyzed. We retrospectively analyzed the peri- and postoperative data and the recurrence rate of four subgroups of NMVHs: subcostal, suprapubic, lumbar, and epigastric. We also conducted a literature review. RESULTS: No difference was found between the four subgroups in terms of demographic data, defect characteristics, admission data, and complications. Subcostal defects required a shorter operating time. Obesity was found to be a risk factor for recurrence. CONCLUSIONS: In our experience, subcostal defects were easier to perform, with a lower recurrence rate, lesser chronic pain, and faster surgical performance. A more specific prospective randomized trial with a larger sample is awaited. Based on our experience, however, the laparoscopic approach is a safe treatment for NMVHs in specialized centers.

Laparoscopic total mesorectal excision for extraperitoneal rectal cancer: long-term results of a 18-year single-centre experience.

BACKGROUND AND OBJECTIVES: The oncologic efficacy of laparoscopic total mesorectal excision (TME) for middle-low rectal cancer is still under discussion because of the few long-term data. This study reports the results arising from a single-institution experience during a 18-year period. METHODS: Data about 132 consecutive laparoscopic TME performed between January 1994 and January 2012 were analysed with Kaplan-Meier method and a uni- and multi-variate analysis was conducted to define independent survival predictors. RESULTS: A total of 116 sphincter-preserving operations and 16 abdominoperineal resections were performed. Postoperative mortality and morbidity were 0.8 and 18.2%, with a rate of anastomotic leakage of 13.8%. Average follow-up was 85.9 months (range 13-210). Actuarial local recurrence rate was 4.13% at 5 years (any pelvic recurrence developed after 3 years from surgery). Overall and disease-free survival was respectively 83 and 79.8% at 5 years, 71 and 73% at 10 years and then remained constant until 18 years. Survival was correlated only to tumour stage and the type of surgery. CONCLUSIONS: Laparoscopic TME for extraperitoneal rectal cancer shows long-term oncologic outcomes similar to open rectal resections.

A randomized, double-blind, placebo-controlled study to assess QTc interval prolongation of standard dose aflibercept in cancer patients treated with docetaxel.

: The effect of repeated doses of aflibercept on ventricular repolarization in cancer patients was evaluated in an intensive electrocardiogram trial. This randomized, placebo-controlled, double-blind trial was conducted in 87 treated solid tumor patients. Treatment was with 6 mg/kg aflibercept, 1-hour intravenous (n = 43), or placebo (n = 44), combined with ≤75 mg/m docetaxel, every 3 weeks. Electrocardiograms were collected for 6 hours posttreatment using digital 12-lead Holter recorders, at day 1, in cycles 1 and 3. Free and vascular endothelial growth factor-bound aflibercept concentrations were assessed at similar time points. Eighty-four patients (43 placebo and 41 aflibercept) were evaluable for QT interval, Fridericia correction (QTcF) at cycle 1 and 59 (31 placebo and 28 aflibercept) at cycle 3. During cycle 3, from 30 minutes to 6 hours after the start of aflibercept, the maximum observed upper limit of the QTcF 90% confidence interval was 16 ms, for a mean of 8.4 ms. QTcF prolongation above 480 ms and 60 ms above baseline was observed in 1 aflibercept patient (2%). The slope of the relationship between free aflibercept concentration and QTcF was 0.048 (95% confidence interval, 0.013-0.082), corresponding to a 5-ms increase per 100 µg/mL increase in concentration. These results exclude a clinically important effect of aflibercept on ventricular repolarization.

Laparoscopic surgery for colon cancer.

Colon cancer is a major problem in Western countries and complete surgical resection is the main treatment. Since its introduction the laparoscopic approach has been used to achieve bowel resection with a better postoperative course and better aesthetic outcomes. Initial concerns about the radicality of the resection and the oncologic outcomes have been overcome in the last decade. All over the world large trials have been conducted to compare the laparoscopic approach and the traditional laparotomic one. A review of literature has been conducted to find evidence about this issue, revealing 24 relevant trials. The laparoscopic approach showed short-term benefits without compromising oncological safety. However intraoperative complication rates during laparoscopic colon resections seem to be increased, mainly due to the increased rate of intraoperative bowel injury. This finding confirms a great need for training and a wide learning curve for the surgeon. Our review supports the continued use of laparoscopic surgery in patients with colon cancer.

Mucinous histology of colon cancer predicts poor outcomes with FOLFOX regimen in metastatic colon cancer.

Mucinous adenocarcinoma (MA) of colorectal cancer seems associated with reduced responsiveness to chemotherapy. The overexpression of markers of resistance to fluorouracil and oxaliplatin has recently been demonstrated. We revised the outcomes of metastatic MA of the colon treated with FOLFOX. From January 2002 to December 2009, we treated 198 patients with metastatic colon cancer, of which 21 (10.6%) had diagnosis of MA and were compared with 42 control patients with non-mucinous adenocarcinoma (NMA). In MA group, three patients [14%; inhibitory concentration 95: ± 7.5%] reached partial response, and in NMA group, two patients obtained complete response and 16 obtained partial response with an overall response rate of 43% (inhibitory concentration 95: ± 7.6%) with a significant statistical difference (P = 0.027). Median progression-free survival for MA group was 4 months with respect to 8 months for NMA (P = 0.0001); regarding overall survival, we registered a median of 8 months with respect to 18 months for MA and NMA (P = 0.001). In multivariate analysis, MA histology, Eastern Cooperative Oncology Group performance status 2, more than two metastatic sites, and peritoneal metastatic involvement resulted in negative independent prognostic factors. Also in our study, MA is connected to poor prognosis and reduced activity of chemotherapy. In the absence of randomised studies, it may be convenient to analyse this subgroup of patients within the large trials carried out on colorectal cancer.

Laparoscopic incisional and ventral hernia repair (LIVHR) with PARIETEX™ Composite mesh.

OBJECTIVES: Laparoscopic incisional and ventral hernia repair (LIVHR) is widely used although its clinical indications are often debated. The aim of this study was to retrospectively describe the experience of our surgical centre in order to establish the safety, efficacy, and feasibility of LIVHR using PARIETEX(™) Composite mesh (Covidien, Mansfield, MA, USA). MATERIAL AND METHODS: Between January 2007 and November 2010, 87 patients were admitted to the Division of General Surgery of Aosta, with the diagnosis of abdominal wall hernia and underwent laparoscopic repair using PARIETEX(™) Composite mesh. The type and size of surgical defects, mean operative time, morbidity, mortality and rate of recurrence at one-year follow-up were retrospectively analysed. RESULTS: We performed 87 LIVHR: 51.7% for incisional hernia and 48.3% for epigastric or umbilical hernias. Mean operative time was 100 min., conversion rate was 3.4%. The mean size of abdominal defect was 6 cm (range: 2-15); in relation to umbilical hernias, mean size was 5.4 cm (range: 2-8). The mortality rate was 0%; overall morbidity was 16%. At one-year follow-up, we observed two cases of hernia recurrences. CONCLUSIONS: LIVHR using PARIETEX(™) Composite mesh is an effective and safe procedure with very low morbidity and low rates of postoperative pain and recurrence, especially in hernias with diameter of between 5 and 15 cm and in obese patients without previous laparotomies.

A randomised phase II trial of two sequential schedules of docetaxel and cisplatin followed by gemcitabine in patients with advanced non-small-cell lung cancer.

PURPOSE: The aim of this study was to determine the activity and toxicity of two sequential chemotherapy regimens in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). METHODS: Eighty-eight chemonaive patients with stage IIIB/IV NSCLC were randomised to receive either three cycles of 75 mg/m(2) cisplatin plus 75 mg/m(2) docetaxel, both administered on day 1 every 21 days, followed by three cycles of 1,200 mg/m(2) gemcitabine on days 1 and 8 every 3 weeks (arm A), or three cycles of 25 mg/m(2) cisplatin plus 25 mg/m(2) docetaxel on days 1, 8 and 15 every 28 days, followed by three cycles of 1,200 mg/m(2) gemcitabine on days 1 and 8 every 3 weeks (arm B). RESULTS: Of the evaluable patients, 61% in arm A (n = 41) and 36% (n = 44) in arm B completed treatment as per the protocol. The best tumour response rates were as follows (arm A and arm B): complete response: 2.4 and 2.3%; partial response: 39 and 20.4%; stable disease: 26.8 and 13.6%; and progressive disease: 31.8 and 45.4%. The median progression-free and overall survival were 3.9 and 12.3 months in arm A, respectively, 3.1 and 7.7 months in arm B. Grade 3-4 adverse events were more common in arm A. Grade 3-4 neutropenia was the main toxicity observed (56.1% in arm A and 11.4% in arm B). CONCLUSIONS: Our data demonstrate the feasibility of a sequential approach of cisplatin plus docetaxel followed by single-agent gemcitabine. Weekly administration of platinum-docetaxel is associated with an improved safety profile but lower efficacy than the conventional three-weekly schedule (registration ID 2004-001044-72).

Alkaline phosphatase levels as a prognostic factor in metastatic colorectal cancer treated with the FOLFOX 4 regimen: a monoinstitutional retrospective study.

AIMS AND BACKGROUND: Metastatic colorectal cancer has a heterogeneous behavior, and a set of patients will have minimal response and rapid disease progression. To understand this heterogeneity, studies have evaluated biological and clinical prognostic factors. Alkaline phosphatase seems to be a key prognostic factor, so we have reviewed the outcomes of our patients with respect to alkaline phosphatase levels. METHODS AND STUDY DESIGN: Between January 2003 and December 2008, we treated with the FOLFOX 4 regimen 103 consecutive patients with metastatic colorectal cancer. Thirty-two patients had alkaline phosphatase > or =300 U/l. RESULTS: Median time to progression was 4 months for patients with high alkaline phosphatase levels and 8 months for those with low alkaline phosphatase levels. Median overall survival was 8 and 17.5 months, respectively. Only 3 patients in the high alkaline phosphatase group obtained partial response (9.4%) compared to 3 complete responses and 24 partial responses (41.5%) in low alkaline phosphatase group. Toxicity was substantially different, with more grade 3-4 neutropenia, diarrhea and oral mucositis in the high than low alkaline phosphatase group. CONCLUSIONS: Alkaline phosphatase is an uncomplicated and potent prognostic factor. Patients with high alkaline phosphatase levels had a poor prognosis.

Comparison of short- and medium-term results between laparoscopically assisted and totally laparoscopic right hemicolectomy: a case-control study.

BACKGROUND: This study aimed to compare the short- and medium-term results obtained by totally laparoscopic right colectomy (TL) with those obtained by laparoscopically assisted right colectomy (LAC) for the treatment of right colon cancer. METHODS: A retrospective study compared two nonstatistically different groups (50 TL and 50 LAC cases) managed for nonmetastatic malignant tumors. The study outcomes included operative time, length of minilaparotomy, intraoperative complications, postoperative pain, time to resumption of the gastrointestinal functions, permanence of abdominal drain, analgesic therapy duration, postoperative complications, hospitalization time, number of harvested lymph nodes, and distant metastases onset. RESULTS: The mean operative times were 78 ± 25 min (TL group) and 92 ± 22 min (LAC group) (p < 0.05). The findings showed a lower postoperative pain level associated with a reduction in analgesic consumption (p > 0.05) and earlier restoration of digestive function in the TL group than in the LAC group. The mean hospital stays were approximately 5 days (TL) and 7 days (LAC) (p < 0.05). No complications occurred either intra- or postoperatively, and similarly, the TL group experienced no mortality. In comparison, the LAC group had a 30% complication rate (p < 0.05). The complications included one case of intraoperative small bowel lesion, three cases of postoperative respiratory infections, three cases of anastomotic leakage, two cases of intestinal occlusion, three cases of minilaparotomy infection, one case of postoperative femoral neurosis, one case of postoperative heart attack, and one case of postoperative pancreatitis. The mortality rate was 0%. Neither group had a recurrence of the neoplastic disease during a 4-year follow-up period. CONCLUSIONS: The findings seem to demonstrate that TL right colectomy is feasible and safe, yielding results comparable with those of the open approach but offering improved postoperative patient comfort. The limits of this retrospective comparative study do not allow definitive conclusions to be drawn despite the encouraging data for the next prospective randomized studies.

Randomised multicenter phase II study of two schedules of docetaxel and gemcitabine or cisplatin/gemcitabine followed by docetaxel as first line treatment for advanced non-small cell lung cancer.

BACKGROUND: In the attempt to optimize the efficacy of chemotherapy in advanced non-small cell lung cancer (NSCLC) several strategies need to be investigated including the use of non-platinum combinations and the sequential use of different agents. PATIENTS AND METHODS: In a phase II randomised study 165 patients with stage IIIB or IV NSCLC were assigned to receive docetaxel 40 mg/m(2) days 1 and 8 plus gemcitabine 1200 mg/m(2) days 1 and 8 every 21 days (arm A, N=54) or docetaxel 50 mg/m(2) days 1 and 15 plus gemcitabine 1600 mg/m(2) days 1 and 15 every 28 days (arm B, N=57) or gemcitabine 1200 mg/m(2) days 1 and 8 plus cisplatin 100mg/m(2) day 2 every 21 days for 3 cycles followed by docetaxel 75 mg/m(2) day 1 every 21 days for 3 cycles (arm C, N=54). The primary endpoint of the trial was overall response rate. Secondary end points included safety, progression-free and overall survival. RESULTS: Response rate was 22.2%, 23.2% and 33.3% after 3 cycles, whereas at the end of treatment was 24.1%, 12.5% and 27.8% in arm A-C, respectively. Median time to progression was similar in all the 3 arms: 6.7 months in arm A (95% CI: 4.8-9.7), 5.6 in arm B (5.0-7.9) and 6.6 in arm C (5.7-9.1). The median survival time was 10.7 months in arm A (95% CI: 6.8-15.6), 8.9 in arm B (7.4-12.5) and 14.6 in arm C (8.0-22.4) and 1-year survival rate was 46.3%, 37.9% and 53.9%, respectively. Grade 3-4 haematological toxicities were more frequent in arm C while non-haematological were more common in the gemcitabine and docetaxel arms. CONCLUSIONS: The results of this phase II randomised clinical trial do not indicate a clear superior efficacy of one of the tested combinations according to the planned statistical design and none of these regimens is sufficiently active or less toxic to warrant further investigation in a phase III study.

Laparoscopic resection of duodenal gangliocytic paraganglioma. A case report.

Paraganglioma is an exceedingly rare tumour of the duodenum that arises in close proximity to the ampulla of Vater. To date a total of 133 cases of duodenal paraganglioma have been reported in the literature; of these, 27 (20%) were histologically gangliocytic paragangliomas. This neoplasm generally behaves in a benign fashion, although instances of recurrence and/or lymph node metastasis have been described. The treatment consists in endoscopic polypectomy or surgical resection in relation to the histological features and the macroscopic extent of the neoplasm. We present a case of a benign duodenal gangliocytic paraganglioma treated by a laparo-endoscopic approach. We report a case of gangliocytic paraganglioma in a 75-year-old woman admitted to the General Surgery Division of Aosta Regional Hospital (Aosta-Italy), complaining of melaena and anaemia. Upper gastrointestinal endoscopy followed by enteroscopy with a video-capsula, revealed a pedunculated neoplasm in the second portion of the duodenum, with ulceration of the overlying mucosa. Multiple biopsies were performed during the endoscopic examination and showed the cellular pattern of benign paraganglioma. After stabilisation of the patient's clinical status, we performed a resection of the neoplasm via a laparoscopic transduodenal approach and a concomitant intraoperative duodenoscopy. The histological features showed a gangliocytic paraganglioma without a malignant cell pattern. The size of the neoplasm was 4 cm. The resection margins were free of neoplastic infiltration. The postoperative stay was 9 days and there were no intraoperative or postoperative complications. The patient is currently in good health without any tumour recurrence. Transduodenal laparoscopic resection with intraoperative duodenoscopy is a valuable treatment for benign gangliocytic paraganglioma of the duodenum which is unresectable by upper gastrointestinal endoscopy. This approach affords the advantages of the minimally invasive technique and fulfils the surgical tenets of the open transduodenal approach, if en bloc resection of the neoplasm with the adjacent duodenal wall is performed.

Mitomycin C plus capecitabine (mixe) in anthracycline- and taxane-pretreated metastatic breast cancer. A multicenter phase II study.

BACKGROUND: Capecitabine is considered the treatment of choice for anthracycline- and taxane-pretreated metastatic breast cancer. Mitomycin C seems to improve the activity of capecitabine by up-regulation of thymidine phosphorylase. PATIENTS AND METHODS: Fifty-five women with metastatic breast cancer previously treated with anthracyclinetaxane were treated with mitomycin C 10 mg/m2 on day 1 every six weeks and capecitabine 1000 mg/m2 on days 2-15 every three weeks. RESULTS: An overall response rate of 38% was found, consisting of 3 (5%) complete responses (CR) and 18 (33%) partial responses (PR); 8 patients (14%) had a stable disease (SD) for more than 4 months. The combination was well-tolerated, with the main toxicities being neutropenia, diarrhea and fatigue; other toxicities were of mild to moderate intensity without impairment in the quality of life of the patients. CONCLUSION: Capecitabine is confirmed as the drug of choice in the treatment of anthracycline- and taxane-pretreated metastatic breast cancer and its combination with mitomycin appears to improve its efficacy.

Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial.

BACKGROUND: Promising findings obtained using a weekly regimen of 5-fluorouracil (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients. METHODS: From January 1998 to January 2003, 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion (stage pT3 N0) and/or lymph node metastasis (stage pT2 or pT3 N1, N2, or N3), were enrolled in a trial of adjuvant chemotherapies; 201 patients were randomly assigned to receive the PELFw regimen, consisting of eight weekly administrations of cisplatin (40 mg/m2), LV (250 mg/m2), epidoxorubicin (35 mg/m2), 5-FU (500 mg/m2), and glutathione (1.5 g/m2) with the support of filgrastim, and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU (375 mg/m2 daily) and LV (20 mg/m2 daily, 5-FU/LV). Disease-free and overall survival were estimated and compared between arms using hazard ratios (HRs) and Kaplan-Meier estimates. All statistical tests were two-sided. RESULTS: The 5-year survival rates were 52% in the PELFw arm and 50% in the 5-FU/LV arm. Compared with the 5-FU/LV regimen, the PELFw regimen did not reduce the risk of death (HR = 0.95, 95% confidence interval [CI] = 0.70 to 1.29) or relapse (HR = 0.98, 95% CI = 0.75 to 1.29). Less than 10% of patients in either arm experienced a grade 3 or 4 toxic episode. Neutropenia (occurring more often in the PELFw arm) and diarrhea and mucositis (more prevalent in the 5-FU/LV arm) were the most common serious side effects. Nevertheless, only 19 patients (9.4%) completed the treatment in the PELFw arm and 85 (43%) patients completed the treatment in the 5-FU/LV arm. CONCLUSIONS: Our study found no benefit from an intensive weekly chemotherapy in gastric cancer. The extent of toxicity experienced by the patients in the adjuvant setting suggests that, in gastric cancer, chemotherapy may be more safely administered preoperatively.

Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study.

BACKGROUND: Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. METHODS: 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute--Common Toxicity Criteria. RESULTS: 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7-58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent neurological toxicity 6 months after the end of chemotherapy. CONCLUSION: A significant proportion of patients with advanced ovarian cancer treated with first-line carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering re-treatment with the same agents in sensitive recurrent disease.

Mitomycin C and capecitabine combination (MiXe) in heavily pretreated metastatic breast cancer patients. A dose-finding study.

BACKGROUND: No standard chemotherapy has been defined for metastatic breast cancer patients pretreated with anthracyclines and taxanes. In preclinical studies, mitomycin C (MMC) and capecitabine showed a synergistic effect by up-regulation of thymidine phosphorylase, and both drugs were active against breast cancer with a lack of overlapping toxicity, making their combination a well-tolerated regimen. PATIENTS AND METHODS: A dose-finding study was carried out in order to determine the maximum tolerable dose of MMC combined with fixed-dose capecitabine and to describe the dose-limiting toxicities. RESULTS: Twenty-one patients were enrolled, with metastatic breast cancer pretreated at least with anthracyclines and taxanes (3 at dose level I, 15 at dose level II, 3 at dose level III). At dose level III (MMC 12 mg/m2 and capecitabine 1000 mg/m2 days 2-15) dose-limiting toxicities were recorded in 2 patients (G4 thrombocytopenia, neutropenic fever, G4 neutropenia); dose level II (MMC 10 mg/m2 and capecitabine 1000 mg/m2 days 2-15) was extended for a better safety evaluation. No severe toxicity was noted at this dose level, and therefore this dose was recommend for the phase II study. With regard to activity, 4 partial responses and 2 stable diseases (28%) were recorded. CONCLUSION: Our data show that the combination is feasible, well tolerated and active in this set of patients.

Long-term survival in locally advanced oral cavity cancer: an analysis of patients treated with neoadjuvant cisplatin-based chemotherapy followed by surgery.

BACKGROUND: Neoadjuvant chemotherapy has been reported to be extremely active in head and neck cancer but has failed to give a statistically significant improvement in survival. METHODS: From 1981 to 1994, 33 operable patients with locally advanced oral cavity cancer received cisplatin-based chemotherapy before surgery. Postoperative radiotherapy was performed in high-risk patients. RESULTS: The overall clinical and pathologic complete response rates to neoadjuvant chemotherapy were 48% and 30%, respectively. At a median follow-up of 7.0 years (range, 0.3-15.3+ years), the 5-year and 10-year overall survival rates were 54.5% and 39.5%, and the disease-specific median survival was 6.6 years for all patients (8.3 and 2.3 years for stages III and IV, respectively). The univariate analysis showed a positive relationship between survival and male sex (p = .05), pathologic (p = .02), and clinical (p = .03) complete response. The Cox proportional hazard regression model confirmed the independent prognostic value of the clinical response with a 4.67 (95% CI, 1.70-12.86) hazard ratio. A second primary tumor occurred in six patients (18%), with a median of occurrence of 9 years (range, 7-11 years). CONCLUSIONS: This study confirms the prolonged survival expectancy largely exceeding 5 years for selected patients with stage IV and for most with stage III locally advanced oral cavity cancer achieving a clinical and/or pathologic complete response to chemotherapy.

Differences in transplant-related complications between hematologic malignancies and solid tumors receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

Multiple factors contribute to transplant-related complications after high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation, including conditioning regimens, number of infused stem cells and clinical characteristics of patient at transplant. We compared the transplant-related complications of 141 patients affected with hematological malignancies with those of 109 patients with solid tumors. The total number of peripheral blood stem cell transplantations performed was 339. High-dose chemotherapy mainly consisted of melphalan-, busulphan- or thiotepa-based regimens. Despite the equal number of infused CD34+ cells, patients with a hematological malignancy showed a slower absolute neutrophil count (days to neutrophils > 0.5 x 10(9)/L, 10.6 +/- 3.6 for hematological malignancies versus 9.1 +/- 1.2 for solid tumors, P < 0.0001) and platelet recovery (days to platelets > 20 x 10(9)/L, 16.4 +/- 9.8 for hematological malignancies versus 12.3 +/- 4.1 for solid tumors, P < 0.0001) than patients with a solid tumor. A significantly higher requirement of red blood cell (3.3 +/- 4.1 versus 2.0 +/- 1.9, P < 0.0029) and platelet units (7.5 +/- 10.4 versus 4.2 +/- 3.4, P < 0.0001) was observed for hematological malignancies than for solid tumors. Five graft failures were documented exclusively in patients with a hematological malignancy. Moreover, such patients displayed a longer duration of mucositis (P < 0.0028) and hospital stay (P < 0.0001), but no difference was observed in terms of febrile episodes. Transplant-related mortality was similar between the two groups. In conclusion, patients with a hematological malignancy overall have more complications than those with a solid tumor.

High-dose chemotherapy with mitoxantrone + melphalan and autologous stem cell rescue in metastatic breast cancer patients: a study of feasibility and tolerability.

Hematological and extra-hematological toxicity of mitoxantrone-containing regimens with autologous stem cell rescue was evaluated in 32 metastatic breast cancer patients. The schedule was the final part of two high-dose chemotherapy programs, including an induction phase with three courses of conventional chemotherapy with epirubicin (120 mg/m2) and cyclophosphamide (600 mg/m2) plus three courses of docetaxel (100 mg/m2) and a first high-dose chemotherapy consisting of cyclophosphamide (6000 mg/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2) or melphalan (160 mg/m2) plus thiotepa (600 mg/m2). The final second autograft phase included mitoxantrone (60 mg/m2) associated with melphalan (160 mg/m2) and autologous stem cell rescue infusion. The median duration of severe neutropenia and thrombocytopenia was 9 (range, 7-13) and 11.5 (range, 9-29) days. The median number of units of erythrocytes and platelets transfused was 1 (0-11) and 4 (1-9), respectively. Fever for a median of 2 (0-8) days developed in 71.8% of the patients. Mucositis was observed in 81.2% (WHO grade 3-4 in 25%). No acute or late cardiac toxicity was observed. One patient died because of a transplant-unrelated cause. The response according to the program phase showed an increased rate of complete response, from 12.5% at the end of conventional chemotherapy to 21.9% after the first high-dose chemotherapy course, to increase to 43.9% after the treatment with mitoxantrone-melphalan. We conclude that a conditioning regimen with high dose mitoxantrone-melphalan fits well within the high-dose chemotherapy program.