Vincent Moutardier

RADIOTHERAPY AND IMMEDIATE TWO-STAGE BREAST RECONSTRUCTION WITH A TISSUE EXPANDER AND IMPLANT: COMPLICATIONS AND ESTHETIC RESULTS

PURPOSE To report complications, failure rate, and esthetic results in patients undergoing immediate breast reconstruction with a tissue expander and implant, with or without adjuvant treatment. METHODS AND MATERIALS We reviewed the records of the 77 patients who underwent immediate breast reconstruction with an expander/implant between January 1999 and December 2000. Complications were assessed using the Common Toxicity Criteria, version 2, scale. Esthetic results were assessed by the physician using five criteria. RESULTS Of the 77 patients, 55 had received adjuvant radiotherapy. The median follow-up was 25 months. Complications appeared to correlate with radiotherapy (14% for nonirradiated patients; 51% for irradiated patients; p = 0.006) and adjuvant chemotherapy (54% with chemotherapy [CHT] vs. 25% without CHT; p = 0.02). Breast reconstruction failed in 21% of patients (9% of nonirradiated patients and 24% of irradiated patients; p = 0.1), and chemotherapy was associated with a worse rate of failure (34% with CHT vs. 6% without CHT, p = 0.005). Adjuvant tamoxifen, however, correlated neither with complications (45% with tamoxifen vs. 39% without; p = 0.15) nor with failure (21% with tamoxifen and 23% without, p = 0.79). Esthetic results were acceptable in 60% of cases. CONCLUSION Immediate breast reconstruction with an expander/implant can be considered even for patients requiring adjuvant treatment. However, the complication and failure rates are three times higher after postexpander radiotherapy.

Resection of the Inferior Vena Cava for Neoplasms With or Without Prosthetic Replacement: A 14-Patient Series

ObjectiveTo review the outcome of resection of the suprarenal or infrarenal inferior vena cava (IVC) and possible indications for prosthetic replacement. Summary Background DataInvolvement of the IVC has long been considered a limiting factor for curative surgery for advanced tumors because the surgical risks are high and the long-term prognosis is poor. Prosthetic replacement of the IVC is controversial. MethodsThe authors retrospectively reviewed a 7-year series of 14 patients who underwent en bloc resection including a circumferential segment of the IVC. The tumor was malignant in 12 patients and benign in 2. The resected segment of the IVC was located above the kidneys in eight patients and below in six. Resection was performed without extracorporeal circulation in all patients. ResultsIn all but one patient, IVC resection was associated with multivisceral resection, including extended nephrectomy (n = 8), major hepatic resection (n = 3), digestive resection (n = 3), and infrarenal aortic replacement (n = 2). Prosthetic replacement of the IVC was performed in eight patients cases and was more common after resection of a suprarenal (6/8) than an infrarenal segment of the IVC (2/6). One patient died of multiorgan failure. Major complications occurred in 29% of patients. Symptomatic complications of prosthetic replacement occurred in one patient (acute postoperative thrombosis, successfully treated by surgical disobstruction). Graft-related infection was not observed. Marked symptoms of venous obstruction developed in three of the six patients who did not undergo venous replacement. In patients undergoing surgery for malignant disease, the estimated median survival was 37 months and the actuarial survival rate was 67% at 1 year. ConclusionMultivisceral resection including a segment of IVC is justified to achieve complete extirpation in selected patients with extensive abdominal tumors. Prosthetic replacement of the IVC may be required, particularly in cases of suprarenal resection. It is a safe procedure with a low complication rate and good functional results.

Salvage Abdominoperineal Resection After Failure of Conservative Treatment in Anal Epidermoid Cancer

PURPOSERadiotherapy alone or with combined chemotherapy is the first therapeutic option for epidermoid carcinoma of the anal canal. Failure of this conservative treatment may benefit of salvage abdominoperineal resection. This study was designed to analyze postoperative outcome and oncologic results in a single anticancer institution.METHODSMedical charts of 36 patients (median age, 57.9 years) who underwent salvage abdominoperineal resection after failure of conservative treatment between 1987 and 2002 were reviewed retrospectively. There were 15 patients treated for immediate failure (Group I) and 21 patients for recurrence (Group II). Twenty-two patients have undergone primary use of flap reconstruction of the perineal wound. There were ten rectus abdominis myocutaneous flaps, nine omental flaps, two gracilis muscular flaps, and one combined flap.RESULTSThere was no postoperative mortality. Median follow-up was 67 (range, 15–155) months. Primary closure of the perineum was obtained in 33 patients (92 percent). Secondary wound breakdown occurred in 23 of 33 patients (70 percent). Complications unrelated to the perineal wound occurred in 13 patients. The overall crude five-year survival after salvage abdominoperineal resection was 69.4 percent. The crude five-year survival in Group I and Group II was 60.7 and 71.5 percent respectively (P = 0.28). The crude five-year, disease-free survival in Groups I and II was 31.1 and 48.2 percent respectively (P = 0.10). Twenty-three patients experienced recurrences after salvage abdominoperineal resection (64 percent) with a mean delay of 30 months.CONCLUSIONSDespite high incidence of perineal morbidity, salvage abdominoperineal resection for epidermoid carcinomas of the anal canal has a high long-term survival rate.

Neoadjuvant preoperative chemoradiation in patients with pancreatic cancer

PURPOSE To assess the toxicity and efficacy of preoperative chemoradiation in pancreatic cancer. METHODS AND MATERIALS Between November 1996 and December 2001, 32 patients with biopsy-proven pancreatic adenocarcinoma (28 head; 4 body) were treated by chemoradiation consisting of either split-course therapy (two courses of 15 Gy separated by a 2-week break, n = 10) or standard-fractionation therapy (45 Gy during 5 weeks, n = 22). Concurrent chemotherapy included continuous infusion of 5-fluorouracil and a cisplatin bolus. Pancreatic resection was scheduled for 4-6 weeks after completion of chemoradiation treatment. RESULTS All 32 patients completed the chemoradiation protocol. Only 2 cases of Grade 3 toxicity (weight loss, vomiting) and one fatal Grade 4 infection occurred. Of the 32 patients, 19 underwent curative resection. Two patients had a complete pathologic response. One patient died 36 months after diagnosis of late treatment-related toxicity (acute superior mesenteric artery thrombosis) with no evidence of disease. The 2-year overall survival rate for the entire group and the resected patients was 37.3% (95% confidence interval 18.2-56.4%) and 59.3% (95% confidence interval 34.1-84.9%), respectively. CONCLUSION Preoperative chemoradiation with 5-fluorouracil and cisplatin is feasible and promising.

Neoadjuvant 5 fluorouracil-cisplatin chemoradiation effect on survival in patients with resectable pancreatic head adenocarcinoma: a ten-year single institution experience.

Objectives: It is the aim of this study to assess the outcome of patients who received neoadjuvant 5-fluorouracil-cisplatin chemoradiation (CRT) for stage I/III pancreatic adenocarcinoma. Methods: Eligible patients (n = 101) received radiation therapy (45 Gy) associated with continuous infusion of 5-fluorouracil accompanied by a cisplatin bolus. Results: Of the 102 patients enrolled in the study, 26 patients had progression of cancer during treatment and were deemed unresectable; 1 patient died during CRT of septic shock. Sixty-two of 75 remaining patients underwent pancreaticoduodenectomy. The overall median survival of all 102 patients in the study was 17 months, with a 5-year survival of 10%. For patients who underwent resection, the median survival was 23 months. Correspondingly, the median survival was 11 months for the 40 unresected patients (p = 0.002). The 5-year survivals for resected and unresected patients were 18 and 0% (p = 0.01), respectively. A complete pathological response to neoadjuvant CRT was noted for 8 patients (13%). Margin and lymph node positivity was present in 5 (8%) and 15 (24%) patients, respectively. There was documented local recurrence in 8 (13%) and distant recurrence in 36 (58%) patients, with the liver being the most common site. Conclusion: Neoadjuvant 5-fluorouracil-based CRT had a limited impact on survival but appeared to be associated with improved local control.

Treatment of hepatocellular carcinoma using percutaneous radiofrequency thermoablation: Results and outcomes in 56 patients

The aim of this study was to evaluate the efficacy of and tolerance for radiofrequency thermoablation (RFTA) in patients with hepatocellular carcinoma (HCC). From March 1999 to September 2001, a total of 56 patients (46 men and 10 women) whose mean age was 67.8 years (range 51 to 76 years) underwent RFTA for 71 HCCs at our institution. RFTA was carried out in 45 patients with one lesion less than 6 cm in diameter, in seven patients with two lesions less than 4 cm in diameter each, and in four patients with three lesions less than 3 cm in diameter each. The mean diameter of the lesions was 4.1 cm (range 0.8 to 6.0 cm). The etiology of the cirrhosis was alcoholism in 31 patients, post-hepatitis C in 19 patients, post-hepatitis B in four patients, and hemochromatosis in two patients. Forty-five patients were classified as Child stage A and 11 were Child stage B. No ascites, prothrombin time >60%, and platelet count <60,000/mm3 were needed. Two types of cooled needles were used depending on the size of the lesion (a needle 15 cm in length was used for 2 or 3 cm tumors, and a cluster of needles was used for tumors larger than 4 cm). Helical computed tomography was performed 8 weeks after treatment. The main criterion for a complete response was the presence of a hypodense lesion without contrast enhancement. Mean follow-up was 14 months. Complete tumor destruction was achieved in 50 (89.2%) of 56 patients after one session and in 52 (92.8%) of 56 after two sessions. Twelve months later, a complete response was confirmed in 45 patients (80.3%), four patients had a local recurrence and new liver nodules, and three patients had died (one of bone metastasis, one of acute alcoholic hepatitis, and one of bronchial carcinoma). Thirty-nine patients (69.6%) were still in complete remission 36 months later, and a new HCC had developed in six patients. At 36 months 49 of 56 patients were alive and 39 of 56 were free of disease. Patients with HCCs that developed following viral cirrhosis had a worse prognosis than those with HCCs that occurred after alcoholic cirrhosis (2-year survival, 57.7% vs. 77.7%; P = 0.0241). It was concluded that radiofrequency ablation is an effective treatment for HCC, although the prognosis is better in patients who develop HCC after alcoholic cirrhosis compared to those in whom HCC occurs after viral cirrhosis.

Hemorrhage after Duodenopancreatectomy: Impact of Neoadjuvant Radiochemotherapy and Experience with Sentinel Bleeding

Postoperative hemorrhage (PH) after duodenopancreatectomy (DP) is frequently lethal. The aim of this study was to delineate guidelines of management. Between August 1994 and July 2003, 172 patients underwent DP for cancer. Altogether, 26 patients were subjected to an institutional protocol (IP) with standard-dose chemoradiation (CRT) and 4 patients to an extrainstitutional protocol (EIP) with high-dose CRT. Sixteen patients (9.3%) were reoperated for PH. Hemorrhage occurred in 23% of irradiated patients (4 EIP, 3 IP) and in 6% of nonirradiated patients [confidence interval (CI) 1.8-6.5]. Pancreatic leak occurred in nine patients with PH (56%). Sentinel bleeding (SB) was noted in eight patients (50%) with a mean delay of 10 days after DP. Overall mortality after hemorrhage was 56%. Morality rates of patients with EIP or IP were, respectively, 100% and 0%. Mortality rates of patients with or without SB were similar. Mortality rates of axial bleeding (hepatic artery, mesenteric vessels) or lateral bleeding (pancreas remnant, splenic vessels) were, respectively, 88% and 25% (CI 1.6-8.6). Completion of pancreatectomy was achieved in 75% without rebleeding. Preoperative high-dose CRT increased the risk of fatal PH. Because SB occurs before massive hemorrhage, prompt reoperation could reduce mortality. Completion of pancreatectomy was essential during reintervention. Axial bleeding supports high mortality. Moving to the left, the pancreatojejunostomy could avoid contact of pancreatic juice with axial vessels in the case of pancreatic leakage. Ligating the gastroduodenal artery during DP had to leave a stump of around 1 cm to facilitate hemorrhage control without ligating the common hepatic artery.

Colorectal function preservation in posterior and total supralevator exenteration for gynecologic malignancies: an 89-patient series

OBJECTIVE The objective of this study was to analyze our experience with colorectal function preservation at the time of pelvic exenteration. METHODS Between January 1980 and December 2001, 201 pelvic exenterations for gynecologic malignancies were performed in our hospital. Ninety-eight were supralevator exenterations and 89 were selected for this study because low colorectal anastomosis (LCRA) was performed. There were locally advanced or recurrent cancers including 50 cervical, 28 ovarian, 11 endometrial, and 3 vaginal malignancies and 5 pelvic sarcomas. RESULTS Thirty-nine patients (44%) had a history of previous irradiation. There were were 50 posterior and 39 total exenterations. A diverting stomy and/or pelvic filling were performed respectively in 44 (49.4%) and 26 (29%) cases. The postoperative mortality rate was 4.5% (4/89). Seventeen patients experienced a colorectal anastomotic fistula (AF). AF occurred significantly more frequently in irradiated patients (14/17 = 82%). The mortality rate related to AF was 6% (1/17). Ultimately the functional colorectal anastomosis rate was 71.9%, respectively 61.5 and 80% in irradiated and nonirradiated patients. CONCLUSIONS Colorectal function preservation in supralevator exenteration for gynecologic malignancies can be achieved safely in a majority of patients. In irradiated patients a systematically diverting stomy may result in a low mortality rate.

Pancreatic Cancer-Induced Cachexia Is Jak2-Dependent in Mice

Cancer cachexia syndrome is observed in 80% of patients with advanced‐stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the Pdx1‐cre;LSL‐KrasG12D;INK4a/arffl/fl mice model, the pathways involved in muscle, liver, and white adipose tissue wasting. These mice, which develop systematically pancreatic cancer, successfully reproduced many human symptoms afflicted with this disease, and particularly cachexia. Using the profiling analysis of pancreatic cancer‐dependent cachectic tissues we found that Jak2/Stat3 pathways, p53 and NFkB results activated. Thus, our interest was focused on the Jak2 pathways because it is pharmacologically targetable with low toxicity and FDA approved drugs are available. Therefore, Pdx1‐cre;LSL‐KrasG12D;INK4a/arffl/fl mice were treated with the Jak2 inhibitor AG490 compound daily starting at 7 weeks old and for a period of 3 weeks and animals were sacrificed at 10 weeks old. Body weight for control mice was 27.84 ± 2.14 g, for untreated Pdx1‐cre;LSL‐KrasG12D;INK4a/arffl/fl was 14.97 ± 1.99 g, whereas in animals treated with the AG490 compound the weight loss was significantly less to 24.53 ± 2.04 g. Treatment with AG490 compound was efficient since phosphorylation of Jak2 and circulating interleukin‐6 (IL6) levels were significantly reduced in cachectic tissues and in mice respectively. In conclusion, we found that Jak2/Stat3‐dependent intracellular pathway plays an essential role since its pharmacological inhibition strongly attenuates cachexia progression in a lethal transgenic pancreatic cancer model. J. Cell. Physiol. 229: 1437–1443, 2014.

A reappraisal of preoperative chemoradiation for localized pancreatic head ductal adenocarcinoma in a 5-year single-institution experience.

Resection of localized pancreatic head ductal adenocarcinoma (LPHDA) has a limited impact on survival. Mechanisms of improvement provided by preoperative chemoradiation therapy (CRT) remain under debate. This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT. Among 87 patients with LPHDA, 17 had a pancreaticoduodenectomy alone (group I). Thirtynine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy (group II). Thirty-one with initially unresectable cancers were similarly treated by CRT (group III). Patients in groups II and III were restaged after completion of CRT. In patients with resectable disease, resection was planned. Patients in groups I and II were statistically comparable in terms of age, sex, and pretherapeutic stage. Median survival and 2-year overall survival in group I were 13.7 months and 31%, respectively. In group II, 23 patients (59%) had a pancreaticoduodenectomy (group IIa) and 16 patients (41%) did not have resection (group IIb). Median survival and 2-year overall survival were as follows: group IIa, 26.6 months and 51%; and group IIb, 6.1 months and 0%, respectively. In group IIa, pathologic examination revealed eight major responses (35%) including two sterilized specimens, and none of the patients had locoregional recurrence. In group III, none of the patients had resection, and median survival was 8 months with one 2-year survivor. Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy. However, a high histologic response rate and excellent local control can also be achieved.