Richard Nakache

The role and limitations of 18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scan and computerized tomography (CT) in restaging patients with hepatic colorectal metastases following neoadjuvant chemotherapy: comparison with operative and pathological findings.

BackgroundRecent data confirmed the importance of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the selection of patients with colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before hepatic resection in selected cases may improve outcome. The influence of chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases is not known.MethodsPatients were assigned to either neoadjuvant treatment or immediate hepatic resection according to resectability, risk of recurrence, extrahepatic disease, and patient preference. Two-thirds of them underwent FDG-PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and FDG-PET/CT. Those without extensive extrahepatic disease underwent open exploration and resection of all the metastases according to original imaging findings. Operative and pathological findings were compared to imaging results.ResultsTwenty-seven patients (33 lesions) underwent immediate hepatic resection (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET: 93.3 vs 49%, Pu2009<u20090.0001; CT: 87.5 vs 65.3, Pu2009=u20090.038). CT had a higher sensitivity than FDG-PET in detecting CR metastases following neoadjuvant therapy (65.3 vs 49%, Pu2009<u20090.0001). Sensitivity of FDG-PET, but not of CT, was lower in group 2 patients whose chemotherapy included bevacizumab compared to patients who did not receive bevacizumab (39 vs 59%, Pu2009=u20090.068).ConclusionsFDG-PET/CT sensitivity is lowered by neoadjuvant chemotherapy. CT is more sensitive than FDG-PET in detecting CR metastases following neoadjuvant therapy. Surgical decision-making requires information from multiple imaging modalities and pretreatment findings. Baseline FDG-PET and CT before neoadjuvant therapy are mandatory.

Pancreatic Incidentalomas: High Rate of Potentially Malignant Tumors

BACKGROUNDnPancreatic incidentaloma (PI) is an increasingly common diagnosis that has received little attention. We characterized these tumors and compared them with symptomatic pancreatic tumors (nonincidentaloma [NI]).nnnSTUDY DESIGNnA retrospective database of 475 consecutive pancreatectomies that were performed from January 1995 to June 2007 at our institution was analyzed. Data for PI and NI patient cohorts were compared.nnnRESULTSnSixty-four PIs (13.5%) and 411 NIs (86.5%) were identified; 21% of pancreatic body and tail tumors versus 9% of tumors located in the pancreatic head were incidentally diagnosed (p = 0.001). Twenty-two PIs (34%) versus 278 NIs (67%) were malignant (p < 0.0001), 38 PIs (60%) were premalignant, and the remaining 4 (6%) had little or no risk for malignant progression. Intrapapillary mucinous cystic tumor was the most common diagnosis in the PI group (23.4%, n = 15). Of these, 13.3% (n = 2) were invasive versus 40.6% (n = 15) in the NI group (p = 0.02). Likewise, pathologic features for ductal adenocarcinomas were more favorable in PI versus NI tumors. Overall, PI patients had prolonged median disease-specific survival: 145 versus 46 months (p = 0.001). Median disease-specific survival for PI versus NI patients treated for adenocarcinoma were 22 versus 19 months, respectively (p = 0.4); 5-year disease-specific survival for PI versus NI patients treated for intrapapillary mucinous cystic tumor/mucinous cystadenoma were 94% versus 68%, respectively (p = 0.07).nnnCONCLUSIONSnOperation for PI is common, and a substantial proportion of these lesions might be malignant or premalignant. Resection of these early tumors in asymptomatic individuals is associated with improved survival, as compared with patients with symptomatic disease.

Response to chemotherapy predicts survival following resection of hepatic colo-rectal metastases in patients treated with neoadjuvant therapy

Prognosis of patients following resection of CRC metastases to the liver has traditionally been predicted by clinical risk factors. In the era of neoadjuvant chemotherapy, determination of new prognostic indicators of outcome are necessary.

Limb desmoid tumors: A possible role for isolated limb perfusion with tumor necrosis factor-alpha and melphalan

BACKGROUNDnThe management of extensive, recurrent limb desmoid tumors is extremely difficult. The failure of multimodality treatments, such as repeated resections, radiotherapy, systemic chemotherapy, or endocrine manipulations, can end up with multilating surgery or even amputation, similar problems sometimes encountered in soft tissue sarcoma of the limbs. The high rate of limb salvage achieved by isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and melphalan for extensive, high-grade soft tissue sarcoma led us to implement this modality in difficult cases of limb desmoids.nnnMETHODSnDuring a 4-year period, 6 patients aged 14 to 52 years were treated. All were significantly symptomatic and candidates for amputation or mutilating surgery. Five had lower and one had upper limb lesions. Two had multifocal disease. At ILP, 3 to 4 mg TNF and 1 to 1.5 mg/kg melphalan were delivered during a 90-minute period. One patient had a double perfusion. All patients underwent definitive resective operation 6 to 8 weeks after perfusion.nnnRESULTSnNo systemic complications were observed, and local complications included reversible skin redness and blisters. Response rate was 83% with 33% (2 of 6) complete response and 50% (3 of 6) partial response. In 1 patient less than 50% regression was observed. Limb salvage rate was 100%; even the patient with stabilization of disease could be locally resected. Local recurrence during a follow-up period of 7 to 55 months (median 45 months) occurred in 2 patients at 8 and 24 months, respectively; the first underwent amputation, whereas for the second a wide excision was possible.nnnCONCLUSIONSnILP with TNF and melphalan can be used as a limb preservation modality in patients with recurrent desmoids and significant symptoms who would otherwise require multilating surgery to control their neoplasm.

Long-term Outcome and Risk Factors of Failure after Bile Duct Injury Repair

BackgroundThe real long-term outcome of a hepaticojejunostomy (HJ) to repair bile duct injury (BDI) is unclear, and the risk factors for repair failure are partially defined.Study DesignA retrospective, nonrandomized study of the long-term outcome of biliary reconstructions after major BDIs. All injuries occurred in association with cholecystectomy.ResultsTwenty-nine patients were referred with complete transection of the common (n = 16), right (n = 5), or right sectoral (n = 4) hepatic ducts or of >1 major duct (n = 4) between October 2002 and January 2007. Mean follow-up was 24xa0months, range 12–60xa0months. Original repairs were “immediate” in 14, “delayed” (within 24–72h) in 5, and “elective” (after >8xa0weeks) in 10, and strictures developed in 9, 5, and 1 of those HJs, respectively. The surgical outcomes were significantly better when the intervention took place electively (p = 0.003). Original HJ repairs were done by a hepatobiliary surgeon (n = 23) or by a general surgeon (n = 6): the outcome was significantly better for the former (p < 0.001).ConclusionsThe 51.7% incidence of strictures after BDI repair in this study was higher than reported in the literature, probably because of selection bias secondary to the referral pattern. The timing of repair and the surgeon’s expertise are significant risk factors of failure.

Pancreaticoduodenectomy in Elderly Adults: Is It Justified in Terms of Mortality, Long-Term Morbidity, and Quality of Life?

To evaluate long‐term morbidity, mortality, and quality of life (QoL) after pancreaticoduodenectomy (PD) in elderly adults.

Perioperative Complications After Neoadjuvant Chemotherapy With and Without Bevacizumab for Colorectal Liver Metastases

PurposeBevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM).MethodsRetrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, nu2009=u2009134), or chemotherapy alone (group 2, nu2009=u200957). We compared demographics, surgical characteristics, and perioperative course.ResultsPerioperative complications developed in 35xa0% of patients in group 1, and 47xa0% in group 2 (pu2009=u20090.11). Of those complications, 15 (11.2xa0%) in group 1, and 5 (8.8xa0%) in group 2 were considered major (pu2009=u20090.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10xa0%, compared with 0 in group 2, pu2009=u20090.56.ConclusionNeoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.

Solid pseudopapillary neoplasm of the pancreas: Management and long-term outcome

BACKGROUNDnSolid pseudopapillary neoplasm (SPN) of pancreas is a rare pancreatic neoplasm with a low metastatic potential. Our aim was to study the clinical-pathological characteristics, and long-term outcome of this tumor.nnnMATERIALSnRretrospective single center study of patients operated for SPN of pancreas. Clinical and pathological data were collected.nnnRESULTSnFrom 1995 to 2016, 1320 patients underwent pancreatic resection. SPN was confirmed in 32 cases (2.46%), including 29 (90.6%) female and three (9.4%) male, with a mean age of 28.4xa0±xa012.2 years. SPN was the most common pathology among female patients under age of 40 (72.4%). Abdominal pain was the most frequent presenting symptom (48%), whereas none of the patients presented with jaundice. Mean tumor diameter was 5.9xa0cm (range, 0.9-14xa0cm). All patients underwent margin-negative surgical resection. Two patients demonstrated gross malignant features, including liver metastases at presentation (nxa0=xa01), and adjacent organ and vascular invasion (nxa0=xa01). Microscopic malignant features were present in thirteen patients (40.6%). Recurrence occurred in the retroperitoneal lymph nodes (nxa0=xa01, 7 years post resection) and in the liver (nxa0=xa02, 1 and 5 years post resection). Mean follow-up was 49.2 months (range, 1-228 months). Five and 10-year disease-free survival was 96.5% and 89.6% respectively.nnnCONCLUSIONSnSPNs are low-grade tumors with a good prognosis. Margin-negative surgical resection is curative in most patients. However, almost 15% of patients demonstrate malignant features including invasion of adjacent organs or metastatic disease. Patients with malignant disease are still expected to have long survival, and aggressive surgical approach is advocated.

Number of evaluated lymph nodes and positive lymph nodes, lymph node ratio, and log odds evaluation in early-stage pancreatic ductal adenocarcinoma: numerology or valid indicators of patient outcome?

BackgroundWe evaluated the prognostic significance and universal validity of the total number of evaluated lymph nodes (ELN), number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in a relatively large and homogenous cohort of surgically treated pancreatic ductal adenocarcinoma (PDAC) patients.MethodsProspectively accrued data were retrospectively analyzed for 282 PDAC patients who had pancreaticoduodenectomy (PD) at our institution. Long-term survival was analyzed according to the ELN, PLN, LNR, and LODDS.ResultsOf these patients, 168 patients (59.5xa0%) had LN metastasis (N1). Mean ELN and PLN were 13.5 and 1.6, respectively. LN positivity correlated with a greater number of evaluated lymph nodes; positive lymph nodes were identified in 61.4xa0% of the patients with ELNu2009≥u200913 compared with 44.9xa0% of the patients with ELNu2009<u200913 (pu2009=u20090.014). Median overall survival (OS) and 5-year OS rate were higher in N0 than in N1 patients, 22.4 vs. 18.7xa0months and 35 vs. 11xa0%, respectively (pu2009=u20090.008). Mean LNR was 0.12; 91 patients (54.1xa0%) had LNRu2009<u20090.3. Among the N1 patients, median OS was comparable in those with LNRu2009≥u20090.3 vs. LNRu2009<u20090.3 (16.7 vs. 14.1xa0months, pu2009=u20090.950). Neither LODDS nor various ELN and PLN cutoff values provided more discriminative information within the group of N1 patients.ConclusionsOur data confirms that lymph node positivity strongly reflects PDAC biology and thus patient outcome. While a higher number of evaluated lymph nodes may provide a more accurate nodal staging, it does not have any prognostic value among N1 patients. Similarly, PLN, LNR, and LODDS had limited prognostic relevance.

Neoadjuvant FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer: An intention to treat analysis

OBJECTIVEnTo assess clinical and pathologic efficacy of neoadjuvant FOLFIRINOX for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC).nnnMETHODSnPatients receiving neoadjuvant FOLFIRINOX for LAPC and BRPC treated between 2014 and 2017 were identified. Post-treatment patients achieving resectability were referred for surgery, whereas unresectable patients continued chemotherapy. Clinical and pathological data were retrospectively compared with control group consisting of 47 consecutive patients with BRPC undergoing pancreatic and portal vein resection between 2008 and 2017.nnnRESULTSnThirty LAPC and 23 BRPC patients were identified. Reasons for unresectability included disease progression (70%), locally unresectable disease (18%), and poor performance status (11%). Three patients (10%) with LAPC, and 20 (87%) with BRPC underwent curative surgery. Compared with control group, perioperative complication rate (4.3% versus 28.9%, pxa0=xa00.016), and pancreatic fistula rate (0 versus 14.8%, pxa0=xa00.08) were lower. Peripancreatic fat invasion (52.2% vs 97.8%, pxa0=xa00.001), lymph node involvement (22% vs 54.3%, pxa0=xa00.01), and surgical margin involvement (0 vs 17.4%, pxa0=xa00.04) were higher in the control group. Median survival was 34.3 months in BRPC patients operated after FOLFIRINOX and 26.1 months in the control group (pxa0=xa00.07). Three patients (13%) with complete pathological response are disease-free after mean follow-up of 19 months.nnnCONCLUSIONSnWhereas neoadjuvant FOLFIRINOX rarely achieves resectability in patients with LAPC (10%), most BRPC undergo resection (87%). Neoadjuvant FOLFIRINOX leads to complete pathological response in 13% of cases, tumor downstaging, and a trend towards improved survival compared with patients undergoing up-front surgery.