Long-term survival after pancreatic resection for renal cell carcinoma metastasis.

BACKGROUND: Surgical resection of pancreatic metastasis (PM) is the only reported curative treatment for renal cell carcinoma. However, there is currently little information regarding very long-term survival. The primary objective of this study was to determine the 10-year survival of this condition using the largest surgical series reported to date. METHODS: Between May 1987 and June 2003, we conducted a retrospective study of 62 patients surgically treated for PM from renal cell carcinoma at 12 Franco-Belgian surgical centers. Follow-up ended on May 31, 2012. RESULTS: There were 27 male (44 %) and 35 female (56 %) patients with a median age of 54 years [31-75]. Mean disease-free interval from resection of primary tumor to reoperation for pancreatic recurrence was 9.8 years (median 10 years [0-25]). During a median follow-up of 91 months [12-250], 37 recurrences (60 %) were observed. After surgical resection of repeated recurrences, overall median survival time was 52.6 months versus 11.2 months after nonoperative management (p = 0.019). Cumulative 3-, 5-, and 10-year overall survival (OS) rates were 72, 63, and 32 %, respectively. The corresponding disease-free survival rates were 54, 35, and 27 %, respectively. Lymph node involvement and existence of extrapancreatic metastases before PM were associated with poor overall survival. CONCLUSIONS: Aggressive surgical management of single or multiple PM, even in cases of extrapancreatic disease, should be considered in selected patients to allow a chance of long-term survival.

Management of postoperative pancreatic fistula after pancreaticoduodenectomy.

A postoperative pancreatic fistula (POPF) is the main complication after cephalic pancreaticoduodenectomy (CPD). Unlike its prevention, the curative management of POPFs has long been poorly codified. This review seeks best practices for managing POPFs after CPD. The diagnosis of a POPF is based on two signs: (i) an amylase level in drained fluid more than 3 times the upper limit of the blood amylase level; and (ii) an abnormal clinical course. In the standardised definition of the International Study Group of Pancreatic Surgery, a purely biochemical fistula is no longer counted as a POPF and is treated by gradual withdrawal of the drain over at most 3 weeks. POPF risk can be scored using pre- and intraoperative clinical criteria, many of which are related to the quality of the pancreatic parenchyma and are common to several scoring systems. The prognostic value of these scores can be improved as early as Day 1 by amylase assays in blood and drained fluid. Recent literature, including in particular the Dutch randomised trial PORSCH, argues for early systematic detection of a POPF (periodic assays, CT-scan with injection indicated on standardised clinical and biological criteria plus an opinion from a pancreatic surgeon), for rapid minimally invasive treatment of collections (percutaneous drainage, antibiotic therapy indicated on standardised criteria) to forestall severe septic and/or haemorrhagic forms, and for the swift withdrawal of abdominal drains when the risk of a POPF is theoretically low and evolution is favourable. A haemorrhage occurring after Day 1 always requires CT angiography with arterial time and monitoring in intensive care. Minimally invasive treatment of a POPF (radiologically-guided percutaneous drainage or, more rarely, endoscopic drainage, arterial embolisation) should be preferred as first-line treatment. The addition of artificial nutrition (enteral via a nasogastric or nasojejunal tube, or parenteral) is most often useful. If minimally invasive treatment fails, then reintervention is indicated, preserving the remaining pancreas if possible, but the expected mortality is higher.

Cystic dystrophy in heterotopic pancreas.

Cystic dystrophy in heterotopic pancreas, or paraduodenal pancreatitis, is a rare and complicated presentation involving heterotopic pancreatic tissue in the duodenal wall. This condition is present in 5% of the general population but disease mainly affects middle-aged alcoholic-smoking men with chronic pancreatitis (CP). It may be purely duodenal or segmental (pancreatico-duodenopathy). Its pathophysiology arises from alcohol toxicity with obstruction of small ducts of heterotopic pancreatic tissue present in the duodenal wall and the pancreatic-duodenal sulcus, leading to repeated episodes of pancreatitis. The symptomatology includes episodes of acute pancreatitis, weight loss, and vomiting due to duodenal obstruction. Imaging shows thickening of the wall of the second portion of the duodenum with multiple small cysts. A stepwise therapeutic approach is preferred. Conservative medical treatment is favored in first intention (analgesics, continuous enteral feeding, somatostatin analogues), which allows complete symptomatic regression in 57% of cases associated with a 5% rate of complications (arterial thrombosis and diabetes). Endoscopic treatment may also be associated with conservative measures. Surgery achieves a complete regression of symptoms in 79% of cases but with a 20% rate of complications. Surgery is indicated in case of therapeutic failure or in case of doubt about a malignant tumor. Pancreaticoduodenectomy and duodenal resection with pancreatic preservation (PPDR) seem to be the most effective treatments. PPDR has also been proposed as a first-line treatment for purely duodenal location of paraduodenal pancreatitis, thereby preventing progression to an extended segmental form.

Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma.

BACKGROUND: Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients. PATIENTS AND METHODS: A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-ß receptor, CXCR4, and LKB1. RESULTS: High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002). CONCLUSIONS: CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.

Long-term survival after portal vein arterialization for portal vein thrombosis in orthotopic liver transplantation.

Portal vein thrombosis is a relatively common finding during liver transplantation. The management of portal vein thrombosis during liver transplantation is technically demanding and ensures adequate portal flow to the liver graft. Eversion thromboendovenectomy and bypass using a patent splanchnic vein and cavoportal hemitransposition are the most often used procedures to treat portal vein thrombosis. There have been anecdotal reports of portal vein arterialization. We report a case of portal vein arterialization during orthotopic liver transplantation for decompensated cirrhosis. When thromboendovenectomy failed to restore sufficient portal flow and completion of arterial anastomosis between the recipient hepatic artery and the donor celiac trunk, a calibrated end-to-side anastomosis between the donor splenic artery and the donor portal vein was performed. With a 6-year follow-up, there are no symptoms related to portal hypertension, liver function is normal. However, an aneurismal dilatation of the portal branches has progressively developed. Calibrated portal vein arterialization is a possible option for portal vein thrombosis in liver transplantation, allowing long-term patient and graft survival.

[Nosocomial infection with SARS-Cov-2 within departments of digestive surgery]. / Infection nosocomiale à SARS-Cov-2 dans les services de chirurgie digestive.

INTRODUCTION: The COVID-19 pandemic imposed a drastic reduction in surgical activity in order to respond to the influx of hospital patients and to protect uninfected patients by avoiding hospitalization. However, little is known about the risk of infection during hospitalization or its consequences. The aim of this work was to report a series of patients hospitalized on digestive surgery services who developed a nosocomial infection with SARS-Cov-2 virus. METHODS: This is a non-interventional retrospective study carried out within three departments of digestive surgery. The clinical, biological and radiological data of the patients who developed a nosocomial infection with SARS-Cov-2 were collected from the computerized medical record. RESULTS: From March 1, 2020 to April 5, 2020, among 305 patients admitted to digestive surgery departments, 15 (4.9 %) developed evident nosocomial infection with SARS-Cov-2. There were nine men and six women, with a median age of 62 years (35-68 years). All patients had co-morbidities. The reasons for hospitalization were: surgical treatment of cancer (n = 5), complex emergencies (n = 5), treatment of complications linked to cancer or its treatment (n = 3), gastroplasty (n = 1), and stoma closure (n = 1). The median time from admission to diagnosis of SARS-Cov-2 infection was 34 days (5-61 days). In 12 patients (80%), the diagnosis was made after a hospital stay of more than 14 days (15-63 days). At the end of the follow-up, two patients had died, seven were still hospitalized with two of them on respiratory assistance, and six patients were discharged post-hospitalization. CONCLUSIONS: The risk of SARS-Cov-2 infection during hospitalization or following digestive surgery is a real and potentially serious risk. Measures are necessary to minimize this risk in order to return to safe surgical activity.

Nosocomial infection with SARS-Cov-2 within Departments of Digestive Surgery.

INTRODUCTION: The COVID-19 pandemic imposed a drastic reduction in surgical activity in order to respond to the influx of hospital patients and to protect uninfected patients by avoiding hospitalization. However, little is known about the risk of infection during hospitalization or its consequences. The aim of this work was to report a series of patients hospitalized on digestive surgery services who developed a nosocomial infection with SARS-Cov-2 virus. METHODS: This is a non-interventional retrospective study carried out within three departments of digestive surgery. The clinical, biological and radiological data of the patients who developed a nosocomial infection with SARS-Cov-2 were collected from the computerized medical record. RESULTS: From March 1, 2020 to April 5, 2020, among 305 patients admitted to digestive surgery departments, 15 (4.9%) developed evident nosocomial infection with SARS-Cov-2. There were nine men and six women, with a median age of 62 years (35-68 years). All patients had co-morbidities. The reasons for hospitalization were: surgical treatment of cancer (n=5), complex emergencies (n=5), treatment of complications linked to cancer or its treatment (n=3), gastroplasty (n=1), and stoma closure (n=1). The median time from admission to diagnosis of SARS-Cov-2 infection was 34 days (5-61 days). In 12 patients (80%), the diagnosis was made after a hospital stay of more than 14 days (15-63 days). At the end of the follow-up, two patients had died, seven were still hospitalized with two of them on respiratory assistance, and six patients were discharged post-hospitalization. CONCLUSIONS: The risk of SARS-Cov-2 infection during hospitalization or following digestive surgery is a real and potentially serious risk. Measures are necessary to minimize this risk in order to return to safe surgical activity.

The value of 18F-FDG positron emission tomography to differentiate benign from malignant intraductal papillary mucinous neoplasms: A prospective multicenter study.

OBJECTIVE: To assess the value of 18F-FDG PET/CT in differentiating between benign and malignant intraductal papillary mucinous neoplasms (IPMN) of the pancreas. SUMMARY BACKGROUND DATA: Malignant or high-risk IPMN require surgical resection but surgery should be avoided in patients with IPMN carrying a low risk of malignancy. 18F-FDG PET has been studied mostly in small, single center, retrospective series. METHODS: Prospective, non-comparative, multicenter French study. The primary endpoint was the specificity of PET/CT for identifying malignant IPMN (in situ or invasive carcinoma). Final diagnosis was obtained from pathological examination of the resected specimen. RESULTS: Among 120 patients analyzed, 99 had confirmed IPMN, including 24 with malignant lesions, namely 9 with carcinoma in situ and 15 with invasive carcinoma. The 18F-FDG PET/CT was positive in 44 and 31 patients in the overall and IPMN populations respectively. In the 99 IPMN patients, PET/CT showed 13 true positive, 18 false positive, 57 true negative and 11 false negative results. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of malignancy were 54.2%, 76.0%, 83.8% and 41.9% respectively, versus 64.9%, 75.9%, 82.9% and 54.5% in the overall population. We could not identify a cut-off value for SUVmax to distinguish benign from malignant lesions. Conventional imaging included computed tomography, magnetic resonance cholangiopancreatography and endoscopic ultrasound. In IPMN patients who underwent the 3 techniques, sensitivity, specificity, NPV and PPV were 66.7%, 84.4%, 84.4% and 66.7% respectively. CONCLUSIONS: In this study, 18F-FDG PET/CT did not perform better than conventional imaging to differentiate malignant from benign IPMN.

Morphological imaging and CT histogram analysis to differentiate pancreatic neuroendocrine tumor grade 3 from neuroendocrine carcinoma.

PURPOSE: To compare morphological imaging features and CT texture histogram parameters between grade 3 pancreatic neuroendocrine tumors (G3-NET) and neuroendocrine carcinomas (NEC). MATERIALS AND METHODS: Patients with pathologically proven G3-NET and NEC, according to the 2017 World Health Organization classification who had CT and MRI examinations between 2006-2017 were retrospectively included. CT and MRI examinations were reviewed by two radiologists in consensus and analyzed with respect to tumor size, enhancement patterns, hemorrhagic content, liver metastases and lymphadenopathies. Texture histogram analysis of tumors was performed on arterial and portal phase CT images. images. Morphological imaging features and CT texture histogram parameters of G3-NETs and NECs were compared. RESULTS: Thirty-seven patients (21 men, 16 women; mean age, 56±13 [SD] years [range: 28-82 years]) with 37 tumors (mean diameter, 60±46 [SD] mm) were included (CT available for all, MRI for 16/37, 43%). Twenty-three patients (23/37; 62%) had NEC and 14 patients (14/37; 38%) had G3-NET. NECs were larger than G3-NETs (mean, 70±51 [SD] mm [range: 18 - 196mm] vs. 42±24 [SD] mm [range: 8 - 94mm], respectively; P=0.039), with more tumor necrosis (75% vs. 33%, respectively; P=0.030) and lower attenuation on precontrast (30±4 [SD] HU [range: 25-39 HU] vs. 37±6 [SD] [range: 25-45 HU], respectively; P=0.002) and on portal venous phase CT images (75±18 [SD] HU [range: 43 - 108 HU] vs. 92±19 [SD] HU [range: 46 - 117 HU], respectively; P=0.014). Hemorrhagic content on MRI was only observed in NEC (P=0.007). The mean ADC value was lower in NEC ([1.1±0.1 (SD)]×10-3 mm2/s [range: (0.91 - 1.3)×10-3 mm2/s] vs. [1.4±0.2 (SD)]×10-3 mm2/s [range: (1.1 - 1.6)×10-3 mm2/s]; P=0.005). CT histogram analysis showed that NEC were more heterogeneous on portal venous phase images (Entropy-0: 4.7±0.2 [SD] [range: 4.2-5.1] vs. 4.5±0.4 [SD] [range: 3.7-4.9]; P=0.023). CONCLUSION: Pancreatic NECs are larger, more frequently hypoattenuating and more heterogeneous with hemorrhagic content than G3-NET on CT and MRI.

[Postoperative imaging of the pancreas and duodenum]. / Imagerie post-opératoire du pancréas et du duodénum.

Pancreatic surgery is a frequent therapeutic approach for benign and malignant conditions. CT has become the imaging method of reference to detect early postoperative complications and to detect recurrent disease during long-term follow-up. Knowledge of the normal postoperative anatomy is essential for accurate interpretation of CT scans. The purpose of this paper is to illustrate the normal and abnormal CT appearances of common surgical procedures involving the pancreas.

18F-FDG PET/CT in pancreatic adenocarcinoma: A role at initial imaging staging?

Pancreatic ductal adenocarcinoma represents 90% of all pancreatic tumors. The only hope for prolonged survival in patients with this condition still remains surgery with complete R0 resection. Initial imaging has a pivotal role to identify patients who are eligible to curative surgery and those who may benefit of neoadjuvant chemotherapy. This review provides an analysis of the recent literature on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in pancreatic adenocarcinoma. Performances of FDG PET in the detection of lymph node involvement and metastatic spread at initial staging and those in the assessment of response to treatment are described.

Acute cholangitis: Diagnosis and management.

Acute cholangitis is an infection of the bile and biliary tract which in most cases is the consequence of biliary tract obstruction. The two main causes are choledocholithiasis and neoplasia. Clinical diagnosis relies on Charcot's triad (pain, fever, jaundice) but the insufficient sensitivity of the latter led to the introduction in 2007 of a new score validated by the Tokyo Guidelines, which includes biological and radiological data. In case of clinical suspicion, abdominal ultrasound quickly explores the biliary tract, but its diagnostic capacities are poor, especially in case of non-gallstone obstruction, as opposed to magnetic resonance cholangiopancreatography and endoscopic ultrasound, of which the diagnostic capacities are excellent. CT scan is more widely available, with intermediate diagnostic capacities. Bacteriological sampling through blood cultures (positive in 40% of cases) and bile cultures is essential. A wide variety of bacteria are involved, but the main pathogens having been found are Escherichia coli and Klebsiella spp., justifying first-line antimicrobial therapy by a third-generation cephalosporin. Systematic coverage of Enterococcus spp. and anaerobic infections remains debated, and is usually recommended, in case of severity criteria for Enterococcus severity levels, or anaerobic bilio-digestive anastomosis for anaerobes. Presence of a biliary stent is the only identified risk-factor associated with infections by multidrug-resistant pathogens. Along with antimicrobial therapy, endoscopic or radiological biliary drainage is a crucial management component. Despite improved management, mortality in cases of acute cholangitis remains approximately 5%.

Right portal vein ligation is as efficient as portal vein embolization to induce hypertrophy of the left liver remnant.

BACKGROUND: Aim of this retrospective study was to compare induction of left liver hypertrophy after right portal vein ligation (PVL) and right portal vein embolization (PVE) before right hepatectomy for liver metastases. MATERIALS AND METHODS: Between 1998 and 2005, 18 patients underwent a PVE, whereas 17 patients underwent a PVL during a first stage laparotomy. RESULTS: There was no complication related to PVE or PVL. After a similar interval time (7 +/- 3 vs 8 +/- 3 weeks), the increase of the left liver volume was similar between the two groups (35 +/- 38 vs 38 +/- 26%). After PVE and PVL, right hepatectomy was performed in 12 and 14 patients, respectively. Technical difficulties during the right hepatectomy were similar according to duration of procedure (6.4 +/- 1 vs 6.7 +/- 1 h, p = 0.7) and transfusion rates (33 vs 28%, p = 0.7). Mortality was nil in both groups, and morbidity rates were respectively 58% for the PVE group and 36% for the PVL group (p = 0.6). CONCLUSION: Right PVL and PVE result in a comparable hypertrophy of the left liver. During the first laparotomy of a two-step liver resection, PVL can be efficiently and safely performed.

Pancreatocolonic fistula complicating noninvasive intraductal papillary mucinous tumor of the pancreas.

Intraductal papillary mucinous tumors (IPMT) of the pancreas are a distinct clinicopathological entity that is increasingly recognized and whose natural history and clinical presentation are now better understood. Nevertheless, only rare cases of pancreatobiliary or pancreatodigestive fistulas complicating IPMT have been described so far and their clinicopathological significance and association with cancer remain controversial. We report a case of pancreatocolonic fistula complicating a noninvasive IPMT, and review the published literature. Unlike previous reports, IPMT complicated by fistula in nearby organs does not seem to be more often associated with invasive carcinoma: frequency is comparable in resected IPMT with or without internal fistula. Since fistulas are not a reliable clinicopathological predictor of invasive malignancy, en-bloc resection should not be routinely performed especially if extended resection increases the immediate risks or the long-term risks of surgery.

[Digestive obstruction: an unusual complication of hereditary multiple exostoses]. / Obstruction digestive : une complication exceptionnelle d'une maladie exostosante.

Hereditary multiple exostoses is an autosomal dominant bone disorder characterized by multiple cartilaginous tumors growing outward from metaphyses of long bones. These tumors are usually located in long bones of the limbs. Exostosis also called osteochondroma can cause many complications, the most serious being malignant transformation as chondrosarcoma. We report a rare phenotype of this disease in a young male patient who presents digestive symptoms caused by a voluminous degenerated lumbar exostosis with anterior abdominal development.

[Surgical complications of pancreatectomy]. / Complications chirurgicales des pancréatectomies.

The mortality for pancreatectomy has decreased to a very low level in recent years but morbidity remains high. The most frequent post-operative complications of pancreaticoduodenectomy (PD) are delayed gastric emptying (DGE) in 20% and pancreatic fistula (PF) in 10-15%. DGE is associated with other abdominal complications in half the cases; these must be delineated by CT scan and specifically treated. Isolated DGE usually resolves within three weeks with the use of nasogastric suction and pro-kinetic drugs. FP following PD may be preventable with the use of temporary trans-jejunal intubation of Wirsung's duct or by intussusception of the pancreatic margin into the jejunal lumen. FP occurring after PD will heal with conservative management (total parenteral nutrition, peripancreatic drainage, somatostatin analogues) in 80-90% of cases but secondary complications such as peritonitis, arterial erosion and pseudo-aneurysm may be life-threatening. Early hemorrhage (in the first 48-72 hours) must be treated by re-operation. Late hemorrhage (usually secondary to PF) and ischemic complications are rare (3% and 1% respectively), difficult to treat, and associated with high mortality. PF is also the main complication of distal pancreatectomy and enucleation of pancreatic tumors (10-20% and 30% respectively). These PF resolve with conservative treatment in more than 95% of cases but may justify an ERCP sphincterotomy if drainage is prolonged. After medial pancreatectomy, PF occurs in 20-30% of cases, arising from either of the two transected pancreatic surfaces.

[Lymph node resection for carcinoma of the pancreas]. / Le curage ganglionnaire dans le cancer du pancréas.

Several factors argue for extended lymphadenectomy in surgery for pancreatic adenocarcinoma: 1) lymph node extension is an adverse prognostic factor; 2) some tumor recurrences are only loco-regional suggesting that initial resection was insufficient; 3) some retrospective studies suggest that extension of lymphadenectomy improves post-resection survival. Extended lymphadenectomy, including circumferential dissection of both the celiac axis and the superior mesenteric artery and resection of para-aortic nodes, was evaluated by 4 randomized trials; globally there was no survival benefit. Extended lymphadenectomy increases, at least transiently, the risk of post-operative diarrhea. Its influence on the rate of loco-regional recurrences has not been evaluated. However, this technique should not be definitively and globally precluded since a more radical resection was associated with a trend toward better long-term survival in the trial with the largest number of patients.

[Not Available]. / Le curage ganglionnaire dans le cancer du pancréas.

A. Sauvanet Several factors argue for extended lymphadenectomy in surgery for pancreatic adenocarcinoma: 1) lymph node extension is an adverse prognostic factor; 2) some tumor recurrences are only loco-regional suggesting that initial resection was insufficient; 3) some retrospective studies suggest that extension of lymphadenectomy improves post-resection survival. Extended lymphadenectomy, including circumferential dissection of both the celiac axis and the superior mesenteric artery and resection of para-aortic nodes, was evaluated by 4 randomized trials; globally there was no survival benefit. Extended lymphadenectomy increases, at least transiently, the risk of post-operative diarrhea. Its influence on the rate of loco-regional recurrences has not been evaluated. However, this technique should not be definitively and globally precluded since a more radical resection was associated with a trend toward better long-term survival in the trial with the largest number of patients.

[Not Available]. / Le curage ganglionnaire dans le cancer du pancréas.

A. Sauvanet Several factors argue for extended lymphadenectomy in surgery for pancreatic adenocarcinoma: 1) lymph node extension is an adverse prognostic factor; 2) some tumor recurrences are only loco-regional suggesting that initial resection was insufficient; 3) some retrospective studies suggest that extension of lymphadenectomy improves post-resection survival. Extended lymphadenectomy, including circumferential dissection of both the celiac axis and the superior mesenteric artery and resection of para-aortic nodes, was evaluated by 4 randomized trials; globally there was no survival benefit. Extended lymphadenectomy increases, at least transiently, the risk of post-operative diarrhea. Its influence on the rate of loco-regional recurrences has not been evaluated. However, this technique should not be definitively and globally precluded since a more radical resection was associated with a trend toward better long-term survival in the trial with the largest number of patients.

[Neoplastic portal vein thrombosis and hepatic metastasis from colorectal cancer. A rare association]. / Thrombose portale tumorale et métastase hépatique de cancer colorectal. Une association peu connue.

It is rare for portal vein thrombosis to complicate colorectal liver metastases. However malignant portal vein thrombosis must be anticipated when considering hepatic resection. While this finding may influence long-term survival, it does not absolutely contraindicate hepatic resection. We report here a case of colorectal metastasis to the liver with associated macroscopic malignant portal vein thrombosis treated with hepatic resection; the patient is free from recurrence at 5-year follow-up.