B. Groot Koerkamp

Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer: Upfront surgery versus neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer

Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer.

Low skeletal muscle mass is associated with increased hospital expenditure in patients undergoing cancer surgery of the alimentary tract

Background Low skeletal muscle mass is associated with poor postoperative outcomes in cancer patients. Furthermore, it is associated with increased healthcare costs in the United States. We investigated its effect on hospital expenditure in a Western-European healthcare system, with universal access. Methods Skeletal muscle mass (assessed on CT) and costs were obtained for patients who underwent curative-intent abdominal cancer surgery. Low skeletal muscle mass was defined based on pre-established cut-offs. The relationship between low skeletal muscle mass and hospital costs was assessed using linear regression analysis and Mann-Whitney U-tests. Results 452 patients were included (median age 65, 61.5% males). Patients underwent surgery for colorectal cancer (38.9%), colorectal liver metastases (27.4%), primary liver tumours (23.2%), and pancreatic/periampullary cancer (10.4%). In total, 45.6% had sarcopenia. Median costs were €2,183 higher in patients with low compared with patients with high skeletal muscle mass (€17,144 versus €14,961; P<0.001). Hospital costs incrementally increased with lower sex-specific skeletal muscle mass quartiles (P = 0.029). After adjustment for confounders, low skeletal muscle mass was associated with a cost increase of €4,061 (P = 0.015). Conclusion Low skeletal muscle mass was independently associated with increased hospital costs of about €4,000 per patient. Strategies to reduce skeletal muscle wasting could reduce hospital costs in an era of incremental healthcare costs and an increasingly ageing population.

Histological and Molecular Subclassification of Pancreatic and Nonpancreatic Periampullary Cancers: Implications for (Neo) Adjuvant Systemic Treatment

The benefit of adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC) has been confirmed in randomized controlled trials. For nonpancreatic periampullary cancers (NPPC) originating from the distal bile duct, duodenum, ampulla, or papilla of Vater, the role of adjuvant therapy remains largely unclear. This review describes methods for distinguishing PDAC from NPPC by means of readily available and recently developed molecular diagnostic methods. The difficulties of reliably determining the exact origin of these cancers pathologically also is discussed. The review also considers the possibility of unintentional inclusion of NPPC in the most important adjuvant trials on PDAC and the subsequent implications for interpretation of the results. The authors conclude that correct determination of the origin of periampullary cancers is essential for clinical management and should therefore be systematically incorporated into clinical practice and future studies.

Perioperative and long-term outcome of intrahepatic cholangiocarcinoma involving the hepatic hilus after curative-intent resection: comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short‐ and long‐term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma. Methods: A total of 912 patients with mass‐forming peripheral intrahepatic cholangiocarcinoma, 101 patients with hilar type intrahepatic cholangiocarcinoma, and 159 patients with hilar cholangiocarcinoma undergoing curative resection from 2000 to 2015 were included from two multi‐institutional databases. Clinicopathologic characteristics and short‐ and long‐term outcomes were compared among the 3 groups. Results: Patients with hilar type intrahepatic cholangiocarcinoma had more aggressive tumor characteristics (eg, higher frequency of vascular invasion and lymph nodes metastasis) and experienced more extensive resections in comparison with either peripheral intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma patients. The odds of lymphadenectomy and R0 resection rate among patients with hilar type intrahepatic cholangiocarcinoma were comparable with hilar cholangiocarcinoma patients, but higher than peripheral intrahepatic cholangiocarcinoma patients (lymphadenectomy incidence, 85.1% vs 42.5%, P < .001; R0 rate, 75.2% vs 88.8%, P < .001). After curative surgery, patients with hilar type intrahepatic cholangiocarcinoma experienced a higher rate of technical‐related complications compared with peripheral intrahepatic cholangiocarcinoma patients. Of note, hilar type intrahepatic cholangiocarcinoma was associated with worse disease‐specific survival and recurrence‐free survival after curative resection versus peripheral intrahepatic cholangiocarcinoma (median disease‐specific survival, 26.0 vs 54.0 months, P < .001; median recurrence‐free survival, 13.0 vs 18.0 months, P = .021) and hilar cholangiocarcinoma (median disease‐specific survival, 26.0 vs 49.0 months, P = .003; median recurrence‐free survival, 13.0 vs 33.4 months, P < .001). Conclusion: Mass‐forming intrahepatic cholangiocarcinoma with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma, which showed distinct clinicopathologic characteristics, worse long‐term outcomes after curative resection, in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.

Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin

Abstract Background: Biliary tract cancer (BTC) is an uncommon cancer with an unfavorable prognosis. Since 2010, the standard of care for patients with unresectable BTC is palliative treatment with gemcitabine plus cisplatin, based on the landmark phase III ABC-02 trial. This current study aims to evaluate the efficacy and safety of gemcitabine and cisplatin in patients with unresectable cholangiocarcinoma and gallbladder cancer in daily practice that meet the criteria for the ABC-02 trial in comparison to patients who did not. Methods: Patients diagnosed with unresectable BTC between 2010 and 2015 with an indication for gemcitabine and cisplatin were included. We divided these patients into three groups: (I) patients who received chemotherapy and met the criteria of the ABC-02 trial, (II) patients who received chemotherapy and did not meet these criteria and (III) patients who had an indication for chemotherapy, but received best supportive care without chemotherapy. Primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS). Results: We collected data of 208 patients, of which 138 (66.3%) patients received first line chemotherapy with gemcitabine and cisplatin. Median OS of 69 patients in group I, 63 patients in group II and 65 patients in group III was 9.6 months (95%CI = 6.7–12.5), 9.5 months (95%CI = 7.7–11.3) and 7.6 months (95%CI = 5.0–10.2), respectively. Median PFS was 6.0 months (95%CI = 4.4–7.6) in group I and 5.1 months (95%CI = 3.7–6.5) in group II. Toxicity and number of dose reductions (p = .974) were comparable between the two chemotherapy groups. Conclusion: First-line gemcitabine and cisplatin is an effective and safe treatment for patients with unresectable BTC who do not meet the eligibility criteria for the ABC-02 trial. Median OS, PFS and treatment side effects were comparable between the patients who received chemotherapy (group I vs. group II).

Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma

The role of routine lymph node dissection (LND) in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The objective of this study was to investigate the trends of LND use in the surgical treatment of ICC.

Surgery for perihilar cholangiocarcinoma

Perihilar cholangiocarcinoma (PHC) arises at or near the biliary confluence, with an incidence of about one in 100 000. Primary sclerosing cholangitis is the most important risk factor, with a lifetime cancer risk of 10 per cent. Patients typically present with painless jaundice. Imaging shows intrahepatic biliary dilatation with an abrupt cut-off at the confluence. Staging includes abdominal CT and magnetic resonance cholangiopancreatography (MRCP); CT is preferred to assess vascular involvement and metastatic disease, whereas MRCP better delineates the biliary extent of the tumour. The additional yield for metastatic disease is about 1 per cent for chest CT and 5 per cent for PET–CT, at the cost of false-positive results. Establishing a diagnosis for a patient with perihilar obstruction can be challenging. If a large mass (over 5 cm) is seen in the liver hilum, a diagnosis of gallbladder cancer invading the hepatoduodenal ligament or intrahepatic cholangiocarcinoma growing towards the biliary confluence is more likely than PHC. Sometimes a diagnosis of gallbladder cancer is made only during surgery or at pathological examination after resection. This distinction is important because resection of gallbladder cancer invading the hepatoduodenal ligament appears futile. Up to 15 per cent of patients who undergo resection for presumed PHC have a non-malignant stricture. A common benign diagnosis is IgG4associated cholangitis (IAC). The HISORt criteria predict the presence of IAC based on histology, imaging, serology, organ manifestation and response to treatment (steroids). Typical findings for IAC on imaging are smooth concentric biliary wall thickening with a visible lumen, absence of a mass, skip lesions and involvement of the intrapancreatic bile duct. A fourfold increase in IgG4 nearly excludes PHC. However, in one study1 only 78 per cent of patients with IAC had a raised level of IgG4, whereas 14 per cent of those with cholangiocarcinoma had an increased level. If IAC is likely, a course of steroids should be considered. The carbohydrate antigen (CA) 19-9 level is often increased in patients with PHC, but may also be raised in nonmalignant biliary obstruction. Brush cytology has an excellent specificity but cannot exclude cancer owing to poor sensitivity. Other benign diagnoses include stone disease, benign stricture in primary sclerosing cholangitis and granulomatous/sclerosing cholangitis. Percutaneous tumour biopsy is typically avoided because of concern about tumour dissemination. Meanwhile, the risk of follow-up is the development of unresectable disease. Without surgery, the median overall survival (OS) of patients with PHC is about 8 months. After resection with curative intent, the median OS is approximately 40 months, with a 5-year OS rate of about 35 per cent2. Unfortunately, cure (10-year recurrence-free survival) is rare and mostly seen in patients with papillary or well differentiated PHC3. Most Western centres consider surgery if complete resection (R0) seems feasible in the absence of metastatic disease. About 20 per cent of patients have liver or peritoneal metastases on imaging at initial presentation; an additional 20 per cent have occult metastatic disease at surgical exploration. A Japanese study4 reported that, in patients with metastatic disease, survival after resection was similar to that associated with palliative chemotherapy. Endoscopic ultrasonography can determine the involvement of extraregional (such as aortocaval or truncal) lymph nodes; survival of these patients after resection is worse, although long-term survival is possible. The extent of biliary tumour and vascular involvement determine the feasibility of complete resection. Vascular involvement may require portal vein (PV) or hepatic artery reconstruction. A large meta-analysis5 found a twofold worse OS for patients requiring PV reconstruction. Hepatic artery reconstruction is rarely performed in Western centres; small Japanese series have shown poor survival. Biliary extent of the tumour is classified using the Bismuth classification. Bismuth IV represents the most extensive biliary involvement in which the secondorder bile ducts are isolated on both sides. A Japanese study6 reported a 5-year OS rate of 33 per cent after resection for Bismuth IV tumours. PV reconstruction or Bismuth IV resection may benefit selected patients in experienced centres. The expected benefit of surgery should be compared with the expected surgical mortality. Resection for PHC is associated with one of the highest

Association of the location of pancreatic ductal adenocarcinoma (head, body, tail) with tumor stage, treatment, and survival: a population-based analysis

Abstract Background: The association between pancreatic ductal adenocarcinoma (PDAC) location (head, body, tail) and tumor stage, treatment and overall survival (OS) is unclear. Methods: Patients with PDAC diagnosed between 2005 and 2015 were included from the population-based Netherlands Cancer Registry. Patient, tumor and treatment characteristics were compared with the tumor locations. Multivariable logistic and Cox regression analyses were used. Results: Overall, 19,023 patients were included. PDAC locations were 13,451 (71%) head, 2429 (13%) body and 3143 (16%) tail. Differences were found regarding metastasized disease (head 42%, body 69%, tail 84%, p < .001), size (>4 cm: 21%, 40%, 51%, p < .001) and resection rate (17%, 4%, 7%, p < .001). For patients without metastases, median OS did not differ between head, body, tail (after resection: 16.8, 15.0, 17.3 months, without resection: 5.2, 6.1, 4.6 months, respectively). For patients with metastases, median OS differed slightly (2.6, 2.4, 1.9 months, respectively, adjusted HR body versus head 1.17 (95%CI 1.10–1.23), tail versus head 1.35 (95%CI 1.29–1.41)). Conclusions: PDAC locations in body and tail are larger, more often metastasized and less often resectable than in the pancreatic head. Whereas survival is similar after resection, survival in metastasized disease is somewhat less for PDAC in the pancreatic body and tail.