Surgery for cholangiocarcinoma Cillo, Umberto; Fondevila, Constantino; Donadon, Matteo ...
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Journal Article
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Surgical resection is the only potentially curative treatment for patients with cholangiocarcinoma. For both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA), 5‐year ...overall survival of about 30% has been reported in large series. This review addresses several challenges in surgical management of cholangiocarcinoma. The first challenge is diagnosis: a biopsy is typically avoided because of the risk of seeding metastases and the low yield of a brush of the bile duct. However, about 15% of patients with suspected pCCA are found to have a benign diagnosis after resection. The second challenge is staging; even with the best preoperative imaging, a substantial percentage of patients has occult metastatic disease detected at staging laparoscopy or early recurrence after resection. The third challenge is an adequate volume and function of the future liver remnant, which may require preoperative biliary drainage and portal vein embolization. The fourth challenge is a complete resection: a positive bile duct margin is not uncommon because the microscopic biliary extent of disease may be more extensive than perceived on imaging. The fifth challenge is the high post‐operative mortality that has decreased in very high volume Asian centres, but remains about 10% in many Western referral centres. The sixth challenge is that even after a complete resection most patients develop recurrent disease. Recent randomized controlled trials found conflicting results regarding the benefit of adjuvant chemotherapy. The final challenge is to determine which patients with cholangiocarcinoma should undergo liver transplantation rather than resection.
Several studies found that the systemic immune‐inflammation index (SII) is a prognostic factor for mortality in patients with solid tumors. It is unknown whether an increased SII in generally healthy ...individuals reflects a risk for developing cancer. Our objective was to investigate the association between the SII and incident cancers in a prospective cohort study. Data were obtained from the Rotterdam Study; a population‐based study of individuals aged ≥45 years, between 2002 and 2013. The SII at baseline was calculated from absolute blood counts. The association between the SII and the risk of any solid incident cancer during follow‐up was assessed using Cox proportional hazard models. Individuals with a prior cancer diagnosis were excluded. Data of 8,024 individuals were included in the analyses. The mean age at baseline was 65.6 years (SD 10.5 years) and the majority were women. During a maximum follow‐up period of 10.7 years, 733 individuals were diagnosed with cancer. A higher SII at baseline was associated with a 30% higher risk of developing a solid cancer (HR of 1.30 95% CI; 1.11–1.53), after adjustment for age, sex, socioeconomic status, smoking, BMI and type 2 diabetes. The absolute cumulative 10‐year cancer risk increased from 9.7% in the lowest quartile of SII to 14.7% in the highest quartile (p‐value = 0.009). The risk of developing cancer was persistent over time and increased for individuals with the longest follow‐up. In conclusion, a high SII is a strong and independent risk indicator for developing a solid cancer.
What's new?
The systemic immune‐inflammation index (SII) incorporates blood counts of neutrophils, lymphocytes, and platelets. Several studies have found that the SII can help to predict mortality in patients with solid tumors. Might the SII also be useful in evaluating future cancer risk? In this prospective epidemiologic study, the authors found that an increased SII is independently associated with as much as a 30% higher risk of a future diagnosis of a solid cancer. These results indicate that inflammatory cells could play a role in the etiology of cancer. Further research is needed.
Summary Background 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and ...fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. Methods We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan–Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. Findings We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0–16·0) to 32·7 months (23·1–42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7–26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5–34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8–16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3–81·6, I2 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2–31·9, I2 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2–92·2, I2 64%). Interpretation Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months—longer than that reported with gemcitabine (6–13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. Funding None.
OBJECTIVE:This trial followed a structured nationwide training program in minimally invasive distal pancreatectomy (MIDP), according to the IDEAL framework for surgical innovation, and aimed to ...compare time to functional recovery after minimally invasive and open distal pancreatectomy (ODP).
BACKGROUND:MIDP is increasingly used and may enhance postoperative recovery as compared with ODP, but randomized studies are lacking.
METHODS:A multicenter patient-blinded randomized controlled superiority trial was performed in 14 centers between April 2015 and March 2017. Adult patients with left-sided pancreatic tumors confined to the pancreas without vascular involvement were randomly assigned (1:1) to undergo MIDP or ODP. Patients were blinded for type of surgery using a large abdominal dressing. The primary endpoint was time to functional recovery. Analysis was by intention to treat. This trial was registered with the Netherlands Trial Register (NTR5689).
RESULTS:Time to functional recovery was 4 days interquartile range (IQR) 3–6) in 51 patients after MIDP versus 6 days (IQR 5–8) in 57 patients after ODP (P < 0.001). The conversion rate of MIDP was 8%. Operative blood loss was less after MIDP (150 vs 400 mL; P < 0.001), whereas operative time was longer (217 vs 179 minutes; P = 0.005). The Clavien–Dindo grade ≥III complication rate was 25% versus 38% (P = 0.21). Delayed gastric emptying grade B/C was seen less often after MIDP (6% vs 20%; P = 0.04). Postoperative pancreatic fistulas grade B/C were seen in 39% after MIDP versus 23% after ODP (P = 0.07), without difference in percutaneous catheter drainage (22% vs 20%; P = 0.77). Quality of life (day 3–30) was better after MIDP as compared with ODP, and overall costs were non-significantly less after MIDP. No 90-day mortality was seen after MIDP versus 2% (n = 1) after ODP.
CONCLUSIONS:In patients with left-sided pancreatic tumors confined to the pancreas, MIDP reduces time to functional recovery compared with ODP. Although the overall rate of complications was not reduced, MIDP was associated with less delayed gastric emptying and better quality of life without increasing costs.
Background
The development of the Da Vinci robotic platform has drastically altered the paradigm of minimal invasive pancreatic surgery. However, the evidence of robotic total pancreatectomy (RTP) is ...still limited. Here we report an alternative approach of RTP, starting with pancreatoduodenectomy (the pancreatic head-first approach).
Methods
The patient was a 55-year-old female with a diagnosis of diffuse PNET in the head, body, and tail of the pancreas. The da Vinci Xi robotic system was used for RTP. Our technique of RTP consists of three steps: (1) pancreatoduodenectomy, (2) (en bloc) distal pancreatectomy, and (3) reconstructions.
Results
The operative time was 490 min with an estimated blood loss of 100 ml. The postoperative course was uneventful, and the patient was discharged on postoperative day 10.
Conclusions
RTP is a technically challenging procedure; however, the pancreatic head-first approach of RTP has several advantages.
Inflammation is a risk factor for morbidity and mortality in the elderly. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that integrates the information of the ...leukocyte differentials into one variable. We aimed to assess whether the NLR is a risk indicator for overall and cause-specific mortality in the general population. We analyzed data (2002–2014) from the Rotterdam Study, a long-standing, population-based, prospective cohort study in a community-dwelling ageing population. The association between the NLR and time to all-cause mortality was assessed with Cox proportional hazard models. We additionally assessed cardiovascular, cancer and other mortality. The multivariable analyses were adjusted for age, gender, socio-economic status (SES), smoking status, body mass index, type 2 diabetes, and history of cancer and cardiovascular disease (CVD). Data of 8715 individuals were included. The mean age was 65.9 years (SD 10.5) and the majority were women (57.1%). The NLR was higher in men, higher age categories, smokers and among individuals with lower SES, prevalent diabetes, or a history of cancer or CVD. During the 11.7 years follow-up period, 1641 individuals died. Survival among individuals in the 3rd, 4th, and 5th quintile of the NLR was significantly poorer than that of those in the 1st quintile (P < 0.001). In the multivariable analysis, NLR levels were independently and significantly associated with an increased risk of all-cause mortality (HR 1.64; 95% CI 1.44–1.86), cardiovascular mortality (HR 1.92; 95% CI 1.49–2.48), and other mortality (HR 1.86; 95% CI 1.54–2.24). No significant association was found for cancer mortality (HR 1.20; 95% CI 0.95–1.51). The NLR is a strong and independent risk indicator for mortality in the elderly population. Its clinical value needs to be established in further studies.
Objective
To analyze the natural history of small asymptomatic pancreatic neuroendocrine tumors (PanNET) and to present a matched comparison between groups who underwent either initial observation or ...resection. Management approach for small PanNET is uncertain.
Methods
Incidentally discovered, sporadic, small (<3 cm), stage I–II PanNET were analyzed retrospectively between 1993 and 2013. Diagnosis was determined either by pathology or imaging characteristics. Intention-to-treat analysis was applied.
Results
A total of 464 patients were reviewed. Observation was recommended for 104 patients (observation group), and these patients were matched to 77 patients in the resection group based on tumor size at initial imaging. The observation group was significantly older (median 63 vs. 59 years,
p
= 0.04) and tended towards shorter follow-up (44 vs. 57 months,
p
= 0.06). Within the observation group, 26 of the 104 patients (25 %) underwent subsequent tumor resection after a median observation interval of 30 months (range 7–135). At the time of last follow-up of the observation group, the median tumor size had not changed (1.2 cm,
p
= 0.7), and no patient had developed evidence of metastases. Within the resection group, low-grade (G1) pathology was recorded in 72 (95 %) tumors and 5 (6 %) developed a recurrence, which occurred after a median of 5.1 (range 2.9–8.1) years. No patient in either group died from disease. Death from other causes occurred in 11 of 181 (6 %) patients.
Conclusions
In this study, no patient who was initially observed developed metastases or died from disease after a median follow-up of 44 months. Observation for stable, small, incidentally discovered PanNET is reasonable in selected patients.
Neoadjuvant therapy may improve survival compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer, but high-quality evidence is lacking.
We systematically ...searched for randomised trials comparing neoadjuvant therapy with upfront surgery for resectable and borderline resectable pancreatic cancer published since database inception until December 2020. The primary outcome was overall survival (OS) by intention-to-treat with subgroup analyses for resectability status. Meta-analyses using a random-effects model were performed. Certainty of evidence was assessed using the GRADE approach.
Seven trials with 938 patients were included. All trials included a neoadjuvant gemcitabine-based chemo(radio)therapy arm. None of the studies used adjuvant FOLFIRINOX. Neoadjuvant therapy improved OS (hazard ratio HR 0.66, 95% confidence interval CI 0.52–0.85; P = 0.001; I2 = 46%) compared with upfront surgery. This represents an increase in median OS from 19 to 29 months. In the subgroup of resectable pancreatic cancer (i.e., venous contact ≤180°, no arterial contact), no statistically significant difference in OS was observed (HR 0.77, 95% CI 0.53–1.12; P = 0.18; I2 = 20%). In the subgroup of borderline resectable pancreatic cancer (i.e. venous contact >180°, any arterial contact), neoadjuvant therapy improved OS (HR 0.61, 95% CI 0.44–0.85; P = 0.004; I2 = 59%). The GRADE certainty of evidence was high for the outcome of OS.
Neoadjuvant therapy improves OS compared with upfront surgery in patients with borderline resectable pancreatic cancer. More evidence is required on whether neoadjuvant therapy improves survival for patients with resectable pancreatic cancer.
•Neoadjuvant therapy was superior for borderline resectable pancreatic cancer.•For patients with resectable pancreatic cancer, no difference was demonstrated.•More evidence is required for patients with resectable pancreatic cancer.•A limitation of the study is the use of gemcitabine-based adjuvant regimens.
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