Caregiver-reported quality of communication in pancreatic and periampullary cancer.

BACKGROUND: Communication between caregivers and clinical team members is critical for transitional care, but its quality and potential impact on outcomes are not well understood. This study reports on caregiver-reported quality of communication with clinical team members in the postpancreatectomy period and examines associations of these reports with patient and caregiver outcomes. METHODS: Caregivers of patients with pancreatic and periampullary malignancies who had undergone pancreatectomy were surveyed. Instrument measures assessed care experiences using the Caregiver Perceptions About Communication with Clinical Team Members (CAPACITY) instrument. The instrument has two main subscales: communication, assessing the extent to which providers helped caregivers comprehend details of clinical visits, and capacity, defined as the extent to which providers assessed whether caregivers were able to care for patients. RESULTS: Of 265 caregivers who were approached, 240 (90.6%) enrolled in the study. The mean communication and capacity subscale scores were 2.7 ± 0.6 and 1.5 ± 0.6, respectively (range, 0-4 [higher = better]). Communication subscale scores were lower among caregivers of patients who experienced (vs. those who did not experience) a 30-day readmission (2.6 ± 0.5 vs. 2.8 ± 0.6, respectively; p = .047). Capacity subscale scores were inversely associated with restriction in patient daily activities (a 0.04 decrement in the capacity score for every 1 point in daily activity restriction; p = .008). CONCLUSIONS: After pancreatectomy, patients with pancreatic and periampullary cancer whose caregivers reported worse communication with care providers were more likely to experience readmission. Caregivers of patients with greater daily activity restrictions were less likely to report being asked about the caregiver's skill and capacity by clinicians. PLAIN LANGUAGE SUMMARY: This prospective study used a validated survey instrument and reports on the quality of communication between health care providers and caregivers as reported by caregivers of patients with pancreatic and periampullary cancer after pancreatectomy. In an analysis of 240 caregivers enrolled in the study, lower communication scores (the extent to which providers helped caregivers understand clinical details) were associated with higher odds of 30-day patient readmission to the hospital. In addition, lower capacity scores (the extent to which providers assessed caregivers' ability to care for patients) were associated with greater impairment in caregivers. The strikingly low communication quality and capacity assessment scores suggest substantial room for improvement, with the potential to improve both caregiver and patient outcomes.

Prognostic Impact of Para-Aortic Lymph Node Metastasis in Resected Non-Pancreatic Periampullary Cancers.

BACKGROUND: Surgery remains debatable in para-aortic lymph node (PALN, station 16b1) metastasis in non-pancreatic periampullary cancer (NPPAC). This study examined the impact of PALN metastasis on outcomes following pancreaticoduodenectomy (PD) in NPPAC. METHODS: A retrospective analysis of patients with NPPAC who were explored for PD with PALN dissection was performed. Based on the extent of nodal involvement on final histopathology, they were stratified as node-negative (N0), regional node involved (N+) and metastatic PALN (N16+) and their outcomes were compared. RESULTS: Between 2011 and 2022, 153/887 PD patients underwent a PALN dissection, revealing N16+ in 42 patients (27.4%), of whom 32 patients underwent resection. The 3-years overall survival (OS) for patients with N16+ was 28% (95% confidence interval [CI] 13-60%), notably lower than the 67% (95% CI 53-83.5%; p = 0.007) for those without PALN metastasis. Stratified by nodal involvement, the median OS for N+ and N16+ patients was similar (28.4 months and 26.2 months, respectively). The N0 subgroup had a significantly longer 3-years OS of 87.5% (95% CI 79-96.7%; p = 0.0051). Interestingly, 10 patients not offered resection following N16+ identified on frozen section had a median survival of only 9 months. The perioperative morbidity and mortality in patients undergoing PD with PALN dissection were similar to standard resections. CONCLUSION: In a select group of patients with NPPAC, PD in isolated PALN metastasis was associated with improved OS. The survival in this group of patients was comparable with regional node-positive patients and significantly better than palliative treatment alone.

Preoperative profiles of plasma amino acids and derivatives distinguish periampullary cancer and benign disease.

Periampullary cancers, including pancreatic ductal adenocarcinoma, ampullary-, cholangio-, and duodenal carcinoma, are frequently diagnosed in an advanced stage and are associated with poor overall survival. They are difficult to differentiate from each other and challenging to distinguish from benign periampullary disease preoperatively. To improve the preoperative diagnostics of periampullary neoplasms, clinical or biological markers are warranted.In this study, 28 blood plasma amino acids and derivatives from preoperative patients with benign (N = 45) and malignant (N = 72) periampullary disease were analyzed by LC-MS/MS.Principal component analysis and consensus clustering both separated the patients with cancer and the patients with benign disease. Glutamic acid had significantly higher plasma expression and 15 other metabolites significantly lower plasma expression in patients with malignant disease compared with patients having benign disease. Phenylalanine was the only metabolite associated with improved overall survival (HR = 0.50, CI 0.30-0.83, P < 0.01).Taken together, plasma metabolite profiles from patients with malignant and benign periampullary disease were significantly different and have the potential to distinguish malignant from benign disease preoperatively.

Ferumoxtran-10-enhanced MRI for pre-operative metastatic lymph node detection in pancreatic, duodenal, or periampullary adenocarcinoma.

OBJECTIVES: To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology. METHODS: Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs. RESULTS: Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively. CONCLUSION: USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma. CLINICAL RELEVANCE STATEMENT: Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy. REGISTRATION: The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 . KEY POINTS: LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers.

Anomalies of the right hepatic artery in periampullary cancer treatment: are pathological and clinical outcomes different? A single tertiary referral center retrospective analysis.

PURPOSE: Anomalies of the right hepatic artery (RHA) may represent an additional challenge in pancreatoduodenectomy (PD). The aim of this study is to assess the potential impact of variations in hepatic arterial anatomy on perioperative outcomes. METHODS: PDs performed for periampullary malignancies between 2017 and 2022 were retrospectively enrolled and subdivided in two groups: modal pattern of vascularization (MPV) and anomalous pattern of vascularization (APV). A propensity score matching (PSM) analysis was conducted to homogenize the two study populations. The two groups were then compared in terms of perioperative outcomes and pathological findings. RESULTS: Thirty-eight patients (16.3%) out of 232 presented a vascular anomaly: an accessory RHA in 7 cases (3%), a replaced RHA in 26 cases (11.2%), and a replaced HA in 5 cases (2.1%). After PSM, 76 MPV patients were compared to the 38 APV patients. The incidence rate of postoperative complications was comparable between the two study populations (p=0.2). Similarly, no difference was detected in terms of histopathological data, including margin status. No difference was noted in terms of intraoperative hemorrhage and vascular resection. CONCLUSION: When PDs are performed in high-volume centers, the presence of an APV of the RHA does not relate to a significant impact on perioperative complications. Moreover, no influence was noted on histopathological findings.

Sex and gender differences in treatment intention, quality of life and performance status in the first 100 patients with periampullary cancer enrolled in the CHAMP study.

BACKGROUND: Periampullary cancer is a term for cancers arising in or in close proximity to the pancreas. Pancreatic cancer is the 3rd leading cause of cancer death for both sexes and while surgery is the only option for cure, chemotherapy is given in both the adjuvant and palliative settings. The aim of this study was to investigate any sex and gender differences in patients with pancreatic and other periampullary adenocarcinomas enrolled in a prospective, observational trial. METHODS: The study cohort consists of the first 100 patients, 49 women and 51 men, enrolled in the Chemotherapy, Host Response and Molecular dynamics in Periampullary cancer (CHAMP) study, an ongoing study of patients undergoing neoadjuvant, adjuvant or first-line palliative chemotherapy treatment. Twenty-five patients had surgery with curative intent and subsequent adjuvant treatment, and 75 patients were treated with palliative chemotherapy. Data regarding health-related quality of life (HRQoL, EORTC-QLQ-C30) at baseline, demographic and clinicopathological factors were examined and stratification by treatment intention according to sex. Overall survival (OS) was calculated through Kaplan-Meier analysis. RESULTS: There was a statistically significant difference between male and female patients treated with curative intent, with fewer women having undergone surgery (18 vs 7, p = 0.017), also after adjustment for age, tumor location and performance status. No statistical differences were found between the sexes regarding age, comorbidities, or clinicopathological factors. Before start of chemotherapy treatment, health-related quality of life (HRQoL) was lower in female than in male patients. However, HRQoL was not associated with performance status in female patients, whereas in male patients several HRQoL indicators were significantly positively associated with poorer performance status at baseline. CONCLUSIONS: This study shows no clear differences between the sexes regarding biological factors concluding that gender bias might be responsible for the discrepancy between men and women being offered curative surgery. The observed difference between women and men regarding the association between HRQoL and performance status is unprecedented. Altogether these findings underline the importance of taking gender into consideration when assessing eligibility for curative surgery in order to improve biological outcome and decrease suffering in both sexes. TRIAL REGISTRATION: NCT03724994.

Trajectories of immune-related serum proteins and quality of life in patients with pancreatic and other periampullary cancer: the CHAMP study.

BACKGROUND: There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP). METHODS: Proximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts. RESULTS: In total nine proteins; chemokine (C-C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman's Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19-9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain. CONCLUSIONS: This is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as "chemo brain". It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition. TRIAL REGISTRATION: Clinical Trial Registration: NCT03724994.

Robotic approach mitigates the effect of major complications on survival after pancreaticoduodenectomy for periampullary cancer.

BACKGROUND: Major complications (MCs) after pancreaticoduodenectomy (PD) are a known independent predictor of worse oncologic outcomes. There are limited data on the effect of major complications on long-term outcomes after robotic PD (RPD). The aim of this study is to compare the effect of MC on overall (OS) and disease-free survival (DFS) after RPD and open PD (OPD). METHODS: This is a single-center, retrospective review of a prospectively maintained database of all patients undergoing PD for periampullary cancer including ampullary adenocarcinoma, distal cholangiocarcinoma, and duodenal carcinoma. Univariate analysis was performed on all clinical, pathologic, and treatment factors. MCs were defined as Clavien-Dindo ≥ grade 3. Kaplan-Maier survival analysis was performed with log-rank test for group comparison. Multivariable Cox regression analysis was used to identify factors associated with overall survival (OS) in both the OPD and RPD groups. RESULTS: A total of 190 patients with ampullary carcinoma (n = 98), cholangiocarcinoma (n = 55), and duodenal adenocarcinoma (n = 37) were examined over the study period with 61.1% (n = 116) undergoing RPD and 38.9% (n = 74) undergoing OPD. There was no significant difference in patient demographics between the RPD and OPD cohorts. Furthermore, R0 resection rates, tumor size, and lymph node involvement were similar between the RPD and OPD cohorts. OPD had higher rate of MC (40.5% vs 28.3% in RPD, p = 0.011) including clinically relevant pancreatic fistula (25.7% vs 8.6%, p = 0.001) and wound infection (34.5% vs 13.8%, p < 0.001). MCs were associated with a lower OS in the OPD cohort (HR = 2.18, 95%CI 1.0-4.55, p = 0.038). MCs were not associated with OS in the RPD cohort (HR = 1.55, 95%CI 0.87-2.76, p = 0.14). CONCLUSION: MCs are associated with worse patient outcomes after OPD but not after RPD. Robotic approach mitigates and possibly abrogates the negative effects of MCs on patient outcomes after PD for malignancy and is associated with improved adjuvant chemotherapy completion rates.

Quantitative, qualitative and spatial analysis of lymphocyte infiltration in periampullary and pancreatic adenocarcinoma.

Immunotherapeutic modalities are currently revolutionizing cancer treatment. In pancreatic cancer, however, early clinical trials have been disappointing. The optimization of immunotherapeutic strategies requires better understanding of the inflammatory tumor microenvironment. Therefore, the aim of our study was to perform a detailed in situ description of lymphocyte infiltration patterns in resected pancreatic and other periampullary cancers. Multiplexed immunofluorescence imaging was applied to tissue microarrays with tumors from a cohort of 175 patients with resected periampullary adenocarcinoma. A panel of immune cell markers including CD4, CD8α, FoxP3, CD20, CD45RO and pan-cytokeratin was applied to allow for simultaneous spatial analysis of multiple lymphocyte populations. The majority of lymphocyte populations were significantly more abundant in intestinal (I-type) compared to pancreatobiliary (PB-type) tumors. Hierarchical cluster analysis revealed several immune cell signatures of potential clinical relevance. Notably, in the stromal compartment of PB-type tumors, high infiltration of B cells, CD8α+ CD45RO+ and single-positive CD4+ T cells, but low levels of FoxP3+ CD45ROhigh and single-positive CD8α+ T cells were associated with improved overall survival (OS). The study also defined prognostic relevant topographical patterns of lymphocytic infiltration, in particular proximity of CD8α+ cells to cancer cells. Moreover, the presence of lymphocytes with potential T-helper capacities (CD4+ ) in the nearest vicinity to CD8α+ cells was associated with a prolonged OS. Our data demonstrate that the composition and clinical impact of immune infiltrates in periampullary adenocarcinoma differ by morphological type as well as localization. Furthermore, spatial in situ analysis identified potential immunological mechanisms of prognostic significance.

Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information.

BACKGROUND: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC). METHODS: Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis. RESULTS: Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC). CONCLUSIONS: The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed. TRIAL REGISTRATION: clinicaltrials.gov ( NCT01919151 ).

Chemotherapy, host response and molecular dynamics in periampullary cancer: the CHAMP study.

BACKGROUND: Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the "Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)" study aims to monitor these processes to gain new insight into this perplexing disease. METHODS: The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. DISCUSSION: Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. TRIAL REGISTRATION: This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.

Pancreaticoduodenectomy: Outcomes of a complex surgical procedure from a developing country.

BACKGROUND: Pancreaticoduodenectomy (PD) plays an integral part in the management of pancreatic, periampullary and duodenal cancers, along with a few other pathologies of this region. Despite advances in surgery PD continues to have significant morbidity and noteworthy mortality. The aim of this study is to provide an in-depth report on the patient characteristics, indications and the outcomes of PD) in a tertiary cancer hospital in Pakistan. MATERIALS AND METHODS: The study population included patients who underwent PD between January 1, 2014 and march 31, 2019, at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC) in Pakistan. The data was retrospectively analyzed from the Hospital Information System (HIS), which is a prospectively maintained patient electronic database of SKMCH&RC. Patient characteristics, procedural details and post-operative outcomes according to internationally accepted definitions were reported. RESULTS: A total of 161 patients underwent PD at our hospital in the study period at a median age of 53 years, ranging from 19 to 78 years. 62% of the patients were males while 37% were females. Jaundice was the most common presenting symptom (64.6%), followed by abdominal pain (26.7%). PD with pancreaticogastrostomy was performed in 110 patients (68.3%), while pancreaticojejunostomy was performed in the rest of the cohort. Surgical site infection (SSI) was observed in 64 patients (40%). The incidence of Pancreatic Fistula grade C based on the International Study Group on Pancreatic Fistula (ISGPF) definition was 7.45% (n = 12). The 30 days mortality rate was 3.1%. Median survival of the cohort was 21 ±1.13 months and disease-free survival was 16±2.62 months. CONCLUSION: PD can be performed with acceptable morbidity and mortality in a resource constrained country, as long as it is undertaken in a high-volume center. This is in keeping with data published from other well-reputed international centers.

Expression of peritumoral SPARC during distal cholangiocarcinoma progression and correlation with outcome.

Objectives: Distal cholangiocarcinoma (dCCA) is a malignancy with a dismal prognosis. One of the hallmarks is the presence of a rich desmoplastic stroma believed to contribute to tumor progression and treatment resistance. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein implicated in tumor-stroma interaction with prognostic correlation across several malignancies. The aim of the present study was to evaluate the expression pattern and prognostic significance of SPARC in resected dCCA and paired lymph node metastasis.Materials and methods: SPARC expression was evaluated in 59 resected dCCA samples and 25 paired lymph node metastases as well as 10 benign bile duct samples using immunohistochemistry. Stromal SPARC expression was scored semi quantitatively. Survival was estimated using the Kaplan-Meier method with associated log-rank test.Results: SPARC expression was absent in normal bile ducts. In dCCA, peritumoral stromal SPARC was detectable in 47/59 (80%) of samples with 40/59 (68%) classified as high stromal SPARC expression. There was a significantly lower proportion of SPARC positive stroma in paired lymph node metastasis 17/25 (68%) than the corresponding primary tumors 24/25 (96%) (p = .016). Stromal SPARC expression was associated with the presence of lymph node metastasis; high SPARC expression 31/40 (78%) versus low SPARC expression 9/19 (47%) (p = .013). In the present material there was no significant association between stromal SPARC expression and survival.Conclusions: Stromal SPARC expression occurs frequently in dCCA. Although significantly lower than in primary tumors stromal SPARC is frequently retained in paired lymph node metastasis suggesting a possible role in the metastatic process of dCCA.

Robotic-assisted versus open pancreaticoduodenectomy for patients with benign and malignant periampullary disease: a systematic review and meta-analysis of short-term outcomes.

BACKGROUND: Although several non-randomized studies comparing robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) recently demonstrated that the two operative techniques could be equivalent in terms of safety outcomes and short-term oncologic efficacy, no definitive answer has arrived yet to the question as to whether robotic assistance can contribute to reducing the high rate of postoperative morbidity. METHODS: Systematic literature search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases. Prospective and retrospective studies comparing RPD and OPD as surgical treatment for periampullary benign and malignant lesions were included in the systematic review and meta-analysis with no limits of language or year of publication. RESULTS: 18 non-randomized studies were included for quantitative synthesis with 13,639 patients allocated to RPD (n = 1593) or OPD (n = 12,046). RPD and OPD showed equivalent results in terms of mortality (3.3% vs 2.8%; P = 0.84), morbidity (64.4% vs 68.1%; P = 0.12), pancreatic fistula (17.9% vs 15.9%; P = 0.81), delayed gastric emptying (16.8% vs 16.1%; P = 0.98), hemorrhage (11% vs 14.6%; P = 0.43), and bile leak (5.1% vs 3.5%; P = 0.35). Estimated intra-operative blood loss was significantly lower in the RPD group (352.1 ± 174.1 vs 588.4 ± 219.4; P = 0.0003), whereas operative time was significantly longer for RPD compared to OPD (461.1 ± 84 vs 384.2 ± 73.8; P = 0.0004). RPD and OPD showed equivalent results in terms of retrieved lymph nodes (19.1 ± 9.9 vs 17.3 ± 9.9; P = 0.22) and positive margin status (13.3% vs 16.1%; P = 0.32). CONCLUSIONS: RPD is safe and feasible as surgical treatment for malignant or benign disease of the pancreatic head and the periampullary region. Equivalency in terms of surgical radicality including R0 curative resection and number of harvested lymph nodes between the two groups confirmed the reliability of RPD from an oncologic point of view.

Prognostic impact of para-aortic lymph node metastases in non-pancreatic periampullary cancer.

BACKGROUND: Resection of the para-aortic lymph node (PALN) group Ln16b1 during pancreatoduodenectomy remains controversial because PALN metastases are associated with a worse prognosis in pancreatic cancer patients. The present study aimed to analyze the impact of PALN metastases on outcome after non-pancreatic periampullary cancer resection. METHODS: One hundred sixty-four patients with non-pancreatic periampullary cancer who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005 and 2016 were retrospectively investigated. The data were supplemented with a systematic literature review on this topic. RESULTS: In 67 cases, the PALNs were clearly assigned and could be histopathologically analyzed. In 10.4% of cases (7/67), tumor-infiltrated PALNs (PALN+) were found. Metastatic PALN+ stage was associated with increased tumor size (P = 0.03) and a positive nodal stage (P < 0.001). The median overall survival (OS) of patients with metastatic PALN and non-metastatic PALN (PALN-) was 24.8 and 29.5 months, respectively. There was no significant difference in the OS of PALN+ and pN1 PALN patients (P = 0.834). Patients who underwent palliative surgical treatment (n = 20) had a lower median OS of 13.6 (95% confidence interval 2.7-24.5) months. Including the systematic literature review, only 23 cases with PALN+ status and associated OS could be identified; the average survival was 19.8 months. CONCLUSION: PALN metastasis reflects advanced tumor growth and lymph node spread; however, it did not limit overall survival in single-center series. The available evidence of the prognostic impact of PALN metastasis is scarce and a recommendation against resection in these cases cannot be given.

Usefulness of newly modified fully covered metallic stent of 12 mm in diameter and anti-migration feature for periampullary malignant biliary strictures: Comparison with conventional standard metal stent.

BACKGROUNDS: Fully covered self-expandable metal stent (FCSEMS) are preferred for distal malignant biliary stricture (MBS). However, stent migration is a major adverse event of FCSEMS, especially for far distal MBS. We evaluated the usefulness of newly modified FCSEMS (M-FCSEMS) having 12 mm in diameter and anti-migration feature to minimize stent migration compared with the conventional FCSEMS (C-FCSEMS). METHODS: Total 102 patients were enrolled between January 2015 and September 2017 in this prospective comparative study; 50 were allocated to the M-FCSEMS group and 52 to the C-FCSEMS group. The primary outcome was stent migration, and the secondary outcomes were other adverse events, stent occlusion rate, and stent patency during the follow-up period. RESULTS: The baseline characteristics of the two groups did not significantly differ. Endoscopic stent placement was technically successful in all patients. Stent migration occurred in 8.0% (4/50) of the patients in the M-FCSEMS group and 23.1% (12/52) of those in the C-FCSEMS group (P = 0.036). The other adverse events, including stent-related pancreatitis and cholecystitis did not significantly differ between the two groups (P = 0.415). Stent occlusion occurred in 23.9% (11/46) of the patients in the M-FCSEMS group and 37.5% (15/40) in the C-FCSEMS group (P = 0.171). Stent patency was significantly longer in the M-FCSEMS group than in the C-FCSEMS group (228 vs 157 days, P = 0.048). CONCLUSIONS: Modified FCSEMS with 12-mm diameter and anti-migration feature significantly decreased the risk of stent migration and had longer patency compared with C-FCSEMS in patients with periampullary MBS.

Combination of CEUS and MRI for the diagnosis of periampullary space-occupying lesions: a retrospective analysis.

BACKGROUND: The value of magnetic resonance imaging (MRI), contrast-enhanced ultrasound (CEUS), and the combination of CEUS and MRI (CCWM) for the diagnosis of periampullary space-occupying lesions (PSOL) was investigated. METHODS: A total of 102 patients diagnosed with PSOLs by surgery or biopsy were recruited retrospectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI, CEUS, and CCWM were analyzed. RESULTS: MRI, CEUS, and CCWM allowed for the accurate detection of 91.17, 92.15, and 99.01% of PSOLs, respectively. The specificity, PPV, and accuracy of CCWM were significantly different from MRI and CEUS (p < 0.05). However, there the sensitivity and NPV were not significantly different among the three diagnostic technologies. In addition, the specificity, PPV, and accuracy were not significantly different between MRI and CEUS (all p > 0.05). CONCLUSIONS: CCWM is valuable for differentiating benign and malignant PSOL, which provides important guiding significances for the clinic.

Enhanced recovery after surgery protocol enhances early postoperative recovery after pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy (PD). METHODS: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube (NGT) was removed on postoperative day (POD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on POD2; semisolid diet by POD3; abdominal drain was removed on POD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula (POPF); normal diet was allowed on POD5. Discharge criteria on POD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications (defined as per the ISGPS definitions). RESULTS: NGT was removed on POD1 in 45 (90%) patients, abdominal drain removed by POD4 in 41 (82%) and 43 (86%) patients were discharged on POD6. There was no 30-day postoperative mortality. Three (6%) patients had delayed gastric emptying (DGE). None had postoperative hemorrhage and POPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay (LOS) with age (P < 0.05) and a marginal relation between LOS and postoperative albumin (P = 0.05). CONCLUSIONS: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LOS and postoperative complications.

Pancreaticoduodenectomy for periampullary cancer: does the tumour entity influence perioperative morbidity and long-term outcome?

BACKGROUND: Malignant tumours of the periampullary region include ductal adenocarcinoma of the pancreas (Pan-Ca), distal bile duct cancer (DBDC) and adenocarcinoma of the ampulla (Amp-Ca). The present retrospective clinical study was designed to evaluate the influence of tumour entity on postoperative complications and identify risk factors predicting survival and morbidity. METHODS: We retrospectively analysed data from all patients who underwent pancreatic resection for periampullary cancer with curative intent (R0 or R1). Demographic data, risk factors, perioperative complications and survival rates for the different subtypes were assessed. RESULTS: A total of 225 patients with periampullary cancer were identified: 124 (55.1%) had Pan-Ca, 55 (24.4%) had DBDC and 46 had (20.4%) Amp-Ca. Sixty-nine patients (30.7%) had major complications (grade IIIb-V). Patients with DBDC had significantly more grade C pancreatic fistulas. Univariate analysis revealed male gender, BMI >30, R1-status, and low-grade tumour differentiation as risk factors for major complications. Overall in-hospital-mortality was 6.7%. CONCLUSIONS: Further research will be needed to implement more individualized therapy.

PET/MRI in pancreatic and periampullary cancer: correlating diffusion-weighted imaging, MR spectroscopy and glucose metabolic activity with clinical stage and prognosis.

PURPOSE: To correlate the clinical stage and prognosis of pancreatic or periampullary cancer with the imaging biomarkers on diffusion-weighted imaging, magnetic resonance spectroscopy and glucose metabolic activity derived from integrated PET/MRI. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained. The study group comprised 60 consecutive patients with pancreatic or periampullary cancer who underwent PET/MRI before treatment. The imaging biomarkers were the minimal apparent diffusion coefficient (ADCmin), choline levels, standardized uptake values, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the tumours. The relationships between these biomarkers and clinical TNM stage were evaluated using the Pearson test and the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUROC) was used to evaluate accuracy. The correlation between the imaging biomarker and progression-free survival (PFS) was investigated using the Cox proportional hazards model. RESULTS: ADCmin was significantly lower in N1 and TNM stage 3+ tumours. Choline levels significantly higher in T4 tumours. TLG was significantly higher in T4, N1 and TNM stage 3+ tumours. MTV was significantly higher in T4, N1, M1, and TNM stage 3+ tumours (all P < 0.05). The MTV/ADCmin ratio exhibited the highest AUROC for predicting T4, N1, M1, and advanced TNM stages tumours, and was an independent predictor of PFS (P = 0.018) after adjustment for age, sex, tumour size and stage. CONCLUSION: The imaging biomarkers from integrated PET/MRI may predict clinical stage and PFS in patients with pancreatic or periampullary cancer.