Determinants and clinical significance of negative scintigraphic findings in primary hyperparathyroidism: a retrospective observational study.

AIM: In patients with recurrent primary hyperparathyroidism (pHPT) or preceding thyroid operation, scintigraphic localization of the pathological parathyroid gland is sometimes unsuccessful. Reason for diagnostic failure, and its clinical relevance is poorly understood. METHODS: This retrospective observational study in patients suffering from a pHPT evaluated independent predictors of a negative preoperative scintigraphy (SC) result, and its relevance for intraoperative outcome using logistic regression analysis. RESULTS: Among 86 pHPT patients scheduled for parathyroid operation, 63 (73%) had a history of a preceding thyroid or parathyroid operation. Preoperative SC could not identify an adenoma in 30 patients (34.9%), and in 12 patients (14.0%), the surgeon was subsequently unable to localize abnormal parathyroid tissue. Preoperative parathyroid hormone concentration was the only significant independent predictor of a negative SC finding (non-linear and indirect association). Independent from surgical history, an unsuccessful intraoperative focus localization was exclusively predicted by preoperative ultrasonographic (US) and SC findings (OR per diagnostic category 2.98; 95%-CI 1.03-8.58, p=0.043, and OR 2.26; 95%-CI: 1.10-4.63, p=0.027, respectively). Compared to exclusive US, however, the combination of SC and US significantly increased the sensitivity and predictive power to identify patients at a high risk for a complicated surgical procedure. CONCLUSION: In patients before parathyroidectomy, a low preoperative parathyroid hormone concentration is significantly associated with a high likelihood for a negative SC finding. Combining US with SC before operation significantly increases the chance to identify patients prone to negative intraoperative findings.

Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around the hepatic artery for prevention of postpancreatectomy haemorrhage: randomized clinical trial (PANDA trial).

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. METHODS: In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. RESULTS: Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). CONCLUSION: A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. REGISTRATION NUMBER: NCT02588066 (http://www.clinicaltrials.gov).

Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach-A Real World Data Analysis.

After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment.

Rare SARS-CoV-2 antibody development in cancer patients.

SARS-CoV-2 antibody development and immunity will be crucial for the further course of the pandemic. Until now, it has been assumed that patients who are infected with SARS-CoV-2 will develop antibodies as has been the case with other coronaviruses, like MERS-CoV and SARS-CoV. In the present study, we analyzed the development of antibodies in 77 patients with an oncologic diagnosis 26 days after positive RT-qPCR testing for SARS-CoV2. RT-qPCR and anti-SARS-CoV2-antibody methods from BGI (MGIEasy Magnetic Beads Virus DNA/RNA Extraction Kit) and Roche (Elecsys Anti-SARS-CoV-2 immunoassay) were used, respectively, according to the manufacturers' specifications. Surprisingly, antibody development was detected in only 6 of 77 individuals with a confirmed history of COVID-19. Despite multiple testing, the remaining patients did not show measurable antibody concentrations in subsequent tests. These results undermine the previous hypothesis that SARS-CoV2 infections are regularly associated with antibody development and cast doubt on the provided immunity to COVID-19. Understanding the adaptive and humoral response to SARS-CoV2 will play a key role in vaccine development and gaining further knowledge on the pathogenesis.

SARS-CoV-2 infections in cancer outpatients-Most infected patients are asymptomatic carriers without impact on chemotherapy.

Oncologic patients are regarded as the population most at risk of developing a severe course of COVID-19 due to the fact that malignant diseases and chemotherapy often weaken the immune system. In the face of the ongoing SARS-CoV-2 pandemic, how particular patients deal with this infection remains an important question. In the period between the 15 and 26 April 2020, a total of 1227 patients were tested in one of seven oncologic outpatient clinics for SARS-CoV-2, regardless of symptoms, employing RT-qPCR. Of 1227 patients, 78 (6.4%) were tested positive of SARS-CoV-2. Only one of the patients who tested positive developed a severe form of COVID-19 with pneumonia (CURB-65 score of 2), and two patients showed mild symptoms. Fourteen of 75 asymptomatic but positively tested patients received chemotherapy or chemo-immunotherapy according to their regular therapy algorithm (±4 weeks of SARS-CoV-2 test), and 48 of 78 (61.5%) positive-tested patients received glucocorticoids as co-medication. None of the asymptomatic infected patients showed unexpected complications due to the SARS-CoV-2 infection during the cancer treatment. These data clearly contrast the view that patients with an oncologic disease are particularly vulnerable to SARS-CoV-2 and suggest that compromising therapies could be continued or started despite the ongoing pandemic. Moreover the relatively low appearance of symptoms due to COVID-19 among patients on chemotherapy and other immunosuppressive co-medication like glucocorticoids indicate that suppressing the response capacity of the immune system reduces disease severity.

Surgical complications and cardiovascular comorbidity - Substantial non-immunological confounders of survival after living donor kidney transplantation.

BACKGROUND: Surgical complications following kidney transplantation compromise immediate graft survival. However, the role of early surgical complications in the impairment of long-term survival is not completely established due to various other influences, such as patient comorbidities. The purpose of this study was to characterize the impact of surgical complications and overlapping patient comorbidities on graft function and survival after living donor kidney transplantation (LDKT). METHODS: Two groups of patients following LDKT between 1995 and 2014 with (n = 65) or without (n = 294) Clavien-Dindo grade 3 and 4 complications were analyzed. Type of surgical revision, graft and patient survival, general patient characteristics, pre-transplant renal function, immunosuppression, and immunological characteristics (HLA mismatch, panel-reactive antibodies, rejections) were determined. Post-transplant graft function as well as long-term graft and patient survival were quantified. RESULTS: Graft survival was 84.4/97.6% (1y), 75.2/92.7% (3y), and 62.1/87.6% (5y) with/without surgical revision, patient survival was 95.3/99.3%, 90.0/97.5%, and 84.7/93.7%, respectively. Surgical revision was required in 18%, which affected graft survival (p = 0.008) to a comparable extent as pre-existing cardiopulmonary/-vascular disease. Initially impaired graft function recovered to an equal level without complications following surgical revision. Whereas pre-existing cardiopulmonary/-vascular disease affected graft loss and patient survival, surgical revision had no particular impact on patient survival. These observations were confirmed by Cox regression. CONCLUSION: Long-term graft survival following LDKT is independently impaired by both postoperative complications and cardiovascular comorbidities. Although both factors may interact, a complication-free postsurgical course may improve graft survival, thereby reducing the need for dialysis restart and enhancing long-term recipient survival.

Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a Randomized Controlled Trial.

Treatment of donation after brain death (DBD) donors with low-dose dopamine improves the outcomes after kidney and heart transplantation. This study investigates the course of liver allografts from multiorgan donors enrolled in the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were randomly assigned to receive low-dose dopamine. Dopamine was infused at 4 µg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5 hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at 32 European centers. Donors and recipients of both groups were very similar in baseline characteristics. Pretransplant laboratory Model for End-Stage Liver Disease score was not different in recipients of a dopamine-treated versus untreated graft (18 ± 8 versus 20 ± 8; P = 0.12). Mean cold ischemia time was 10.6 ± 2.9 versus 10.1 ± 2.8 hours (P = 0.24). No differences occurred in biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus 14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at 2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and 65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor pretreatment with dopamine has no short-term or longterm effects on outcome after LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the standard of care in hemodynamically stable DBDs.

Over-the-scope clip (OTSC®) closure of a recto-acetabular fistula.

A 25-year-old male Syrian refugee presented in our hospital with recurrent hip infections after having undergone hip arthroplasty abroad following destruction of his right hip joint by shell splinters in the Syrian civil war. The patient underwent hip arthroplasty revision with implantation of a cement spacer. CT-scan with rectal contrast media filling revealed a recto-acetabular fistula. Consecutively, the patient underwent ileostomy formation. The fistula was then successfully closed by endoscopic over-the-scope clipping (OTSC®). Fistulas between intestines and joints rarely develop and in the few cases published mostly extensive abdominal rescue surgery has been performed. Here, we present a case of a traumatic recto-acetabular fistula that was successfully closed by OTSC. This innovative method could represent a safe and suitable option to effectively close fistulas between joints and intestines thereby avoiding extensive rescue surgery with bowel resection or permanent ostomy.

ß2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer.

Catecholamines stimulate epithelial proliferation, but the role of sympathetic nerve signaling in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Catecholamines promoted ADRB2-dependent PDAC development, nerve growth factor (NGF) secretion, and pancreatic nerve density. Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras+/G12D;Pdx1-Cre (KC) mice. ADRB2 blockade together with gemcitabine reduced NGF expression and nerve density, and increased survival of LSL-Kras+/G12D;LSL-Trp53+/R172H;Pdx1-Cre (KPC) mice. Therapy with a Trk inhibitor together with gemcitabine also increased survival of KPC mice. Analysis of PDAC patient cohorts revealed a correlation between brain-derived neurotrophic factor (BDNF) expression, nerve density, and increased survival of patients on nonselective ß-blockers. These findings suggest that catecholamines drive a feedforward loop, whereby upregulation of neurotrophins increases sympathetic innervation and local norepinephrine accumulation.

Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).

Prognostic Value of Preoperative Serum Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 After Resection of Ampullary Cancer.

BACKGROUND: The purpose of this study is to investigate the prognostic value of pre-resection serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 after resection of ampullary cancer (AC) in consideration of intestinal (IT) and pancreatobiliary (PT) subtypes. METHODS: Overall survival (OS) analysis of patients undergoing curative resection of ampullary cancer. RESULTS: Elevated preoperative CEA (P = 0.013) and CA 19-9 levels (P = 0.030) were significant prognostic factors. Subgroup analysis, however, showed both markers having prognostic value only for the IT subgroup. Pre-resection CEA within normal range identified a subgroup of IT patients with an excellent median survival of 145 months. Compared to other AC patients, this low-risk ITCEA- subpopulation was characterized by less frequent advanced pT stages (pT3/pT4, 41 vs. 62%; P = 0.047) and lymph node involvement (pN+, 30 vs. 65%; P = 0.001). OS of this subgroup was significantly better compared to other AC patients (145 vs. 25 months; HR = 3.8; P < 0.001). By multivariate survival analysis, the patient age, the PT subtype, and an elevated pre-resection serum CEA value were identified as independent prognostic variables. CONCLUSIONS: In AC, the histomorphologic subclassification is highly relevant regarding the prognostic value of preoperative serum CEA and CA 19-9. IT-patients with normal preoperative CEA represent a favorable subgroup with excellent long-term survival.

Incidence, outcome and risk stratification tools for venous thromboembolism in advanced pancreatic cancer - A retrospective cohort study.

INTRODUCTION: Venous thromboembolism (VTE) is frequent in advanced pancreatic cancer (APC). Recent studies demonstrated that the Khorana score - an established risk stratification tool for VTE in cancer - performs poorly in identifying pancreatic cancer patients at high risk for VTE. MATERIALS AND METHODS: We performed a retrospective cohort study in order to define incidence, treatment and outcome of VTE as well as the performance of VTE risk stratification tools (Khorana score, CONKO score and aPTT ratio) in a "real life" clinical cohort of APC patients undergoing palliative chemotherapy. RESULTS AND CONCLUSIONS: One hundred and seventy-two eligible APC patients from our comprehensive cancer center were identified. VTE after start of palliative chemotherapy was diagnosed in 71 patients (41.3%). Most VTE events were asymptomatic (n=50, 29.1%) with only 21 symptomatic events (12.2%). On multivariate analysis - including age, performance status and carbohydrate antigen 19-9 (CA 19-9) - symptomatic VTE was an independent risk factor for death (hazard ratio [HR]: 2.22, 95% CI: 1.05-2.60, p<0.05). Khorana score, CONKO score and aPTT ratio alone were not able to predict the risk for symptomatic VTE. High risk patients could only be identified by using a combination of either Khorana or CONKO score with aPTT ratio (30% vs. 10% symptomatic VTE events in high vs. low risk patients, p<0.05). The combination of Khorana or CONKO score with aPTT thus may represent a novel risk stratification tool for symptomatic VTE in APC and should further be validated within prospective clinical trials.

Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma.

PURPOSE: Acinar cell carcinoma (ACC) of the pancreas is a very rare cancer, constituting 1 % of all malignant non-endocrine pancreatic tumors. Only very limited data exist to guide treatment in patients with advanced ACC. METHODS: Between 2000 and 2015, 15 patients with ACC were diagnosed and/or treated at our high-volume comprehensive cancer center. Medical records and correlating serum levels of the potential serum tumor markers CA 19-9, CEA and lipase were analyzed retrospectively. RESULTS: A substantial antitumor activity was observed for treatment regimens containing 5-FU and oxaliplatin with partial responses or prolonged disease stabilizations (>12 months) observed in 6 out of 7 patients (86 %). Activity was also observed for single-agent 5-FU and its oral prodrugs. Serum lipase levels were elevated in 7 of 12 patients with advanced disease (58 %), whereas CEA and CA 19-9 seemed to be of minor importance for ACC (elevated pre-treatment levels in 4/12 and 3/12 cases, respectively). In selected patients, repeated serum lipase measurements were available and accurately predicted response to chemotherapy and relapse after surgery. CONCLUSIONS: 5-FU- and oxaliplatin-containing regimens are active in advanced ACC. Lipase kinetics may be a useful novel tool to monitor the course of disease as well as treatment effects in ACC.

Isolated pulmonary metastases define a favorable subgroup in metastatic pancreatic cancer.

PURPOSE: Liver metastasis represents the first site of dissemination in >80% of metastatic pancreatic cancer (PC) patients. Pulmonary metastasis as first site of dissemination in PC is a rare event and might define a biologically distinct subgroup in metastatic PC. METHODS: Consecutive PC patients who were diagnosed or treated with isolated pulmonary metastases at our high-volume comprehensive cancer center were included in a prospectively maintained database between 2002 and 2015. Medical records and correlating computed tomography findings (CT) were retrospectively analyzed. RESULTS: A total of 40 PC patients with isolated pulmonary metastases were identified. Pulmonary metastases represented disease recurrence after initial resection of PC in 22 patients and disease progression of locally advanced pancreatic cancer in 5 patients. 14 out of 27 PC patients (56%) had received chemoradiotherapy for localized disease prior to pulmonary metastasis. Data on 1st-line treatment for pulmonary metastases was available for 38 patients: most patients (71%) received a gemcitabine-based chemotherapy regimen, 5 patients (13%) received best supportive care. After a median follow-up of 37.3 months, median survival after diagnosis of pulmonary metastasis was estimated with 25.5 months (95% CI 19.1-31.8); a significantly improved survival after diagnosis of pulmonary metastasis was observed for patients with less than 10 lung metastases (31.3 vs 18.7 months, p = 0.003) and for an unilateral localization of lung involvement (31.3 vs 21.8 months, p = 0.03). CONCLUSIONS: Our results suggest a favorable outcome of PC patients with isolated pulmonary metastases. Further research is warranted to elucidate the specific molecular characteristics of this rare subgroup.

Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head is justified in elderly patients: A Retrospective Cohort Study.

BACKGROUND: The increasing elderly population is an inevitable trend worldwide in developed countries. Therefore, we aimed to assess the experience of a tertiary pancreatic center with a very homogenous population comprising only patients diagnosed with PDAC of the pancreatic head in patients older than 75 years of age compared to their younger counterparts regarding the benefit in life expectancy and tumor biological aggressiveness. METHODS: 300 patients underwent partial pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD) for PDAC of the pancreatic head between 2002 and 2012 and were evaluated with regard to their co-morbidities, clinicopathological and perioperative variables, postoperative morbidity, mortality and long term survival. Therefore, two groups according to the age at the procedure (A: <75 years, n = 241, B: ≥75 years, n = 59) were designed. RESULTS: There were no differences between groups with regard to gender, performed procedure (PPPD or PD), operation time, blood loss, tumor invasiveness and grade of tumor differentiation, R-status, lymph node ratio, 30-day mortality, length of stay and adjuvant chemotherapy. Extended resections including total pancreatectomy were slightly more often performed in younger patients (p = 0.071) and trended toward a higher rate of surgical complications in patients <75 years of age (p = 0.183). A higher rate of preoperative co-morbidities in elderly patients (group B), was associated with more postoperative non-surgical complications (p = 0.002) in this group of patients. However, the median overall survival (19.2 vs. 18.4 months) did not differ significantly between groups. CONCLUSIONS: Major pancreatic surgery for ductal adenocarcinoma of the pancreatic head is justified in elderly patients. With careful patients' selection and prudent perioperative management, elderly patients will have a similar long term outcome despite the higher rate of postoperative morbidity based on non-surgical complications.

Genetic engineering of mesenchymal stromal cells for cancer therapy: turning partners in crime into Trojan horses.

Mesenchymal stromal cells (MSCs) are adult progenitor cells with a high migratory and differentiation potential, which influence a broad range of biological functions in almost every tissue of the body. Among other mechanisms, MSCs do so by the secretion of molecular cues, differentiation toward more specialized cell types, or influence on the immune system. Expanding tumors also depend on the contribution of MSCs to building a supporting stroma, but the effects of MSCs appear to go beyond the mere supply of connective tissues. MSCs show targeted "homing" toward growing tumors, which is then followed by exerting direct and indirect effects on cancer cells. Several research groups have developed novel strategies that make use of the tumor tropism of MSCs by engineering them to express a transgene that enables an attack on cancer growth. This review aims to familiarize the reader with the current knowledge about MSC biology, the existing evidence for MSC contribution to tumor growth with its underlying mechanisms, and the strategies that have been developed using MSCs to deploy an anticancer therapy.

Treatment options for chylous ascites after major abdominal surgery: a systematic review.

BACKGROUND: Chylous leakage is a relevant clinical problem after major abdominal surgery leading to an increased length of stay. DATA SOURCES: A systematic search of MEDLINE/PubMed and the Cochrane Library was performed according to the PRISMA statement. The search for the MeSH terms "chylous ascites" and/or "lymphatic fistula" retrieved a total of 2,348 articles, of which 36 full-text articles were reviewed by 2 independent investigators. RESULTS: Chylous ascites is described with an incidence of up to 11%, especially after pancreatic surgery. The incidence is increasing with the number of lymph nodes harvested. In patients treated with total parenteral nutrition, conservative treatment is demonstrated to be effective in up to 100% of cases. CONCLUSIONS: The extent of abdominal surgery mainly predicts the risk of chylous ascites. Conservative treatment has been shown to be effective in almost all cases and is the treatment of choice.

Histomorphologic and molecular phenotypes predict gemcitabine response and overall survival in adenocarcinoma of the ampulla of Vater.

BACKGROUND: The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS). METHODS: Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study. Those were compared with 206 matching patients with periampullary pancreatic cancer (ie, pancreatic ductal adenocarcinoma, PDAC). IT and PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, ß-Catenin, and Villin. Multivariate survival analysis was performed. RESULTS: OS of PT patients was less compared with IT patients (25 vs 98 months; P < .001), whereas it was comparable with patients with PDAC (25 vs 14 months; P = .123). PT patients receiving adjuvant gemcitabine chemotherapy featured improved OS (32 vs 13 months; P = .013), whereas gemcitabine tended to be associated with decreased OS in IT patients (35 vs 112 months; P = .193). Besides histopathologic classification, expression of CK7 and MUC2 were important prognostic variables. PT patients with CK7-positivity or MUC2-negativity were segregated into an even poorer prognostic group. CONCLUSION: PapCa is not a separate tumor entity. We demonstrate important differences between IT-PapCa and PT-PapCa not only in long-term survival but also in response to adjuvant gemcitabine. Tumor biology and clinical course of PT tumors resemble those of PDAC. PT tumors should therefore be treated like PDAC.

ALK expression is absent in pancreatic ductal adenocarcinoma.

PURPOSE: It has not yet been clearly defined whether anaplastic lymphoma kinase (ALK) expression can be detected in pancreatic ductal adenocarcinoma (PDAC). METHODS: Within a retrospective study, archival PDAC surgical specimens were screened for ALK expression in tumor and normal tissue by immunohistochemistry (IHC) with the use of a specific ALK detection kit on a tissue microarray (TMA). RESULTS: PDAC tumor tissue was available from 99 resected cases: fifty-eight out of 99 patients (59 %) had nodal-positive disease, and 80 patients (81 %) had pT3 tumors. Forty-nine patients underwent R0 resection, and in 48 cases, resection status was classified R1. Regarding ALK expression, five cases showed faint immunoreactivity on TMA, which was negative on whole mount sections. All other 94 cases showed no ALK expression. CONCLUSION: In 99 PDAC cases, no ALK expression was detected by IHC; ALK thus may not serve as a relevant drug target in PDAC.