Natural killer cells in pancreatic cancer stroma

Pancreatic cancer remains one of medicine’s largest areas of unmet need. With five-year survival rates of < 8%, little improvement has been made in the last 50 years. Typically presenting with advance stage disease, treatment options are limited. To date, surgery remains the only potentially curative option, however, with such late disease presentation, the majority of patients are unresectable. Thus, new therapeutic options and a greater understanding of the complex stromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer patients. Natural killer (NK) cells are crucial effector units in cancer immunosurveillance. Often used as a prognostic biomarker in a range of malignancies, NK cells have received much attention as an attractive target for immunotherapies, both as cell therapy and as a pharmaceutical target. Despite this interest, the role of NK cells in pancreatic cancer remains poorly defined. Nevertheless, increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to light. Here, we review the role of NK cells in pancreatic cancer, examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy.     

Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison

BackgroundManagement of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC.MethodsThis is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups.Results1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14–2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22–2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54–0.69; p<0.001).ConclusionCurative approaches may guarantee long-term survival in case of recurrence.     

Impact of body mass index in elderly patients treated with laparoscopic liver resection for hepatocellular carcinoma

BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI) on perioperative and oncological outcome in elderly patients(> 70 years old) treated with laparoscopic liver resection for hepatocellular carcinoma(HCC).METHODS Retrospective multicenter study including 224 elderly patients(> 70 years old) operated by laparoscopy for HCC(196 with a BMI < 30 and 28 with BMI ≥ 30), o...     

Routine postoperative imaging is important after ureteroscopic stone manipulation

PURPOSE: Improved fiber optics and advanced intracorporeal lithotripsy devices have significantly decreased the incidence of complications during ureteroscopic procedures. Despite recent reports suggesting that radiographic imaging may not be necessary in all individuals after routine ureteroscopy silent obstruction may develop in some, ultimately resulting in renal damage. We determined the incidence of postoperative silent obstruction at our institution and assessed the need for routine functional radiographic studies after ureteroscopy. MATERIALS AND METHODS: We retrospectively reviewed the charts of 320 patients who underwent a total of 459 ureteroscopic procedures for renal or ureteral calculi in a 3-year period. Complete followup with imaging was available for 241 patients (75%). Average patient age was 47.2 years. The variables of interest reviewed included preoperative pain, preoperative obstruction, targeted calculous site, stone-free rate, postoperative pain and postoperative obstruction. Mean followup was 5.4 months (range 2 to 43). RESULTS: A total of 241 patients with complete followup were identified in this analysis. Preoperative pain was present in 202 patients (84%) and 168 (70%) had preoperative obstruction. Overall targeted calculous clearance was successful in 73% of the patients and an additional 15.8% had residual fragments less than 4 mm. The renal, proximal or mid and distal ureteral stone-free rate was 32.1%, 81.9% and 90.5%, while in an additional 46.4%, 6.3% and 6.7% of cases, respectively, residual fragments were less than 4 mm. Of the 241 patients 30 (12.3%) had obstruction postoperatively due to residual stone in 25 (83.3%), stricture in 3 (10%), edema of the ureteral orifice in 1 (3.3%) and a retained encrusted stent in 1 (3.3%). Postoperatively obstruction correlated with postoperative pain in 23 of the 30 patients (76.7%). Pain was present postoperatively in 30 of the 211 patients (14%) without evidence of ureteral obstruction postoperatively. However, silent obstruction developed in 7 patients (23.3%) or 2.9% of the total cohort. All 7 patients underwent secondary ureteroscopy to alleviate obstruction. A single patient ultimately received chronic hemodialysis for renal failure, 1 was lost to followup and in 5 there was documented successful resolution of the cause of obstruction. CONCLUSIONS: Our analysis suggests that silent obstruction remains a potentially significant complication after stone management. Relying on postoperative pain to determine the necessity of postoperative imaging places patients at risk for progressive renal failure due to unrecognized obstruction. Therefore, we recommend that imaging of the collecting system should be performed by excretory urography, spiral computerized tomography or ultrasound within 3 months after routine ureteroscopic stone treatment to avoid the potential complications of unrecognized ureteral obstruction.     

Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system.

PURPOSE: Mucositis occurs in almost all patients treated with radiotherapy for head and neck cancer. The aim of this multicenter, double-blind, prospective, randomized trial was to evaluate the clinical efficacy of an economically viable antimicrobial lozenge (bacitracin, clotrimazole, and gentamicin [BcoG]) in the alleviation of radiation-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: One hundred thirty-seven eligible patients were randomized to treatment with either antimicrobial lozenge (69 patients) or placebo lozenge (68 patients). The primary end point of the study was the time to development of severe mucositis from the start of radiotherapy. Secondary end points included severity and duration of mucositis, pain measurement, radiation therapy interruption, and quality of life. Mucositis was scored using a validated mucositis scoring system. RESULTS: Toxicity profiles were similar between the two arms of the study. The median time to development of severe mucositis from the start of radiotherapy was 3.61 weeks on BCoG and 3.96 weeks on placebo (P =.61). There were no statistically significant differences between the arms in the extent of severe mucositis as measured by physician, in oral toxicities as recorded by patients, or in radiotherapy delays. CONCLUSION: This study was conducted on the basis of a pilot study that demonstrated the BCoG lozenge to be tolerable and microbiologically efficacious. A validated mucositis scoring system was used. However, in this group of patients treated with conventional radiotherapy, the lozenge did not impact significantly on the severity of mucositis. Whether such a lozenge would be beneficial in treatment situations where rate of severe mucositis is higher (ie, in patients treated with unconventional fractionation or with concomitant chemotherapy) is unknown.     

Citrate and vitamin E blunt the shock wave-induced free radical surge in an in vitro cell culture model

Free radical formation plays a major role in shock wave lithotripsy induced renal damage. Moreover, previous studies suggest that free radicals may also promote de novo calcium oxalate crystallization of previously damaged urothelium. Citrate is a known inhibitor of renal stone formation and has also been used as a free radical scavenger. Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we investigated the influence of two free radical scavengers, citrate and vitamin E, on the prevention of the shock wave-induced free radical surge. Suspensions of MDCK cells were placed in containers for shock wave exposure. Six groups of six containers each were examined: (a) no scavengers 0 shocks, (b) no scavengers 100 shocks, (c) citrate 0 shocks, (d) citrate 100 shocks, (e) vitamin E 0 shocks, (f) vitamin E 100 shocks. An unmodified HM3 was used to deliver 100 shocks at 24 kV. The cell groups that were not shocked acted as the control group and were handled identically, except for the lack of shock wave exposure. After shock wave administration, the containers were emptied and cell suspensions were immediately centrifuged. The supernatant was examined for lactate dehydrogenase (LDH) and 8-isoprostane (8-IP), markers of cellular injury and free radical formation, respectively. Intracellular LDH uniformly increased in all groups exposed to shock wave energy. Similarly, 8-IP increased in all shocked groups. However, the 8-IP increase was significantly reduced when the free radical scavengers were employed. As citrate is a well-known inhibitor of calcium nephrolithiasis, its mechanism of action may be further enhanced, based on its ability to reduce free radical formation, by a protective effect on the urothelium. These data further support the use of citrate based medications during the peri-operative period of shock wave lithotripsy, not only to inhibit stone formation and facilitate fragment passage, but also to reduce the incidence of shock wave induced renal damage. Further studies are warranted to clinically test this hypothesis.