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Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

Over the last three decades, continuous technological improvement in scope design and advanced techniques for rigid and flexible nephroscopy have significantly improved the morbidity and efficiency of percutaneous renal surgery. This chapter highlights basic and advanced rigid and flexible nephroscopy techniques with a focus on their application for the treatment of urinary stone disease.

In a phase 1–2 trial involving patients with advanced pancreatic cancer, sotorasib (a KRAS G12C inhibitor) resulted in a response in 21% of the patients and a median progression-free survival of 4 months.

Background For patients with synchronous liver metastases (LM) from rectal cancer, a consensus on surgical sequencing is lacking. We compared outcomes between the reverse (hepatectomy first), classic (primary tumor resection first), and combined (simultaneous hepatectomy and primary tumor resection) approaches. Methods A prospectively maintained database was queried for patients with rectal cancer LM diagnosed before primary tumor resection who underwent hepatectomy for LM from January 2004 to April 2021. Clinicopathological factors and survival were compared between the three approaches. Results Among 274 patients, 141 (51%) underwent the reverse approach; 73 (27%), the classic approach; and 60 (22%), the combined approach. Higher carcinoembryonic antigen level at LM diagnosis and higher number of LM were associated with the reverse approach. Combined approach patients had smaller tumors and underwent less complex hepatectomies. More than eight cycles of pre-hepatectomy chemotherapy and maximum diameter of LM > 5 cm were independently associated with worse overall survival (OS) ( p = 0.002 and 0.027, respectively). Although 35% of reverse-approach patients did not undergo primary tumor resection, OS did not differ between groups. Additionally, 82% of incomplete reverse-approach patients ultimately did not require diversion during follow-up. RAS/TP53 co-mutation was independently associated with lack of primary resection with the reverse approach (odds ratio: 0.16, 95% CI 0.038–0.64, p = 0.010). Conclusions The reverse approach results in survival similar to that of combined and classic approaches and may obviate primary rectal tumor resections and diversions. RAS/TP53 co-mutation is associated with a lower rate of completion of the reverse approach.

The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC.

•During 2006–2010 in Vietnam, influenza viruses co-circulated most years and often peaked multiple times each year.•22% of patients with ILI enrolled in the National Influenza Surveillance System (NISS) in Vietnam were influenza positive.•9.3% of ILI patients in NISS in Vietnam were reported as subsequently hospitalized, of which 19% were influenza positive.•NISS suggests influenza is an important cause of ILI and reported subsequent hospitalization among outpatients in Vietnam. Influenza virus infections result in considerable morbidity and mortality both in the temperate and tropical world. Influenza surveillance over multiple years is important to determine the impact and epidemiology of influenza and to develop a national vaccine policy, especially in countries developing influenza vaccine manufacturing capacity, such as Vietnam. We conducted surveillance of influenza and influenza-like illness in Vietnam through the National Influenza Surveillance System during 2006–2010. At 15 sentinel sites, the first two patients presenting each weekday with influenza-like illness (ILI), defined as fever and cough and/or sore throat with illness onset within 3 days, were enrolled and throat specimens were collected and tested for influenza virus type and influenza A subtype by RT-PCR. De-identified demographic and provider reported subsequent hospitalization information was collected on each patient. Each site also collected information on the total number of patients with influenza-like illness evaluated per week. Of 29,804 enrolled patients presenting with influenza-like illness, 6516 (22%) were influenza positive. Of enrolled patients, 2737 (9.3%) were reported as subsequently hospitalized; of the 2737, 527 (19%) were influenza positive. Across all age groups with ILI, school-aged children had the highest percent of influenza infection (29%) and the highest percent of subsequent hospitalizations associated with influenza infection (28%). Influenza viruses co-circulated throughout most years in Vietnam during 2006–2010 and often reached peak levels multiple times during a year, when >20% of tests were influenza positive. Influenza is an important cause of all influenza-like illness and provider reported subsequent hospitalization among outpatients in Vietnam, especially among school-aged children. These findings may have important implications for influenza vaccine policy in Vietnam.

Background and AimsThe MUC13 transmembrane mucin is highly and constitutively expressed in the small and large intestine. Although MUC13 polymorphisms have been associated with human inflammatory bowel diseases and susceptibility to Escherichia coli infection in pigs, the biological functions of MUC13 are unknown. This study aimed to explore whether MUC13 modulates intestinal inflammation.MethodsMuc13−/− mice were generated, phenotyped and challenged with the colitis-inducing agent, dextran sodium sulphate (DSS). Colitis was assessed by clinical symptoms and intestinal histopathology. Intestinal epithelial cell apoptosis and proliferation, macrophage infiltration and cytokine production were also quantified. Apoptosis of human LS513 intestinal epithelial cells in response to apoptotic agents, including DSS, was also measured, following knockdown of MUC13 with siRNA.ResultsMuc13−/− mice were viable, fertile and developed normally, with no spontaneous intestinal pathology except mild focal neutrophilic inflammation in the small and large intestines of old mice. In response to DSS challenge, Muc13−/− mice developed more severe acute colitis, as reflected by increased weight loss, rectal bleeding, diarrhoea and histological colitis scores compared with wild-type mice. Increased numbers of F4/80+ macrophages in inflamed mucosa of Muc13−/− mice were accompanied by increased expression of intestinal IL-1β and TNFα mRNA. Muc13−/− mice had significantly increased intestinal epithelial cell apoptosis within 3 days of DSS exposure. LS513 cells were more susceptible to DSS, actinomycin-D, ultraviolet irradiation and TRAIL-induced apoptosis when MUC13 was knocked down by siRNA.ConclusionsThese novel findings indicate a protective role for Muc13 in the colonic epithelium by inhibiting toxin-induced apoptosis and have important implications for intestinal infections, inflammatory diseases and the development of intestinal cancer.

Background Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. Methods Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed. Results A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT ( p < 0.001). Conclusions Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit.

Background Liver venous deprivation (LVD) is known to induce better future liver remnant (FLR) hypertrophy than portal vein embolization (PVE). The role of LVD, compared with PVE, in inducing FLR hypertrophy and allowing safe hepatectomy for patients with extensive colorectal liver metastases (CLM) and high-risk factors for inadequate hypertrophy remains unclear. Methods Patients undergoing LVD ( n  = 22) were matched to patients undergoing PVE ( n  = 279) in a 1:3 ratio based on propensity scores, prior to planned hepatectomy for CLM at a single center (1998–2023). The propensity scores accounted for high-risk factors for inadequate hypertrophy, namely pre-procedure standardized FLR (sFLR), body mass index, number of systemic therapy cycles, an extension of PVE to segment IV portal vein branches, prior resection, and chemotherapy-associated liver injury. Results The matched cohort included 78 patients (LVD, n  = 22; PVE, n  = 56). Baseline characteristics were comparable. The number of tumors in the whole liver was similar but more LVD patients had five or more tumors in the left liver (32% vs. 11%; p =  0.024). Post-procedure sFLR was similar but LVD patients had a significantly higher degree of hypertrophy (16% vs. 11%; p =  0.017) and kinetic growth rate (3.9 vs. 2.4% per week; p =  0.006). More LVD patients underwent extended right hepatectomy (93% vs. 55%; p =  0.008). Only one patient had postoperative hepatic insufficiency after PVE, and no patients died within 90 days of hepatectomy. Conclusion In patients with extensive CLM and high-risk factors, LVD is associated with better FLR hypertrophy compared with PVE and allows for safely performing curative-intent extended major hepatectomy.