Glofitamab as a salvage treatment for B-cell lymphomas in the real world: A multicenter study in Taiwan.

BACKGROUND: Glofitamab is a bispecific antibody with promise for treating relapsed/refractory B-cell lymphoma according to a phase 1/2 clinical trial. This study examined its real-world effectiveness. METHODS: This was an investigator-initiated, multicenter retrospective study including 34 patients who had relapsed/refractory B-cell lymphomas after at least three prior lines of therapy and received glofitamab monotherapy in a compassionate use program in Taiwan between January 2021 and October 2022. RESULTS: At a median follow-up of 15.9 months, 56% of patients responded to glofitamab and 23% achieved complete remission. Response to the previous line of therapy significantly correlated with response to glofitamab (p = .020). Most responses were durable; only five out of the 19 responders had documented disease recurrence at the data cutoff date. The estimated progression-free survival (PFS) was 3.2 months, and the estimated 1-year PFS was 33% for the entire cohort. PFS was better for responders than nonresponders (median PFS, 16.9 vs. 1.8 months; 1-year PFS, 60% vs. 0%). Forty-three cytokine release syndrome (CRS) events were observed, three of which were grade 3; all were manageable without glofitamab discontinuation. No immune effector cell-associated neurotoxicity was reported. Among seven hepatitis B virus (HBV) carriers (six had antiviral prophylaxis) and 14 patients with remote HBV (four had antiviral prophylaxis), no HBV reactivation was observed. CONCLUSIONS: In this real-world cohort, glofitamab exhibited effectiveness comparable to trial results without excessive CRS or new safety issues. With appropriate prophylaxis, glofitamab-treated patients with chronic or remote HBV infection are unlikely to experience virus reactivation.

Tumor Marker Trajectories and Survival Analysis in Patients With Normal Carcinoembryonic Antigen Ranges After Colorectal Cancer Resection.

BACKGROUND: Evidence regarding postoperative CEA for predicting long-term outcomes of colorectal cancer remains controversial, especially in patients with normal postoperative CEA. OBJECTIVE: To investigate the risk difference among different postoperative CEA trajectories in patients with normal postoperative CEA after curative colorectal cancer resection. DESIGN: This cohort study was conducted at a comprehensive cancer center and included data retrieved from a prospectively collected database between January 2006 and December 2018. SETTINGS: Retrospective cohort study. PATIENTS: Patients with colorectal cancer who underwent surgery for primary stage I to III colorectal adenocarcinoma were included and those with postoperative CEA >5 ng/mL were excluded. INTERVENTIONS: Standard curative radical resection was performed. MAIN OUTCOME MEASURES: Ten-year overall survival and disease-free survival were analyzed. RESULTS: The study population (n = 8156) was categorized into 6 trajectories: persistent-ultralow (n = 2351), persistent-low (n = 2474), gradually decrease (n = 401), persistent-medium (n = 1727), slightly increase (n = 909), and around-upper-limit (n = 394). The median follow-up time was 7.8 years, and the median time frame in which CEA was measured to determine trajectory was 2.6 years. The persistent-ultralow group had the highest 10-year overall survival (85.1%) and disease-free survival (82.7%). The around-upper-limit group had the lowest 10-year overall survival (55.5%) and disease-free survival (53.4%). The adjusted HR trend was comparable to the crude HR of the persistent-ultralow group. Consequently, the higher initial serum CEA groups had higher HRs of overall survival and disease-free survival. The adjusted HR of overall survival was 2.96 (95% CI, 2.39-3.66) and of disease-free survival was 2.66 (95% CI, 2.18-3.69) for the around-upper-limit groups. LIMITATIONS: Retrospective design. CONCLUSIONS: The postoperative serum CEA trajectory is an independent factor associated with long-term outcomes. Although CEA levels were all within normal range, higher levels of postoperative serum CEA trajectory correlated with worse long-term oncological outcomes. See Video Abstract. TRAYECTORIAS DE MARCADORES TUMORALES Y ANLISIS DE SUPERVIVENCIA EN PACIENTES CON RANGOS NORMALES DE ANTGENO CARCINOEMBRIONARIO POSTERIOR A RESECCIN DE CNCER COLORRECTAL: ANTECEDENTES:La evidencia sobre el CEA post operatorio para la predicción de los resultados a largo plazo del cáncer colorrectal sigue siendo controversial, especialmente en pacientes con CEA post quirúrgico normal.OBJETIVO:Investigar la diferencia de riesgo entre diferentes trayectorias postoperatorias del CEA en pacientes con CEA post quirúrgico normal tras la resección curativa del cáncer colorrectal.DISEÑO:Este estudio de cohorte se realizó en un centro oncológico integral e incluyó datos recuperados de una base de datos recopilada prospectivamente entre enero de 2006 y diciembre de 2018.AJUSTES:Estudio de cohorte retrospectivo.PACIENTES:Se incluyeron pacientes con el diagnostico de CCR que fueron sometidos a cirugía por adenocarcinoma colorrectal primario en estadio I-III. Se excluyeron pacientes con CEA postoperatorio >5 ng/mL.INTERVENCIONES:Se realizó una resección radical curativa estandarizada.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron la supervivencia general a diez años y la supervivencia libre de enfermedad.RESULTADOS:La población de estudio (n = 8156) fue clasificada en seis trayectorias, que incluyeron ultrabajo persistente (n = 2351), bajo persistente (n = 2474), disminución gradual (n = 401), medio persistente (n = 1727), aumento leve (n = 909) y alrededor del límite superior (n = 394). La mediana del tiempo de seguimiento fue de 7,8 años y la mediana del período de tiempo en el que el CEA fue medido para determinar la trayectoria fue de 2,6 años. El grupo ultrabajo persistente tuvo la mayor supervivencia general a 10 años (85,1 %) y supervivencia libre de enfermedad (82,7 %). El grupo alrededor del límite superior tuvo la supervivencia general a 10 años más baja (55,5 %) y la supervivencia libre de enfermedad (53,4 %). La tendencia del índice de riesgo ajustado fue comparable al índice de riesgo bruto del grupo ultrabajo persistente. En consecuencia, los grupos con CEA sérico iniciales más altos tenían índices de riesgos más altos de supervivencia general y supervivencia libre de enfermedad. Los índices de riesgos ajustados de supervivencia general/supervivencia libre de enfermedad fueron 2,96/2,66 (intervalo de confianza del 95 %: 2,39-3,66/2,18-3,69) para los grupos cercanos al límite superior.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:La trayectoria del CEA sérico postoperatorio es un factor independiente asociado con resultados a largo plazo. Aunque los niveles de CEA se encontraban todos dentro del rango normal, los niveles más altos de trayectoria del CEA en suero posoperatorio se correlacionaron con peores resultados oncológicos a largo plazo. (Traducción-Dr Osvaldo Gauto ).

Using oral tegafur/uracil (UFT) plus leucovorin as adjuvant chemotherapy in stage II colorectal cancer: a propensity score matching study from Taiwan.

BACKGROUND: Early-stage colorectal cancer had excellent outcomes after curative resection, typically. However, a perplexing survival paradox between stage II and stage III was noted. This paradox could be influenced by the administration of routine postoperative adjuvant chemotherapy and the presence of high-risk factors in stage II CRC. The objective of the study was to investigate the influence of high-risk factors on patients with stage II CRC and assess the efficacy of oral tegafur/uracil (UFT) plus leucovorin as adjuvant chemotherapy for stage II CRC patients. METHODS: A retrospective study was conducted using propensity score matching at a single medical institution. A total of 1544 patients with stage II colorectal cancer who underwent radical surgery between January 2004 and January 2009 were included. The intervention used was tegafur/uracil plus leucovorin as adjuvant chemotherapy. The main outcome measures were disease-free survival and overall survival. RESULTS: After propensity score matching, 261 patients were included in three groups: no-treatment, half-year treatment, and one-year treatment. The clinical characteristics of each group tended to be more consistent. The Cox proportional hazard models showed that tegafur/uracil treatment or not was a significant independent factor for oncological outcome. Kaplan-Meier analysis also showed significantly better disease-free survival and overall survival. Further investigation revealed that tegafur/uracil duration was an independent factor for oncological outcome. While the survival curve did not reach statistical significance, the one-year UFT treatment group demonstrated the best treatment trend. CONCLUSIONS: This study suggests that tegafur/uracil plus leucovorin is a feasible adjuvant chemotherapy regimen for patients with stage II colorectal cancer after curative surgical treatment. Prolonged tegafur/uracil plus leucovorin treatment for 12 months showed a trend towards better outcomes in patients with stage II colorectal cancer.

Flow Cytometry Analysis Reveals a Wide Cytologic and Immunophenotypic Spectrum of Peripheral B Lymphocytes in Angioimmunoblastic T-Cell Lymphoma.

INTRODUCTION: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma commonly associated with B-cell dysregulation. Correlations involving B-cell dysregulation and clinicopathological features remain unclear. METHODS: We prospectively collected blood samples from 11 AITL patients and 17 healthy controls. The percentages of B-cell subpopulations and lymphocytes with IL-21 production were assessed using flow cytometry. Peripheral blood lymphocyte morphology was evaluated microscopically. RESULTS: Six of 11 (54.5%) patients presented with polyclonal hypergammaglobulinemia. Three of 11 (27.3%) tumor biopsies showed monoclonal immunoglobulin gene rearrangement. The patients exhibited significantly lower levels of naive (p < 0.001) and class-switched (p < 0.001) B cells than controls. The percentages of IgD-CD27- B cells (p = 0.007) and antibody-secreting cells (ASCs) (p = 0.001) were increased. Blood smears revealed atypical lymphocytes and immature plasma cells with morphological diversity. In comparison to normal controls, IL-21 production significantly increased in CD4+ (p < 0.001) and CD8+ (p = 0.020) T cells. B-cell clonality, RHOA G17V mutation, and the presence of sheets of clear cells and immature/mature plasma cells in lymph nodes were significantly associated with percentages of class-switched B cells and ASCs. The patients with circulating EBV DNA had a lower percentage of naive B cells (p = 0.009). CONCLUSIONS: Our results demonstrated a wide spectrum of peripheral B-cell morphologies and immunophenotypes of peripheral B cells in AITL. These findings correspond to dysregulated B-cell immunity and heterogeneous clinicopathological features.

Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC. METHODS: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies. RESULTS: After reviewing 3,626 articles, we identified 10 studies including a total of 48,696 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57-0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54-0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.52; 95% CI: 1.23-10.10; p = 0.02). CONCLUSIONS: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. However, upfront PTR seemed to increase OS in RCSs with PSM or IPTW. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required.

Effect of short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy on organ preservation in locally advanced rectal cancer.

PURPOSE: We analyzed the effectiveness, safety, and mid-term oncological outcomes of short-course radiotherapy (SCRT) and oxaliplatin-based consolidation chemotherapy in patients with locally advanced rectal cancer (LARC). METHODS: We retrospectively evaluated 64 patients with LARC who underwent SCRT and tegafox (tegafur-uracil/leucovorin plus oxaliplatin) or mFOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) consolidation chemotherapy before surgery between January 2015 and December 2020. Tumor response, patient compliance, toxicity, surgical outcomes, overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: Sixty-four patients with a mean age of 58.67 years (44 males) were included; 48 (75%) had tumors within 5 cm of the anal verge. Additionally, 93.8% of the patients underwent at least 2 months of chemotherapy, and three required dose reduction. Grade III toxicity occurred in 2 patients, and 10 had a clinical complete response and opted for non-operative management. One patient experienced tumor progression and underwent further treatment without surgery. Among the 53 patients who underwent surgery, 51 (96.2%) had sphincter preservation, 3 had Clavien-Dindo grade III complications, and no mortality occurred. The complete response rate for the entire cohort was 23.4%. Moreover, 47 patients (74.6%) had a neoadjuvant rectal score of < 16 after treatment. After a median follow-up time of 32.01 months, 6 (9.3%) had local recurrence, and 17 (26.6%) had distant metastasis. The 3-year OS, DFS and stoma-free rates were 89.5%, 65.5%, and 78.1% respectively. CONCLUSION: SCRT followed by oxaliplatin-based consolidation chemotherapy is safe and effective for tumor downstaging in LARC, further improving the sphincter preservation rate.

Potential short-term outcome advantage of low vs. high ligation of inferior mesenteric artery for sigmoid and rectal cancer: propensity score matching analysis.

BACKGROUND: Whether to ligate the inferior mesenteric artery at its root during anterior resection for sigmoid colon or rectal cancer is still under debate. This study compared the surgical outcomes, postoperative recovery, and anastomotic leakage between high and low ligation of the inferior mesenteric artery through a subgroup analysis. METHODS: This was a retrospective analysis of prospectively collected data. All patients who underwent colorectal resection for rectosigmoid cancer between December 2016 and December 2019 were enrolled. According to the surgical ligation level of the inferior mesenteric artery, the patients were categorized into either the high or low ligation group. The investigated population was matched using the propensity score method. RESULTS: Overall, 894 patients with sigmoid or rectal cancer underwent elective anterior resection with high (577 patients) or low (317 patients) ligation of the inferior mesenteric artery. After the propensity score matching, 245 patients in each group were compared. High ligation of the inferior mesenteric artery was associated with higher incidence of anastomotic leakage (14.9% vs. 5.6%, P = 0.041) for mid- to low-rectum tumors and a higher incidence of complications (8.6% vs. 3.3%, P = 0.013) of grades 1-2 according to the Clavien-Dindo classification system. CONCLUSION: Compared with high ligation, low ligation of the inferior mesenteric artery resulted in lower likelihood of morbidity and mortality in rectal and sigmoid cancers. Moreover, low ligation was less likely to result in anastomosis leakage in mid- to low-rectal cancers.

Transrectal natural orifice specimen extraction in left hemicolectomy for tumours around the splenic flexure: Old wine in new bottles.

AIM: Laparoscopic anterior resection with natural orifice specimen extraction (NOSE) has favourable short-term outcomes. However, NOSE is rarely adopted for left hemicolectomy procedures. This study aimed to review the feasibility, safety and short-term outcomes of transrectal NOSE in patients undergoing laparoscopic left hemicolectomy. METHOD: All consecutive patients who underwent laparoscopic left hemicolectomy surgery with transrectal NOSE in a single institution between January 2018 and December 2020 were reviewed. Transrectal NOSE was performed with an enterotomy at the upper rectum. The specimen was brought out via a transanal endoscopic microsurgery scope inserted through the anus. A supplementary video demonstrates this technique. Surgical outcomes, including complications, postoperative short-term recovery and the level of pain intensity, are presented. RESULTS: Twenty patients were reviewed. There were no immediate postoperative complications and no wound infections in these patients. The average time to tolerate a soft diet was 3.6 days, and the average postoperative hospital stay was 4.5 days. The average score on the numerical rating scale of postoperative pain was 3.0 on postoperative day 1. The median follow-up time was 23.5 months. CONCLUSION: Laparoscopic left hemicolectomy with transrectal NOSE is a safe and feasible procedure that leads to early postoperative recovery and a short hospital stay.

New presentations and exacerbations of immune thrombocytopenia after coronavirus disease 2019 vaccinations: the Taiwan experience.

Immune thrombocytopenia (ITP) is a condition that is distinct from thrombosis with thrombocytopenia syndrome (TTS) that may also occur after coronavirus disease 2019 (COVID-19) vaccinations. Previous reports revealed an increased ITP incidence after ChAdOx1, a vaccine for COVID-19. Our study aimed to highlight the key features of ITP after COVID-19 vaccination. From April to October 2021, we collected data on 23 patients, including nine men and 14 women, with ITP from five hospitals across Taiwan who received either the ChAdOx1 or mRNA-1273 vaccine before development or exacerbation of ITP. Our findings revealed that both ChAdOx1 and mRNA-1273 vaccines were associated with ITP. Many patients responded well to steroids and immune suppressants, which may also suggest that the nature of thrombocytopenia is more like ITP rather than TTS. Lack of thrombosis, low D-dimer level, and negative anti-PF4 result could help to exclude TTS, which is also a rare but a far more lethal condition.

Comparison of short-term and medium-term outcomes between intracorporeal anastomosis and extracorporeal anastomosis for laparoscopic left hemicolectomy.

BACKGROUND: Few studies have evaluated the feasibility and safety of intracorporeal anastomosis (IA) for left hemicolectomy. Here, we aimed to investigate the potential advantages and disadvantages of laparoscopic left hemicolectomy with IA and compare the short- and medium-term outcomes between IA and extracorporeal anastomosis (EA). METHODS: We retrospectively analyzed 133 consecutive patients who underwent laparoscopic left hemicolectomies from July 2016 to September 2019 and categorized them into the IA and EA groups. Patients with stage 4 disease and conversion to laparotomy or those lost to follow-up were excluded. Postoperative outcomes between IA and EA groups were compared. Short-term outcomes included postoperative pain score, bowel function recovery, complications, duration of hospital stay, and pathological outcome. Medium outcomes included overall survival and disease-free survival for at least 2 years. RESULTS: After excluding ineligible patients, the remaining 117 underwent IA (n = 40) and EA (n = 77). The IA group had a shorter hospital stay, a shorter time to tolerate liquid or soft diets, and higher serum C-reactive protein level on postoperative day 3. There was no difference between two groups in operative time, postoperative pain, specimen length, or nearest margin. A 2-year overall survival (IA vs. EA: 95.0% vs. 93.5%, p = 0.747) and disease-free survival (IA vs. EA: 97.5% vs. 90.9%, p = 0.182) rates were comparable between two groups. CONCLUSIONS: Laparoscopic left hemicolectomy with IA was technically feasible, with better short-term outcomes, including shorter hospital stays and shorter time to tolerate liquid or soft diets. The IA group had higher postoperative serum C-reactive protein level; however, no complications were observed. Regarding medium-term outcomes, the overall survival and disease-free survival rates were comparable between IA and EA procedures.

Analysis of latent T-cell epitopes in Epstein-Barr virus isolated from extranodal nasal-type natural killer/T-cell lymphoma in Taiwanese population.

Extranodal nasal-type natural killer (NK)/T-cell lymphoma (NKTCL) is an aggressive lymphoma that is prevalent among East Asian and South American populations. Although Epstein-Barr virus (EBV) is commonly detected in NKTCL, there are limited studies that have analyzed the EBV genomic variations in NKTCL. In this study, 8 EBV latent genes were analyzed using targeted gene sequencing in 23 formalin-fixed paraffin-embedded tissues derived from 18 patients with NKTCL. Five cases with paired samples were comparatively analyzed. The consistency of EBV sequencing data between tissue samples was high (96.3%-98.7%), whereas that of variant calling among the tissue samples and plasma samples (74.3%-79.2%) was low. The highest densities of non-synonymous variants were detected in the EBNA3B gene. Among the 74 known T-cell epitopes, 363 non-synonymous variants were identified in 32 (43.2%) epitopes. Additionally, the AVFDRKSDAK (A1S/P and V2F/M/L) and YHLIVDTDSL (I4L and L10R/V/G/H) epitopes were associated with 5 patterns of amino acid changes in EBNA3B and EBNA-2, respectively. The frequency of variation in the human leukocyte antigen (HLA)-restricted epitopes with corresponding HLA types common among Taiwanese population was significantly low (P = 0.011), whereas that in anchor residues was significantly high (P = 0.012). In conclusion, this study demonstrated the genomic diversity of EBV in NKTCL and its correlation with the HLA-restricted epitope variations in Taiwanese population. The findings of this study provide useful insights for the development of novel therapeutic strategies for NKTCL.

Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis.

BACKGROUNDS: The inflammatory biomarker "C-reactive protein to albumin ratio (CAR)" has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. METHODS: We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. RESULTS: A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808-2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321-2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. CONCLUSIONS: High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

Short- and medium-term outcomes of intracorporeal versus extracorporeal anastomosis in laparoscopic right colectomy: a propensity score-matched study.

BACKGROUNDS: Though better short-term outcomes were frequently reported, differences in specimen parameters and the rate of subsequent peritoneal recurrence between intracorporeal anastomosis (IA) and extracorporeal anastomoses (EA) for laparoscopic right hemicolectomy have not been analyzed. We aimed to compare the pathologic differences and oncological outcomes between these two approaches. METHODS: We retrospectively analyzed 217 consecutive patients who underwent laparoscopic right hemicolectomies from September 2016 to April 2018 and classified them into IA and EA groups, based on the approach used. Propensity score matching analysis was performed, after which 101 patients were included in each group with the patients matched for demographics, tumor stage, and localization. RESULTS: The IA group had a longer operative time, shorter length of stay, shorter time to first flatus and tolerating a soft diet, and better pain scale scores at postoperative day 3. No inter-group differences in conversion, postoperative complication, mortality, or readmission rates were found. The IA group had a longer resected colon length (23.67 vs. 19.75 cm, p = 0.010) and nearest resected margin (7.51 vs. 5.40 cm, p = 0.010) for cancer near the hepatic flexure. There are comparable 3-year overall survival (87.7% vs. 89.6%, p = 0.604) and disease-free survival (75.0% vs. 75.7%, p = 0.842) between the IA and EA groups. The rate of peritoneal recurrence was similar between the two groups (5.9% vs. 7.9%, p = 0.580). CONCLUSIONS: The overall survival, disease-free survival, and the rate of peritoneal recurrence were comparable between the IA and EA procedures. IA ensures better recovery and comparable complications to EA and achieved a more precise tumor excision; thus, IA can be considered a safe procedure for patients with right-sided colon lesions.

Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?

BACKGROUND: Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients. PATIENTS AND METHODS: Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses. RESULTS: Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup. Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257-0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172-.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219-1.150, p = 0.103) for EC subgroup compared with SC subgroup. Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346-9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788-7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found. CONCLUSIONS: Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.

Molecular heterogeneity unravelled by single-cell transcriptomics in patients with essential thrombocythaemia.

Significant phenotypic heterogeneity exists in patients with all subtypes of myeloproliferative neoplasms (MPN), including essential thrombocythaemia (ET). Single-cell RNA sequencing (scRNA-Seq) holds the promise of unravelling the biology of MPN at an unprecedented level of resolution. Herein we employed this approach to dissect the transcriptomes in the CD34+ cells from the peripheral blood of seven previously untreated ET patients and one healthy adult. The mutational profiles in these patients were as follows: JAK2 V617F in two, CALR in three (one type I and two type II) and triple-negative (TN) in two. Our results reveal substantial heterogeneity within this enrolled cohort of patients. Activation of JAK/STAT signalling was recognized in discrepant progenitor lineages among different samples. Significantly disparate molecular profiling was identified in the comparison between ET patients and the control, between patients with different driver mutations (JAK2 V617F and CALR exon 9 indel), and even between patients harbouring the same driver. Intra-individual clonal diversity was also found in the CD34+ progenitor population of a patient, possibly indicating the presence of multiple clones in this case. Estimation of subpopulation size based on cellular immunophenotyping suggested differentiation bias in all analysed samples. Furthermore, combining the transcriptomic information with data from targeted sequencing enabled us to unravel key somatic mutations that are molecularly relevant. To conclude, we demonstrated that scRNA-Seq extended our knowledge of clonal diversity and inter-individual heterogeneity in patients with ET. The obtained information could potentially leapfrog our efforts in the elucidation of the pathogenesis of the disease.

RHOA G17V mutation in angioimmunoblastic T-cell lymphoma: A potential biomarker for cytological assessment.

BACKGROUND: The World Health Organization, in a 2016 revision, introduced recurrent genetic abnormalities for classifying mature T- and NK-cell neoplasms. However, the role of genetic analyses from lymph node aspiration cytology is still not elucidated. We hypothesize that the use of genetic analyses may increase the accuracy of diagnosis from cytological preparations. METHODS: Fifty-seven formalin-fixed paraffin-embedded (FFPE) samples were collected for next-generation sequencing (NGS) targeting potential driver mutations including TET2, DMN3TA, IDH2, RHOA, STAT3, and STAT5B. Competitive allele-specific TaqMan polymerase chain reaction (cast-PCR) was performed to validate the mutation status by using FFPE and preoperative fine needle aspiration cytology (FNAC) samples. RESULTS: Among these six candidate genes, only IDH2 and RHOA mutations were significantly more frequent in nodal subtypes, angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) (P = .002 and <0.001, respectively). All genes exhibited different mutation patterns except RHOA with a hotspot mutation involving the Gly17 residue. The RHOA G17V mutation was found in 15 (75%) of 20 AITL and two (22%) of nine PTCL, NOS. Cast-PCR using FFPE samples showed 100% concordance with NGS. Among 12 lymph node aspirates, the preliminary diagnoses were suspicious for lymphoma (3, 25%), atypical lymphoid cells (3, 25%) and benign/negative (6, 50%). Cast-PCR detected the RHOA G17V mutation in six (75%) of eight RHOA-mutated aspirates and revealed negative results in all (100%) of four wild-type aspirates, with an 83.3% (10/12) concordance comparing to FFPE samples. CONCLUSIONS: The RHOA G17V mutation serves as a useful biomarker for cytological assessment in AITL. The use of cast-PCR is valuable in the diagnosis of malignant lymphomas from cytological preparations, and thus avoiding the potential risks of invasive procedures.

Primary tumor location in stage III colon cancer has prognostic impact on subsequent liver metastasis.

BACKGROUND AND OBJECTIVES: We aim to investigate whether a difference exists between right-sided and left-sided colon cancer at the same disease stage and subsequent liver metastasis and identify whether tumor location can independently influence survival. METHODS: Right-sided colon cancer was defined as malignancy arising from the cecum to the transverse colon; left-sided colon cancer was defined as malignancy arising from the splenic flexure to the sigmoid colon. Clinicopathological features and survival data were collected for analysis. RESULTS: Overall, 1442 patients were included for analysis. The median follow-up time was 58.2 months. Patients with left-sided colon cancer had better 5-year overall survival (75.2% vs 61.7%, P = 0.005), 5-year cancer-specific survival (81.6% vs 73.4%, P = 0.001), and 5-year recurrence-free survival (70.9% vs 66.5%, P = 0.033) compared with patients having right-sided colon cancer. After the presentation of subsequent liver metastasis, patients with primary left-sided colon cancer had better 3-year cancer-specific survival ( P < 0.001). In the multivariate analysis, cancer location was an independent prognostic factor for cancer-specific survival (right vs left, HR: 1.276, 95% CI: 1.002-1.625). CONCLUSIONS: The primary tumor location can serve as a prognostic factor for treatment outcomes either in primary stage III colon cancer or subsequent liver metastasis.

Improving nanowire sensing capability by electrical field alignment of surface probing molecules.

We argue that the structure ordering of self-assembled probing molecular monolayers is essential for the reliability and sensitivity of nanowire-based field-effect sensors because it can promote the efficiency for molecular interactions as well as strengthen the molecular dipole field experienced by the nanowires. In the case of monolayers, we showed that structure ordering could be improved by means of electrical field alignment. This technique was then employed to align multilayer complexes for nanowire sensing applications. The sensitivity we achieved for detection of hybridization between 15-base single-strand DNA molecules is 0.1 fM and for alcohol sensors is 0.5 ppm. The reliability was confirmed by repeated tests on chips that contain multiple nanowire sensors.

The oncologic outcome and prognostic factors for solitary colorectal liver metastasis after liver resection.

BACKGROUND: Studies on prognostic factors for patients undergoing surgery to treat solitary liver metastases originating from colorectal cancer (CRC) are limited. This study aimed to analyze significant prognostic factors associated with tumor recurrence and long-term survival after liver resection for solitary colorectal liver metastasis. METHODS: Data from 230 patients with solitary liver metastases from CRC who received liver resection between 2010 and 2019 were retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) were accessed with the Kaplan-Meier method and log-rank test. Cox regression multivariate analysis identified independent variables associated with RFS and OS. Nomograms were developed to predict patient outcomes after surgery. RESULTS: The 3- and 5-year OS rates were 72.3% and 59.8%, respectively. The 3- and 5-year RFS rates were 40.0% and 27.1%, respectively. Multivariate analysis revealed age ≥ 70 years, resection margin width < 10 mm, initial N2 stage, hypoalbuminemia before surgery, and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 after surgery as independent prognostic factors for OS. For RFS, initial N2 stage, hypoalbuminemia before surgery, NLR ≥ 3 after surgery, elevated carcinoembryonic antigen (CEA) levels after surgery, and CEA ratio (after/before liver resection) < 0.3 were identified as independent prognostic factors. CONCLUSION: This study demonstrated that initial N2 stage, hypoalbuminemia before liver resection, and NLR ≥ 3 after liver resection exert a significant association on the RFS and OS of patients undergoing surgery for solitary liver metastases from CRC. Thus, upfront chemotherapy, prompt postoperative chemotherapy, and intensive postoperative surveillance are mandatory for patients having these adverse factors.

Comparison of laparoscopic and open surgery for colorectal malignancy in obese patients: a propensity score-weighted cohort study.

BACKGROUND: Insufficient evidence exists to ascertain the long-term prognosis in patients with obesity undergoing laparoscopic surgery versus open surgery for colorectal cancer. METHODS: Employing an institutional database from 2009 to 2019, we assessed individuals with a body mass index of ≥30 kg/m2 who underwent surgery for primary stage I-III colorectal adenocarcinoma. We used propensity score-weighted analysis to compare short-term and oncologic outcomes between laparoscopic and open surgical approaches. RESULTS: This study enrolled 473 patients (open vs. laparoscopic surgery: 220 vs. 253; median follow-up period, 60 mo). The laparoscopy group showed a significantly longer operative time (252 vs. 212 min), a higher anastomotic-leakage rate (5.14% vs. 0.91%), and a greater proportion of Clavien-Dindo class > III complications (5.93% vs. 1.82%). The open group showed a higher wound infection rate (7.27% vs. 3.16%) and a higher readmission rate (6.36% vs. 2.37%). After propensity-score weighting, laparoscopy was inferior to open surgery in terms of long-term overall survival (hazard ratio: 1.43), disease-free survival (1.39), and recurrence rate (21.1% vs. 14.5%). In the subgroup analysis, female patients, older individuals, stage III patients, patients with rectal cancer, and those who underwent surgery after 2014 showed inferior long-term outcomes after laparoscopy. CONCLUSIONS: Laparoscopic colorectal cancer surgery for patients with obesity requires significant caution. Despite good short-term outcomes, this procedure is associated with hidden risks and poor long-term prognoses. In female patients, older individuals, stage III patients, patients with rectal cancer, and those treated in the late surgery era subgroups, caution is advised when performing laparoscopic surgery.