Primary Surgery Followed by Selective Chemoradiotherapy Versus Preoperative Chemoradiotherapy Followed by Surgery for Locally Advanced Rectal Cancer: A Randomized Clinical Trial.

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial.

Background: Microsatellite stable (MSS) and RAS-mutant metastatic colorectal cancer (mCRC) patients are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Chemotherapy and anti-angiogenesis therapy have been reported to potentially promote immunotherapy response. This study aims to assess the preliminary anti-tumor activity and safety of sintilimab plus bevacizumab, oxaliplatin and capecitabine as a treatment option for patients with RAS-mutant MSS mCRC. Methods: This study was an open-label, single-arm, phase II trial in China. Patients with unresectable, RAS-mutant and MSS metastatic colorectal adenocarcinoma received treatment by intravenous sintilimab (200 mg, day 1) plus bevacizumab (7.5 mg/kg, day 1), oxaliplatin (135 mg/m2, day 1) and oral capecitabine (1 g/m2, day 1-14) in each 21-day cycle. The primary endpoints included objective response rate (ORR) and adverse events. Biomarker analysis was performed to identify potential predictors of good response to treatment. This study is registered with ClinicalTrials.gov, number NCT04194359. Findings: Between April 2021 and December 2021, 25 patients were enrolled. Two (8%) patients showed complete response (CR), 19 (76%) had partial response (PR) and 4 (16%) presented with stable disease. ORR reached 84% (95% CI, 63.9-95.5) and the disease control rate was 100% (95% CI, 86.3-100). The median progression-free survival (PFS) was 18.2 months for the full analysis set. The most common treatment-related adverse events (TRAEs) in all grades were anemia (21/25, 84%), neutropenia (20/25, 80%), and hand-foot syndrome (14/25, 56%). The most frequent grade 3 or 4 TRAEs were neutropenia (3/25, 12%) and increased alanine transaminase (2/25, 8%). No grade 5 adverse events occurred. In the exploration of biomarkers, 5 patients could be characterized as TTN/OBSCN "double-hit" after treatment, and the copy number variants burden was significantly decreased in tumor tissues after treatment compared with the baseline. Nanostring panel RNA sequencing analysis indicated a better tumor immune microenvironment cell infiltration in CR/PR patients compared with non-CR/PR patients as well as the PFS-long (≥12.5 months) group compared with the PFS-short group. Interpretation: Combination treatment with sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line treatment demonstrated a promising antitumor activity and a manageable safety profile in RAS-mutant, MSS and unresectable mCRC. Exploratory biomarker assessment analysis showed that some RAS-mutant and MSS patients changed into "immune-hot" subtype after the treatment. Funding: This study was supported by the Key R&D Program of Zhejiang Province (2021C03125 to Ying Yuan), the National Natural Science Foundation of China (81872481 to Ying Yuan, 82072624 to Kefeng Ding), the Fundamental Research Funds for the Central Universities (No. 226-2022-00009 to Kefeng Ding), and the Zhejiang Provincial Natural Science Foundation of China (No. LY22H160024 to Hanguang Hu).

FOSL2 promotes intertumoral infiltration of T cells and increases pathological complete response rates in locally advanced rectal cancer patients.

The outcome of neoadjuvant chemoradiotherapy (nCRT) remains highly unpredictable for individuals with locally advanced rectal cancer (LARC). We set out to characterize effective biomarkers that promote a pathological complete response (pCR). We quantified the abundances of 6483 high-confidence proteins in pre-nCRT biopsies of 58 LARC patients from two hospitals with pressure cycling technology (PCT)-assisted pulse data-independent acquisition (PulseDIA) mass spectrometry. Compared with non-pCR patients, pCR patients achieved long-term disease-free survival (DFS) and had higher tumor immune infiltration, especially CD8+ T cell infiltration, before nCRT. FOSL2 was selected as the candidate biomarker for predicting pCR and was found to be significantly upregulated in pCR patients, which was verified in another 54 pre-nCRT biopsies of LARC patients by immunohistochemistry. FOSL2 expression was able to predict pCR by multiple reaction monitoring (MRM) with high efficiency (Area under curve (AUC) = 0.939, specificity = 1.000, sensitivity = 0.850), and high FOSL2 expression was associated with long-term DFS (p = 0.044). When treated with simulated nCRT, FOSL2 sufficiency resulted in more significant inhibition of cell proliferation, and more significant promotion of cell cycle arrest and cell apoptosis. Moreover, CXCL10 secretion with abnormal cytosolic dsDNA accumulation was found in FOSL2-wildtype (FOSL2-WT) tumor cells over nCRT, which might elevate CD8+ T-cell infiltration and CD8+ T-cell-mediated cytotoxicity to promote nCRT-induced antitumor immunity. Our study revealed proteomic profiles in LARC patients before nCRT and highlighted immune activation in the tumors of patients who achieved pCR. We identified FOSL2 as a promising biomarker to predict pCR and promote long-term DFS by contributing to CD8+ T-cell infiltration.

Vemurafenib effectively controlled Chemotherapy-refractory Intrahepatic Cholangiocarcinoma with BRAF V600E Mutation: a case report and literature review.

HINTERGRUND: Die Chemotherapie ist die erste Behandlungsoption für das lokal fortgeschrittene oder metastasierte intrahepatische Cholangiokarzinom (ICC). Nach einer Erstlinien-Chemotherapie gibt es jedoch keine Standardzweitlinienbehandlung oder zielgerichtete Wirkstoffe für diese Patienten. FALLPRäSENTATION: Hier stellen wir einen fortgeschrittenen ICC-Patienten vor, der eine radikale Entfernung und eine adjuvante Chemotherapie (Gemcitabin + Cisplatin) erhalten hat. Aber der Patient bleibt nur 6 Monate frei von Krankheitsanzeichen (No Evidence of Disease) nach dem Ende der Chemotherapie. Dann erhielt er eine palliative Operation, Strahlentherapie und systemische Chemotherapie (Tegafur+Oxaliplatin (SOX) und Nab-Paclitaxel+Gemcitabin (AG)). Leider war die Krankheit immer noch nicht unter Kontrolle. Als eine BRAF-V600E-Mutation im Tumorgewebe durch eine Next Generation Sequencing Analyse (NGS) gezeigt wurde, begann dieser Patient mit der Einnahme von Vemurafenib in einer Dosierung von 720-960 mg zweimal täglich und erreichte ein progressionsfreies Überleben von 7 Monaten mit signifikanter Remission der klinischen Symptome. SCHLüSSELWöRTER: Die BRAF V600E Mutation ist bei ICC ziemlich selten, daher wird sie in der Klinik nicht routinemäßig untersucht. Allerdings kann Präzisionsmedizin durch die NGS-Technologie verwirklicht werden, sodass die Ärzte bei der Behandlung der auf Chemotherapie-refraktären ICC die personalisierten genomischen Informationen nutzen können.

Phase II study of anlotinib in combination with oxaliplatin and capecitabine for patients with RAS/BRAF wild-type metastatic colorectal adenocarcinoma as the first-line therapy.

BACKGROUND: Anlotinib, an oral small molecule tyrosine kinase inhibitor targeting VEGFR 1/2/3, FGFR 1-4, PDGFR a/ß, and c-kit, had demonstrated prolonged progression-free survival (PFS) in refractory metastatic colorectal cancer (mCRC). This multicenter, single-arm, phase II, exploratory study was conducted to evaluate the efficacy and safety of anlotinib combined with capecitabine and oxaliplatin as first-line treatment for unresectable RAS/BRAF wild-type mCRC. METHODS: Patients aged 18-75 with RAS/BRAF wild-type unresectable mCRC, without prior systemic treatment, and ECOG performance status ≤1 were enrolled. Eligible patients received capecitabine (850 mg/m2, p.o., bid, on day 1-14 every 21 days), oxaliplatin (130 mg/m2, i.v., on day 1 every 21 days), and anlotinib (12 mg, p.o., qd, on days 1-14 every 21 days) as induction therapy. Following 6 cycles of therapy, patients who achieved response or stable disease received capecitabine and anlotinib as maintenance therapy until tumor progression. The primary endpoint was objective response rate (ORR) according to RECIST (version: 1.1), and the secondary endpoints were PFS, disease control rate (DCR), duration of response (DOR), and safety. RESULTS: Between November 2019 and February 2021, 31 patients were enrolled. One patient was excluded for refusing treatment. The primary endpoint of ORR was 76.7% (95% CI, 57.7-90.1) with 1 patient achieving a complete response and 22 patients partial response. DCR was 93.3% (95% CI, 77.9-99.2). At a median follow-up of 14.1 months (95% CI, 9.9-18.3), median PFS was 11.3 months (95% CI, 7.1-14.1), and DOR was 7.9 months (95% CI, 5.5-12.7). Twenty-five (83.3%) patients experienced grade 3 or 4 treatment-emergent adverse events (TEAEs). No grade 5 TEAE was reported. The most common grade 3 or 4 TEAEs (>10%) were hypertension (15/30; 50%), neutrophil count decreased (8/30; 26.7%), and diarrhea (4/30; 13.3%). A total of 18 (60%) patients had TEAEs that resulted in dose reduction, interruptions, or delays. CONCLUSIONS: Anlotinib combined with capecitabine and oxaliplatin showed considerable ORR, DCR, PFS, and DOR in the first-line therapy of mCRC with manageable toxicity profiles. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04080843.

Accuracy of Magnetic Resonance Imaging in Staging Rectal Cancer with Multidisciplinary Team: A Single-Center Experience.

Purpose: To investigate the accuracy of magnetic resonance imaging (MRI) in preoperative staging diagnosis for rectal cancer with multidisciplinary team (MDT) discussion. Methods: The retrospective study included 377 patients of rectal cancer with preoperative MRI staging from February 2015 to April 2018, in which 137 patients (36 received MDT discussion) received neoadjuvant therapy, 240 did not (97 received MDT discussion) and direct surgery was given. With postoperative pathological stage as the standard, the accuracy of MRI in preoperative staging for rectal cancer with MDT discussion was compared with non-MDT. Results: For direct surgery group, 21 out 97 (21.6%) patients changed their therapy strategy due to the change of the stage assessment after MDT. The accuracy of MRI for the diagnosis of preoperative N stage with MDT was significantly higher than those without MDT (56.2% vs. 42.1%, P=0.021). And for those without lymph node metastasis, the accuracy of MRI was higher after MDT (61.2% vs. 37.8%, P=0.009). For neoadjuvant therapy group, 7 out of 36 (19.4%) patients altered their therapy after MDT because of the changed stage. MDT improved the accuracy of restaging N stage with MRI (70.0% vs. 33.3%, P=0.003). The accuracy of MRI in staging T stage seemed not improved after MDT in both groups. Conclusions: In conclusion, MDT discussion increased the accuracy of MRI in preoperative staging diagnosis for rectal cancer. This mode could give a more accurate clinical stage of patients, which was in favor of choosing a preferable therapy strategy.

[Analysis of factors affecting soft tissue infection after oral and maxillofacial debridement].

PURPOSE: To explore the factors affecting soft tissue infection after oral and maxillofacial debridement. METHODS: Fifty hundred patients with debridement were enrolled in this study from January 2013 to June 2016. The patients were divided into 2 groups according to soft tissue infection, 18 cases in infection group and 482 cases in non-infection group. Age, mean time to surgery, average length of stay, duration of antibiotics use, abbreviated injury scale (AIS), combined injuries, maxillofacial fractures, soft tissue injury, type of fracture, and history of diabetes were recorded and analyzed using SPSS 19.0 software package. RESULTS: The factors influencing soft tissue infection after oral and maxillofacial surgery were the aged, longer hospital stay, longer operation time, longer antibiotics use time, higher AIS score, Jaw bone injury and diabetes. CONCLUSIONS: The factors influencing soft tissue infection after oral and maxillofacial debridement are various. The aged, longer operation time, higher AIS score, jaw bone involvement lip and chin injury as well as diabetes might be the independent factors. Health care providers should give preventive measures to reduce the incidence of infection, according to specific factors.

The paradigm of tumor shrinkage and rapid liver remnant hypertrophy for conversion of initially unresectable colorectal liver metastasis: a case report and literature review.

BACKGROUND: For colorectal liver metastasis (CRLM) patients, hepatic resection is currently the sole cure offering the chance of long-term survival. Tumor shrinkage and planned liver remnant hypertrophy are the two key strategies for conversion of initially unresectable CRLM. First conducted in 2012, associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows rapid liver growth. As a means to induce hypertrophy, portal vein embolization (PVE) has been widely applied before extending hepatectomy. Recently, Peng et al. present a new approach of terminal branches portal vein embolization (TBPVE), offering an efficient way to amplify FLR and making chances for surgery in 2 weeks. CASE PRESENTATION: We reported a 61-year-old woman with synchronous hepatic metastasized carcinoma of the colon sigmoideum underwent TBPVE after 6 cycles of neoadjuvant therapy in order to perform a planned right trisectionectomy. Rapid liver remnant hypertrophy and remarkable tumor shrinkage were achieved, and laparoscopic sigmoidectomy and right trisectionectomy were successfully performed. The postsurgical course was uneventful and 7 months of recurrence-free survival have been witnessed. CONCLUSIONS: The dual tactics of tumor shrinkage and planned rapid liver remnant hypertrophy will make concerted efforts to further increase the clinical candidacy for curative resection, which are valuable for further investigation.

Giant cell tumor of the tendon sheath: Magnetic resonance imaging findings in 38 patients.

The present study aimed to investigate the value of magnetic resonance imaging (MRI) in the diagnosis of giant cell tumor of the tendon sheath (GCTTS), including localized (L-) and diffuse (D-) types. A total of 38 patients with GCTTS, including 31 with L-GCTTS and 7 with D-GCTTS, diagnosed by surgery and pathology, were retrospectively analyzed. All patients underwent MRI examination. Of the 31 patients with L-GCTTS, the tumors were located in the hand and wrist (18 patients), the ankle and foot (10 cases), the knee joint (2 cases) and the temporomandibular joint (1 case). All 31 lesions were either located in relation to a tendon or were partially/completely enveloping it and all were well marginated. With respect to the 7 D-GCTTS patients, the tumors were located in the ankle and foot (6 cases) or the hand and wrist (1 cases). All 7 lesions presented as an aggressive soft tissue mass infiltrating the tendon sheath and adipose tissue around the joint. The characteristic internal signal of GCTTS, including L-GCTTS and D-GCTTS, was demonstrated by MRI examination. MRI is currently the optimal modality for preoperative assessment of tumor size, extent and invasion of adjacent joint and tenosynovial space.

Preoperative Gross Classification of Gastric Adenocarcinoma: Comparison of Double Contrast-Enhanced Ultrasound and Multi-Detector Row CT.

The aim of this study was to compare the accuracy of multi-detector computed tomography (MDCT) with double contrast-enhanced ultrasound (DCEUS), in which intravenous microbubbles are used alongside oral contrast-enhanced ultrasound, in determining the gross classification of patients with gastric carcinoma (GC). Altogether, 239 patients with GC proved by histology after endoscopic biopsy were included in this study. DCEUS and MDCT were performed pre-operatively. The diagnostic accuracies of DCEUS and MDCT in determining the gross classification were calculated and compared. The overall accuracy of DCEUS in determining the gross appearance of GC was higher than that of MDCT (84.9% vs. 79.9%, p < 0.001). There was no significant difference in accuracy between DCEUS and MDCT for Borrmann I and IV classifications of advanced gastric cancer (χ(2), p = 0.323 for Borrmann type I, p = 0.141 for Borrmann type IV). The accuracy of DCEUS for early GC and Borrmann II and III classifications of GC was higher than that of MDCT (χ(2), p = 0.000 for all). DCEUS may be regarded as a valuable complementary tool to MDCT in determining the gross appearance of gastric adenocarcinoma pre-operatively.

Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients.

[Functional MR study of hepatic fibrosis].

The accurate diagnosis and staging of hepatic fibrosis is crucial for treatment and prognosis of liver disease. The current gold standard is liver biopsy, but it cannot be used in population-based screening, and has well known drawbacks if used for monitoring of disease progression or treatment results. Functional MR, as a non-invasive method, is increasingly used in hepatic fibrosis and became the current hot spot. Most recently available functional MR imaging techniques including diffusion weighted imaging, perfusion weighted imaging and MR spectroscopy can detect cirrhosis or fibrosis reasonably accurately. However, to date only MR elastography has been able to stage fibrosis or diagnose mild disease. MR diffusion weighted appears next most promising.

A large functional somatostatinoma in the pancreatic tail: atypical CT appearances.

Somatostatinomas are extremely rare endocrine tumors, and those with diameters above 2 cm are reported to increase the risk of metastasis significantly. We report a case of a large functional somatostatinoma in the pancreatic tail without metastases. A 46-year-old woman with a history of recurrent mild upper abdominal pain and diarrhea for 10 months was admitted to our hospital. Multiple-phase spiral computed tomography revealed a 10 cm x 8 cm, ill-defined, elliptic mass in the body and tail of the pancreas. There was a slightly heterogeneous enhancement on hepatic arterial phase and isodensity to the pancreatic parenchyma with small dotted necrosis within the middle region of the mass on hepatic portal venous and parenchymal phase, with patent splenic vein, dilated collaterals at the splenic hilum and no dilated pancreatic duct, resembling a diffuse infiltration tumor. To the best of our knowledge, this is the first description of multiple-phase spiral computed tomography findings of a functional somatostatinoma in the pancreatic tail and the largest thus far on reported computed tomography, with some differences compared with the previous reports.

Primary hepatic sarcomas: CT findings.

Primary hepatic sarcomas are rare tumors that are difficult to diagnose clinically. Different primary hepatic sarcomas may have different clinical, morphologic, and radiological features. In this pictorial review, we summarized computed tomography (CT) findings of some relatively common types of hepatic sarcomas, including angiosarcoma, epithelioid hemangioendothelioma (EHE), liposarcoma, undifferentiated embryonal sarcoma (UES), leiomyosarcoma, malignant fibrous histiocytoma (MFH), and carcinosarcoma (including cystadenocarcinosarcoma). To our knowledge, hepatic cystadenocarcinosarcoma has not been described in the English literature. The CT findings in our case are similar to that of cystadenocarcinoma, a huge, multilocular cystic mass with a large mural nodule and solid portion. The advent of CT has allowed earlier detection of primary hepatic sarcomas as well as more accurate diagnosis and characterization. In addition, we briefly discuss the MRI findings and diagnostic value of primary hepatic sarcomas.