Changes in Skeletal Muscle Volume During Preoperative Chemotherapy Affect the Outcome of Pancreatic Cancer.

BACKGROUND: This study aimed to investigate the effects of changes in clinicopathological factors during preoperative chemotherapy for pancreatic cancer, including skeletal muscle volume, on recurrence and prognosis after pancreatectomy. METHODS: Data from 41 patients who underwent resection for pancreatic cancer after preoperative chemotherapy from 2012 to 2021 were retrospectively reviewed. Skeletal muscle volume was substituted for the psoas muscle area (PMA) at the level of the third lumbar vertebra. We investigated the relationship of clinicopathological factors during preoperative chemotherapy with disease-free survival (DFS) and overall survival (OS). The association between clinicopathological factors and a decrease in PMA was investigated. RESULTS: In the multivariate analyses for DFS and OS, the factors associated with recurrence were as follows: decrease in PMA (P = 0.003) and the absence of adjuvant therapy (P = 0.03), and the factors associated with poor prognosis were as follows: decrease in PMA (P = 0.04) and the absence of adjuvant therapy (P = 0.008), and the resectability of borderline resectable and unresectable-locally advanced tumors (P = 0.033). All patients with partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1) had no decrease in PMA (P = 0.01). The proportion of patients with Evans classification ≥ II was significantly higher in the group without a decrease in PMA (P = 0.02). The proportion of patients with an average relative dose intensity of adjuvant therapy ≥0.6 was significantly higher in the group without a decrease in PMA (P = 0.02). CONCLUSION: Changes in preoperative skeletal muscle volume during preoperative chemotherapy for pancreatic cancer is a potential predictor of recurrence and prognosis after pancreatectomy.

A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial).

Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

The effectiveness of relugolix compared with leuprorelin for preoperative therapy before laparoscopic myomectomy in premenopausal women, diagnosed with uterine fibroids: protocol for a randomized controlled study (MyLacR study).

BACKGROUND: The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low back pain in women with uterine fibroids. Treatment can also help women recover from low hemoglobin levels and possibly shrink the fibroids. However, evidence of preoperative use of relugolix before laparoscopic myomectomy is limited. Nevertheless, the treatment could reduce interoperative blood loss, decrease the risk of developing postoperative anemia, and shorten the operative time. Thus, we aim to test whether 12-week preoperative treatment with relugolix (40 mg orally, once daily) is similar to or not worse than leuprorelin (one injection every 4 weeks) to reduce intraoperative blood loss. METHODS: Efficacy and safety of preoperative administration of drugs will be studied in a multi-center, randomized, open-label, parallel-group, noninferiority trial enrolling premenopausal women ≥ 20 years of age, diagnosed with uterine fibroids and scheduled for laparoscopic myomectomy. Participants (n = 80) will be recruited in the clinical setting of participating institutions. The minimization method (predefined factors: presence or absence of fibroids ≥ 9 cm and the International Federation of Gynecology and Obstetrics [FIGO] type 1-5 fibroids) with randomization is used in a 1:1 allocation. Relugolix is a 40-mg oral tablet taken once a day before a meal, for 12 weeks, up to the day before surgery. Leuprorelin is a 1.88 mg, or 3.75 mg subcutaneous injection, given in three 4-week intervals during patient visits before the surgery. For the primary outcome measure of intraoperative bleeding, the blood flow is collected from the body cavity, surgical sponges, and collection bag and measured in milliliters. Secondary outcome measures are hemoglobin levels, myoma size, other surgical outcomes, and quality-of-life questionnaire responses (Kupperman Konenki Shogai Index and Uterine Fibroid Symptoms-Quality of Life). DISCUSSION: Real-world evidence will be collected in a clinical setting to use pre-treatment with an oral gonadotropin-releasing hormone antagonist to reduce intraoperative bleeding in women who undergo laparoscopic myomectomy. TRIAL REGISTRATION: jRCTs031210564 was registered on 19 January 2022 in the Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ).

Role of Preoperative Radiation Therapy for Resectable Gastric Cancer.

PURPOSE: While surgery is the primary curative treatment for resectable gastric and gastroesophageal junction (GEJ) cancer, rates of locoregional and distant recurrence remain high with surgery alone, especially in more advanced disease. Multimodal approaches with perioperative therapy including chemotherapy and/or radiation therapy (RT) have thus evolved as ways to reduce the rates of disease recurrence and improve survival outcomes. This review article provides a comprehensive literature review on the role of preoperative RT for resectable gastric and GEJ cancer. METHODS: A literature review on the role of preoperative RT for resectable gastric and GEJ cancer was conducted. RESULTS: Preoperative RT has the potential to facilitate tumor downstaging and improved R0 resection, allowing for better locoregional control and thereby survival. For resectable locally advanced GEJ cancer, preoperative chemoradiotherapy (CRT) is currently a standard of care option along with perioperative chemotherapy, based on evidence from randomized trials. In resectable gastric cancer, however, the role of preoperative CRT is less defined with no randomized data to date, although phase II single-arm studies have shown promising results. Current standard of care for gastric cancer remains perioperative chemotherapy, with consideration for preoperative CRT in select cases. CONCLUSION: Results from ongoing and future randomized controlled trials are expected to help define the role of preoperative CRT compared to perioperative chemotherapy alone as well as postoperative CRT for gastric and GEJ cancer.

Association between fibrosis around the tumor and postoperative infectious complication in patients with esophageal cancer who underwent preoperative therapy.

BACKGROUND: Multidisciplinary treatment combining chemotherapy, chemo radiation therapy (CRT), and surgery has been utilized for advanced esophageal cancer. However, preoperative treatment could cause postoperative inflammation and complications. We hypothesized that fibrosis surrounding tumor tissue caused by preoperative treatment could induce postoperative systemic inflammation and influence postoperative complications. METHODS: Surgical specimens from patients with thoracic esophageal cancer who underwent preoperative CRT (38 cases) or chemotherapy (77 cases) and those who received no preoperative treatment (49 cases) were evaluated to measure the fibrotic area adjacent to the tumor (10 mm from the tumor edge) by applying Azan staining. Pleural effusion and peripheral blood serum interleukin-6 levels were analyzed to evaluate local and systemic postoperative inflammation in 37 patients. RESULTS: The fibrotic areas around the tumors were significantly larger in patients who underwent preoperative CRT than in patients who underwent chemotherapy (p < 0.001) or who had received no preoperative therapy (p < 0.001). Infectious complications were higher in patients who underwent preoperative CRT than chemotherapy (p = 0.047) or surgery alone (p < 0.001). The patients with larger fibrotic areas had more infectious complications (p = 0.028). Multivariate analysis showed that both a large fibrotic area and preoperative CRT were correlated with infectious complications, but not significantly. Pleural effusion interleukin-6 was significantly higher in patients who underwent preoperative CRT than in patients who received no preoperative therapy (p = 0.013). CONCLUSIONS: A large fibrotic peritumoral esophageal tissue area after preoperative treatment could cause postoperative inflammatory response and infectious complications.

The Clinical Outcomes of Thoracoscopic Versus Open Lobectomy for Non-Small-Cell Lung Cancer After Neoadjuvant Therapy: A Multi-Center Retrospective Cohort Study.

BACKGROUND: The safety and efficacy of video-assisted thoracic surgical (VATS) versus open lobectomy for non-small-cell lung cancer (NSCLC) following neoadjuvant therapy remained controversial. The aim of this study was to compare the outcomes of VATS with those of open lobectomy for NSCLC after neoadjuvant therapy. METHODS: Patients who had undergone VATS or open lobectomy for NSCLC following neoadjuvant therapy in nine hospitals in China from July 2014 to July 2020 were retrospectively reviewed. The clinical characteristics and overall survival (OS) of patients were analyzed using Cox regression models and propensity score matching. RESULTS: We identified 685 patients, 436 (63.6%) who had undergone VATS lobectomy and 249 (36.4%) who had undergone open lobectomy. Patients who had undergone VATS lobectomy tended to have had fewer nodes removed than those who had undergone open lobectomy. However, compared with open group, the VATS group had a better perioperative outcome, such as smaller blood loss volumes and shorter postoperative stays. The groups had a similar operation durations and postoperative complications, and there was a nonsignificant difference between their 30-day mortality rates. After propensity score matching, there was no significant different between the OS of the groups, and only postoperative adjuvant therapy was associated with worse OS. CONCLUSION: This multi-center analysis of patients with NSCLC who had undergone surgery subsequent to neoadjuvant therapy reveals that VATS lobectomy tended to have a better perioperative outcome, and have a similar OS compared to open lobectomy. These findings suggest that VATS lobectomy is appropriate for NSCLC following neoadjuvant therapy.

Electrocardiographic characteristics of bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy.

OBJECTIVE: Patients treated with preoperative chemotherapy and immunotherapy for bladder cancer may be at increased risk of cardiotoxicity and electrophysiological abnormalities. This study aimed to analyze their electrocardiographic (ECG) alterations. METHODS: Patients with bladder cancer who were hospitalized and receiving tislelizumab plus nab-paclitaxel (TnP) were enrolled prospectively. ECG, cardiac biomarkers, and echocardiography were performed at baseline and the end of TnP. RESULTS: A total of 60 patients (76.7% males), including 30 muscle-invasive and 30 non-muscle-invasive bladder cancer, received three or four cycles of TnP, respectively. Hypertension was the commonest comorbidity (41.7%), and 25 patients (41.7%) were prescribed cardiovascular drugs. In comparison with baseline characteristics, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were within normal ranges after TnP. However, echocardiographic parameter of left ventricular ejection fraction slightly decreased after TnP (62.81 ± 3.81% to 61.10 ± 4.37%, p = .011). The incidence of abnormal ECG increased from 65.0% at baseline to 76.7%, of which only a higher prevalence of fragmented QRS (fQRS) was observed (33.3% to 50.0%, p = .013; mainly in inferior leads). ECG parameters of QT dispersion (QTd) were prolonged significantly after the regimen (39.50 ± 11.37 to 44.20 ± 15.85 ms, p = .019). CONCLUSION: In bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy, the main ECG abnormality was fQRS and QTd, with relatively normal cardiac biomarkers and echocardiographic parameters. Regular ECG screening should be carried out carefully to detect potential cardiotoxicity in the long-term follow-up.

Preoperative therapy in melanoma: Evolving perspectives in clinical trials.

We reviewed phase II and III trials beginning after 2010 studying preoperative therapy in melanoma (61 trials). Compared to standard adjuvant treatment, neoadjuvant immune checkpoint inhibitors (ICIs) show improved outcomes with approximately 70-80% recurrence free survival at 2 years. Several biomarkers demonstrate predictive value for pathological response (higher PD-L1 expression) and survival (IFN-γ signatures, CD8 + cell density). A number of 'non-standard' treatment mechanisms are being studied in combination with ICI therapies such as TLR-9 agonists, and anti-LAG3 checkpoint inhibitors, which show promise for alternative therapy options in the neoadjuvant setting. Finally, trials for advanced unresectable melanomas show improved survival compared to definitive systemic treatment when upfront systemic therapies lead to resectability. To conclude, in the preoperative setting for melanoma, ICIs have potential to improve outcomes for patients, and will likely change the standard treatment approach for advanced resectable disease.

Efficacious Primary Pasireotide Therapy in a Case of a Large Invasive Adrenocorticotropin-secreting Pituitary Tumor.

A 41-year-old woman presented with a headache, diplopia, weight gain, moon face, and central obesity. Her plasma adrenocorticotropin (ACTH) level was 25.5 pmol/L (116 pg/mL) (normal range, 1.6-13.9 pmol/L [7.2-63.3 pg/mL]), serum cortisol level was 397.3 nmol/L (14.4 µg/dL) (normal range, 195.1-540.7 nmol/L [7.1-19.6 µg/dL]), and urinary free cortisol was 413.9 nmol/day (150.3 µg/day) (normal range, <221.5 mmol/day [<80.3 µg/day]). ACTH-dependent hypercortisolism was present, with cortisol suppression using a high-dose dexamethasone suppression test. Cushing disease was diagnosed and a contrast-enhanced magnetic resonance imaging scan demonstrated a 36-mm pituitary tumor with right cavernous sinus invasion. Before surgery, 20 mg pasireotide long-acting-release was initiated, and her symptoms rapidly improved. After 1 month, obvious tumor shrinkage was observed, ACTH and cortisol levels decreased, and diplopia resolved; therefore, we continued medical therapy. After 11 months, her ACTH and cortisol levels normalized, and most of the tumor had disappeared. The clinical course in this case suggests that pasireotide may be useful for preoperative treatment and primary medical therapy, at least in some patients with Cushing disease caused by a large tumor predicted to have difficulty achieving remission by surgery.

Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer.

Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer (GC)/gastroesophageal junction cancer (GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy (LTG) for GC/GEJC patients who have received preoperative therapy (PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients. Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405 received LTG (LTG group) and 106 received PT+LTG (PT-LTG group) at Nanfang Hospital between June 2018 and September 2022. The surgical outcomes were compared between the two groups. Results: The surgical duration was significantly longer in the PT-LTG group (P<0.001), while the incidence of intraoperative complications (P=1.000), postoperative complications (LTG group vs. PT-LTG group: 26.2% vs. 23.6%, P=0.587), the classification of complication severity (P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups (LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio (OR)=14.094, 95% confidence interval (95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG (OR=0.945, 95% CI: 0.371-2.408, P=0.905). Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.

Current Value of Perioperative Therapies for Resectable or Borderline Resectable Pancreatic Cancer.

Invasive pancreatic ductal carcinoma is a representative refractory malignant tumor, and even with the development of early diagnosis and treatment techniques, the treatment outcome has been remarkably poor. Surgical resection is the curative treatment for resectable pancreatic cancer and borderline resectable pancreatic cancer. However, the survival rate in patients with pancreatic cancer treated by resection alone is low because of the high postoperative recurrence rate. In this review article, we report recent studies on perioperative treatment for pancreatic cancer. Perioperative therapy is the addition of chemotherapy or radiation therapy before or after surgery to improve resectability and curative effects. Because it is difficult to cure redsecttable pancreatic cancer by surgery alone, multidisciplinary treatment combined with perioperative adjuvant chemotherapy is the current standard of care. Although perioperative chemotherapy and chemoradiotherapy have been investigated for borderline resectable pancreatic cancer, the effectiveness of preoperative treatment has not been sufficiently proven. Potentially curative pancreatic cancer is treated by surgery plus perioperative therapy; treatment cannot be either alone. We regard the successful completion of surgery and perioperative care as the key to improving treatment outcomes. Therefore, ongoing randomized controlled trials for the treatment of BR-pancreatic cancer are expected to induce further improvements survival outcomes of patients with BR-pancreatic cancer.

PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: A biomolecular exploratory, phase II trial.

This is a phase II study of PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC, respectively). Twenty-nine patients are enrolled in the study. The objective response rate (ORR) is 60%, and the R0 resection rate is 90% (9/10). The 12-month progression-free survival (PFS) rate and 12-month overall survival (OS) rate are 64% and 72%, respectively. Grade 3 or higher adverse events are anemia (8%), thrombocytopenia (8%), and jaundice (8%). Circulating tumor DNA analysis reveals that patients with a >50% decline in maximal somatic variant allelic frequency (maxVAF) between the first clinical evaluation and baseline have a longer survival outcome and a higher response rate and surgical rate than those who are not. PD-1 blockade plus chemoradiotherapy as preoperative therapy displays promising antitumor activity, and multiomics potential predictive biomarkers are identified and warrant further verification.

Determinants of Pre-Surgical Treatment in Primary Rectal Cancer: A Population-Based Study.

When preoperative radiotherapy (RT) is best used in rectal cancer is subject to discussions and guidelines differ. To understand the selection mechanisms, we analysed treatment decisions in all patients diagnosed between 2010-2020 in two Swedish regions (Uppsala with a RT department and Dalarna without). Information on staging and treatment (direct surgery, short-course RT, or combinations of RT/chemotherapy) in the Swedish Colorectal Cancer Registry were used. Staging magnetic resonance imaging (MRI) permitted a division into risk groups, according to national guidelines. Logistic regression explored associations between baseline characteristics and treatment, while Cohen's kappa tested congruence between clinical and pathologic stages. A total of 1150 patients without synchronous metastases were analysed. Patients from Dalarna were older, had less advanced tumours and were pre-treated less often (52% vs. 63%, p < 0.001). All MRI characteristics (T-/N-stage, MRF, EMVI) and tumour levels were important for treatment choice. Age affected if chemotherapy was added. The correlation between clinical and pathological T-stage was fair/moderate and poor for N-stage. The MRI-based risk grouping influenced treatment choice the most. Since the risk grouping was modified to diminish the pre-treated proportion, fewer patients were irradiated with time. MRI staging is far from optimal. A stronger wish to decrease irradiation may explain why fewer patients from Dalarna were irradiated, but inequality in health care cannot be ruled out.

Borrmann Type Predicts Response to Preoperative Therapy in Advanced Gastric Cancer.

PURPOSE: The Borrmann classification system is widely used to classify advanced gastric cancer (GC). No studies have focused on the relationship between Borrmann type and response to preoperative therapy. METHODS: Patients with advanced GC who received preoperative therapy followed by curative-intent gastrectomy from September 2016 through September 2021 were identified. Clinicopathologic characteristics were compared by Borrmann type. Logistic regression models were fit to analyze the relationship between Borrmann type and pCR rate. RESULTS: Of the 227 patients who underwent gastrectomy during the period studied, 73 had pretreatment endoscopic images available for analysis. We classified the tumors as follows: Borrmann type 1, 4 (6%); type 2, 17 (23%); type 3, 33 (45%); and type 4, 19 (26%). Nine patients (12%) achieved pCR; 6 of these (67%) had type 1/2 GC and 3 (33%) had type 3. Multivariable logistic regression showed that Borrmann type 3/4 was the only independent factor associated with pCR (odds ratio 0.12; p = 0.023), but 2-year overall survival rates did not differ by Borrmann type (p = 0.216). CONCLUSION: Patients with Borrmann type 3/4 advanced GC have a lower likelihood of achieving pCR after preoperative therapy than those with type 1/2 GC. Determining the Borrmann type preoperatively can guide treatment decision-making.

Preoperative Systemic Therapy for Breast Cancer.

The indications for preoperative/neoadjuvant systemic therapy in breast cancer have changed over the past few years. In this article, the authors review the current data for use of neoadjuvant therapy in inoperable and operable settings. The evolution of various neoadjuvant regimens used in triple-negative breast cancer, human epidermal growth factor receptor 2 (HER2) overexpressing/gene-amplified (HER2+) tumors, and hormone receptor positive breast cancer is discussed as well as the role of neoadjuvant chemotherapy in tailoring adjuvant treatment.

Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer.

BACKGROUND: Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values. METHODS: Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0-1 and 2-3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method. RESULT: One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0-1 group and was 16.13 months in TRG 2-3 group. TRG 2-3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P < 0.001). CONCLUSION: TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.

Oral metronomic chemotherapy as a feasible preoperative therapy in advanced resectable oral cavity squamous cell carcinomas- a preliminary experience.

Introduction: Surgery is an important component of multimodality treatment in advanced oral cavity cancers. But in low-middle-income countries like India, with limited centres offering complex head and neck surgeries, prolonged waiting times for surgery is a major problem. An increase in waiting times for treatment has been shown to be a negative prognosticator in head and neck cancer and many patients can develop interim progression making them ineligible for radical treatment. We share our preliminary experience of using oral metronomic chemotherapy as a preoperative treatment in patients expecting delay in surgery. Methods: This was a retrospective analysis of case records of patients with resectable Stage III and Stage IV (IVA & IVB) oral cavity cancers who had received preoperative oral metronomic chemotherapy (POMT). The POMT schedule consisted of oral Methotrexate 15 mg/m2 weekly, Celecoxib 200 mg twice daily and Erlotinib 100 mg daily. Clinico-radiological assessments were done prior to surgery using standard response assessment criteria. Results: A total of 68 patients received POMT with a median age of 55 years (range: 34-73 years). Forty-eight (70%) were males, 29 (42%) had carcinoma tongue and majority (N = 52, 76%) had Stage IVA cancer. Mean duration of POMT administration was 30.45 days (standard deviation: 8.22). Thirty-seven (54%) patients had partial responses and another 23 (34%) had stable disease. Two (3%) had disease progression on POMT. Fifty-eight (85%) underwent surgery after POMT. Margin positive resection was seen in two patients. Half of the patients who received POMT did not experience any toxicity. Grade 3/4 toxicities were seen in four (6%) patients. Conclusions: POMT is a feasible strategy worth considering in cases where there are prolonged waiting times to surgery.

Current status and future perspective of neoadjuvant therapy in locally advanced and borderline resectable pancreatic adenocarcinoma: a narrative review.

BACKGROUND AND OBJECTIVE: The concept of neoadjuvant approach for patients with locally advanced pancreatic cancer (LAPC) has been evolving with the advancement in therapeutic modalities. In this narrative review, we aimed to discuss the updates and future perspectives on the treatment of LAPC. METHODS: We discussed the recent literature and up-to-date evidence along with the future perspectives for the treatment of LAPC using the neoadjuvant approach. Reviewed literatures were searched by systematic search of PubMed and Google Scholar, including articles published in English between January 1st, 2013, and October 31st, 2021. KEY CONTENT AND FINDINGS: We aimed to review the efficacy outcomes of modern-era chemotherapy regimens and chemoradiation therapy for LAPC based on the results of up-to-date clinical trials and pivotal observational studies. Moreover, we aimed to discuss the role of conversion surgery and studies on the prediction of resectability after neoadjuvant therapy along with the necessity of adjuvant therapy for patients who have received neoadjuvant systemic treatments. Finally, we have addressed several unanswered questions regarding the optimal management of patients with LAPC and determined the future directions by introducing some ongoing trials. CONCLUSIONS: Current chemotherapy and chemoradiation therapy has improved clinical outcomes and the conversion surgery rate in patients with LAPC. Future randomized clinical trials and biomarker studies are needed to provide better evidence that can aid in the selection of optimal treatment modalities for individual patients.

Targeting STAT3 Signaling Facilitates Responsiveness of Pancreatic Cancer Cells to Chemoradiotherapy.

The debate is ongoing regarding the potential role of preoperative chemoradiotherapy (CRT) for patients with pancreatic ductal adenocarcinoma (PDAC), and whether it should be reserved for borderline resectable or unresectable tumors. However, treatment response is heterogeneous, implicating the need to unveil and overcome the underlying mechanisms of resistance. Activation of the transcription factor STAT3 was recently linked to CRT resistance in other gastrointestinal cancers such as rectal and esophageal cancers, but its role in PDAC needs to be clarified. Protein expression and phosphorylation of STAT3 was determined in PDAC cell lines and connected to transcriptional activity measured by dual-luciferase reporter gene assays. Inhibition of STAT3 signaling was achieved by RNAi or the small-molecule inhibitor napabucasin. We observed a positive correlation between STAT3 signaling activity and CRT resistance. Importantly, genetical and pharmacological perturbation of the IL-6/STAT3 pathway resulted in CRT sensitization specifically in those cell lines, in which STAT3 activity was augmented by IL-6. In conclusion, our data underscore the general importance of IL-6/STAT3 signaling for CRT resistance and suggest that pathway inhibition may represents a putative treatment strategy in order to increase the fraction of patients with PDAC who are candidates for surgical approaches.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.