Important Predictive Factors for the Prognosis of Patients With Peritoneal Metastasis of Gastric Cancer.

BACKGROUND: This study investigated predictive factors for patients with peritoneal metastases of gastric cancer (PMGC) who underwent conversion cytoreductive surgery (C-CRS) and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) after responding to induction chemotherapy (laparoscopic HIPEC [LHIPEC]) followed by concomitant systemic and intraperitoneal chemotherapy (bidirectional intraperitoneal and systemic chemotherapy [BIC]). METHODS: Diagnostic laparoscopy was performed for 62 patients with PMGC between January 2017 and December 2022. The patients underwent LHIPEC and BIC induction chemotherapy using intraperitoneal docetaxel (30 mg/m2) and cisplatin (30 mg/m2), and intravenous chemotherapy for three cycles. The predictive parameters for progression-free and overall survival were analyzed using Kaplan-Meier and Cox regression analyses. The optimal cutoff values for Ki-67 parameters were assessed using receiver operating characteristic curve analysis. RESULTS: The study retrospectively examined 36 (58 %) of 62 patients who responded to induction therapy and underwent C-CRS or HIPEC. A Ki-67 index lower than 10 (p = 0.000), lymph node involvement (LNI) less than 2 (p = 0.039), and an omental lesion size score lower than 0.5 cm (p = 0.002) were predictive of recurrence-free and overall survival in addition to completeness of cytoreduction and the peritoneal cancer index. Cox regression analysis showed that the independent factors associated with recurrence-free survival were decreased Ki-67 expression (≥10 % vs <10 %) (hazard ratio [HR] 4.7; 95 % confidence interval [CI] 1.6-5.210; p = 0.020) and LNI higher than 2 (HR 1.92; 95% CIS 0.923-4.0; p = 0.023). CONCLUSIONS: Lymph node involvement and decreased Ki-67 expression are independent predictive factors of recurrence-free survival for patients with PMGC after induction chemotherapy.

Metastatic neuroendocrine carcinoma: Liver metastases presenting with diffuse nodular calcifications on CT.

We report a case of the 46-year-old female patient, who presented with diffuse nodular liver calcifications on computed tomography. Histopathology of the calcified nodules revealed neuroendocrine tumors (NETs). Calcified NET liver metastases are extremely rare and need to be considered in the differential diagnosis with other benign and malignant liver calcification.

Metronomic Temozolomide (mTMZ) and Bevacizumab-The Safe and Effective Frontier for Treating Metastatic Neuroendocrine Tumors (NETs): A Single-Center Experience.

Addressing the persistent challenges in treating metastatic neuroendocrine tumors (NETs) demands ongoing refinement and innovation in therapeutic strategies. This study investigates the potential advantages of combining metronomic temozolomide (mTMZ) with bevacizumab for patients diagnosed with metastatic NETs, particularly focusing on those with a Ki-67 index under 55%. Data from 30 patients were analyzed, using key performance indicators such as progression-free survival (PFS), overall survival (OS), and response rates to therapy, to gauge the treatment's efficacy. The results were encouraging: the median PFS recorded was 16.3 months, and the OS was 25.9 months. The disease control rate (DCR) reached an impressive 86.7%, and the objective response rate (ORR) stood at 63.3%. The treatment regimen was well-tolerated, with no reported instances of grade 4 toxicities. Such a safety profile indicates that this regimen may be particularly advantageous for older, fragile patients who might struggle with conventional dosage levels. These initial findings suggest that the mTMZ and bevacizumab combination could potentially rival the conventional temozolomide-capecitabine therapy in managing metastatic NETs. We aimed to meticulously assess the efficacy of the mTMZ and bevacizumab combination in treating metastatic NETs. Given the initial promising results, a more conclusive understanding of its efficacy will require further research through larger, multicenter prospective clinical trials.

Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+ rectal cancer: Istanbul R-02 phase II randomized study.

Radiation therapy (RT) is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer (LARC): short-course RT (SC-RT) alone or long-course RT (LC-RT) with concurrent fluorouracil (5-FU) chemotherapy. The Phase II single-arm KROG 11-02 study using intermediate-course (IC) (33 Gy (Gray)/10 fr (fraction) with concurrent capecitabine) preoperative chemoradiotherapy (CRT) demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT. The current trial aim to compare the pathological/oncological outcomes, toxicity, and quality of life results of LC-CRT and IC-CRT in cases of LARC. The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group. Concurrent chronomodulated capecitabine (Brunch regimen) 1650 mg/m2/daily chemotherapy treatment was applied in both groups. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module (EORTC QLQ-CR29) was administered at baseline and at three and six months after CRT. A total of 60 patients with LARC randomized to receive IC-CRT (n = 30) or LC-CRT (n = 30) were included in this phase II randomized trial. No significant difference was noted between groups in terms of pathological outcomes, including pathological response rates (ypT0N0-complete response: 23.3% vs. 16.7%, respectively, and ypT0-2N0-downstaging: 50% for each; p = 0.809) and Dworak score-based pathological tumor regression grade (Grade 4-complete response: 23.3 vs. 16.7%, p = 0.839). The 5-year overall survival (73.3 vs. 86.7%, p = 0.173) rate was also similar. The acute radiation dermatitis (p < 0.001) and any hematological toxicity (p = 0.004) rates were significantly higher in the LC-CRT group, while no significant difference was noted between treatment groups in terms of baseline, third month, and sixth month EORTC QLQ-CR29 scores.

Robotic vs. laparoscopic intersphincteric resection for low rectal cancer: a case matched study reporting a median of 7-year long-term oncological and functional outcomes.

Aim of this study was to compare operative, long-term oncological and functional outcomes of laparoscopic (LISR) and robotic (RISR) intersphincteric resection in low-lying rectal cancer. Retrospective analysis of prospectively maintained database was performed. 115 cases (LISR, n = 55; RISR, n = 60) were performed by a single surgeon (January 2011-January 2020). Clinical characteristics did not differ between the groups. Operating time was longer in RISR (160.0 ± 45.7 vs. 205.0 ± 36.5 min, p = 0.035). There was no conversion in RISR, whereas in LISR, two patients (3.6%) converted to open surgery. Complete mesorectum was 61.8% and 83.3% for LISR and RISR (p = 0.046), respectively. Circumferential radial margin involvement was 10.9% and 8.3% in LISR and RISR (p = 0.365), respectively. Median follow-up was 82.8 (30-138) months for LISR and 83.6 (30-138) months for RISR. Three-, five-, and seven-year overall survival rates (OS) for LISR and RISR were: 88.6%, 80.4%, 73.4% and 90.4%, 86.3%, 76.9%, respectively. Three-, five-, and seven-year disease-free survival (DFS) rates for LISR and RISR were 80.5%, 75.2%, 70.4% and 84.4%, 81.4%, 79.8% (p = 0.328), respectively. Three-, five-, and seven-year local recurrence-free survival rates in LISR and RISR were: 96.1%, 92.6%, 88.4% and 96.7%, 94.2%, 90.4% (p = 0.573), respectively. Mean Wexner score for LISR (n = 32) and RISR (n = 40) was: 10.5 ± 4.7 and 9.8 ± 4.2 (p = 0.782), respectively. Colostomy-free survival in LISR and RISR was: 3 years 94.5%/95.2%, 5 years 89.1%/91.7%, and 7 years 83.6%/85.0%. RISR is associated with better mesorectal integrity, no conversion, and lower postoperative complication rate. RISR has longer operation time. Oncological and anorectal functional outcomes are similar in both groups.

A new approach for leptomeningeal metastases: chemotherapy administered through lumbar intrathecal port.

BACKGROUND: Intrathecal chemotherapy is a local therapeutic modality used for treatment of leptomeningeal metastases. However, the techniques currently used, i.e. repeated lumbar puncture and Ommaya reservoir, have certain disadvantages. Lumbar intrathecal port (LIP) placement is a relatively novel technique, which has been used for pain management in cancer patients. OBJECTIVE: To investigate the use of LIP for intrathecal administration of chemotherapeutic agents in patients with leptomeningeal metastases. METHODS: Retrospective study of 13 patients treated with intrathecal chemotherapy for secondary leptomeningeal involvement of a primary solid tumor were included in this retrospective study. The patients received intrathecal chemotherapy through a LIP. RESULTS: The patients received a total of 123 intrathecal chemotherapy doses. No grade 3-4 toxicity, technical problem or severe complication developed. During a median of 136 days of follow-up (range, 67-376 days), 12 patients died (92.3%). The treatment resulted in symptom improvement in all patients and self-rated overall health and quality of life improved, compared with baseline. CONCLUSIONS: The LIP system, which has been used for intrathecal pain management for decades, appears to offer a safe alternative for intrathecal chemotherapy in patients with leptomeningeal metastases. Further studies are warranted to clarify its potential use in this setting.

Intersphincteric Resection for Low Rectal Cancer: Parameters Affecting Functional Outcomes and Survival Rates.

INTRODUCTION: The development of new surgical techniques and devices, as well as the improvements in neoadjuvant chemoradiotherapy enabled intersphincteric resection (ISR), has reduced permanent colostomy usage. The aim of this study was to assess the long-term oncological and functional outcomes of patients who underwent partial ISR for rectal cancer located less than 5cm from the anal verge. MATERIALS AND METHODS: A series of 106 consecutive patients with very low rectal cancer underwent curative partial ISR from January 2006 to September 2019 were retrospectively evaluated. One-hundred-three (97%) of 106 patients received neoadjuvant chemo-radiotherapy. Overall survival (OS), disease-free survival (DFS), and local recurrence (LR) rates were calculated using Kaplan-Meier methods. The Wexner incontinence score and Kirwan classification were used to evaluate patients' functional results. RESULTS: The median follow up was 60 months (range, 18-174). The estimated five-year overall and disease-free survival rates were 89% and 81.6%, respectively. Five-year local recurrence and distant metastasis rates were 6.6% and 10.4%, respectively. There was no in-hospital and 30-day mortality. The median Wexner score was 9 (range, 0-20) for 72 patients. Age (<65 years, p=0.027) and gender (male, p=0.019) had a positive effect on functional outcomes after surgery. One and five years colostomy-free survival rates were 96% and 89%, respectively. CONCLUSION: Intersphincteric resection techniques are feasible for patients with very low rectal cancer, providing good oncological and functional outcomes.

A new approach for leptomeningeal metastases: chemotherapy administered through lumbar intrathecal port / Un nuevo abordaje para el tratamiento de las metástasis leptomeníngeas: uso de catéter implantado para el suministro de quimioterapia vía intratecal lumbar

ABSTRACT Background: Intrathecal chemotherapy is a local therapeutic modality used for treatment of leptomeningeal metastases. However, the techniques currently used, i.e. repeated lumbar puncture and Ommaya reservoir, have certain disadvantages. Lumbar intrathecal port (LIP) placement is a relatively novel technique, which has been used for pain management in cancer patients. Objective: To investigate the use of LIP for intrathecal administration of chemotherapeutic agents in patients with leptomeningeal metastases. Methods: Retrospective study of 13 patients treated with intrathecal chemotherapy for secondary leptomeningeal involvement of a primary solid tumor were included in this retrospective study. The patients received intrathecal chemotherapy through a LIP. Results: The patients received a total of 123 intrathecal chemotherapy doses. No grade 3-4 toxicity, technical problem or severe complication developed. During a median of 136 days of follow-up (range, 67-376 days), 12 patients died (92.3%). The treatment resulted in symptom improvement in all patients and self-rated overall health and quality of life improved, compared with baseline. Conclusions: The LIP system, which has been used for intrathecal pain management for decades, appears to offer a safe alternative for intrathecal chemotherapy in patients with leptomeningeal metastases. Further studies are warranted to clarify its potential use in this setting.

RESUMEN Antecedentes: La quimioterapia intratecal es una modalidad terapéutica local utilizada para el tratamiento de metástasis leptomeníngeas. Sin embargo, las técnicas empleadas actualmente, es decir, las punciones lumbares repetidas y el depósito de Ommaya, tienen algunos inconvenientes. La colocación de un puerto intratecal lumbar (LIP) es una técnica relativamente nueva que se ha utilizado para el tratamiento del dolor en pacientes con cáncer. Objetivo: Investigar el uso de LIP para la administración intratecal de agentes quimioterapéuticos en pacientes con metástasis leptomeníngeas. Métodos: Este estudio retrospectivo incluyó un total de 13 pacientes tratados con quimioterapia intratecal por afectación leptomeníngea secundaria de un tumor sólido primario. Los pacientes recibieron quimioterapia intratecal a través de un LIP. Resultados: Los pacientes recibieron un total de 123 dosis de quimioterapia intratecal. No se desarrolló toxicidad de grado 3-4, ni se presentaron problemas técnicos o complicaciones graves. Durante un promedio de 136 días de seguimiento (rango, 67-376 días), murieron 12 pacientes (92,3 %). El tratamiento dio como resultado una mejoría de los síntomas en todos los pacientes. La salud general autoevaluada y la calidad de vida mejoraron en comparación con los valores iniciales. Conclusiones: El sistema LIP que se ha utilizado para el manejo del dolor intratecal durante décadas, parece ofrecer una alternativa segura para la quimioterapia intratecal en pacientes con metástasis leptomeníngeas. Serán necesarios más estudios para determinar su uso potencial en este ámbito.

Gallbladder Uptake Mimicking Liver Metastasis on 177Lu-DOTATATE Posttherapy Scan Gallbladder Uptake on 177Lu-DOTATATE Scan.

ABSTRACT: We represent the case of a 61-year-old man with atypical carcinoid tumor of the lung. On posttherapy 177Lu-DOTATATE whole-body scan, focal intense uptake in the inferomedial side of the liver was detected. Pretherapy 68Ga-DOTATATE PET/CT showed no sign of liver metastasis, and posttherapy diagnostic dynamic liver MRI is used to exclude metastatic liver disease. Focal intense uptake was attributed to physiological gallbladder uptake.

Y90 selective internal radiation therapy and peptide receptor radionuclide therapy for the treatment of metastatic neuroendocrine tumors: combination or not?

BACKGROUND: Peptide receptor radionuclide therapy and selective internal radiation therapy are effective radionuclide therapy modalities for unresectable metastatic neuroendocrine tumor patients that cannot be controlled with somatostatin analogs. The present study is intended to evaluate the therapeutic efficacy and toxicity of the combined therapy of selective internal radiation therapy and peptide receptor radionuclide therapy and stand-alone selective internal radiation therapy in patients with neuroendocrine tumor, a liver-dominant disease. METHODS: This cohort consists of 27 patients with metastatic neuroendocrine tumor and liver-dominant disease. They were grouped as the patients who were treated with selective internal radiation therapy for unresectable liver metastasis (n = 15) and the patients who received a combination of selective internal radiation therapy and peptide receptor radionuclide therapy (n = 12) for hepatic and extrahepatic metastasis. Treatment efficacy and treatment-associated toxicity were retrospectively assessed in both groups. RESULTS: The objective treatment response and stable disease were found in 13 patients (86.6%) in the selective internal radiation therapy group and eight patients (66.6%) in the selective internal radiation therapy + peptide receptor radionuclide therapy group. The median overall survival rate was found to be 34.9 months, in the selective internal radiation therapy group and 67.5 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.217). The median progression-free survival data was not reached, and the mean values of progression-free survival were 53.1 ± 9.9 months in the selective internal radiation therapy group, and 27.2 ± 5.9 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.561). Temporary lymphopenia was the most common side effect. Grade 1-2 hepatotoxicity was observed to be 6.6% in the selective internal radiation therapy group, while it was not observed in selective internal radiation therapy + peptide receptor radionuclide therapy group. CONCLUSIONS: In the neuroendocrine tumors with liver-dominant metastatic disease, personalized selective internal radiation therapy and peptide receptor radionuclide therapy and their combinations result in increased survival rates. Selective internal radiation therapy alone could be an effective treatment in patients with liver-limited and -dominant disease.

Robotic versus laparoscopic sphincter-saving total mesorectal excision for mid or low rectal cancer in male patients after neoadjuvant chemoradiation therapy: comparison of long-term outcomes.

The aim of our study was to compare long term outcomes of robotic and laparoscopic sphincter-saving total mesorectal excision (TME) in male patients with mid-low rectal cancer (RC) after neoadjuvant chemoradiotherapy (NCRT). The study was conducted as a retrospective review of a prospectively maintained database, and we analyzed 14 robotic and 65 laparoscopic sphincter-saving TME (R-TME and L-TME, respectively) performed by one surgeon between 2005 and 2013. Patient characteristics, perioperative recovery, postoperative complications and pathology results were compared between the two groups. The patient characteristics did not differ significantly between the two groups. Median operating time was longer in the R-TME than in the L-TME group (182 min versus 140 min). Only two conversions occurred in the L-TME group. No difference was found between groups regarding perioperative recovery and postoperative complication rates. The median number of harvested lymph nodes was higher in the RTME than in the L-TME group (32 versus 23, p = 0.008). The median circumferential margin (CRM) was 10 mm in the R-TME group, 6.5 mm in the L-TME group (p = 0.047. The median distal resection margin (DRM) was 27.5 mm in the R-TME, 15 mm in the L-TME group (p = 0.014). Macroscopic grading of the specimen in the R-TME group was complete in all patients. In the L-TME group, grading was complete in 52 (80%) and incomplete in 13 (20%) cases (p = 0.109). Median follow-up 87 months (1-152). Whereas local recurrence was seen in eight cases (10.12%) and distant metastasis was seen in 18 cases (22.7%). Overall, 5 years survival was 83.3% in R-TME, 75% in L-TME groups. R-TME is a safe and feasible procedure that facilitates performing of TME in male patients with mid to low RC after NCRT.

Synchronous presentation of muscle-invasive urothelial carcinoma of bladder and peritoneal malign mesothelioma.

INTRODUCTION: Cancer is one of the most important leading cause of death in man and woman in the world. The occurrence of new cancer has become more frequent in recent years due to strict screening protocols and occupational and environmental exposure to carcinogens. The incidence of secondary malignancies has also increased due to close medical follow-up and advanced age. Herein, we report a case and its management diagnosed as synchronous peritoneal malignant mesothelioma and muscleinvasive urothelial carcinoma.

Prognostic significance of carbonic anhydrase IX overexpression in stage III non-small cell lung cancer patients after neoadjuvant treatment.

BACKGROUND: To assess the prognostic importance of carbonic anhydrase IX (CA IX), a hypoxic biomarker, after neoadjuvant treatment in Stage III non-small cell lung cancer (NSCLC) patients. METHODS: Tissue CA IX expression was examined after surgical resection in 77 patients who had undergone neoadjuvant treatment. The effects of CA IX overexpression and other clinical factors on disease-free survival and overall survival were investigated. RESULTS: In multivariate analysis, number of neoadjuvant chemotherapy (CT) courses and gender emerged as significant independent predictors for disease-free survival, where administration of 2-3 courses of neoadjuvant chemotherapy (CT) (HR, 3.2 [95% CI 1.3-7.6], p = 0.009) and female gender were associated with poor survival (HR, 3.2 [95% CI 1.3-7.7], p = 0.009). The only significant independent predictor for overall survival was recurrence (HR, 5.6 [95% CI 2.4-12.8], p < 0.001). On the other hand, CA IX overexpression was not associated with disease free survival (p = 0.560) or overall survival (p = 0.799). DISCUSSION: Our results do not suggest a prognostic role for CA IX overexpression in stage III NSCLC patients who received neoadjuvant treatment.

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study.

AIM: To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy (HART) and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS: A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS: In the early phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2 patients had grade III-IV hematologic toxicity, and 1 patient had grade V toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade IV tenesmus. Complete pathological response was achieved in 6 patients (21%), while near-complete pathological response was obtained in 9 (31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively. CONCLUSION: Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Delayed versus immediate surgery following short-course neoadjuvant radiotherapy in resectable (T3N0/N+) rectal cancer.

PURPOSE: Preoperative short-course radiotherapy (SCRT) followed by surgery has shown advantage over surgery alone in patients with resectable rectal carcinoma (RC); however, the importance of the timing of surgery after SCRT has not been well defined. This study aimed to investigate the effect of this duration on treatment outcomes. METHODS: Patients who underwent surgery after SCRT (25 Gy/500 cGy/daily/5fr, monday-friday) for resectable and infraperitoneal rectal adenocarcinoma (T3N0/(+)) were included into the study. Patients were divided into two groups in terms of the timing of surgery: delayed surgery (>4 weeks) or immediate surgery (<4 weeks). RESULTS: A hundred and thirty-six patients were included in the study. Median time between RT and surgery was 4 ± 5.7 (1-58) weeks, where 68% (n = 93) patients underwent delayed surgery (≥4 weeks). The two groups did not differ in terms of surgical margin positivity, pathological tumor regression, N downstaging, or T downstaging (p > 0.05 for all). However, the number of positive lymph nodes was higher in the immediate surgery group [median 3 (0-18) vs. 1 (0-17), p = 0.009]. Median follow-up time was 36 ± 9 (6-93) months. Delayed surgery group had significantly longer mean overall survival (p = 0.038); however, the two groups did not differ in terms of local recurrence, mean time to local recurrence, or mean disease-free survival. CONCLUSIONS: Our findings seem to support the benefit of a longer time interval between radiotherapy and surgery after short-course neoadjuvant radiotherapy in resectable rectal cancer in terms of overall survival. However, there is a need to better define patient characteristics that might benefit from delayed surgery.

Chronomodulated oxaliplatin plus Capecitabine (XELOX) as a first line chemotherapy in metastatic colorectal cancer: A Phase II Brunch regimen study.

PURPOSE: The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first-line XELOX chemotherapy in patients with metastatic colorectal cancer. METHODS: A total of 30 treatment-naïve colorectal cancer patients with metastatic disease were included. Oxaliplatin 130 mg/m(2) on day 1 plus chronomodulated oral capecitabine 2000 mg/m(2) per day were administered (50 % dose at 8:00 a.m. and 50 % dose at 12:00 noon on days 1-14, every 21 days). All adverse events, treatment responses and survival were evaluated. In addition, pharmacokinetic profile of capecitabine was examined in a subset of 5 patients. RESULTS: Median age was 57.1 years (range 32-77 years). Median follow-up was 19 months (range 3-36 months). Three patients (10 %) had complete response, 13 patients (43.3 %) had partial response and 4 patients (13.3 %) had stabile disease. Ten patients had progressive disease at their first evaluation (33.3 %). The median progression-free survival (PFS) was 10 months (range 2-36 months). There were no grade 4 toxicities. One patient (3.3 %) had grade 3 neutropenia. Hand-foot syndrome developed in three patients (10 %): 6.6 %, grade 1 and 3.3 %, grade 2. CONCLUSIONS: Chronomodulated XELOX seems to represent a promising therapeutic option in the first-line treatment of metastatic colorectal carcinoma due to good tumor control and favorable toxicity profile. Phase III randomized trials are required to assess the actual clinical efficacy and side effect profile of this regimen.

The Impact of Phosphohistone-H3-Assisted Mitotic Count and Ki67 Score in the Determination of Tumor Grade and Prediction of Distant Metastasis in Well-Differentiated Pancreatic Neuroendocrine Tumors.

This study investigated the impact of phosphohistone-H3 (PHH3)-assisted mitotic count by comparing its performance with conventional mitotic count and Ki67 score as well as the status of distant metastasis. A total of 43 surgically resected pancreatic neuroendocrine tumors (panNET) with complete follow-up information has been subjected to a standardized assessment with respect to mitotic count (both conventional and PHH3-assisted) and Ki67 score. Five participants assessed mitotic count and the time spent was recorded in both methods. All tumors were assigned to a G1 category of mitotic rate on conventional mitotic count that failed to identify three tumors with a G2 category of mitotic rate on PHH3. Near-perfect and fair agreements were achieved among observers when using PHH3 and conventional method, respectively. The mean time spent to determine mitotic count on PHH3-stained slides was significantly shorter (p < 0.001). The performance of PHH3-assisted mitotic grade category was significant as the three cases with a G2 mitotic category were associated with distant metastasis (p = 0.01). Despite its performance, the PHH3-assisted mitotic count downgraded 17 cases that were classified as G2 based on Ki67 scores in this series. The Ki67 grade category was either the same or higher than the mitotic grade category. Ten patients developed distant metastasis. Eleven tumors exhibited vascular invasion characterized by intravascular tumor cells admixed with thrombus. Our results indicate that PHH3-assisted mitotic count facilitates an accurate mitotic count with a perfect agreement among observers. The small size of this cohort is an important limitation of the current study, a G2 mitotic grade category based on PHH3 immunohistochemistry was one of the correlates of panNETs with distant metastasis. While the prognostic impact of PHH3-assisted mitotic count needs to be clarified in larger cohorts, Ki67 scores designated higher grade category in all cases; thus, it was the best determinant of the tumor grade. More importantly, the presence of vascular invasion along with the Ki67 grade category was found to be independent predictors of distant metastasis.