Intracholecystic Papillary-tubular Neoplasm (ICPN) of the Gallbladder: A Case Report Focusing on an Unexpected Pathological Finding.

BACKGROUND: Intracholecystic papillary neoplasms (ICPNs) represent a rare benign entity characterized by intraluminal polypoid lesions in the gallbladder. The incidence of ICPNs ranges from 0.4% to 0.61% in all gallbladder specimens. CASE PRESENTATION: In this report, we present a case of a young Caucasian woman who underwent elective laparoscopic cholecystectomy due to gallbladder polyps. The histological examination revealed the presence of an intracholecystic papillary neoplasm (ICPN) with a tubulopapillary growth pattern, exhibiting gastric morphology and displaying both low and high-grade dysplasia. A thorough review of the existing literature was conducted, with a specific focus on the histological features. CONCLUSION: A comprehensive understanding of neoplastic polyps of the gallbladder is still limited. Pathological examination of these lesions is crucial for identifying key features that can influence patient outcomes and survival.

The Berne-Donovan technique for diverticulization of a severe lateral non-traumatic duodenal fistula.

BACKGROUND: The duodenal «diverticulization¼ is a surgical technique described by Berne and colleagues in 1968 for the treatment of combined duodenal pancreatic injuries. It consisted of closure of the duodenal injury by suture and tube duodenostomy, gastric antrectomy with end-to-side isoperistaltic Billroth II gastrojejunostomy, and abdominal drainage. As evidenced from the literature in few reports, this technique has also been adopted for lateral duodenal lacerations in non traumatic conditions. Most biliary disease may be responsible for duodenal injury. CASE PRESENTATION: Herein, we describe the application of this emergency technique for the treatment of a wide lateral duodenal laceration discovered intra-operatively during laparoscopic cholecystectomy for acute cholecystitis. A comprehensive critical review of the different surgical methods proposed for duodenal protection in case of severe duodenal lesions has been performed and discussed. CONCLUSION: Duodenal injuries represent a challenging condition, especially for surgeons with limited experience in this field. The key-message of this report is to consider emergency surgical techniques in difficult unexpected intra-operative situations which may occur during routine surgical practice. KEY WORDS: Duodenal diverticulization, Duodenal fistula, Laparoscopic cholecystectomy, Surgical repair.

Inflammatory Microenvironment in Early Non-Small Cell Lung Cancer: Exploring the Predictive Value of Radiomics.

Patient prognosis is a critical consideration in the treatment decision-making process. Conventionally, patient outcome is related to tumor characteristics, the cancer spread, and the patients' conditions. However, unexplained differences in survival time are often observed, even among patients with similar clinical and molecular tumor traits. This study investigated how inflammatory radiomic features can correlate with evidence-based biological analyses to provide translated value in assessing clinical outcomes in patients with NSCLC. We analyzed a group of 15 patients with stage I NSCLC who showed extremely different OS outcomes despite apparently harboring the same tumor characteristics. We thus analyzed the inflammatory levels in their tumor microenvironment (TME) either biologically or radiologically, focusing our attention on the NLRP3 cancer-dependent inflammasome pathway. We determined an NLRP3-dependent peritumoral inflammatory status correlated with the outcome of NSCLC patients, with markedly increased OS in those patients with a low rate of NLRP3 activation. We consistently extracted specific radiomic signatures that perfectly discriminated patients' inflammatory levels and, therefore, their clinical outcomes. We developed and validated a radiomic model unleashing quantitative inflammatory features from CT images with an excellent performance to predict the evolution pattern of NSCLC tumors for a personalized and accelerated patient management in a non-invasive way.

Diagnostic Contribution of Contrast-Enhanced CT as Compared with Unenhanced Low-Dose CT in PET/CT Staging and Treatment Response Assessment of 18F-FDG-Avid Lymphomas: A Prospective Study.

The aim of this study was to assess the added diagnostic value of contrast-enhanced CT (CECT) as compared with unenhanced CT (UECT) in PET/CT staging and treatment response assessment of 18F-FDG-avid lymphomas. Methods: 170 PET/UECT scans followed by CECT scans were prospectively performed for staging (n = 85) and for treatment response assessment (n = 85) of 18F-FDG-avid lymphomas, during a single session using an integrated 64-slice PET/CT scanner. CECT and UECT images were evaluated separately by 2 radiologists, whereas PET images were evaluated by 2 nuclear physicians. Nodal and extranodal UECT and CECT findings were classified according to the Lugano criteria and were successively compared with PET/CT results, considered the gold standard. In the analyzed groups, the agreement rate with the disease status determined via PET was calculated separately for UECT and CECT using the McNemar test on paired data. The added value of the contrast medium was shown by the agreement between the PET and CECT results and the lack of agreement between UECT and PET. Results: CECT enabled the identification of additional extranodal lesions (hepatic, muscular, and gastric) in only 3 staging group cases (3.5%), indicating different stages as compared with UECT, whereas there was absolute agreement between CECT and UECT in terms of treatment response assessment. The added diagnostic value of CECT was lower than the established threshold for clinical relevance (15%). The McNemar test indicated no statistical significance in either group. The incidental findings detected by CECT but not UECT were important for clinical management but not sufficient to alter lymphoma treatment strategy. Conclusion: According to our results, it might be possible to exclude CECT examination of 18F-FDG-avid lymphoma from staging and treatment response assessment, with the consequent advantages of reducing radiation exposure and potential contrast-related risks.

Locoregional therapy and systemic cetuximab to treat colorectal liver metastases.

AIM: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads (DEBIRI) and cetuximab (DEBIRITUX) of unresectable colorectal liver metastases. METHODS: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma (CRC-LM), progression after first line chemotherapy (any type of chemotherapeutic drug and combination was allowed), second line treatment (mandatory), which included for each patient (unregarding the KRas status) two cycles of DEBIRI (using 100-300 µm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m(2) and then 250 mg/m(2); good performance status (0-2) and liver functionality (alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/mL). Data were collected retrospectively and included: tumor response (evaluated monthly for 6 mo then every 3 mo), overall response rate (ORR), KRas status, type and intensity of adverse events (G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival (OS) and progression free survival (PFS). RESULTS: Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo (range, 4.0-6.5). Sixteen patients (40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders (10%) and 16 (40%) partial responders. The most observed side effects (G2) were: post-embolization syndrome (30%), diarrhea (25%), skin rushes (38%) and asthenia (35%). The retrospective evaluation of KRas status (24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo (8-48 range); median PFS was 9.8 mo and OS was 20.4 mo. Future randomized trials are required in this setting to establish a role for DEBIRITUX compared with systemic chemotherapy. CONCLUSION: DEBIRITUX seems to be efficacious after first line chemotherapy for the treatment of unresectable CRC-LM.

Intra-arterial infusion of irinotecan-loaded drug-eluting beads (DEBIRI) versus intravenous therapy (FOLFIRI) for hepatic metastases from colorectal cancer: final results of a phase III study.

BACKGROUND: Metastases to the liver receive most of their blood supply from the arterial route, therefore for patients with hepatic metastases from large bowel cancer, hepatic arterial infusion adopting drug-eluting beads preloaded with irinotecan (DEBIRI) may offer a chance of cure. PATIENTS AND METHODS: In a multi-institutional study, 74 patients were randomly assigned to receive DEBIRI (36) versus systemic irinotecan, fluorouracil and leucovorin (FOLFIRI, 38). The primary end-point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost and influence of molecular markers. RESULTS: At 50 months, overall survival was significantly longer for patients treated with DEBIRI than for those treated with FOLFIRI (p=0.031, log-rank). Median survival was 22 (95% Confidence Interval CI=21-23) months, for DEBIRI and 15 (95% CI=12-18) months for FOLFIRI. Progression-free survival was 7 (95% CI=3-11) months in the DEBIRI group compared to 4 (95% CI=3-5) months in the FOLFIRI group and the difference between groups was statistically significant (p=0.006, log-rank). Extrahepatic progression had occurred in all patients by the end of the study, at a median time of 13 (95% CI=10-16) months in the DEBIRI group compared to 9 (95% CI 5-13) months in the FOLFIRI group. A statistically significant difference between groups was not observed (p=0.064, log-rank).The median time for duration of improvement to quality of life was 8 (95% CI=3-13) months in the DEBIRI group and 3 (95% CI=2-4) months in the FOLFIRI group. The difference in duration of improvement was statistically significant (p=0.00002, log-rank). CONCLUSION: This study showed a statistically significant difference between DEBIRI and FOLFIRI for overall survival (7 months), progression-free survival (3 months) and quality of life (5 months). In addition, a clinically significant improvement in time to extrahepatic progression (4 months) was observed for DEBIRI, a reversal of the expectation for a regional treatment. This suggests a benefit of DEBIRI treatment over standard chemotherapy and serves to establish the expected difference between these two treatment options for planning future large randomized studies.

Trans-arterial chemoembolization of metastatic colorectal carcinoma to the liver adopting DC Bead®, drug-eluting bead loaded with irinotecan: results of a phase II clinical study.

UNLABELLED: Trans-arterial chemoembolization (TACE) is a promising locoregional therapy for the treatment of primary hepatic tumors and liver metastases. The aim of the study was to define the activity and outcome of using DC Bead, drug-eluting bead, a spherical embolic device capable of being loaded with irinotecan. PATIENTS AND METHODS: We conducted a double institutional, single arm, phase II clinical study to evaluate TACE adopting this device in 82 patients presenting with metastatic colorectal carcinoma to the liver after failing chemotherapy. The primary endpoints were tumor shrinkage, safety, feasibility, compliance, and overall survival. RECIST criteria were used to assess responses. Quality of life (QoL) was addressed using Edmonton SAS improvement scale. RESULTS: Out of 103 patients considered, 82 were enrolled and underwent a total of 185 treatments of TACE. The median number of TACE was 2.2 (1-4). A post-embolization syndrome was frequently observed. Adverse observed effects were: right upper quadrant pain (40%), fever (80%), nausea (27%) and increased transaminases (70%). The median follow-up was 29 months. Within one month after treatment, each patient received a computed tomograpic scan. It showed reduction of metastatic contrast enhancement in all patients. Responses were 78% at 3 months. After the first treatment, 75 out 82 patients declared an improvement of their well being lasting more than 18 weeks. The median duration of response was 6 (range 3-10) months; the median follow up was 29 (range 7-48) months. The median survival was 25 (range 6-34) months, with progression free survival at 8 (range 4-16) months. CONCLUSION: We suggest that TACE adopting DC Bead®, drug-eluting bead loaded with irinotecan could be proposed as palliative therapy for unresectable and chemotherapy resistant liver metastases from CRC.

Intra-arterial hepatic chemoembolization (TACE) of liver metastases from ocular melanoma with slow-release irinotecan-eluting beads. Early results of a phase II clinical study.

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and the liver is the predominant site of metastases (LM). If metastases appear, none of the systemic treatments established for cutaneous melanoma so far have any significant impact. Several authors have adopted transarterial chemoembolization (TACE) as palliation. TACE combines hepatic artery embolization with infusion of concentrated doses of chemotherapeutic drugs. DC Beads are new embolic products that can be loaded with irinotecan (IRI). The beads consist of polyvinyl alcohol microspheres modified with sulfonic acid groups and are available at different size ranges from 100 to 900 microns in diameter. The use of IRI as drug-eluting beads seems to optimize TACE in UM. OBJECTIVE: Our purpose was to assess the safety and efficacy of this new kind of TACE in a phase II clinical study. PATIENTS AND METHODS: Ten patients with LM from UM were treated with TACE-containing beads preloaded with IRI (100 mg). RESULTS: All patients had an objective response, three presented a very good partial response and seven obtained a partial response. The median follow-up time from the beginning of therapy was 6.5 months (range 4-9 months). Eight patients are alive at the time of this analysis. The most important adverse event was abdominal pain during the procedure. Adequate supportive treatment with antibiotic and antiemetic prophylaxis, desametazone and intravenous hydration is strictly necessary until stabilization of serum levels of transaminases and to prevent infections. A major analgesic such as morphine must be used before and after the procedure. CONCLUSION: TACE containing beads preloaded with IRI is effective in the treatment of LM from UM. This approach seems to have better efficacy than previous TACE regimens adopted.

Chemoembolization (TACE) of unresectable intrahepatic cholangiocarcinoma with slow-release doxorubicin-eluting beads: preliminary results.

The purpose of this study was to evaluate the safety and efficacy of TACE with microspheres preloaded with doxorubicin in unresectable intrahepatic cholangiocarcinoma (UCH). Twenty patients with UCH were observed; 9 refused, preferring other palliative care or chemotherapy, and 11 agreed to be treated with one or more cycles of DC beads loaded with doxorubicin (100-150 mg) in a TACE procedure between February 2006 and September 2007. A total of 29 individual TACE procedures were performed. Follow-up imaging was performed on all patients before, immediately after, and 4 weeks after each TACE procedure to evaluate the response and need for further treatment. Each patient received i.v hydration, antibiotics, and medications against nausea and pain before TACE. Survival rate was calculated using Kaplan-Meier survival curve. A response rate of 100% followed RECIST criteria was observed. Eight of eleven patients are alive, with a median survival of 13 months. TACE was well tolerated by all patients. One patient developed hepatic abscess requiring antibiotic therapy. No evidence of marrow toxicity has been reported. Only one of nine patients treated with chemotherapy or palliative care is alive (with a median survival of 7 months in this group of patients). In conclusion, we suggest that doxorubicin-eluting beads TACE is a feasible and effective treatment in patients with UCH. Survival seems to be clearly prolonged in the treated group with respect to the palliative group. We consider that doxorubicin-eluting beads TACE of 100-150 mg may be an appropriate palliative therapy for these patients. Further studies are warranted to confirm these interesting preliminary data.