Gallbladder Cancer: Diagnosis and Surgical Management

Gallbladder cancer (GBCa) is a biliary tract malignancy that is common in South America and Southeast Asia, where patients often present with abdominal pain and jaundice. However, most cases of GBCa in the United States are diagnosed incidentally following cholecystectomy. The pre-operative diagnosis and evaluation involves imaging with ultrasound, CT, MRI, and PET. In patients with incidental GBCa, the histopathology directs further management. The surgical management of GBCa ranges from a simple cholecystectomy to liver resection with lymphadenectomy. Bile duct and vascular resections are reserved to obtain negative margins. To date, multiple controversies remain in the management of GBCa. The determination of type of surgery is based predominantly on T stage. The need for liver resection for tumor on the peritonealized surface continues to be debated. The added value of neoadjuvant and peri-operative therapy is being actively investigated. Systemic therapy has greatly evolved encompassing the use of capecitabine, gemcitabine-cisplatin, with recent addition of taxanes, HER2 inhibitors, and immunotherapy using PD-L1 inhibitors including Durvalumab. This chapter describes current diagnosis and treatment practices for GBCa especially determinants of surgical management and the benefits of peri-operative systemic therapy highlighting the recent advances and shortcomings

Confronto sperimentale della resistenza a bending di due differenti tipologie di ingranaggi tramite prove su singolo dente (STBF)

Il lavoro svolto ha riguardato l’analisi comparativa, mediante prove di fatica su singolo dente, della resistenza a fatica (bending) di ruote dentate a denti diritti realizzate con due diversi trattamenti superficiali. Tale analisi è stata effettuata mediante costruzione di curve S-N e confronto della resistenza a fatica a numero di cicli fissato. Le prove sono state eseguite impiegando una macchina a risonanza che è stata dotata di un’attrezzatura appositamente progettata per poter consentire l’esecuzione di prove su ruote dentate. L’attività svolta, oltre alla progettazione dell’attrezzatura di prova, ha riguardato la valutazione della resistenza a fatica delle ruote dentate secondo quanto proposto dalle principali normative di riferimento e il calcolo delle stato di sollecitazione a piede dente con sw di calcolo agli elementi finiti, finalizzato alla scelta dei valori dei carichi di prova. L’attività sperimentale è stata preceduta dalla definizione di un piano di prova elaborato sulla base dei principali approcci statistici proposti in letteratura, con particolare riferimento allo studio del metodo staircase per la determinazione della resistenza a fatica ad alto numero di cicli. I risultati ottenuti hanno permesso di ottenere un’indicazione chiara sull’effetto dei due trattamenti superficiali presi in esame. L’esperienza maturata ha inoltre consentito di individuare le criticità e i vantaggi che la valutazione della resistenza a fatica di ingranaggi mediante prove a singolo dente assume rispetto alla caratterizzazione sperimentale mediante prove su banco

Anaplastic Pancreatic Carcinoma Arising Within a Mucinous Cystic Neoplasm of the Pancreas: A Case Report and a Brief Review of the Literature

Background: Anaplastic pancreatic carcinomas (APCs) are among the least frequently encountered pancreatic malignancies, ranging from 0.5% to 7% of all nonendocrine pancreatic malignancies. Furthermore, few cases of APCs have been described arising within a pancreatic mucinous cystic neoplasm (MCN). Case Presentation: A 36-year-old female presented with left upper quadrant pain and a 10 × 8 cm complex cystic mass in the pancreatic tail. Fine needle aspiration of the cyst showed papillary clusters of cells with mild cytological atypia, cyst fluid carcinoembryonic antigen >4000 ng/mL, and amylase of 25 U/L. After an open distal pancreatectomy and splenectomy, the specimen revealed an MCN with multifocal microscopic foci of invasive well-differentiated adenocarcinoma. After additional sampling, foci of undifferentiated malignancy—morphologically resembling sarcomas but with immunohistochemical staining consistent with anaplastic carcinoma—were identified. The patient had an uneventful recovery and is currently undergoing a regimen of gemcitabine-based adjuvant chemotherapy; she remains disease-free at 5 months after initial diagnosis. Conclusions: In this study, we describe a rare case of APC originating from a large pancreatic MCN lesion. This case underlines the importance of scrupulous pathological evaluation of the entire MCN epithelium and adds to the limited world literature of APC originating from pancreatic MCN lesions

Anaplastic Pancreatic Carcinoma Arising Within a Mucinous Cystic Neoplasm of the Pancreas: A Case Report and a Brief Review of the Literature

Background: Anaplastic pancreatic carcinomas (APCs) are among the least frequently encountered pancreatic malignancies, ranging from 0.5% to 7% of all nonendocrine pancreatic malignancies. Furthermore, few cases of APCs have been described arising within a pancreatic mucinous cystic neoplasm (MCN). Case Presentation: A 36-year-old female presented with left upper quadrant pain and a 10 × 8 cm complex cystic mass in the pancreatic tail. Fine needle aspiration of the cyst showed papillary clusters of cells with mild cytological atypia, cyst fluid carcinoembryonic antigen >4000 ng/mL, and amylase of 25 U/L. After an open distal pancreatectomy and splenectomy, the specimen revealed an MCN with multifocal microscopic foci of invasive well-differentiated adenocarcinoma. After additional sampling, foci of undifferentiated malignancy—morphologically resembling sarcomas but with immunohistochemical staining consistent with anaplastic carcinoma—were identified. The patient had an uneventful recovery and is currently undergoing a regimen of gemcitabine-based adjuvant chemotherapy; she remains disease-free at 5 months after initial diagnosis. Conclusions: In this study, we describe a rare case of APC originating from a large pancreatic MCN lesion. This case underlines the importance of scrupulous pathological evaluation of the entire MCN epithelium and adds to the limited world literature of APC originating from pancreatic MCN lesions

FOLFIRINOX as Initial Treatment for Localized Pancreatic Adenocarcinoma: A Retrospective Analysis by the Trans-Atlantic Pancreatic Surgery Consortium

Background: Large pragmatic studies of patients who received 5-fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) as initial treatment for localized pancreatic ductal adenocarcinoma (PDAC) are lacking. This study aimed to provide realistic estimates of oncologic outcomes in these patients. Methods: This international retrospective cohort study included all consecutive patients presenting with localized PDAC who received at least 1 cycle of (m)FOLFIRINOX as initial treatment in 5 referral centers from the United States and the Netherlands (2012-2019). Primary outcome was median overall survival (OS), calculated from the date of tissue diagnosis, assessed using Kaplan-Meier estimates. Log-rank test was used to compare OS between groups. A Cox proportional hazards regression model was used to assess prognostic baseline factors for OS. All statistical tests were 2-sided. Results: Overall, 1835 patients were included, of whom 958 (52.2%) had locally advanced (LA), 531 (28.9%) had borderline resectable (BR), and 346 (18.9%) had potentially resectable (PR) PDAC. The median number of (m)FOLFIRINOX cycles was 6 (interquartile range = 4-8). Subsequent treatment included second chemotherapy (12.9%), radiotherapy (49.0%), and resection (37.9%). The resection rate was 17.6% for LA, 53.1% for BR, and 70.5% for PR PDAC (P 1 mm) was 55.2% for LA, 62.6% for BR, and 79.2% for PR PDAC (P 500 U/mL, and body mass index ≤18.5 kg/m2. Conclusions: This large international cohort study provides realistic estimates of resection rates and survival in patients with LA, BR, and PR PDAC who started (m)FOLFIRINOX treatment in PDAC referral centers

Neoadjuvant Radiotherapy After (m)FOLFIRINOX for Borderline Resectable Pancreatic Adenocarcinoma: A TAPS Consortium Study

BACKGROUND: The value of neoadjuvant radiotherapy (RT) after 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan, with or without dose modifications [(m)FOLFIRINOX], for patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is uncertain. METHODS: We conducted an international retrospective cohort study including consecutive patients with BR PDAC who received (m)FOLFIRINOX as initial treatment (2012-2019) from the Trans-Atlantic Pancreatic Surgery Consortium. Because the decision to administer RT is made after chemotherapy, patients with metastases or deterioration after (m)FOLFIRINOX or a performance score ≥2 were excluded. Patients who received RT after (m)FOLFIRINOX were matched 1:1 by nearest neighbor propensity scores with patients who did not receive RT. Propensity scores were calculated using sex, age (≤70 vs >70 years), WHO performance score (0 vs 1), tumor size (0-20 vs 21-40 vs >40 mm), tumor location (head/uncinate vs body/tail), number of cycles (1-4 vs 5-8 vs >8), and baseline CA 19-9 level (≤500 vs >500 U/mL). Primary outcome was overall survival (OS) from diagnosis. RESULTS: Of 531 patients who received neoadjuvant (m)FOLFIRINOX for BR PDAC, 424 met inclusion criteria and 300 (70.8%) were propensity score-matched. After matching, median OS was 26.2 months (95% CI, 24.0-38.4) with RT versus 32.8 months (95% CI, 25.3-42.0) without RT (P=.71). RT was associated with a lower resection rate (55.3% vs 72.7%; P=.002). In patients who underwent a resection, RT was associated with a comparable margin-negative resection rate (>1 mm) (70.6% vs 64.8%; P=.51), more node-negative disease (57.3% vs 37.6%; P=.01), and more major pathologic response with <5% tumor viability (24.7% vs 8.3%; P=.006). The OS associated with conventional and stereotactic body RT approaches was similar (median OS, 25.7 vs 26.0 months; P=.92). CONCLUSIONS: In patients with BR PDAC, neoadjuvant RT following (m)FOLFIRINOX was associated with more node-negative disease and better pathologic response in patients who underwent resection, yet no difference in OS was found. Routine use of RT cannot be recommended based on these data