Hepatic Artery Infusion Chemotherapy for Primary and Secondary Malignancies of the Liver: State of the Art and Current High-Level Evidence.

BACKGROUND: Hepatic artery infusion chemotherapy (HAI) has been proposed as a valuable adjunct for multimodal therapy of primary and secondary liver malignancies. This review provides an overview of the currently available evidence of HAI, taking into account tumor response and long-term oncologic outcome. SUMMARY: In colorectal liver metastases (CRLM), HAI in combination with systemic therapy leads to high response rates (85-90%) and conversion to resectablity in primary unresectable disease in up to 50%. HAI in combination with systemic therapy in CRLM in the adjuvant setting shows promising long-term outcomes with up to 50% 10-year survival in a large, non-randomized single-center cohort. For hepatocellular carcinoma patients, response rates as high as 20-40% have been reported for HAI and long-term outcomes compare well to other therapies. Similarly, survival for patients with unresectable intrahepatic cholangiocarcinoma 3 years after treatment with HAI is reported as high as 34%, which compares well to trials of systemic therapy where 3-year survival is usually below 5%. However, evidence is mainly limited by highly selected, heterogenous patient groups, and outdated chemotherapy regimens. The largest body of evidence stems from small, often non-randomized cohorts, predominantly from highly specialized single centers. KEY MESSAGE: In well-selected patients with primary and secondary liver malignancies, HAI might improve response rates and, possibly, long-term survival. Results of ongoing randomized trials will show whether a wider adoption of HAI is justified, particularly to increase rates of resectability in advanced malignant diseases confined to the liver.

Safety and efficacy of laparoscopic digestive tract nutrition reconstruction combined with conversion therapy for patients with unresectable and obstructive gastric cancer.

Background: To explore the safety, efficacy, and survival benefits of laparoscopic digestive tract nutrition reconstruction (LDTNR) combined with conversion therapy in patients with unresectable gastric cancer with obstruction. Methods: The clinical data of patients with unresectable gastric cancer with obstruction who was treated in Fujian Provincial Hospital from January 2016 to December 2019, were analyzed. LDTNR was performed according to the type and degree of obstruction. All patients received the epirubicin + oxaliplatin + capecitabine regimen as conversion therapy. Results: Thirty-seven patients with unresectable obstructive gastric cancer underwent LDTNR, while thirty-three patients received chemotherapy only. In LDTNR group patients, the proportion of nutritional risks gradually decreased, the rate of severe malnutrition decreased, the proportion of neutrophil-lymphocyte ratio (NLR) <2.5 increased, the proportion of prognosis nutrition index (PNI) ≥45 increased, and the Spitzer QOL Index significantly increased at day 7 and 1 month postoperatively (P<0.05). One patient (6.3%) developed grade III anastomotic leakage and was discharged after the endoscopic intervention. The median chemotherapy cycle of patients in LDTNR group was 6 cycles (2-10 cycles), higher than that in Non-LDTNR group (P<0.001). Among those who received LDTNR therapy, 2 patients had a complete response, 17 had a partial response, 8 had stable disease, and 10 had progressive disease, which was significantly better than the response rate in Non-LDTNR group(P<0.001). The 1-year cumulative survival rates of the patients with or without LDTNR were 59.5% and 9.1%. The 3-year cumulative survival rate with or without LDTNR was 29.7% and 0%, respectively (P<0.001). Conclusions: LDTNR can improve the inflammatory and immune status, increase compliance with chemotherapy, and have potential benefits in improving the safety and effectiveness of and survival after conversion treatment.

Conversion surgery by hand-assisted laparoscopic surgery following chemotherapy for rectal cancer with H3 liver metastases: a case report.

Background: Recent advancements in molecularly targeted chemotherapy for stage IV colorectal cancer have enabled the possibility of complete resection in primary colorectal cancer, which often involves distant liver or lung metastases, by aggressive surgical resection followed by multi-combination chemotherapy. Case description: A 73-year-old man treated previously for hyperuricemia, hypertension, and a dissecting abdominal aortic aneurysm was referred to us after an incidental finding of multiple liver masses on abdominal ultrasound during follow-up for the aneurysm. A detailed examination by contrast-enhanced computed tomography revealed a ring-enhancing mass larger than 5 cm in diameter in segment 3 of the liver and more than 6 low-density areas with total diameter of 1 to 2 cm in both lobes. A barium enema examination revealed a Borrmann type 2 lesion covering two-thirds of the circumference of the colon, with a 5-cm major axis in the rectosigmoid colon. Biopsy revealed a well-differentiated adenocarcinoma. The patient was diagnosed with stage IV rectal cancer. Because there was no intestinal obstruction, we administered 9 cycles of bevacizumab with capecitabine and oxaliplatin as chemotherapy. Subsequent diagnostic imaging revealed the metastatic lesions in liver segment 3 had reduced to 2 low-density areas with a diameter of 8 mm, and the other hepatic metastases had disappeared; the main tumor had flattened and shrunk. Therefore, we used hand-assisted laparoscopic surgery (HALS) to perform anterior resection of the rectosigmoid colon and partial resection of liver segment 3 as conversion therapy. The patient was discharged 10 days after surgery. The rectal lesion was a well-differentiated adenocarcinoma with a depth of invasion of p-MP and a spread of L0, V0, and pN0. The partial hepatectomy did not indicate viable cancer cells; only necrotic, lysed tissue was observed. Postoperative chemotherapy involved 4 cycles of bevacizumab with capecitabine and oxaliplatin. At more than 42 months postoperatively, no metastasis or recurrence has been observed. Conclusions: This rare case demonstrates that conversion surgery can be a viable option following systemic chemotherapy in patients with advanced colon cancer and H3 liver metastases.

Advances in Treatment Models of Advanced Gastric Cancer.

The prognosis of advanced gastric cancer (AGC) is extremely poor, and the therapeutic effect of traditional palliative chemotherapy is far from satisfactory. To overcome this bottleneck, palliative surgery resection, perioperative chemotherapy combined with surgical resection, hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), radiation therapy, molecular-targeted therapy have been explored in AGC. Although considerable progress has been achieved, there is still no overwhelming therapeutic method. Due to the high heterogeneity of AGC, it is particularly vital to reshaped the paradigm of gastric cancer therapy according to the characteristics of clinical classifications and molecular subtypes.

Successful Treatment of Advanced Intrahepatic Cholangiocarcinoma With a High Tumor Mutational Burden and PD-L1 Expression by PD-1 Blockade Combined With Tyrosine Kinase Inhibitors: A Case Report.

Advanced intrahepatic cholangiocarcinoma (iCCA) is not suitable for surgical treatment. Guided by the concept of precision medicine, preoperative systematic treatment may reshape the clinical outcomes of advanced intrahepatic cholangiocarcinoma patients. We describe the case of a 38-year-old female who has been diagnosed with stage IV intrahepatic cholangiocarcinoma with a high tumor mutational burden and positively programmed death-ligand 1 (PD-L1) expression. The patient was treated with programmed cell death 1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs). After 7 cycles of combination therapy, she underwent radical resection and no tumor cells were found in the postoperative histopathological examination. In addition, the patient's survival time had reached 25 months, as of August 2021. To date, this is the first case of successful radical resection after combined immunotherapy with TKIs for advanced PD-L1-positive intrahepatic cholangiocarcinoma with a high tumor mutational burden (TMB). The case provides a new approach to the treatment of advanced intrahepatic cholangiocarcinoma.

Complete Response for Advanced Hepatocellular Carcinoma by Conversion Surgery Therapy Following a Good Response of Regorafenib Despite Rapid Progressive Disease with Sorafenib.

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.

Clearance of circulating tumor DNA in a high-risk stage-IV rectal carcinoma patient with synchronous liver metastases after conversion surgery is correlated with pathologic complete response.

Colorectal cancer is the third most common cancer worldwide, and its incidence continues to grow. Approximately one-third of patients with colorectal cancer develop liver metastases during the natural course of disease. Complete surgical resection is associated with very low mortality in colorectal liver metastasis patients, but only a small fraction of colorectal liver metastasis patients fulfill the selection criteria for surgical treatment. We herein describe a high-risk stage-IV rectal carcinoma patient who was initially unresectable according to the National Comprehensive Cancer Network guidelines with a clinical risk score of 4 but received conversion surgery combined with systemic chemotherapy and achieved a favorable long-term clinical outcome (pathologic complete response) of approximately 28 months. Furthermore, serial circulating tumor DNA monitoring using next-generation sequencing provided a comprehensive view of the patient's clinical and pathologic status for better clinical decision support over the course of the disease. The absence of circulating tumor DNA/cells after conversion surgery was correlated with pathologic complete response. This case study not only demonstrated that a curative oncosurgical approach could be considered for high-risk colorectal liver metastasis patients under specific circumstances but also highlighted the role of circulating tumor DNA monitoring to gain further insight into the evolution of a patient's response over time.

Bund katholischer Ärzte: Homeopathic Conversion Therapists in 21st Century Germany.

Even in modern Germany of the 21st century there is still homophobia and other intolerances towards different sexualities and genders. These are also evident in the presence of so-called conversion therapies, which are still offered although there are already legal efforts. Among those groups, the Bund katholischer Ärzte (Association of Catholic Doctors) is a unique curiosity. Although this group is no longer really active, it is currently moving into the German focus again due to criminal charges and reporting in the tabloid press. The aim of this publication is to bring the Bund katholischer Ärzte not only into a more scientific but also into a more international focus. Furthermore, it is an ideal example to show what strange effects homophobia can produce.