Einleitung/Background

Although therapeutic recommendations for the surgical treatment of synchronously occurring liver metastases in the treatment of PDAC are existing, a metachronous metastasis after resection of the primum continues to pose major challenges for the treating physicians.

Even if large-scale case-series and randomized trials on this topic are missing, small case series and case reports already show a benefit for resections of metachronous isolated lung metastases. On the basis of a case study, we are presenting an (aggressive) surgical therapy approach which led to a significant OAS increase.

Material and methods:

We are presenting the case of a 79-year-old female patient with newly emerged pulmonary nodules in both lungs 42 months after initial surgical treatment of neoadjuvant treated PDAC. The nodules were surgically removed (with histological confirmation of the PDAC metastasis). After another 12 months, the patient showed new nodules in the right lung which were treated with microwave ablation. 27 months after this treatment, we detected another three foci in the left lung which were surgically removed. (with the histological confirmation of PDAC metastases).

Result:

After this last treatment the patient is now free of signs of disease

Conclusion:

Despite the lack of corresponding literature recommendations, the clinical oncological course, in this case, is justifying the repeated surgical procedures.

This case underlines that there must be an opinionated and willful surgical representative in the tumor board.

Molecular patterns, laboratory values and clinical parameters which help to identify patients who are more likely to benefit from such therapies are desirable.

Introduction

CRC is the third most common tumor entity in the Western world. New CRC cases will increase from 1.9 million to 3.2 million untill 2040. Although environmental factors are an increasing risk factor today, genetic aberrations play a key role in CRC development and tumorigenesis. In particular, the K-ras oncogene seems to be of immense importance as a "gatekeeper" of the adenoma-carcinoma sequence.

Whether the mutation status per se has a prognostic power for overall survival or leeds to a higher probability of metastatic formations remains unclear.

Methods

The aim of our study was to find out whether the K-ras mutation status itself influences the probability for metastatic formations or not. We performed a retrospective workup of over 600 patients treated in three centers. Primarily, the distributions were represented by means of descriptive statistics. Statistical analyses were then used to show a difference in cancer-specific survival and metastasis formation for patients with or without K-ras mutation.

Results

The hypothesis that K-RAS status affects the cancer-specific survival was evaluated and rejected using Kaplan-Meier curves and log rank tests. Neither the univariate nor the multivariate analysis showed a significant difference. The K-ras mutation status showed a slightly higher metastasis rate in the case of right-sided tumors.

Conclusion

With our study results, the prognostic significance of K-ras mutation status for the distribution of metastasis can be refuted. Only for the subgroup of right-sided carcinomas with a K-ras point mutation on codon thirteen, there seems to be a slightly higher probability of metastasis.

Einleitung/Background
A minority of hepatocellular carcinoma (HCC) patients is susceptible to
conventional immune checkpoint blockade (ICB). Interestingly, the immune-exhausted class, which is associated with poor response to ICB, is also linked to “highly activated”, aberrant TGF-beta signaling. In HCC, the receptor tyrosine kinase Axl collaborates with TGF-beta by the phosphorylation of Smad3 at serine-213 in the linker region (Smad3L-Ser213) causing an aberrant, tumor-promoting TGF-beta signaling, which most likely also translates into the TME. As underlying mechanisms remain unclear, we aim to assess how Smad3L-Ser213-linked TGF-beta signatures shape an immuno-suppressive TME.

Methoden/Methods
We used RNA-seq analysis of HCC models to identify targets of the Axl/TGF-beta
signaling. Modulation of Axl/TGF-beta activity and analyses in publicly available data sets of HCC patients were employed to verify target expression.

Ergebnisse/Results
HCC cells showing aberrant TGF-beta signaling together with either proficiency or
deficiency in Axl expression, were subjected to RNA-seq analysis. Uridine phosphorylase (UPP)1 as the most promising target is associated with poor prognosis and immune evasion. Interference with Smad3L-Ser213 phosphorylation by inhibition of 14-3-3ζ or c-JNK confirmed UPP1 as a target of aberrant TGF-beta signaling. Genetic intervention with UPP1 reduced cell invasion and migration, while proliferation and survival of HCC cells remained unaffect

Zusammenfassung/Conclusion
We identified UPP1 as a target of Axl-driven, aberrant TGF-beta signaling in HCC
cells. The link to immune escape and poor prognosis provides a clear rationale for further assessing its impact in reshaping the TME based on in vivo models and analyses in prospective HCC patient samples

Background:
Minimally invasive surgery is becoming the method of choice for esophageal resection for cancer worldwide.

Methods:
Retrospective analysis of prospectively collected clinical data in a tertiary care center with a detailed description of our program progression.

Results:
Between 2010 and 2023, 136 transthoracic esophagus resections were carried out in total. The study group comprises 116 operations, 69 completely minimally invasive and 47 in hybrid technique. 80,0% of the study group were operated within a multimodal approach. The median operation time was 431 min (±103). The R0 resection rate was 100%. Fourty-two patients (36,2%) had no postoperative complications. Postoperative Morbidity Clavien-Dindo >IIIb was 27 %. Postoperative 90d mortality was 1,7%. The mean number of harvested lymph nodes in the last fourth of cancer patients was 31. The anastomosis insufficiency rate for reoperation was 4% (Ivor-Lewis 4,2%, McKeown 5%).

Conclusions:
With extensive expertise in minimally invasive abdominal and thoracic high-end surgery, implementing a minimally invasive esophagus resection program is feasible with a clinical and oncologic outcome within generally accepted limits.

Einleitung/Background

Up to 40% of patients at the initial diagnosis of pancreatic cancer are without secondary blastomas. These occur more often in the liver and peritoneum, rarely in the adrenal glands and bones. There are only 10 case reports in the English literature describing metastasis to the colo-rectum.

Methoden/Methods

An 82-year-old patient presented to the emergency room with abdominal pain, nausea, vomiting and stool retention. The CT scan showed the picture of a mechanical colon ileus. The patient had been treated oncologically for UICC stage IV pancreatic adenocarcinoma of the pancreatic tail. Metastases in the liver segment VII and in the rectum had been radiologically and histologically confirmed, whereas a metastasis in the stomach had been described only radiologically. Since the initial diganosis the patient had received palliative chemotherapy which stabilized the disease for 19 months. A laparotomy with deep anterior rectum resection and creation of a stoma of the descending colon was performed. Histological workup confirmed the metastasis. The postoperative course was uneventful, palliative chemotherapy was continued and the patient lived another 8 months.

Ergebnisse/Results

Colo-rectal metastasis from pancreatic carcinoma has rarely been described. The most commopn location of secondary blastomas were the sigmoid colon and the transverse colon. The mean survival rate was 7 months after the initial diagnosis, our patient survived for 27 months.

Zusammenfassung/Conclusion

This is the 11th case of colon metastasis from pancreatic cancer in the English literature. It is important to consider metastasis if a colonic mass occurs in the presence of pancreatic cancer.