Karol Rawicz-Pruszyński

Distinct molecular subtypes of gastric cancer: from Laurén to molecular pathology

In Western countries the majority of gastric cancers (GC) are usually diagnosed in advanced stages reporting a 5-year survival rate of only 26%. The Laurén classification of GC was most widely used in clinical practice since it reflects GC morphology, epidemiology, tumor biology, clinical management and outcome. Despite the initial promise of individualizing antitumor treatment, the management of GC still remains relatively broad and general. Apart from clinical staging, molecular profiling enables targeting of the identified underlying alterations, rather than histology. In contrast to breast carcinoma, molecular classification of GC does not yet imply treatment modality. Molecular classifications of GC and their therapeutic implications are therefore extensively studied. The current proposed molecular divisions of GC come from three different parts of the world where different standard treatment modalities for advanced GC are recommended. Wider use of GC molecular subtyping may solve problems, such as susceptibility to novel systemic therapy regimens or selection of patients for aggressive surgery and targeted adjuvant/conversion therapy. In any case, the rapid entry of novel molecular targeted therapies into routine oncology practice clearly underscores the urgent need for clinicians to be aware of these new possibilities.

Duodenal obstruction due to annular pancreas associated with carcinoma of the duodenum

Annular pancreas, the second most common anomaly of the pancreas, is the development of a ring of pancreatic tissue that surrounds and often embraces the duodenum. It was first described by Tiedelmann in 1818 and named “annular pancreas” by Ecker in 1862 [1]. It is usually present in childhood, with symptoms due to duodenal obstruction. In 50% of cases, clinical manifestations become visible after childhood, with abdominal pain, chronic duodenal obstruction, peptic ulceration, obstructive jaundice, pancreatitis, and pancreatic head mass [2, 3]. Therefore, duodeno-jejunostomy is usually applied to relieve strictures caused by such an annulus. Bypass surgery is the treatment of choice [4]. Primary duodenal carcinoma is rare and represents 0.3% of all gastrointestinal malignancies and 25–35% of malignant tumours of the small intestine [5, 6]. Resectability and the presence of distant metastatic disease are the strongest determinants of outcome for patients with duodenal adenocarcinoma. In cases of cancers of the first and second part of the duodenum, the most common procedure is pancreaticoduodenectomy. Despite advancements in techniques of diagnosis and resection and decreased perioperative mortality and morbidity, 5-year survival varies from 37% [7] to 57% [8]. Malignancy in the setting of annular pancreas is an unusual event, and hence only a few cases associated with pancreatic carcinoma, ampullary carcinoma, and cholangiocarcinoma have been reported [9–13]. Only 1 case of annular pancreas associated with duodenal carcinoma has been reported, but without description of the follow-up [14]. We report a case of duodenal carcinoma in a patient with an annular pancreas treated with radical surgery with complete follow-up data. A 53-year-old lady suffered from nausea, post-prandial fullness, and vomiting, and weight loss. She was diagnosed (endoscopy Figure 1, CT scan of the abdomen Figure 2) to have duodenal obstruction with gastric bezoar. The upper intestinal contrast study findings of annular filling defect in the duodenum, prestenotic dilatation, and reverse peristalsis in the proximal segment were suggestive of annular pancreas. A pathology report of the endoscopic biopsy material taken from the stenotic part of the duodenum revealed suspicion of malignancy, i.e. atypic cells. The patient was scheduled for a laparotomy with intraoperative pathological investigation of the suspected lesion, and if malignancy is proven a pancreaticoduodenectomy is anticipated. During the operation a band of fibrous (probably pancreatic) tissue of hard texture encircling the second part of the duodenum was found (Figure 3). Division of the pancreatic ring was done and the abnormal tissue sent for immediate pathology. Once malignant diagnosis was confirmed, and classical Kausch-Whiple pancreaticoduodenectomy with standard lymphadenectomy was done without perioperative complications. The resection specimen had been routinely fixed in buffered 10% formaldehyde and embedded in paraffin wax (Figure 4). Operative time was 300 min, and blood loss was 420 ml. The postoperative course was uneventful; therefore, the patient was discharged from the hospital on the sixteenth postoperative day. A definitive pathological report confirmed tubular carcinoma (G2) of the duodenum associated with the annular pancreas with no lymph node involvement (pT2N0M0) (Figures 5–8). No adjuvant chemotherapy was administered. The patient was followed-up every 3 months thereafter for the first 3 years. In the first (2008) and second year (2009) of the follow-up, abdominal CT-scan was done without signs of recurrence. After 54 months the patient became heavily jaundiced and cachectic, and was therefore hospitalised. Advanced loco-regional recurrence was found on MR cholangiogram, with no liver metastases. The patient died, and no autopsy was performed. Figure 1 Endoscopic view of the duodenum showing ulceration with duodenal stenosis at the second portion Figure 2 Computed tomography scan image revealing a significant dilatation of the stomach with bezoar and the proximal duodenum Figure 3 Intraoperative view of the annular pancreas encircling the second part of the duodenum Figure 4 Cross-sectional view showing the duodenum surrounded by the pancreas tissue (annular pancreas) Figure 5 Tubular adenocarcinoma of the duodenum. Neoplastic tubules border on normal duodenal glands (four-micron sections of representative blocs of the lesion were stained with haematoxylin and eosin (H + E); 100×) Figure 8 Fragment of the pancreas (annular pancreas), which is not involved in cancerous infiltrate (H + E; 100×) Figure 6 Tubular adenocarcinoma of the duodenum. Neoplastic tubules border on normal duodenal glands (four-micron sections of representative blocs of the lesion were stained with haematoxylin and eosin (H + E); 200×) Figure 7 Neoplastic infiltrate of the muscular coat of the duodenum encompasses both an inner circular layer and an outer longitudinal layer (H + E; 100×) Annular pancreas is a rare congenital abnormality, and in adult patients it presents with clinical features that differ from those seen in newborns [15]. Duodenal obstruction is a rare symptom of annular pancreas in adults. It is necessary to remember about the coexistence of the annular pancreas when patients with pancreatic or periampullary malignancies are complicated with unexpected obstruction of the second portion of the duodenum in proportion to the size [9]. Features in the adult patient include peptic ulceration, duodenal obstruction, acute pancreatitis, and obstructive jaundice. Treatment strategies for annular pancreas with obstructive jaundice remain controversial, but usually pancreaticoduodenectomy is necessary [2]. In adult patients pancreatic head malignancy usually produces jaundice, and more rarely duodenal obstruction. Nearly always the main cause of this clinical picture is pancreatic head carcinoma, but pancreas annulare should be taken into consideration. The duodenal ring should always be verified on pathological examination since it may harbour this rare type of adenocarcinoma. In adult patients with duodenal obstruction due to annular pancreas, consideration of associated or coexisting duodenal malignancy is mandatory. Only radical surgery (pancreaticoduodenectomy) may provide long-term survival in such cases.

Current challenges in gastric cancer surgery: European perspective

Gastric cancer (GC) remains one of the most common causes of cancer death worldwide with expected 5-year survival rates around 25% in Western countries. In order to improve treatment strategy, a most effective staging process should be completed. A novel TNM staging for GC has been proposed recently, along with a separate staging system for GC patients who underwent preoperative therapy (ypStage). Availability of high-quality imaging and access to diagnostic laparoscopy with lavage cytology should be applied while planning the multimodal therapy. In the European setting, GC treatment is based on a combination of surgery and perioperative chemotherapy. However, in selected groups of patients with high risk of locoregional recurrence, adjuvant chemoradiotherapy should be considered. New epidemiological trends of GC in the Western countries include an upward shift in the location of the primary tumour and a relative increase of advanced and diffuse type tumours. These trends dictate modification of surgical techniques towards a more individualized GC treatment approach.

Liver metastases from gastric carcinoma: A Case report and review of the literature

Gastric carcinoma (GC) is the fifth most common malignancy worldwide but the third leading cause of cancer death, and surgery remains the only curative treatment option. Prognosis of patients with liver metastases from gastric carcinoma (LMGC) is poor, and the optimal treatment of metastatic gastric cancer remains a matter of debate. In 2002, a 53-year-old male patient with GC and synchronous oligometastatic lesion in liver VIII segment underwent a total gastrectomy combined with metastasectomy. The pathologic diagnosis was stage IV gastric adenocarcinoma (pT3N2M1), which was treated with adjuvant chemotherapy (cisplatin, epirubicin, leucovorin, and 5-fluorouracil). In 2012, abdominal ultrasound and percutaneous liver biopsy revealed recurrence of the metastasis in the right liver lobe. Progression of the disease was observed after palliative chemotherapy (epirubicin, oxaliplatin, and capecitabine). Nevertheless, an extended right hemihepatectomy, with excision of segments 1, 4A, 5, 6, 7, and 8, was still performed. Pathologic examination confirmed large KRAS- and HER2-negative LMGC. The patient is alive and free of disease 47 months after the repeated hepatectomy and 13 years after removal of the primary GC and synchronous liver metastasis. Based on review of 27 articles, 5-year overall survival rate following gastrectomy and liver metastasectomy may reach 60%, with median survival time up to 74 months. Although the combination of aggressive surgical approach with systemic therapy for LMGC is controversial, it may allow favorable outcome. Careful selection of patients based on evaluable predictive factors for R0 surgical resection of both primary tumor and liver metastases can lead to cure, as shown in our case presentation, where a 10-year relapse-free survival was observed, followed by successful repeated hepatectomy due to liver metastases.

Treatment of peritoneal metastases from gastric carcinoma

Abstract Patients with advanced gastric cancer and positive peritoneal cytology and/or peritoneal dissemination are deemed to be incurable and to hold dismal prognosis. So far, the only treatment option for these patients has been palliative systemic (chemo)therapy. However, for the last three decades, great progress has been made in attempts to treat (potential) peritoneal dissemination by means of complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) after preoperative systemic therapy. This review is focused on the recent achievements of this multimodal strategy. Additionally, the review stands as background for the 4th International Conference “Advances in Surgical Oncology” that was held at the Medical University of Lublin (Poland) in November 2017, and dedicated to cytoreductive surgery and HIPEC for advanced gastric cancer.

Data on the quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies: does it concern patients with gastric cancer?

Abstract Introduction. So far there are no reports devoted exclusively to the quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in metastatic gastric cancer. Current literature concerning this issue was, thus, reviewed in order to: 1) search for such data concerning metastatic gastric cancer; 2) assess if the latest reviews evenly pertain to all peritoneal surface malignancies; and 3) conclude if they are a reliable source of data for patients with metastatic gastric cancer. Materials and Methods. The electronic PubMed/MEDLINE and EMBASE databases were retrieved for studies concerning the influence of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on quality of life in patients with metastatic gastric cancer and regardless of initial diagnosis. The data on the number of patients with particular tumours were analysed and the results were presented in the form of a table. Results. Approximately half of all patients encompassed by the reviews had a form of primary peritoneal surface malignancies. Within peritoneal metastases, the most numerous were colorectal (21-24%) and ovarian cancers (5-15%). Gastric cancers and sarcomas were the smallest defined subgroups (4% each). Conclusions. The promising outcomes in quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in primary peritoneal surface malignancies might differ from rarely reported ones in metastatic gastric cancer. The problem needs further, gastric cancer-devoted investigations.

Advances in surgery for peritoneal surface malignancies

Abstract Currently, patients with isolated peritoneal surface malignancies are treated with a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This combination should now be considered the standard of care for appendiceal cancers (including pseudomyxoma), colorectal cancer and peritoneal mesothelioma, while patients with peritoneal metastases from ovarian or gastric cancer may be treated within clinical trials. At present, 8 clinical centres in Poland perform CRS and HIPEC. The unanswered problems of combined intraperitoneal therapy were an impulse for the organization of the 4th International Conference “Advances in Surgical Oncology” that was held on November 23-24, 2017, in Lublin (Poland), and the Polish chapter of the Peritoneal Surface Oncology Group International (PSOGI) was established as a result of this meeting. This special issue of the Current Issues in Pharmacy and Medical Sciences is dedicated to the current therapeutic difficulties discussed during the two days of the conference – experiences that were exchanged to set in motion further directions for the improvement of intraperitoneal treatment.