J. Mielko

Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study

BACKGROUND Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. PATIENTS AND METHODS Patients with fixed cT3 or cT4 cancer were randomized either to 5 × 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. RESULTS Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. CONCLUSIONS No differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy. CLINICAL TRIAL NUMBER The trial is registered as ClinicalTrials.gov number NCT00833131.

Gastric cancer : Epidemiology, prevention, classification, and treatment

Gastric cancer is the second most common cause of cancer-related deaths in the world, the epidemiology of which has changed within last decades. A trend of steady decline in gastric cancer incidence rates is the effect of the increased standards of hygiene, conscious nutrition, and Helicobacter pylori eradication, which together constitute primary prevention. Avoidance of gastric cancer remains a priority. However, patients with higher risk should be screened for early detection and chemoprevention. Surgical resection enhanced by standardized lymphadenectomy remains the gold standard in gastric cancer therapy. This review briefly summarizes the most important aspects of gastric cancers, which include epidemiology, risk factors, classification, diagnosis, prevention, and treatment. The paper is mostly addressed to physicians who are interested in updating the state of art concerning gastric carcinoma from easily accessible and credible source.

Frey operation for chronic pancreatitis associated with pancreas divisum: case report and review of the literature

Pancreas divisum (PD) is the most common congenital anomaly of the pancreas, which increases susceptibility to recurrent pancreatitis. Usually, after failure of initial endoscopic therapies, surgical treatment combining pancreatic resection or drainage is used. The Frey procedure is used for chronic pancreatitis, but it has not been reported to be applied in an adult patient with PD-associated pancreatitis. The purpose of the paper was to describe effective treatment of this rare condition by the Frey procedure after failure of interventional endoscopic treatment. A 39-year-old female patient was initially treated for recurrent acute pancreatitis. After endoscopic diagnosis of PD, the minor duodenal papilla was incised and a plastic stent was inserted into the dorsal pancreatic duct. During the following 36 months, the patient was hospitalised several times because of recurrent episodes of pancreatitis. Thereafter, local resection of the pancreatic head combined with lateral pancreaticojejunostomy was performed with no complications. After 54 months of follow-up, the patient demonstrates abnormal glucose metabolism, with a need for enzyme supplementation, and she is free of pain. Local resection of the pancreatic head combined with lateral pancreaticojejunostomy (Frey procedure) offers a favourable outcome after failure of endoscopic papillotomy and duct stenting for pancreatitis associated with PD.

Prognostic value of p27kip1 expression in adenocarcinoma of the pancreatic head region

BACKGROUND p27(kip1) is a tumour suppressor gene, functioning as a cyclin-dependent kinase inhibitor, and an independent prognostic factor in breast, colon, and prostate adenocarcinomas. Conflicting data are reported for adenocarcinoma of the pancreas. The aim of this study was to establish the prognostic value of p27(kip1) expression in adenocarcinoma of the pancreatic head region. PATIENTS AND METHODS The study included 45 patients (male/female ratio 2:1; mean age 59, range 38-82 years) with adenocarcinomas of the pancreatic head region: 24 - pancreatic head, 18 - periampullary and 3 - uncinate process. The patients underwent the Kausch-Whipple pancreatoduodenectomy (n=39), pylorus-preserving pancreatoduodenectomy (n=5), or nearly total pancreatectomy (n=1). Eight patients received adjuvant chemotherapy postoperatively. Follow-up time ranged from 3 to 60 months. Tumours were staged according to the pTNM classification (UICC 1997). Immunohistochemistry was done on paraffin-embedded blocks from tumour sections. Quantitative determination of p27(kip1) expression was based on the proportion of p27(kip1) -positive cells (< 5% = negative). Survival analysis was carried out using the Kaplan-Meier method and Cox regression model. RESULTS Positive p27(kip1) expression was detected in 22 tumours (49%), whereas 23 tumours (51%) were p27(kip1)-negative. There were no significant correlations between p27(kip1) index and stage or lymph node involvement. Median survival time in patients with p27(kip1)-positive tumours was 19 months, whereas in patients with p27(kip1)-negative tumours it was 18 months (p=0.53). A significant relationship was found between p27(kip1)-negative tumours and radical resection (p=0.04). Multivariate survival analysis revealed that the localization of the tumour (pancreatic head/uncinate process vs periampullary) was the only significant and independent prognosticator (p = 0.01, Cox regression model). Resection margins involvement and grade remained nearly significant prognostic factors (p=0.07 and p=0.09, respectively). CONCLUSION We conclude that p27(kip1) has limited overall prognostic utility in resected carcinoma of the pancreatic head region, but its potential role as a marker of residual disease needs to be further assessed.

Intraoperative radiotherapy with low energy photons in recurrent colorectal cancer: a single centre retrospective study

Aim of the study Intraoperative radiotherapy (IORT) may improve outcome of surgical treatment of recurrent colorectal cancer (CRC). The aim of this study is to determine the feasibility, safety and long-term results of surgical treatment of recurrent CRC with orthovolt IORT. Material and methods Fifty-nine consecutive CRC patients with local recurrence (LR), undergoing surgery, were included in the retrospective analysis of prospectively collected data. The modified Wanebo classification was used to stage LR (Tr). Twenty-five (43%) patients received IORT using INTRABEAM® PRS 500. The complications were classified according to the Clavien-Dindo classification. Results There were 32 males and 27 females, with a median age of 63 years. Multi-visceral resections were performed in 37 (63%) patients. Median hospitalization time after surgery with IORT was 7 days. One (1.7%) in-hospital postoperative death was reported. Grade 3/4 postoperative complications were found in 11 (19%) patients. Intraoperative radiotherapy had no effect on the postoperative hospitalization time, morbidity and mortality. Median survival after R0 resection was 32 months. Complete resection (R0), no synchronous liver metastases (M0), and no lateral and posterior pelvic wall involvement, were significant predictors of improved survival. Stage of LR was found to be an independent prognostic factor in the multivariate analysis (p = 0.03); Cox regression model). In patients with LR stage < Tr5, a 3-year overall survival (OS) rate was 52%. Conclusions Combination of surgical resection and orthovolt IORT is a safe and feasible procedure that does not increase the risk of postoperative complications or prolongs the hospital stay. Despite aggressive surgery supported by IORT, the advanced stage of LR is a limiting factor of long-term survival.

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.

Awareness of hepatic arterial variants is required in surgical oncology decision making strategy: Case report and review of literature

Surgery for the treatment of pancreatic cancer remains the gold standard, however, the identification of the vascular supply of the pancreas and the nearby organs remains a crucial difficulties in a curative resection. During pancreatic head resection for carcinoma dissection of regional arterial vasculature is mandatory. Normal coeliac and hepatic arterial anatomy occurs in ~50–70% of patients and multiple variations have been described. Knowledge of multiple arterial anomalies is essential in hepato-pancreatico-billary surgery to avoid unnecessary complications. The present study presents coeliac trunk and common hepatic artery (CHA) anomalies along with their clinical importance, as reviewed according to the available literature. Patients diagnosed with cancer of the pancreatic head were hospitalized for staging and planning of radical surgical therapy. Computed tomography (CT) revealed a large tumour mass in the head of the pancreas and CHA, which branched directly from the superior mesenteric artery. A three-dimensional CT reconstruction revealed a demonstrative vascular anomaly, which was confirmed during an operation. Despite the anomalous origin of the CHA, pylorus preserving pancreatoduodenectomy and regional lymph node dissection without intraoperative complications was performed in each case. The patients postoperative clinical course was uneventful and adjuvant chemotherapy could be administered without delay. In the multidisciplinary treatment of pancreatic carcinoma the surgeon and radiologist must be aware of the aberrant anatomy in order to avoid potential complications. As CT scans used for the preoperative staging are of diagnostic value for vascular anomaly, it is required for appropriate surgical decision making.

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.