Ryszard Wierzbicki

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: A prospective multicentre study

PURPOSE To assess local control after preoperative radiation and local excision and to determine an optimal radiotherapy regimen. METHODS Eighty-nine patients with G1-2 rectal adenocarcinoma <3-4 cm; unfavourable cT1N0 (23.6%), cT2N0 (62.9%) or borderline cT2/cT3N0 (13.5%) received 5 × 5 Gy plus 4 Gy boost (71.9%) or 55.8 Gy in 31 fractions with 5-FU and leucovorin (28.1%). Local excision (traditional technique 56.2%, transanal endoscopic microsurgery 41.6%, Kraske procedure 2.2%) was performed 6-8 weeks later. If patients were downstaged to ypT0-1 without unfavourable factors (good responders), this was deemed definitive treatment. Immediate conversion to radical surgery was recommended for remaining patients. RESULTS Good response to radiation was seen in 67.2% of patients in the short-course group and in 80.0% in the chemoradiation group, p = 0.30. Local recurrence at 2 years (median follow-up) in good responders was 11.8% in the short-course group and 6.2% in the chemoradiation group, p = 0.53. In the total group, a lower rate of local recurrence at 2 years was observed in elderly patients (>69 years, median value) when compared to the younger patients; 8.3% vs. 27.7%, Cox analysis hazard ratio 0.232, p = 0.016. A total of 18 patients initially managed with local excision required conversion to abdominal surgery but either refused it or were unfit. In this group, local recurrence at 2 years was 37.1%. CONCLUSIONS This study suggests an acceptable local recurrence rate after preoperative radiotherapy and local excision of small, radiosensitive tumours in elderly patients.

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.

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders

BACKGROUND AND PURPOSE To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer. MATERIALS AND METHODS Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5x5Gy+4Gy boost (N=31) or chemoradiation (50.4Gy+5.4Gy boost, 1.8Gy per fraction+5-fluorouracyl and leucovorin; N=13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin. RESULTS The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure. CONCLUSION Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.

Preoperative radiotherapy and local excision of rectal cancer: Long-term results of a randomised study

BACKGROUND AND PURPOSE It is uncertain whether local control is acceptable after preoperative radiotherapy and local excision (LE). An optimal preoperative dose/fractionation schedule has not yet been established. MATERIAL AND METHODS In a phase III study, patients with cT1-2N0M0 or borderline cT2/T3N0M0 < 4 cm rectal adenocarcinomas were randomised to receive either 5 × 5 Gy plus 1 × 4 Gy boost or chemoradiation: 50.4 Gy in 28 fractions plus 3 × 1.8 Gy boost and 5-fluorouracil with leucovorin bolus. LE was performed 6-8 weeks later. Patients with ypT0-1R0 disease were observed. Completion total mesorectal excision (CTME) was recommended for poor responders, i.e. ypT1R1/ypT2-3. RESULTS Of 61 randomised patients, 10 were excluded leaving 51 for analysis; 29 in the short-course group and 22 in the chemoradiation group. YpT0-1R0 was observed in 66% of patients in the short-course group and in 86% in the chemoradiation group, p = 0.11. CTME was performed only in 46% of patients with ypT1R1/ypT2-3. The median follow-up was 8.7 years. Local recurrence incidences and overall survival at 10 years were respectively for the short-course group vs. the chemoradiation group 35% vs. 5%, p = 0.036 and 47% vs. 86%, p = 0.009. In total, local recurrence at 10 years was 79% for ypT1R1/T2-3 without CTME. CONCLUSIONS This trial suggests that in the LE setting, both local recurrence and survival are worse after short-course radiotherapy than after chemoradiation. Because of the risk of bias, a confirmatory study is desirable. Lack of CTME is associated with an unacceptably high local recurrence rate.

The use of rifaximin in pre-operative period of patients with tumors ofthe gastrointestinal tract – a retrospective study (2013-2016)

ntroduction: One of the most important goals of preparing a patient for elective gastrointestinal cancer surgery is prevention of postoperative complications. The literature gives many ways to prepare for surgery, but only a few suggests that pre-operative use of rifaximin provides benefits in the form of fewer perioperative complications and reduces the severity of pain during this period. O bjective: The presented project is a retrospective analysis of the effectiveness of rifaximin in the prevention of perioperative complications in patients treated in the Unit of General Surgery with the Orthopedic and Urology in the Hospital of the Ministry of the Interior and Administration in Lublin, and a review of international literature in this subject. MATERIALS AND METHODS A retrospective analysis of the results of pre-operative use of rifaximin was performed in 181 patients scheduled for rectal and colorectal cancer between 2013 and 2016 in the General Surgery Unit with the Orthopedic and Urology in the Hospital of the Ministry of Interior and Administration in Lublin. Patients undergoing urgent surgery were excluded from the study. Patients were divided into 2 groups. The first group of 139 patients - patients operated on for rectal and colorectal cancer in 2013 until 2015, in whom rifaximine was not used in the preoperative period. The second group is 42 patients, operated on in 2016, in which the rifaximin was used in the pre-operative period at a dose of 2x2 tablets (400 mg) per day, 12-hour interval, for 7 days before the planned operation. Additionally, a probiotic was administered for 7 days. Drugs were ordained at the Oncological Outpatient Clinic as part of the pre-hospitalization check. R esults: The use of rifaximin in the preoperative period in patients with colorectal cancer had an effect on shortening the time of post-operative hospitalization and reduced post-surgical pain in comparison with the control group. The analysis of the cynumber and intensity of surgical complications in both groups did not differ. C onclusions: Large studies on the influence of rifaximin on the development of colorectal cancer have not been published so far. Only single reports suggest that its use has a positive effect on the perioperative period of patients treated for colorectal cancer including rectum and our retrospective analysis confirms these observations.

Helicobacter pylori associated factors in the development of gastric cancer with special reference to the early-onset subtype

Nowadays, gastric cancer is one of the most common neoplasms and the fourth cause of cancer-related death on the world. Regarding the age at the diagnosis it is divided into early-onset gastric carcinoma (45 years or younger) and conventional gastric cancer (older than 45). Gastric carcinomas are rarely observed in young population and rely mostly on genetic factors, therefore provide the unique model to study genetic and environmental alternations. The latest research on early-onset gastric cancer are trying to explain molecular and genetic basis, because young patients are less exposed to environmental factors predisposing to cancer. In the general population, Helicobacter pylori, has been particularly associated with intestinal subtype of gastric cancers. The significant association of Helicobacter pylori infection in young patients with gastric cancers suggests that the bacterium has an etiologic role in both diffuse and intestinal subtypes of early-onset gastric cancers. In this paper we would like to ascertain the possible role of Helicobacter pylori infection in the development of gastric carcinoma in young patients. The review summarizes recent literature on early-onset gastric cancers with special reference to Helicobacter pylori infection.